Medical Research Report 2013

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Pediatric
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Nursing
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Pediatric Gastroenterology

neuropediatric

PEDIATRIC
UROLOGY

Otolaryngology

Reproductive Endocrinology Ultrasound
G a u c h e r Rheumatology C A R D I O L O G Y
Psychiatry

SHAARE ZEDEK MEDICAL CENTER JERUSALEM

Intensive
Care

2013

Pediatric Pulmonology

Pediatric Rehumatology

Endocrinology

Research Report 2013

Medical Cardiothoracic
Genetics Surgery

Gynecology&
Obstetrics

SHAARE ZEDEK MEDICAL CENTER
JERUSALEM

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P
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Pathology

Research Report
2013

SHAARE ZEDEK MEDICAL CENTER
JERUSALEM

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Neurology

Research & Development

Research Report
2013

Research Report
2013

Shaare Zedek
Medical Center
Jerusalem

Published by the Department of Resource Development and Public Affairs
Shaare Zedek Medical Center, Jerusalem
P.O.B 3235 Jerusalem 91031
Tel: 02-6666622, Fax: 02-6522950

www.szmc.org.il

Project Head: Professor Dan Turner
Assistant Project Head: Dr. Keren-Or Amar
Coordinator: Leora Shoham-Peters
English Editor: Esther Singer
Design and Production: viim.co.il

Research and Development at the Shaare Zedek Medical Center
Internal Medicine

8
13

Division of Internal Medicine
Department of Hematology
Digestive Diseases Institute
Gaucher Clinic
Medical Genetics Institute
Stem Cell Research Laboratory
Institute of Oncology
Integrated Oncology Department
Nephrology Unit
Neurology and Toxicology Service and Unit
Pulmonary Unit
Neurology Department
Department of Geriatrics
Rheumatology Unit
Endocrine Unit
Angiography Unit – Interventional Radiology Unit
Department of Cardiology

14
21
41
45
54
64
67
72
77
81
91
95
98
102
106
110
115

Pediatrics123
Division of Pediatrics
Pediatric Gastroenterology Unit
Pediatric Infectious Diseases Unit
Pediatric Rheumatology Unit
Neuropediatric Unit
Department of Neonatology

3


124
125
135
141
148
156

Division of Pediatric Nephrology
Pediatric Pulmonology Unit
Pediatric Hematology-Oncology
Pediatric Endocrinology Unit

161
167
172
176

Obstetrics, Gynecology IVF

179

In Vitro Fertilization (IVF) Unit
Pediatric Genetics Unit
Reproductive Endocrinology and Genetics Unit
Zohar Preimplantation Genetic Unit (PGD)
Department of Obstetrics and Gynecology
Department of Obstetrics and Maternal Fetal Medicine
Surgery and Anesthesia

180
183
187
193
198
202
209

Department of General Surgery
210
Department of Cardiothoracic Surgery
216
Department of Plastic Surgery
222
Department of Anesthesiology - Perioperative Medicine and Pain Treatment
225
Department of Otolaryngology - Head and Neck Surgery
230
Department of Pediatric Urology
235
Department of Orthopedic Surgery
240
Imaging, Emergency, ICU and Pathology

245

Intensive Care Unit (ICU)
Imaging Department
Ultrasound Unit
Institute of Pathology
Emergency Department

246
251
255
259
261


4

Nursing and Complementary Care
Medical Ethics Department
Consultation - Liaison Psychiatry Unit
Center for Integrated Complementary Medicine
Nursing Division

265
266
269
272
276

Index279

5


A

medical institution on the cutting edge of science
and technological development, Shaare Zedek Medical Center takes considerable pride in our expanding
high-level research.
This latest edition of the Shaare Zedek Research Report testifies to the growing range of studies carried out by our staff.
Our physicians, who embrace research as part of their practice of modern medicine, are not only excellent role models
for the next generations of physicians but clearly demonstrate that research is a central component of what it means
to be a quality caregiver in the 21st century.
Clinical medicine must go hand in hand with advances in science if we are to ensure that our patients receive truly comprehensive attention.
We are confident that the recent agreement between Shaare
Zedek and the Yissum Research Development Company of
the Hebrew University of Jerusalem will lead to significant
discoveries with concrete applications in transfer technology.
We are convinced that the accomplishments made possible
by this agreement will allow us to take giant steps forward in
clinical practice for the betterment of the medical community
both in Israel and around the world.
I would like to express my thanks and appreciation to Prof.
Dan Turner, Managerial Coordinator of Research in the hospital, Dr. Keren-Or Amar, Director of Shaare Zedek’s Research and Development Authority and Ms. Leora ShohamPeters for all their efforts in the compilation and publication
of this report.

Prof. Jonathan Halevy, MD
Director General

7


Research and Development at the
Shaare Zedek Medical Center
Dr. Keren-Or Amar Head, The Research Authority
Prof. Dan Turner Director General Assistant for RD

Over the past several years there has been a significant increase in both the volume and cutting edge research conducted at Shaare Zedek Medical Center. This stems primarily
from the hospital staff’s growing involvement in research and
the increasing recognition of the hospital by other national
and international academic institutions. In addition, several
recent major administrative reforms in the managerial sector have further facilitated research endeavors in the hospital. These major steps include the appointment of a research
affiliate to Director General Prof. Jonathan Halevy in 2009
(Prof. Dan Turner) as an integral partner in the senior hospital management, reflecting the high priority ascribed by
the hospital management to promoting research activity.
This paved the way for an agreement with Yissum, the technology transfer company of the Hebrew University, in June
2011. This strategic collaboration has vastly extended research opportunities and joint projects with laboratories at
the Hebrew University and enables Shaare Zedek's researchers to benefit from Yissum’s professional intellectual property
management services. The immediate result has been the rise
in research projects with a potential for commercialization.
In the last 18 months, Shaare Zedek has signed two license
agreements, and four patents are pending. In addition, more
than ten projects are in different stages of the commercialization process, compared to none in the years preceding these
reforms. Finally, the Shaare Zedek Research Development
Authority, which was established in September 2011 and is
headed by Dr. Keren-Or Amar, has prioritized the coordination of research activities in the hospital. The RD Authority
facilitates and assists the hospital staff in obtaining external


8

and internal research support, handles legal and research contacts with third parties, sets up
research collaborations with external labs and researchers, and coordinates the hospital’s continuous contacts with Yissum and funding agencies. In late 2011, a lawyer (Matan Menachem)
was asked to oversee the legal side of the hospital’s research activity. Much effort has been invested in ensuring timely execution of contracts with industry and other research authorities.
An internal regulatory reform, passed in 2012, now enables parties to conduct legal negotiations while ethics submissions are in process, thereby considerably reducing the start time of
research projects.
However, the rapid development of the hospital’s research activities is first and foremost the
outcome of a growing number research projects initiated by researchers. One clear indication
of the success of this venture is the accelerating number of peer-reviewed articles published by
the physicians and researchers of Shaare Zedek (Figure 1).

Figure 1: Increase in the number of peer-reviewed publications at Shaare Zedek Medical Center
The latest publication of the Israel National Institute for Health Policy (NIHP) Research ranked
Shaare Zedek among the top eight hospitals in terms of number of publications (Glazer et al,
2012) and we assume it would rank even higher if the hospital publications were compared in
terms of number of physicians employed or number of hospital beds . The number of approvals of clinical research projects authorized by the institutional ethics committee (headed by Dr.
Van Dijk) has almost doubled in five years (Figure 2).

9

Research Development

Figure 2: Number of clinical research projects approved by the institutional ethics committee

The contribution of research conducted by physicians to humankind is crucially important,
but it is also our belief that physicians who are involved in research also deliver better clinical
care. Almost every department at Shaare Zedek is involved in clinical research, and high impact basic science projects are conducted in eight research labs. Clinical trials initiated either
by hospital physicians or by the biomedical industry are carried out regularly at the hospital in
which the units, departments, staff and patients serve as the infrastructure for these studies.
A modest animal facility enables in-vivo experiments for small studies. The close collaboration
with Yissum and the affiliation of Shaare Zedek with the Hebrew University has created additional opportunities for using the labs and infrastructure of the University. The stimulating
atmosphere of research activity and the high motivation of the hospital researchers have led to
a high percentage of investigator- initiated clinical studies and basic science projects (Figure 3).


10

Figure 3: Distribution of research projects at Shaare Zedek Medical Center

Clearly, the increase in research interest and the motivation of the hospital staff, coupled with
the administrative reforms initiated by the hospital management, have had a profound impact
on the research environment at Shaare Zedek. We will continue to promote and nurture these
exciting research activities at Shaare Zedek, thus contributing and transforming the future
practice of medicine for the benefit of all.

References
Glazer K, Israeli A, and Katz U. Financial arrangements between universities to hospitals in
Israel, the current situation, failures and recommendations. The Israel National Institute for
Health Policy Research publications, February 2012.

11

Research Development

Internal Medicine
Glasberg Department of Internal Medicine A
Charles W. and Mollie Mark Department of Internal Medicine B
Dyna and Fala Weinstock Hematology Oncology Day Care Center
Dyna and Fala Weinstock Digestive Diseases Institute
Fuld Family Department of Medical Genetics
Chechick Cancer Cell Research Laboratory
David Barton Oncology Services
Mirsky Cancer Research Institute
Parviz Ohebshalom Cancer Pain Palliative Medicine Clinic
Emanuel Hollander Department of Geriatrics
Jack Mildred Mishkin Geriatric Rehabilitation Center
Els Charles Bendheim Department of Cardiology
Harry H. Beren Cardiology Pavilion
Jack Mahfar Cardiology Service Division
Nathan and Vivian Fink Cardiology Rehabilitation Services

Division of Internal
Medicine

T

he Division of Internal Medicine consists of five inpatient departments, eight subspecialty units and several closely associated departments admitting annually about 10,000 patients. The departments – cardiology,
gastroenterology, Gaucher clinic, genetics, geriatrics, hematology, infectious disease, intensive care, nephrology, neurology, oncology, pulmonology, rheumatology – deal with the
entire field of internal medicine, including cardiovascular ailments, infectious diseases, endocrine and metabolic problems (including diabetes), kidney dysfunction, hematological
diseases and others.
Internal Medicine Department A is headed by Prof. Gideon
Nesher, an internist and rheumatologist, and includes two
attending physicians, 4 residents and 2 interns. Internal
Medicine B is directed by Dr. Shoshana Zevin, an internist
and clinical pharmacist. Internal Medicine C was recently expanded from 22 to 34 beds. The Department of Geriatrics, directed by Prof. Moshe Sonnenblick and his deputy Dr. Reuven
Friedmann, consists of three in-patient units, each run by
senior geriatricians (Dr. Deborah Shapira, Dr. Ilya Galperin
and Dr. Lena Feldman) and a rehabilitation unit headed by
a specialist in rehabilitation medicine (Dr. Ezra Shapiro).
The onco-hematology department is directed by Dr. Thomas
Tichler, a veteran oncologist. The department consists of two
subunits, hematology and oncology, served intensively by the
hematology and oncology specialists.
The Division of Internal Medicine is also a training facility


14

and some 35 residents are in different stages of their specialization. The residency program
prides itself on accepting immigrants from various countries as well as Israelis graduating
from foreign medical schools. In addition to teaching residents, the Division is frequented
by large numbers of medical students from the Hebrew University-Hadassah Medical School.
Each year, groups of fourth year students (i.e., in their first year of clinical training) attend
13-week rotations in internal medicine. Sixth year students attend one-month rotations as
sub-interns, in addition to subspecialty clerkships. Finally, we run a 9-week program for Israeli
students studying in Hungary and elsewhere.

Areas of Research Activity
The Division of Internal Medicine is the largest academic center in Shaare Zedek Medical
Center, with about one hundred attending physicians in the various departments and units.
Of these, more than half are engaged in clinical and/or basic research, and more than thirty
have official academic positions, ranging from lecturer, through senior lecturer and associate
professor, to professor. The Division of Internal Medicine actively promotes research, both locally initiated as well as in cooperation with other medical centers in the country and abroad.
Multiple studies are simultaneously conducted under the auspices and sponsorship of large
pharmaceutical companies, as part of phase III randomized clinical trials involving many hospitals and countries. In order to stimulate research, the Division of Internal Medicine provides extensive mentorship to young researchers, including a three-month annual protected
period for research, free access to a senior statistician, as well as up to twenty annual grants
of $5000 each for its attending physicians submitting research proposals after these receive
peer-reviewed approval. The specific fields of research include infection control and hospital
epidemiology, antimicrobial use, medical administration and education. Internal Medicine A
has investigated trends in vasculitis including giant cell arteritis in Jerusalem over a period of
20 years. Internal Medicine B has in particular conducted research on the clinical pharmacology of nicotine and the characteristics of nicotine addiction in the Israeli population, including
a study of nicotine withdrawal during the Sabbath.

Representative Research
The largest study conducted over the last several years, and supported by a large grant from
the Israel Ministry of Health, involving a multi-center study initiated at Shaare Zedek and
conducted simultaneously in the Hadassah hospitals, pioneered intervention to reduce rates
of hospital acquired infections. We developed two detailed checklists, based on published infection control guidelines, for daily use by infection control practitioners in departments and
operating rooms, and assessed their impact on nosocomial infection rates. The checklists included 20 subheadings (±150 items). Projects nurses conducted rounds in study (but not con-

15

Internal Medicine

trol) departments; during each round, the nurses selected 15-20 items for observation, marked
the checklists according to appropriateness of observed behavior and provided on-the-spot
corrective education. Rates of adherence with the checklist, antibiotic use, number of obtained
and positive cultures, and positive staff hand and patient environment cultures were reported
monthly as a report card to relevant personnel and administrators. With active surveillance we
determined the rate of nosocomial infections in the first and last month of this 1-year project.
The baseline nosocomial infection rate was similar in the study and control departments:
37/345 (11%) and 26/270 (10%) respectively. In the last month, the rate in the study department decreased to 16/383 (4%)(p0.01) compared to no change in the control group (21/248
(8%)(NS). The overall rate of adherence to guidelines increased from 80% to 91% (p0.01).
These data show that the use of checklists during infection control rounds, combined with
monthly reports, was associated with a significant decrease in nosocomial infections.

Rate of hospital acquired infections,
in the first and last month of the study
12
10

P=NS

8
% 6

P0.01

4
2
0

Study departments
1st month

Control Departments
last month


16

PUBLICATIONS
1.

Rudensky B, Broide E, Berko N, Wiener-Well Y, Yinnon AM, Raveh D. Direct fluconazole
susceptibility testing of positive Candida blood cultures by flow cytometry. Mycoses 2009;
51: 200-204.

2.

Ben-Chetrit E, Wiener-Well Y, Yinnon AM. Mycobacterium abscessus infection in insulin
injection sites in a diabetic patient. Harefuah 2009;148(11):756-8,794.

3.

Breuer GS, Nesher R, Nesher G. Effect of biopsy length on the rate of positive temporal
artery biopsies. Clin Exp Rheumatol 2009; 27 (suppl. 52): S10-13.

4.

Nesher G, Oren S. Lijovetzky G, Nesher R. Vasculitis of the temporal arteries in the young.
Semin Arthritis Rheum 2009; 39: 96-107.

5.

Breuer GS, Nesher G, Nesher R. Rate of discordant findings in bilateral temporal artery
biopsies to diagnose giant cell arteritis. J Rheumatol 2009, 36:794-796.

6.

Wiener-Well Y, Raveh D, Schlesinger Y, Yinnon AM, Rudensky B. Cefuroxime for empiric
treatment of community-acquired pneumonia: is the a generation gap? Chemotherapy
2009; 55: 97-104.

7.

Friedmann R, Raveh D, Zartzer E, Rudensky B, Broide E, Attias D, Yinnon AM. Prospective
evaluation of carriage and infections due to Extended-Spectrum β-Lactamase producing
Enterobacteriaceae among newly admitted patients. Infect Control Hosp Epid 2009; 30:
534-542.

8.

Melamud B, Shilo S, Munter G. Life-threatening hypoglycemia due to false measurement
of glucose in a peritoneal dialysis patient. Isr Med Assoc J 2010; 12(2): 125-6.

9.

Shapiro DS, Sonnenblick M, Galperin I, Melkonyan L, Munter G. Severe hyponatraemia
in elderly hospitalized patients: prevalence, aetiology and outcome. Intern Med I 2010;
40(8):574-80.

10.

Ben-Chetrit E, Merin O. Images in clinical medicine. Spontaneous tension pneumothorax.
N Engl J Med 2010; 25:362(12).

11.

Ben-Chetrit E, Ben-Chetrit
cy outcomes in women

17

A, Berkun
with familial

Internal Medicine

Y, Ben-Chetrit E.
Mediterranean fever

Pregnanreceiving

colchicine: is amniocentesis justified? Arthritis Care Res (Hoboken) 2010;62(2):143-8.
12.

Lawrence YR, Pokroy R, Berlowitz D, Aharoni D, Hain D, Breuer GS. Splenic infarction: an
update on William Osler’s observations Isr Med Assoc J. 2010; 12:362-365.

13.

Rudensky B, Yinnon AM, Shutin O, Broide E, Wiener-Well Y, Bitran D, Raveh DP. The
cellular immunological reponses of patients undergoing coronary artery bypass grafting
compared with those of patients undergoing valve replacement. Eur J Cardio-Thor Surg
2010; 37: 1056-1062.

14.

Esayag Y, Nikitin I, Bar-Ziv J, Cytter R, Hadas-Halpern I, Zalut T, Yinnon AM. Diagnostic
value of chest radiographs in bedridden patients suspected of having pneumonia. Am J
Med 2010; 123: 88.e1-88.e6.

15.

Wiener-Well Y, Schlesinger Y, Raveh D, Fink D, Yinnon AM. Q fever endocarditis: not always expected. Clin Microbiol Infect 2010; 16: 359-362.

16.

Dejaco C et al.(International Work Group for PMR and GCA): Definition of remission and
relapse in polymyalgia rheumatica: data from a literature search compared with a Delphibased expert consensus. Ann Rheum Dis 2011; 70:447-453.

17.

Segel, R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D, Staretz-Chacham Segel
R, O, Zimran A, Altarescu G. A safety trial of high dose glyceryl triacetate for Canavan
disease. Mol Genet Metab 2011;103(3):203-6.

18.

Altarescu G, Rachmilewitz D, Zevin S. Relationship between CYP2A6 genetic polymorphism, as a marker of nicotine metabolism, and ulcerative colitis. Isr Med Assoc J
2011;13(2):87-90.

19.

Furer V Hersch M, Silvetzki N, Breuer GS, Zevin S. Nicotiana glauca (tree tobacco) intoxication--two cases in one family. J Med Toxicol 2011;7(1):47-51.

20.

Ben- Chetrit E, Ben-Chetrit E. Colchicine dose reduction in patients with normal liver and kidney function: comment on the article by Terkeltaub et al.
Arthritis Rheum 2011;63(11):3647-8.

21.

Wiener-Well Y, Galuti M, Rudensky B, Attias D, Yinnon AM. The importance of bacterial
load on medical and nursing gowns in transmission of virulent organisms in hospitals. Am
J Infect Control 2011; 39: 555-9.


18

22.

Furer V, Hersch M, Silvetzki N, Breuer GS, Zevin S. Mocptoama glauca (tree tobacco)
intoxication – two cases in one family. J Med Toxicol 2011; 7:555-9.

23.

Yinnon AM, Wiener-Well Y, Jerassy Z, Dor M, Freund R, Mazouz B, Lupyan T, Shapira S,
Attias D, Assous MV, Block C, Raveh D, Freier-Dror Y, Moses AE, Benenson S. Increasing implementation of infection control guidelines to reduce nosocomial infections rates:
Pioneering the Report Card. J Hosp Infect, 2012; 81: 169-176.

24.

Ben-Chetrit E, Munter G. Purple urine. JAMA 2012;307(2):193-4.

25.

Winchester Behr T, Sonnenblick M, Nesher G, Munter G. Hyponatraemia in older people
as a sign of adrenal insufficiency: a case-control study. Intern Med J 2012;42(3):306-10.

26.

Breuer GS, Nesher G: What does imaging tell us about polymyalgia rheumatica? Rheumatology 2012; 51:5-6.

27.

Behr TW, Sonnenblick M, Nesher G, Munter G. Hyponatremia in older people as a sign of
adrenal insufficiency: a case-control study. Intern Med J 2012; 42:306-310.

28.

Samuels N, Zisk-Rony RY, Zevin S, Yinnon AM, Oberbaum M. Use of herbal medicine
among patients hospitalized in a department of internal medicine. Accepted for publication.

29.

Wiener-Well Y, Goffman I, Assous MV, Yinnon AM. The clinical significance of isolation
of two different organisms from urine specimens of patients with an indwelling catheter.
Submitted for publication.

30.

Kassirer Y, Rudensky B, Zalut T, Yinnon AM. Improving adherence to blood culture sampling guidelines through educational intervention. Submitted for publication.

31.

Sylvetsky N, Zehavi O, Raveh D, Henshke-Bar-Meir R, Yinnon AM, Zevin S. Impact of a
monitoring unit in the medical department on patient outcome. Submitted for publication.

32.

Amitai S, Assous MV, Lachish T, Kopuit P, Bdolah-Abram T, Yinnon AM, Wiener-Well Y.
Impact on mortality of and risk factors for bacteriuria and urinary tract infection due to
carbapenem-resistant Klebsiella pneumoniae. Submitted for publication.

33.

Novoselsky Persky MA, Yinnon AM, Freier-Dror Y, Henshke R.. Communication between
residents and attending physicians on call after hours. Submitted for publication.

19

Internal Medicine

34.

Zimmerman FS, Assous MV, Bdolah-Abram T, Lachish T, Yinnon AM, Wiener-Well Y. During of carriage of carbapenem-resistant Enterobacteriaceae following hospital discharge.
Submitted for publication.


20

Department of
Hematology

T

he Department of Hematology, directed by Professor
Jacob Rowe, is staffed by six senior physicians, two interns and two residents alongside a dedicated team of
nurses. The Department is a member of the National Cancer
Institute in the United States, which was made possible
through an affiliation with Northwestern University, a member of the Eastern Cooperative Oncology Group.

The primary diseases treated in the Department are leukemia, lymphoma and myeloma. The Department coordinates
bone marrow transplants. At any given time, there are about
twenty leukemia cases being treated, with that number on the
constant rise – including an increasing number of referrals
from other area hospitals. The Department of Hematology
is well known for its extraordinary efforts and personal commitment to provide the highest level of care— which often
involves procuring medications or specialized facilities that
are not covered by third party insurers.

Studies are focused on translational clinical research. The Department is an affiliate of the Feinberg School of Medicine,
Northwestern University in Chicago and as such enters patients into studies conducted by the National Cancer Institute
in the US through participation in the Eastern Cooperative
Oncology Group. Currently a study on acute myeloid leukemia (AML) is being conducted to find a less toxic, but no less
efficacious, regimen for the treatment of older patients with

21

Hematology

this devastating disease. In a major phase III study the use of Clofarabine as a single agent is
being evaluated. Patients who achieve a complete remission are evaluated , for the first time in
a prospective genetically randomized manner, for the performance of a reduced-intensity allogeneic transplantation. A prospective phase III study is also evaluating a less toxic induction
regimen (5-azacytidine) for older patients who are unable to tolerate the rigors of standard
induction therapy. Another major translational study involves a very early look at the bone
marrow of patients receiving induction therapy for AML (on day 5) evaluating both the morphological and immunological characteristics to determine whether an earlier examination of
the bone marrow can provide more accurate prognostic information and , thus, a more tailored
therapy.
The Hematology Department also participates in several phase II and III studies in multiple
myeloma, diffuse-large cell lymphoma and chronic lymphocytic leukemia. New agents are being studied in a phase III study in myeloma and we are participating in a very large international phase III study evaluating the role of Rituximab, administered in varying routes. In chronic
lymphocytic leukemia CLL), the Hematology department has become an important referral
center in Israel for clinical, epidemiologic genetic and immunological research. Several major
studies evaluating newer monoclonal antibodies and less toxic regimens for older patients are
ongoing.

Determining when a patient with acute leukemia is refractory to primary therapy remains controversial. Patients who do not respond fully to AML (induction therapy) are generally considered as refractory and their post-remission therapy is altered. In other words, such patients are
considered to be probably incurable with chemotherapy alone and are usually referred for an
allogeneic transplant if a donor is available. Many publications have considered that patients
who have residual leukemia in the middle of their induction therapy - typically on day 14 - also
have a poor prognosis and all such patients are referred for an allogeneic transplantation, even
if they have a complete response following the completion of induction therapy. Referring all
such patients for an allogeneic transplantation clearly impacts on the morbidity and mortality
of such patients.
In a series of studies in the Eastern Oncology Group over the past two decades, all patients
were evaluated on day 14 and if they had residual leukemia on day 14, a second cycle of induction therapy was offered. Specifically, if a patient achieved a complete response to the first
cycle or after a second cycle of therapy (in other words someone who needs 1 or 2 cycles to
achieve complete remission), their subsequent post-remission therapy was not altered. Hence
the decision as to the future course of action once patients went into complete remission was


22

not altered by the fact that the bone marrow had residual leukemia early on day 14, provided
the patient went into remission after the second cycle.
The analysis showed that patients who achieved a complete remission after 1 or 2 cycles had
an identical prognosis, in contrast to the prevailing view. Therefore, not all patients who have
a positive bone marrow necessarily have a poor prognosis and provided they achieve remission
with a second cycle, they have an identical prognosis as those who are in remission after only
one cycle.

Publications
1.

Rowe JM. Optimal management of adults with ALL. Br. J Haematol 2009; 144:468-483.

2.

Rowe JM. Closer to the truth in AML. Blood 2009; 113: 4129-4130.

3.

Elhasid R, Leshem YA, Ben Arush MW, Rowe JM, Shehadeh N. Insulin-related metabolism following hematopoietic stem cell transplantation in childhood. Pediatr Diabetes
2009; 10:149-154.

23

Hematology

4.

Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan
AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult
patients with Philadelphia-chromosome positive acute lymphoblastic leukaemia confirms
superiority of allogeneic transplant over chemotherapy in the pre-imatinib era: Results
from the international ALL trial MRC UKALLXII/ECOG2993. Blood 2009; 113:4489-4496.

5.

Gregory J, Kim H, Alonzo T, Gerbing R, Woods W, Weinstein H, Shepherd L, Schiffer C,
Appelbaum F, Willman C, Wiernik P, Rowe J, Tallman M, Feusner J. Treatment of children
with acute promyelocytic leukemia: Results of the first North American Intergroup trial
INT0129. Pediatr Blood Cancer 2009; 53:1005-1010.

6.

Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, Volin L, Ruutu T,
Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V,
Bornhäuser M, Einsele H, Kolb HJ, Bertz H, Egger M, Grishina O, Socié G; ATG-Fresenius
Trial Group (Finke J, Rowe JM,. Socié G.) Standard graft-versus-host disease prophylaxis
with or without anti-T-cell globulin in haematopoietic cell transplantation from matched
unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol 2009;
10:855-864.

7.

Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald
GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Anthracycline dose
intensification in acute myeloid leukemia. 2009; 361:1249-1259.

8.

Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G, Paietta E, van der
Jagt R, Houston J, Thomas ML, Cella D, Rowe JM. Treatment of myelodysplastic syndromes patients with erythropoietin with or without granulocyte colony-stimulating factor:
results of a prospective randomized phase III trial by the Eastern Cooperative Oncology
Group (E1996). 2009; 114:2393-400.

9.

Avivi I, Avraham S, Koren-Miachelovitz M, Zuckerman T, Aviv A, Ofran Y, Benyamini N,
Nagler A, Rowe JM, Nagler RM. Oral integrity and salivary profile in myeloma patients undergoing high-dose therapy followed by autologous SCT bone marrow transplant. Bone
Marrow Transplantation 2009; 43:801-806.

10.

Mansour MR, Sulis
Gale RE, Buck G,
stone AH, Ferrando
FBXW7 mutations in

ML, Duke V, Foroni L, Jenkinson S, Koo K, Allen CG,
Richards S, Paietta E, Rowe JM, Tallman MS, GoldAA, Linch DC. Prognostic implications of NOTCH1 and
adults with T-cell acute lymphoblastic leukemia treated on


24

the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol 2009; 27:4352-4356.
11.

Tosello V, Mansour MR, Barnes K, Paganin M, Sulis ML, Jenkinson S, Allen CG, Gale RE,
Linch DC, Palomero T, Real P, Murty V, Yao X, Richards SM, Goldstone A, Rowe J, Basso
G, Wiernik PH, Paietta E, Pieters R, Horstmann M, Meijerink JP, Ferrando A. WT1 mutations in T-ALL. Blood 2009; 114:1038-1045.

12.

Stroopinsky D, Avivi I, Rowe JM, Avigan D, Katz T. Allogeneic induced human FOXP3+IFNg+ T cells exhibit selective suppressive capacity. Eur. J Immunol 2009; 39:2703-15.

13.

Zuckerman T, Rowe JM. Hematopoietic stem cell transplantation for adults with acute
lymphoblastic leukemia. Curr Opin Hematol 2009; 16:453-459.

14.

Rowe JM. Optimal induction and post–remission therapy for AML in first complete remission. Hematology American Society of Hematology Education Program 2009; 396-405.

15.

Goldstone AH, Rowe JM. Transplantation in adult ALL. Hematology American Society of
Hematology Education Program 2009; 593-600.

16.

Rowe JM. Is there a role for intensifying induction therapy in acute myeloid leukemia
(AML)? Best Pract Res Clin Haematol 2009; 22: 475-478.

17.

Rowe JM. Advances and controversies in the biology and therapy of acute leukemia and
myelodysplasia. Best Pract Res Clin Haematol 2009; 22: 509-515.

18.

Fernandez HF, Rowe JM, Tallman MS. Anthracycline dose intensification in acute myeloid
leukemia. Letter. NEJM 2009; 361:2578.

19.

Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, Dewald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour M,
Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics and outcome from the large randomised
prospective trial (UKALL XII/ECOG 2993). Blood 2009; 114:5136-5145.

20.

Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, Goldman JM, Müller
MC, Radich JP, Rudoltz M, Mone M, Gathmann I, Larson RA; IRIS Investigators. (Hughes
TP, Rowe J, Sentini V). Six-year follow-up of patients receiving imatinib for the first-line
treatment of chronic myeloid leukemia. Leukemia 2009; 23:1054-1061.

25

Hematology

21.

Hershko C, Ronson A. Iron deficiency, helicobacter infection and gastritis. Acta Haematol
2009; 122:97-102.

22.

Cortes JE, Baccarani M, Guilhot F, Druker BJ, Branford S, Kim DW, Pane F, Pasquini R,
Goldberg SL, Kalaycio M, Moiraghi B, Rowe JM, Tothova E, De Souza C, Rudoltz M, Yu
R, Krahnke T, Kantarjian HM, Radich JP, Hughes TP. Phase III, Randomized, Open-Label
Study of Daily Imatinimb Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study. J Clin Oncol
2010; 28:424-430.

23.

Litzow MR, Othus M, Cripe LD, Gore SD, Lazarus HM, Lee SJ, Bennett JM, Paietta EM,
Dewald GW, Rowe JM, Tallman MS; for the Eastern Cooperative Oncology Group Leukemia Committee. Failure of three novel regimens to improve outcome for patients with
relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative
Oncology Group. Br J Haematol 2010; 148:217-225.

24.

Fernandez HF, Rowe JM. Induction therapy in acute myeloid leukemia: intensifying and
targeting the approach. Curr Opin Hematol 2010; 17:79-84.

25.

Elhasid R, Rowe JM. Hematopoietic stem cell transplantation in neutrophil disorders:
severe congenital neutropenia, leukocyte adhesion deficiency in chronic granulomatous
disease. Clin Rev Allergy Immunol 2010; 38:61-67.

26.

Elhasid R, Kilic SS, Ben-Arush M, Etzioni A, Rowe JM. Prompt recovery of recipient hematopoiesis after two consecutive haploidentical peripheral blood SCTs in a child with
leukocyte adhesion defect III syndrome. Bone Marrow Transplant 2010; 45:413-414.

27.

Van Vlierberghe P, Palomero T, Khiabanian H, Van der Meulen J, Castillo M, Van Roy N, De
Moerloose B, Philippé J, González-García S, Toribio ML, Taghon T, Zuurbier L, Cauwelier
B, Harrison CJ, Schwab C, Pisecker M, Strehl S, Langerak AW, Gecz J, Sonneveld E,
Pieters R, Paietta E, Rowe JM, Wiernik PH, Benoit Y, Soulier J, Poppe B, Yao X, CordonCardo C, Meijerink J, Rabadan R, Speleman F, Ferrando A. PHF6 mutations in T-cell
acute lymphoblastic leukemia. Nat Genet 2010;42:338-342.

28.

Rowe JM. Getting to the root of (it) ALL. Blood 2010; 115:3649-3650.

29.

Dann EJ, Bar-Shalom R , Tamir A, Epelbaum R, Avivi I, Ben-Shachar M, Gaitini D, Rowe
JM. Dynamic Scoring Model to Elucidate the Significance of Post-induction Interim


26

F18FDG-PET/CT Scanning in Patients with Hodgkin Lymphoma.Haematologica 2010;
95:1198-206.
30.

Lavi R, Rowe JM, Avivi I. Lumbar Puncture: It Is Time to Change the Needle. Eur Neurol
2010; 64:108-113.

31.

Pe’er J, Rowe JM, Frenkel S, Dann EJ. Testicular lymphoma, intraocular (vitreoretinal)
lymphoma, and brain lymphoma: involvement of three immunoprivileged sites in one patient. Am J Hematol 2010; 85:631-633.

32.

Porter DL, Alyea EP, Antin JH, Delima M, Estey E, Falkenburg JH, Hardy N, Kroeger N,
Leis J, Levine J, Maloney DG, Peggs K, Rowe JM, Wayne AS, Giralt S, Bishop MR, van
Besien K. NCI First International Workshop on the Biology, Prevention, and Treatment of
Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation.
Biol Blood Marrow Transplant. 2010;16(11):1467-503. Epub 2010

33.

NCI First International Workshop on the Biology, Prevention and Treatment of Relapse
after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee
on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol
Blood Marrow Transplant 2010; 16(11):1467-503.

34.

Rowe JM. Prognostic Factors in Adult Acute Lymphoblastic Leukaemia. Br J Haematol
2010; 150(4):389-405.

35.

Tallman M, Douer D, Gore S, Powell BL, Ravandi F, Rowe JM, Ranganathan A, Sanz
MA. Treatment of Patients with Acute Promyelocytic Leukemia: A Consensus Statement
on Risk-Adapted Approaches to Therapy. Clinical Lymphoma, Myeloma Leukemia
2010;10(3) S122-S126.

36.

De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe
P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi
PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis
J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink
JP, Cordon-Cardo C, Califano A, Ferrando AA. The TLX1 oncogene drives aneuploidy in
T cell transformation. Nat Med 2010; 16(11):1321-1327.

37.

Wiernik PH, Dutcher JP, Yao X, Venkatraj U, Falkson CI, Rowe JM, Cassileth PA. Phase
II Study of Interleukin-4 in Indolent B-cell Non-Hodgkin Lymphoma and B-cell Chronic

27

Hematology

Lymphocytic Leukemia: A Study of the Eastern Cooperative Oncology Group (E5Y92). J
Immunother 2010; 33(9):1006-1009.
38.

Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, Rowe JM, Lazarus
HM, Luger S, Tallman MS. Zosuquidar, a novel modulator of P-glycoprotein, does not
improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a
randomized, placebo-controlled, trial of the Eastern Cooperative Oncology Group (ECOG
3999). Blood 2010; 116(20):4077-4085.

39.

Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre
S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic
trioxide improves event-free and over-all survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood 2010; 116(19):3751-7.

40.

Elhasid R, Krivoy N, Rowe JM, Sprecher E, Adler L, Elkin H, Efrati E. Influence of glutathione S-transferase A1, P1, M1, T1 polymorphisms on oral busulfan pharmacokinetics in
children with congenital hemoglobinopathies undergoing hematopoietic stem cell transplantation. Pediatr Blood Cancer 2010; 55(6):1172-9.

41.

Rowe JM. The evolving paradigm of prognostic factors in AML: Introduction to the Acute
Leukemia Forum 2010. Best Pract Res Clin Haematol 2010;23(4):453-6.

42.

Tallman M, Douer D, Gore S, Powell BL, Ravandi F, Rowe J, Ranganathan A, Sanz MA.
Treatment of patients with acute promyelocytic leukemia: a consensus statement on riskadapted approaches to therapy. 2010;10:S122-6.

43.

Rowe JM, Kim HT, Cassileth PA, Lazarus HM, Litzow MR, Wiernik PH, Tallman MS.
Adult patients with acute myeloid leukemia who achieve complete remission after one or
two cycles of induction have a similar prognosis: A report on 1,980 patients registered
to six studies conducted by the Eastern Cooperative Oncology Group. Cancer 2010;
116(21):5012-21.

44.

Elhasid R, Krivoy N, Rowe JM, Sprecher E, Efrati E. Glutathione S-transferase T1-null
seems to be associated with graft failure in hematopoietic SCT. Bone Marrow Transplant
2010; 45(12):1728-31.

45.

Gupta V, Tallman MS, He W, Logan BR, Copelan E, Gale RP, Khoury HJ, Klumpp T, Koreth
J, Lazarus HM, Marks DI, Martino R, Rizzieri DA, Rowe JM, Sabloff M, Waller E, Dipersio
JF, Bunjes DW, Weisdorf DJ. Comparable survival after HLA-well-matched unrelated or


28

matched sibling donor transplantation for acute myeloid leukemia in first remission with
unfavorable cytogenetics at diagnosis. Blood 2010; 16;116(11):1839-48.
46.

Rowe JM, Tallman MS. How I treat acute myeloid leukemia. Blood 2010; 116(17):314756.

47.

Mesa RA, Yao X, Cripe LD, Li CY, Litzow M, Paietta E, Rowe JM, Tefferi A, Tallman MS.
Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group
(ECOG) phase-2 trial E4903. Blood 2010; 116(22):4436-8.

48.

Tallman MS, Kim HT, Montesinos P, Appelbaum FR, de la Serna J, Bennett JM, Deben G,
Bloomfield CD, Gonzalez J, Feusner JH, Gonzalez M, Gallagher R, Gonzalez-San Miguel
JD, Larson RA, Milone G, Paietta E, Rayon C, Rowe JM, Rivas C, Schiffer CA, Vellenga
E, Shepherd L, Slack JL, Wiernik PH, Willman CL, Sanz MA. Does microgranular variant
morphology of acute promyelocytic leukemia independently predict for a less favorable
outcome compared with classical M3 APL? A joint study of the North American Intergroup
and the PETHEMA Group. Blood 2010; 116(25):5650-9.

49.

Koren-Michowitz M, le Coutre P, Duyster J, Scheid C, Panayiotidis P, Prejzner W, Rowe
JM, Schwarz M, Goldschmidt N, Nagler A. Activity and tolerability of nilotinib: a retrospective multicenter analysis of chronic myeloid leukemia patients who are imatinib resistant or
intolerant. Cancer 2011; 117(1):230.

50.

Zuckerman T, Benyamini N, Sprecher H, Fineman R, Finkelstein R, Rowe JM, Oren I. SCT
in patients with carbapenem resistant Klebsiella pneumoniae: a single center experience
with oral gentamicin for the eradication of carrier state. 2011; 46(9):1226-30.

51.

Rowe JM. Interpreting data on transplant selection and outcome in adult acute lymphoblastic leukemia (ALL). Biol Blood Marrow Transplant 2011; 17: 576-583.

52.

Ofran Y, Rowe JM. Induction and postremission strategies in acute myeloid leukemia:
what is new? Curr Opin Hematol 2011;18(2):83-8.

53.

Rowe JM. Maintenance therapy in AML with emphasis on the immunotherapeutic options.
Ann Hematol 2011; 90:525-530.

54.

Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Racevskis J, Dewald G, Ketterling RP, Rowe JM, Lazarus HM, Tallman MS. Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia but is

29

Hematology

not improved with gemtuzumab ozogamicin. Blood 2011; 117(20):5306-13.
55.

Buyse M, Squifflet P, Lucchesi KJ, Brune ML, Castaigne S, Rowe JM. Assessment of the
consistency and robustness of results from a multicenter trial of remission maintenance
therapy for acute myeloid leukemia. Trials 2011; 12:86.

56.

Buyse M, Michiels S, Suqifflet P, Lucchesi K, Hellstrand K, Brune ML, Castaigne S,
Rowe JM. Leukemia-free survival as a surrogate endpoint for overall survival in the evaluation of maintenance therapy for patients with acute myeloid leukemia in complete remission. Haematologica 2011; 96(8); 1106-12.

57.

Rowe JM, Ganzel C. Management of acute lymphoblastic lymphoma in adults. Hematology Education, Education program for annual congress of the European Hematology Association 2011; 5(1): 9-19.

58.

Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, Altman JK,
Douer D, Rowe JM, Tallman MS. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011; 118(5): 1248-54.

59.

Ganzel C, Rowe JM, Ruchlemer R. Primary effusion lymphoma in a HIV-negative patient
associated with hypogammaglobulinemia. Am J Hematol 2011; 86(9):777-81.

60.

Avivi I, Fineman R, Haddad N, Katz T, Oren I, Rowe JM, Zuckerman T. Fatal Kaposi sarcoma after allogeneic stem cell transplant. Leuk Lymphoma 2011; 52(12):2402-4.

61.

Ganzel C, Rowe JM. Prognostic factors in adult acute leukemia. Hematol Oncol Clin North
Am 2011; 25(6):1163-87.

62.

Khalil A, Ben Barak A, Zaidman i, Elhasid R, Rowe JM, Ben-Arush M. Polyserositis as a
Manifestation of Graft-Versus-Host Disease. Pediactric Hematology and Oncology 2011;
28:691-693.

63.

Rowe JM. Evaluation Of Prognostic Factors In AML. Best Practice Research Clinical
Haematology 2011; 24: 485-488.

64.

Van Vlierberghe P, Ambesi-Impiombato A, Perez-Garcia A, Haydu JE, Rigo I, Hadler M,
Tosello V, Della Gatta G, Paietta E, Racevskis J, Wiernik PH, Luger SM, Rowe JM, Rue
M, Ferrando AA. ETV6 mutations in early immature human T cell leukemias. J Exp Med
2011; 208(13):2571-9.


30

65.

Smith MR, Neuberg D, Flinn IW, Grever MR, Lazarus HM, Rowe JM, Dewald G, Bennett
JM, Paietta EM, Byrd JC, Hussein MA, Appelbaum FR, Larson RA, Litzow MR, Tallman
MS. Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term followup of US Intergroup Study E2997. Blood 2011; 29;118(13):3525-7.

66.

Bairey O, Ruchlemer R, Rahimi-Levene N, Herishanu Y, Braester A, Berrebi A, Polliack
A, Klepfish A,Shvidel L. Israeli CLL Study Group (ICLLSG). Presenting features and outcome of chronic lymphocytic leukemia patients diagnosed at age 80 years or more. An
ICLLSG study. Ann Hematology 2011; 90:1123-9, 2011.

67.

Avivi I, Hardak E, Shaham B, Igla M, Rowe JM, Dann EJ. Low incidence of long-term respiratory impairment in Hodgkin lymphoma survivors. Ann Hematol. 91(2); 215-21, 2012.

68.

Armand P, Kim HT, Zhang MJ, Perez WS, Dal Cin PS, Klumpp TR, Waller EK, Litzow MR,
Liesveld JL, Lazarus HM, Artz AS, Gupta V, Savani BN, McCarthy PL, Cahn JY, Schouten
HC, Finke J, Ball ED, Aljurf MD, Cutler CS, Rowe JM, Antin JH, Isola LM, Di Bartolomeo
P, Camitta BM, Miller AM, Cairo MS, Stockerl-Goldstein K, Sierra J, Savoie ML, Halter J,
Stiff PJ, Nabhan C, Jakubowski AA, Bunjes DW, Petersdorf EW, Devine SM, Maziarz RT,
Bornhauser M, Lewis VA, Marks DI, Bredeson CN, Soiffer RJ, Weisdorf DJ. Classifying Cytogenetics in Patients with Acute Myelogenous Leukemia in Complete Remission Undergoing Allogeneic Transplantation: A Center for International Blood and Marrow Transplant
Research Study. Biol Blood Marrow Transplant 2012; 18(2);280-8.

69.

Dann EJ, Blumenfeld Z, Bar-Shalom R, Avivi I, Ben-Shachar M, Goor O, Libster D, Gaitini
D, Rowe JM, Epelbaum R. A 10-year experience with treatment of high and standard risk
Hodgkin disease: Six cycles of tailored BEACOPP, with interim scintigraphy, are effective
and female fertility is preserved. Am J Hematol 2012; 87(1):32-6.

70.

Hardak E, Oren I, Dann EJ, Yigla M, Faibish T, Rowe JM, Avivi I. The Increased Risk for
Pneumocystis Pneumonia in Patients Receiving Rituximab-CHOP-14 Can Be Prevented
by the Administration of Trimethoprim/Sulfamethoxazole: A Single-Center Experience.
Acta Haematol 2012; 127(2):110-4.

71.

Ofran Y, Rowe JM. Treatment for relapsed acute myeloid leukemia: what is new? Curr
Opin Hematol 2012; 19(2):89-94.

72.

Ntziachristos P, Tsirigos A, Vlierberghe PV, Nedjic J, Trimarchi T, Flaherty MS, FerresMarco D, da Ros V, Tang Z, Siegle J, Asp P, Hadler M, Rigo I, Keersmaecker KD, Patel

31

Hematology

J, Huynh T, Utro F, Poglio S, Samon JB, Paietta E, Racevskis J, Rowe JM, Rabadan R,
Levine RL, Brown S, Pflumio F, Dominguez M, Ferrando A, Aifantis I. Genetic inactivation
of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia. Nat Med
2012; 6;18(2):298-303.
73.

Stroopinsky D, Katz T, Rowe JM, Melamed D, Avivi I. Rituximab-induced direct inhibition
of T-cell activation. Cancer Immunol Immunother 2012; 61(8):1233-41.

74.

Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T,
Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and
high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before
autologous stem cell transplantation in patients with aggressive lymphoma. Cancer 2012.
In press.

75.

352. Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM. Hyperleukocytosis, leukostasis and leukapheresis: practice management. Blood Rev 2012; 26(3):117-22.

76.

Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman AV, Richards SM, Rowe JM, Tallman MS, Goldstone AH. Outcomes in older adults
with acute lymphoblastic leukemia (ALL): results from the international MRC UKALL XII/
ECOG2993 trial. Br J Haematol 2012; 157(4):463-71.

77.

Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P,
Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A,
Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR,
Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, AbdelWahab O, Levine RL. Prognostic relevance of integrated genetic profiling in acute myeloid
leukemia. N Engl J Med 2012; 22; 366(12):1079-89.

78.

Della Gatta G, Palomero T, Perez-Garcia A, Ambesi-Impiombato A, Bansal M, Carpenter
ZW, De Keersmaecker K, Sole X, Xu L, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Meijerink JP, Califano A, Ferrando AA. Reverse engineering of TLX oncogenic transcriptional
networks identifies RUNX1 as tumor suppressor in T-ALL. Nat Med 2012; 26;18(3):43640.

79.

Samon JB, Castillo-Martin M, Hadler M, Ambesi-Impiombato A, Paietta E, Racevskis J,
Wiernik PH, Rowe JM, Jakubczak JL, Randolph S, Cordon-Cardo C, Ferrando AA. Preclinical analysis of the gamma-secretase inhibitor PF-03084014 in combination with glucocorticoids in T - cell acute lymphoblastic leukemia. Mol Cancer Ther 2012; 11(7):1565-75.


32

80.

Haydu JE, De Keersmaecker K, Duff MK, Paietta E, Racevskis J, Wiernik PH, Rowe JM,
Ferrando A. An activating intragenic deletion in NOTCH1 in human T-ALL. Blood 2012;
119(22):5211-4.

81.

Shlush LI, Chapal-Ilani N, Adar R, Pery N, Maruvka Y, Spiro A, Shouval R, Rowe JM,
Tzukerman M, Bercovich D, Izraeli S, Marcucci G, Bloomfield CD, Zuckerman T, Skorecki
K, Shapiro E. Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and miscrosatellite instability. Blood 2012; 120(3):603-12.

82.

Zuckerman T, Rowe JM. Concise guide to hematology. Eds. Schmaier AH, Lazarus HM.
Blackwell 2012; 235-250.

83.

Ruchlemer R. Two genes, tipifarnib, and AML. Blood 2012; 119:2-3.

84.

Shvidel L, Braester A, Bairey O, Rahimi-Levene N, Herishanu Y, Tadmor T, Klepfish A,
Ruchlemer R, Shtalrid M, Berrebi A, Polliack A; on behalf of the Israeli CLL Study Group.
(2012) Cell surface expression of CD25 antigen (surface IL-2 receptor alpha-chain) is not a
prognostic marker in chronic lymphocytic leukemia: results of a retrospective study of 281
patients. Ann Hematol 2012. In press.

85.

Zuckerman T, Ganzel C, Tallman MS, Rowe JM. How I treat hematologic emergencies in
adults with acute leukemia. Blood 2012. In press.

86.

Ganzel C, Rowe JM. Total ambulatory hemato-oncological care - a myth or reality? Leuk
Lymphoma 2012. In press.

87.

Ganzel C, Rowe JM. Total ambulatory hemato-oncological care - a myth or reality? Leuk
Lymphoma 2012. In press.

88.

Duarte RF, Canals C, Onida F, Olavarria E, Arcese W., Ferrant A., Narni F., Lambertenghi
G., Bacigalupo A., Bunjes D., Rowe J.M., Schmitz N., Sureda A. HLA-Identical Allogeneic
Stem Cell Transplantation (alloSCT) for Patients With Primary Cutaneous T-Cell Lymphoma
(CTCL): A Retrospective Analysis of the Lymphoma Working Party of the European Blood
and Marrow Transplantation Group (EBMT-LWP). 2009 Bone Marrow Transplant Tandem
Meetings. Tampa, Florida, February, 2009. Biology of Blood and Marrow Transplantation
15 (Suppl. 2): 53a.

89.

267. Avigan D., Rosenblatt J., Vasir B., Wu Z., Bissonnette A., Somaiya P., MacNamara
C., Uhl L., Avivi I., Katz T., Zarwan C., Joyce R., Levine J.D., Lowe K., Dombagoda D.,

33

Hematology

Tzachanis D., Boussiotis V., Giallombardo N., Mortellite J., Conway K., Fitzgerald D., Richardson P., Anderson K., Munshi N., Rowe JM, Tsumer M., Bishart L., Kufe D. Fusion Cell
Vaccination In Conjunction With Stem Cell Transplantation Is Well Tolerated, Induces AntiTumor Immunity and Is Associated With Responses In Patients With Multiple Myeloma.
2009 Bone Marrow Transplant Tandem Meetings. Tampa, Florida, February, 2009. Biology of Blood and Marrow Transplantation 2009; 15 (Suppl. 2): 174a,.
90.

268. Duarte R.F., Canals C. , Onida F., Olavarría E., Arcese W., Ferrant A., Narni F.,
Lambertenghi Deliliers G. , Bacigalupo A., Bunjes D. , Rowe J.M., Schmitz N., Sureda
A. HLA-identical allogeneic stem cell transplantation for patients with primary cutaneous
T-cell lymphoma: a retrospective analysis of the Lymphoma Working Party of the European
Blood and Marrow Transplantation Group. Thirty fifth annual meeting of the European
Group for Blood and Marrow Transplantation (EBMT). Göteborg, Sweden, March 2009.
Bone Marrow Transplantation 2009; 43(Suppl. 1), 259a.

91.

269. Elhasid R, Efrati E, Khalil A., Stein J., Zaidman I., Ben Arush M., Rowe J.M., Krivoy
N. Allogeneic transplantation using adjusted blood busulfan levels results in a very low
incidence of veno-occlusive disease, irrespective of the presence of the glutathione Stransferase M1 null genotype. Thirty fifth annual meeting of the European Group for Blood
and Marrow Transplantation (EBMT). Göteborg, Sweden, March 2009. Bone Marrow
Transplantation 2009; 43 (Suppl. 1): 802a.

92.

Zuckerman T., Benyamini N. , Haddad N., Fineman R. , Avivi I., Sabo E., Rowe J.M.,
Oren I. Emergence of uncommon infection in bone marrow transplantation: the modern
Trojan horse? Thirty fifth annual meeting of the European Group for Blood and Marrow
Transplantation (EBMT). Göteborg, Sweden, March 2009. Bone Marrow Transplantation
2009; 43(Suppl. 1): 884a.

93.

Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Dewald G, Ketterling R, Rowe
JM, Lazarus, HM, Tallman MS. A randomized trial of anthracycline dose intensification during induction of younger patients with acute myeloid leukemia: Results of Eastern
Cooperative Oncology Group study E1900. Forty fifth Annual Meeting of the American
Society of Oncology. Orlando, FL, May 2009. J Clin Oncol 2009; 27 (15s): 7003a.

94.

Dann EJ, Badian A, Stravets T, Kertsman E, Phenklbaum S, Zuckerman T, Haddad N,
Elhasid R, Bonstein L, Rowe J.M.
Extracorporeal photochemotherapy for acute and
chronic GVHD, a report of 102 patients treated in a single institution. Fourteenth Congress
of the European Hematology Association, Berlin, Germany, June 2009. Haematologica
2009; 94: 0550a.


34

95.

Brune L, Rowe JM, Buyse ME, Squifflet P, Castaigne S, Allard SE, Hellstrand K. Six-year
outcomes update from a randomized phase 3 trial in AML: durable effect of remission
maintenance immunotherapy with histamine dihydrochloride and low-dose IL-2. Fourteenth Congress of the European Hematology Association, Berlin, Germany, June 2009.
Haematologica 2009; 94: 0845a.

96.

Rosenblatt J, Avivi I, Vasir B, Katz T, Uhl L, Wu Z, Somaiya P, Mills H, Joyce R, Levine
JD, Tzachanis D, Boussiotis V, Glotzbecker B, Francoeur K, Dombagoda D, Tsumer M,
Bisharat L, Giallombardo N, Conway K, Fitzgerald D, Barhad R, Richardson P, Anderson
KC, Munshi NC, Rowe JM, Kufe D, Avigan D. Dendritic Cell Tumor Fusion Vaccination in
Conjunction with Autologous Transplantation for Multiple Myeloma. Fifty first annual meeting of the American Society of Hematology, New Orleans, LA, December 2009. Blood
2009; 114: 783a.

97.

Elhasid R, Zaidman I, Khalil A, Zuckerman T, Haddad N, Katz T, Ben Arush M, Rowe JM.
Allogeneic Stem Cell Transplantation in Congenital Hemoglobinopathies – A Curative Approach When Performed as a Primary Therapeutic Modality: A Single Center Experience.
Fifty first annual meeting of the American Society of Hematology, New Orleans, LA, December 2009. Blood 2009;114: 1144a.

98.

Dann E, Bar-Shalom R, Tamir A, Ben-Shachar M, Avivi I, Zuckerman T, Haddad N, Rosenbaum H, Fineman R, Goor O, Libster D, Blumenfeld Z, Rowe JM, Epelbaum R. For Standard and High-Risk Patients with Hodgkin Lymphoma Six Cycles of Tailored BEACOPP,
Based On Interim Scintigraphy, Are Effective and Female Fertility Is Preserved. Fifty first
annual meeting of the American Society of Hematology, New Orleans, LA, December
2009. Blood 2009;114: 1552a.

99.

O’Brien S, Schiller G, Damon LE, Lister J, Ravandi F, Douer D, Masood A, Ben-Yehuda
D, Rowe JM, Gökbuget N, Aulitzky W, Stock W, Coutre S, Heffner L, Larson ML, Seiter
K, Hagey AE, Deitcher SR, Kantarjian HM. Pivotal Phase 2 Study of Weekly Vincristine
Sulfate Liposomes Injection (VSLI, Marqibo®) in Adults with Philadelphia ChromosomeNegative Acute Lymphoblastic Leukemia (ALL) in Second Relapse or Progressing Following Two Anti‑leukemia Treatment Lines. Fifty first annual meeting of the American Society
of Hematology, New Orleans, LA, December 2009. Blood 2009;114: 3088a.

100. Koren-Michowitz M, le Coutre PD, Duyster J, Scheid C, Panayiotidis P, Prejzner W,
Rowe JM, Schwarz M, Goldschmidt N, Nagler A. Prior Response to Imatinib Predicts
Response to Second Line Treatment with Nilotinib in CML Patients Resistant or Intolerant to Imatinib. Fifty-first annual meeting of the American Society of Hematology,

35

Hematology

New Orleans, LA, December 2009. Blood 2009; 114: 3297a.
101. Fernandez HF, Sun Z, Litzow MR, Luger SM, Paietta EM, Dewald GW, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Tallman MS. Autologous Hematopoietic Cell Transplantation as Consolidation for Younger Patients with Acute Myeloid Leukemia in First Complete Remission: Follow-up of E1900. Fifty-first annual meeting of the American Society of
Hematology, New Orleans, LA, December 2009. Blood 2009;114: 3405a.
102. Witzens-Harig M, van Hazel G, Chamone DFA, Ruffert K, Rowe JM, Lazzarino M, Foà R,
Poddubnaya R, Ho AD, Ivanova V, Vranowsky A, Hipp J, Oertel S. Safety and Efficacy in
Patients Receiving Maintenance Rituximab for Follicular Lymphoma: Early Results From
Phase IIIb MAXIMA Trial. Fifty-first annual meeting of the American Society of Hematology,
New Orleans, LA, December 2009. Blood 2009;114: 3756a.
103. Rosenblatt J, Avivi I, Vasir B, Katz T, Uhl L, Wu Z, Somaiya P, Mills H, Joyce RM, Levine
JD, Tzachanis D., Boussiotis V, Glotzbecker B, Francoeur K, Dombagoda D, Tsumer M,
Bisharat L, Giallombardo N, Conway K, Fitzgerald D, Barhad R, Richardson P, Anderson
KC, Munshi N, Rowe JM, Kufe D, Avigan D. Dendritic cell fusion vaccination in conjunction with autologous transplantation for multiple myeloma. 2010 BMT Tandem Meetings,
Orlando, Florida, February 2010. Biol Blood Marrow Transplant 2010;16:65a.
104. Fielding AK, Buck G, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman
AV, Paietta E, Richards SM, Tallman MS, Rowe JM, Goldstone AH. Imatinib Significantly
Enhances Long-Term Outcomes. In Philadelphia Positive Acute Lymphoblastic Leukaemia; Final Results of the UKALLXII/ECOG2993 Trial. Fifty-second annual meeting of the
American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 169a.
105. Shlush LI, Chapal N, Adar R, Izraeli S, Rowe JM, Skorecki K, Shapiro E, Zuckerman T.
Single-Cell Phylogenetic analysis provides Novel Insight Into Resistance Mechanisms In
AML. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL,
December 2010. Blood 2010; 116:178a.
106. De Keersmaecker K, Real PJ, Della Gatta G, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan P, Kelliher M, Kee BL, Pandolfi
PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis
J, Tallman M, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi SC, Meijerink
J, Cordon-Cardo C, Califano A, Ferrando A. BCL11B Mutations In T-Cell Acute Lymphoblastic Leukemia. Fifty second annual meeting of the American Society of Hematology,
Orlando, FL, December 2010. Blood 2010; 116: 471a.


36

107. Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Richards SM, Rowe JM, Tallman MS, Goldstone AH. Inability to Tolerate Standard Therapy Is
a Major Reason for Poor Outcome In Older Adults with Acute Lymphoblastic Leukemia
(ALL): Results From the International MRC/ECOG Trial. Fifty-second annual meeting of the
American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 493a, .
108. Litzow MR, Buck G, Dewald G, Fielding A, Ketterling R, Lazarus HM, Luger S, Marks DI,
McMillan A, Moorman AV, Paietta E, Richards SM, Rowe JM, Tallman MS, Goldstone AH.
Outcome of 1,229 Adult Philadelphia Chromosome Negative B Acute Lymphoblastic Leukemia (B-ALL) Patients (pts) From the International UKALLXII/E2993 Trial: No Difference
In Results Between B Cell Immunophenotypic Subgroups. Fifty-second annual meeting
of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116:
524a.
109. Strickland SA, Sun Z, Ketterling RP, Cherry AM, Cripe LD, Dewald G, Higgins RR, Lazarus
HM, Litzow MR, Luger SM, Paietta E, Rowe JM, Uno H, Vance GH, Tallman MS. Monosomal Karyotype (MK) In Older Patients with Acute Myeloid Leukemia (AML) on Eastern
Cooperative Oncology Group (ECOG) Therapeutic Trials: Poor Prognostic Impact of MK,
but Not of Monosomy 7. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116:579a.
110. Armand F, Perez W, Zhang M-J, Kim H, Klumpp TR, Dal Cin P, Waller EK, Litzow MR, Liesveld JL, Lazarus HM, Artz A, Gupta V, Savani BN,. McCarthy PL, Cahn J-Y, Schouten H,
Finke J, Ball ED, Aljurf M, Cutler C, Rowe JM, Antin JH, Isola LM, Di Bartolomeo P, Camitta
B, Miller AM, Cairo MS, Stockerl-Goldstein KE, Sierra J, Savoie ML, Halter J, Stiff PJ,
Nabhan C, Jakubowski AA, Bunjes D, Petersdorf EW, Devine SM, Maziarz R, Bornhauser
M, Lewis VA, Marks DI, Bredeson CH, Soiffer R, Weisdorf DJ. Cytogenetics Abnormalities
Predict the Outcome of Allogeneic Transplantation In AML: A CIBMTR Study. Fifty-second
annual meeting of the American Society of Hematology, Orlando, FL, December 2010.
Blood 2010;116 :680a.
111. Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T,
Nagler A. A Multi-Center Prospective Randomized Study Comparing Ibritumomab Tiuxetan (Zevalin) and High-Dose BEAM Chemotherapy (Z-BEAM) Vs. BEAM Alone as the
Conditioning Regimen Prior to Autologous Stem-Cell Transplantation In Patients with Aggressive Lymphoma; Possible Advantage for Z-BEAM In Low-Risk Patients. Fifty-second
annual meeting of the American Society of Hematology, Orlando, FL, December 2010.
Blood 2010; 116: 686a.

37

Hematology

112. Patel JP, Abdel-Wahab O, Gonen M, Figueroa ME, Fernandez HF, Sun Z, Racevskis J,
Van Lierberghe P, Dolgalev I, Cheng J, Viale A, Socci N, Heguy A, Ketterling R, Gallagher
RE, Litzow MR, Rowe JM, Ferrando A, Paietta E, Tallman MS, Melnick RM, Levine R.
High-Throughput Mutational Profiling In AML: Mutational Analysis of the ECOG E1900
Trial. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL,
December 2010. Blood 2010;116: 851a.
113. Geng H, Neuberg D, Paietta E, Deng X, Li Y, Xin Y, Racevskis J, Ketterling R, Richards SM,
Tallman MS, Rowe JM, Litzow MR, Elemento O, Melnick AM. Integrative Genome-Wide
DNA Methylation and Gene Expression Analysis Reveals Biological and Clinical Insights In
Adult Acute Lymphoblastic Leukemia. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 852a.
114. Park JH, Panageas KS, Schymura MJ, Qiao B, Jurcic JG, Rosenblat TL, Altman JK, Douer
D, Rowe JM, Tallman MS. A Population-Based Study In Acute Promyelocytic Leukemia
(APL) Suggests a Higher Early Death Rate and Lower Overall Survival Than Commonly
Reported In Clinical Trials: Data From the Surveillance, Epidemiology, and End Results
(SEER) Program and the New York State Cancer Registry In the United States Between
1992–2007. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 872a.
115. Smith MR, Neuberg D, Flinn IW, Grever MR, Bennett JM, Dewald G, Paietta EM, Litzow
MR, Rowe JM, Lucas D, Kitada S, Jelinek DF, Gribben JG, Byrd JC, Reed JC, Hussein MA, Appelbaum FR, Larson RA, Moore DF, Jr, Tallman MS. Increased Incidence of
Therapy Related Myeloid Neoplasia (t-MN) After Initial Therapy for CLL with FludarabineCyclophosphamide (FC) Vs Fludarabine (F): Long-Term Follow-up of US Intergroup Study
E2997. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL,
December 2010. Blood 2010;116: 924a.
116. Nagler A, Shimoni A, Avivi I, Rowe JM, Beider K, Hardan I, Abraham M, Wald H, Galun
E, Shaw HL, Eizenberg O, Peled A. BKT140 Is a Novel CXCR4 Antagonist with Stem
Cell Mobilization and Antimyeloma Effects: An Open-Label First Human Trial In Patients
with Multiple Myeloma Undergoing Stem Cell Mobilization for Autologous Transplantation.
Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 2260a.
117. Dann EJ, Bairey O, Bar-Shalom R, Izak M, Korenberg A, Akria L, Attias D, Filanovsky K,
Abdach L, Goldschmidt N, Epelbaum R, Rowe JM, Ben Yehuda D, Shpilberg O, Paltiel
OB. Tailored Therapy In Hodgkin Lymphoma, Based on Predefined Risk Factors and Early


38

Interim PET/CT, Can Lead to Modification and Safe Reduction In Therapy: Results of 134
Patients on the Israel National Hodgkin Study. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;116: 2809a.
118. Luger S, Yao X, Paietta E, Ketterling R, Rybka W, Litzow MR, Rowe JM, Larson R, Tallman MS. Tipifarnib Is Well Tolerated as Maintenance Therapy In Acute Myeloid Leukemia
(AML). Significant, but Non-Fatal, Hematologic Toxicity Not Ameliorated by Dose Reduction. Preliminary Results of the Phase III Intergroup Trial E2902. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010;
116: 3315a.
119. Katz T, Stroopinsky D, Rowe JM, Avivi I. Rituximab Directly Decreases T Cell Activation,
Both In Vivo and In Vitro. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL, December 2010. Blood 2010; 116: 3935a.
120. Foá R, Di Rocco A, van Hazel G, Chamone DFA, Ruffert K, Rowe JM, Arcaini L, Poddubnaya I, Ho AD, Ivanova V, Vranovsky A, Witzens-Harig M. Maintenance Rituximab Every
2 Months for 2 Years Is Effective and Well Tolerated In Patients with Follicular Lymphoma
with Both Standard or Rapid Infusion: Updated Results From the Phase IIIb MAXIMA
Study. Fifty-second annual meeting of the American Society of Hematology, Orlando, FL,
December 2010. Blood 2010; 116: 3945a.
121. Bairey O, Ruchlemer R, Rahimi-Levene N, Herishanu Y, Braester A, Klepfish A, and Shvidel L. Presenting Features and Outcome of Elderly Chronic Lymphocytic Leukemia Patients Diagnosed at the Age of 80 Years or Above. An ICLLSG Study. Blood Supplement
2010;116: 4620.
122. Ganzel C, Ben-Yehuda D., Mali A., Goldschmidt N. High incidence of skin rash in patients
with Hairy Cell Leukemia. Presented at the thirty-third International Society of Hematology
meeting, Jerusalem, 2010.
123. Ganzel C, Galina Pogrebijsky G., Krichevsky S., Neuman T., Ben-Yehuda D. The separate
diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL) in a single
patient may not signify a common clonal origin. American Society of Hematology, Fiftysecond annual meeting, 2010, Blood, 2010; 116: 4824.
124. Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T,
Nagler A. A multi-center prospective randomized study comparing yttium-19 ibritumomab
tiuxetan (zevalin) and high-dosed BEAN chemotherapy (Z-BEAN) versus BEAN prior to

39

Hematology

autologous stem cell transplantion in patients with aggressive lymphoma. Thirty-Seventh
annual meeting of the European Group for Blood and Marrow Transplantation EGBMT
(EBMT). Paris, France. Bone Marrow Transplantation 2011; 46: 266a.
125. Ruchlemer R, Elstein D, Broide E, Reinus C, Maayaan H, and Zimran A. Gaucher Disease and LGL Proliferations: Provocative Commonality? Poster at the American Society of
Hematology meeting Blood Supplement, 2011.
126. Vine J, Bar Cohen S, Ruchlemer R, Goldschmidt N, Levin M, Libster D, Gural A, Gatt
ME, Lavie D, Ben-Yehuda D, and Rund D. Polymorphisms in Exons 2 and 7 of the Human
Organic Cation Transporter (hOCT1) (Solute Carrier Family 22, SLC22A1): Correlation with
Imatinib Levels and Clinical Course in Chronic Myeloid Leukemia Patients. Poster at the
American Society of Hematology meeting. Blood Supplement, 2011.
127. Tadmor T, Shvidel L, Aviv A, Ruchlemer R, Bairey O, Yuklea M, Herishanu Y, Braester A,
Rahimi-Levene N Vernea F, Ben-Ezra J, Bejar J, Polliack A. Significance of Bone Marrow
Reticulin Fibrosis in Chronic Lymphocytic Leukemia: a Study of Therapy “Naïve” Patients
with Prognostic Implications. Abstract at the European Hematology Association, 2012.


40

Digestive Diseases
Institute

T

he Digestive Diseases Institute headed by Professor
Eran Goldin was established in 2011 to provide a
framework for the diagnosis and treatment of the
wide variety of gastrointestinal related diseases. The new
concept behind this Institute is to group experts from different disciplines in one comprehensive center and link the
fields of gastro, oncology, surgery and imaging, etc. The goal
is to achieve greater coordination among experts while ensuring a focus on advanced clinical treatment, as well as training
interns and students and carrying out basic and advanced
research of the digestive system.
The Institute is made up of several units including the Endoscopy Unit under the direction of Dr. Dov Wengrover, the
Inflammatory Bowel Diseases Center (headed by Professor
Goldin), the Neurogastroenterology Service and the Pelvic
Floor Unit (directed by Dr. Joseph Lysy) the Pancreatic Biliary
Center (headed by Dr. Alain Dancour), and the Liver Unit (directed by Dr. Yoav Lurie). Additional staff include Dr. Julian
Paz, Dr. Ariella Shitrit and Dr. Ina Gapanovich who act as senior specialists in the Institute.
In the Institute more than 15,000 digestive system procedures are performed every year including video capsular endoscopies, manomatries, and PH monitoring. The Institute
acts as a reference center for complex cases from all over Israel
and abroad. A new center for prevention of malignancies of
the digestive tract was established in 2012.

41

Digestive Diseases

Research is a major area of activity in the Institute, and involves numerous local, national and
international projects of a clinical and basic scientific nature. The research staff includes a
PhD researcher and a lab technician. The Unit for Clinical Studies has three research coordinators.The major research area of the Institute involves inflammatory bowel diseases (IBD), liver
diseases and the investigational projects in endoscopy and new technologies. One research
project involves a study of the recruitment of eotoxin and eosinophiles in IBD in a rat model
of partial portal vein ligation.

publications
1.

Mizrahi M, Adar T, Ilan Y. Idiopathic right-sided endocarditis: an uncommon manifestation
of pulmonary cavitations. Harefuah 2009; 148(4):233-4, 277.

2.

Lalazar G, Adar T, Ilan Y. Point of care continuous C(13)-methacetin breath test improves
decision making in acute liver disease : results of a pilot clinical trial. World J Gastroenterol
2009; 28;15(8):966-72.

3.

Mizrahi M, Adar T, Orenbuch-Harroch E, Elitzur Y. Non-ST elevation myocardial infarction
after high dose intravenous immunoglobulin infusion. Case Report Med. 2009 Feb. 22e

4.

Adar T, Mizrahi M, Pappo O, Scheiman-Elazary A, Shibolet O. Adalimumab-induced autoimmune hepatitis. J Clin Gastroenterol 2010 44(1):e20-2.

5.

Marcus EL, Arnon R, Sheykenman A, Kaine GC, Lysy J. Esophageal obstruction due to
enteral feed bezoar: A case report and literature review. World Journal of Gastrointestinal
Endoscopy 2010; 16(2): 352-356.

6.

Mizrahi M, Lalazar G, Adar T, Raz I, Ilan Y. Assessment of insulin resistance by 13C glucose breath test: a new tool for early diagnosis and follow up for high risk patients. Nutr
J 2010; (27): 9-25.

7.

Mizrahi M, Adar T, Shouval D, Bloom AI, Shibolet O. Endotipsitis – persistent infection of
transjugular intrahepatic portosystemic shunt: pathogenesis, clinical features and management Liver Int 2010; 30(2):175-83.


42

8.

Mizrahi M, Roemi L, Shouval D, Adar T, Korem M, Moses A, Bloom A, Shibolet O. Bactrermia and “Endotipsitis” following transjugular intrahepatic portosystemic shunting.
World J Hepatol 2011; 27; 3(5):130-6.

9.

Oberbaum M, Lysy J, Gropp C. From Nebuchadnezzar to the Randomized Controlled
trial-Milestones in the development of clinical research. Harefuah; 2011.

10.

Levin A, Cohen J. M, Mindrul V, Lysy J. Delayed fecal incontinence following surgery for
anal fissure. Int J Colorectal Dis 2011; 26(12):1595-9.

11.

Mizrahi M, Almogy G, Adar T, Lysy J. Dumping syndrome following Nissen funduplication
in an adult patient diagnosed by continuous online 13C/12C monitoring of 13C-octanoic
acid breath test “a case report”. BMC Gastroenterol. 2011; (19):11-98.

12.

Adar T, Ben Ya’acov A, Lalazar G, Lichtenstein Y, Nahman D, Mizrahi M, Wong V, Muller
B, Rawlin G, Ilan Y.Oral administration of immunoglobulin G-enhanced colostrum alleviates insulin resistance and liver injury and is associated with alterations in natural killer T
cells. Clin Exp Immunol 2012; 167(2):252-60.

13.

Adar T, Tayer-Shifman O, Mizrahi M, Tavdi S, Barak O, Shalit M. Dapsone induced eosinophilic pneumonia. Eur Ann Allergy Clin Immunol 2012; 44(3):144-6.

14.

Shteyer E, Wengrower D, Benuri-Silbiger I, Gozal D, Wilschanski M, Goldin E. retrograde cholangiopancreatography in neonatal cholestasis. J Pediatr Gastroenterol Nutr
2012;55(2):142-5.

15.

Mizrahi MC, Reicher-Atir R, Levy S, Haramati S, Wengrower D, Israeli E, Goldin E. Effects
of guided imagery with relaxation training on anxiety and quality of life among patients with
inflammatory bowel disease. Psychol Health 2012; 27(12):1463-79.

16.

Wengrower D, Zanninelli G, Latella G, Necozione S, Metanes I, Israeli E, Lysy J, Pines M,
Papo O, Goldin E. Losartan reduces trinitrobenzene sulphonic acid-induced colorectal
fibrosis in rats. Can J Gastroenterol 2012; 26(1):33-9.

17.

Dotan I, Alper A, Rachmilewitz D, Israeli E, Odes S, Chermesh I, Naftali Timna, Frazer
G, Bar-Gil Shitrit A, Peles V, Reif S. Maternal Inflammatory bowel disease has short and
long term effect on the health of their offspring. A multicenter study in Israel. Accepted for
publication JCC August 2012.

43

Digestive Diseases

Published Abstracts
1.

Lysy J, Shafra-Tikva S, Goldin E, Greenberg D.”The neighbour around the corner” A
model for an early detection of prostate cancer in the Gastroenterology unit. Gastroenterology 2009.

2.

Ariella S, Adar T, Goldin E, Lysy J. Trapping of balloon in rectocele during rectal manometry is predictive of defecography results. Gastroenterology 2012.


44

Gaucher Clinic

T

he Gaucher Clinic was founded in 1989 as the first national referral out-patient clinic for patients with Gaucher disease by Prof. Ari Zimran, along with Prof.
Ayala Abrahamov who had overseen pediatric patients with
metabolic diseases as part of her out-patient population. In
1993 they were joined by Dr. Deborah Elstein. For the past 19
years this has been the “Gaucher team” and is occasionally
supplemented by young physicians and medical students on
rotation or doing research projects.

Gaucher disease is the most common inherited disorder affecting Ashkenazi Jews, and is especially prevalent in Israel.
Nevertheless, it is still a rather rare disease, and many patients are often treated by physicians who are not familiar
with the manifestations. More importantly, general practitioners are not always aware of new treatment modalities and
adjuvant therapies.
Patients with Gaucher disease come to the clinic for complete
baseline evaluations, follow-up examinations, consultations
regarding specific conditions such as army service, pregnancy
etc., and for treatment. Patients are offered a holistic approach guided by senior specialists in all fields of medicine,
including surgeons, orthopedists, and gynecologists.
Recently we have been able to offer bone mineral density
evaluations using a state-of-the-art DEXA (dual energy x-ray
absorptiometry) machine.

45

Gaucher

The Unit conducts research on low-dose, low-frequency enzyme therapy, type 3c Gaucher
disease, a unique variant of Gaucher disease among Arabs with progressive calcification of
the heart valves, early-onset parkinsonism in patients with Gaucher disease, the ethical considerations involved in providing enzyme therapy to babies with the neuronopathic forms of
Gaucher disease, outcome of pregnancies in women with Gaucher disease, echocardiography
of pulmonary hypertension among patients with Gaucher disease, follow-up of patients who
have undergone orthopedic interventions especially hip replacements, the incidence of cancers in Gaucher disease, use of anesthesia in pregnant and thrombocytopenic patients with
Gaucher disease, and the impact of expensive therapies on national health budgets.

Because of the increased incidence of Parkinson's disease in patients and carriers of Gaucher
disease, we are collaborating on a questionnaire-based study to evaluate the clinical status of
affected patients and obligate carriers. We are also involved in several bone densitometry studies in patients with Gaucher disease, patients with Prader-Willi syndrome, post-partum and
post-lactation, in the over 85 years of age, and after fractures.
Our clinic was the first medical group outside the US to introduce enzymatic replacement
therapy (ERT) with alglucerase (Ceredase ®, Genzyme Inc., MA) in December, 1990 and Prof.
Zimran was also active in lobbying for its registration by the Ministry of Health in Israel. We
participated in the trial with the recombinant form, imiglucerase (Cerezyme®, Genzyme Inc.,
MA) using the low-dose, low-frequency regimen which is still the starting regimen for adults
in Israel. From 1998-2002 our clinic was involved in three pivotal trials testing the safety and
efficacy of the concept of substrate reduction therapy (SRT) with miglustat (Zavesca, Actelion Therapeutics, Allschwil, Switzerland) as an oral therapeutic regimen which can cross the
blood-brain barrier. In 2004 we initiated a seminal Phase I/II clinical trial as a single-center
with a wild-type sequence enzymatic preparation, gene-activated glucocerebrosidase (velaglucerase alfa) by Shire Human Genetic Therapies (Cambridge, MA, USA). We also participated
in all three subsequent Phase III clinical trials with velaglucerase alfa and the extensions of
all four trials. The naïve patients of the seminal trial completed 7 years of exposure and the
patients in the other trials, including those who were switched from Cerezyme, who entered
an extension phase, benefitted from at least 4 years on velaglucerase alfa. This drug (Vpriv)
received both FDA and EMA approval in 2010 and is available commercially in Israel.
In addition, we participated in the seminal Phase III trials in adult and pediatric patients, naive
as well as patients switching over from Cerezyme, with an intravenous ERT, taliglucerase alfa,


46

manufactured by the Israeli biotherapeutics company, Protalix Pharmaceutics (Carmiel, Israel)
which uses a high-yield plant cell system that is readily up-scalable in disposable bioreactors
and free from exposure to mammalian tissues. This drug received FDA and EMA approval in
2012 and is available commercially in Israel.
For the past four years we have also participated in a multi-national, multi-center Phase II
trial with eliglustat tartrate (Genzyme-Sanofi Corporation, Cambridge, MA, USA) an oral SRT
which unlike miglustat cannot cross the blood-brain barrier.
In November 2008, our clinic committed to a pilot study using ambroxol, a well-known oral
over-the-counter treatment for acute or chronic respiratory disorders associated with viscid or
excessive mucus. Although intravenous ERT is still the standard of care for Gaucher disease,
there is considerable interest in small-molecule-based oral pharmacological chaperones. This
investigator-initiated pilot study was successfully completed and we are actively looking to
initiate a clinical trial in the very near future.
The clinic has taken an active interest in the ultra-rare clinical entity of Late-onset Tay-Sachs
disease (LOTS), which is also a lysosomal storage disease, and is predominantly found among
Ashkenazi Jews. We currently are in touch with several of the approximately 100 patients
identified throughout the world.

47

Gaucher

Publications
1.

Pront R, Margalioth EJ, Green R, Eldar-Geva T, Maimoni Z, Zimran A, Elstein D. Prevalence
of low serum cobalamin in infertile couples. Andrologia 2009;41(1):46-50.

2.

Zimran A, Ilan Y, Elstein D. Enzyme replacement therapy for mild patients with Gaucher
disease. Am J Hematol 2009; 84(4):202-4.

3.

Grisaru-Granovsky S, Rabinowitz R, Ioscovich A, Elstein D, Schimmel M. Congenital diaphragmatic hernia: review of the literature in reflection of unresolved dilemmas. Acta Paediatr 2009;98(12):1874-81.

4.

Grabowski GA, Kacena K, Cole JA, Hollak CE, Zhang L, Yee J, Mistry PK, Zimran A, Charrow J, vom Dahl S. Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1.Genet Med 2009;11(2):92100.

5.

Zimran A, Morris E, Mengel E, Kaplan P, Belmatoug N, Hughes DA, Malinova V, Heitner
R, Sobreira E, Mrsić M, Granovsky-Grisaru S, Amato D, vom Dahl S. The female Gaucher
patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis 2009;43(3):264-88.

6.

Lebel E, Elstein D, Zimran A, Itzchaki M. Cementless total hip arthroplasties in Gaucher
disease: long-term follow-up. Am J Orthop 2009;38(3):130-2.

7.

Lebel E, Phillips M, Elstein D, Zimran A, Itzchaki M. Poor results of drilling in early stages
of juxta-articular osteonecrosis in 12 joints affected by Gaucher disease. Acta Orthop
2009;80(2):201-4.

8.

Ilan Y, Elstein D, Zimran A. Glucocerebroside: an evolutionary advantage for patients with
Gaucher disease and a new immunomodulatory agent. Immunol Cell Biol 2009;87(7):51424.

9.

Elstein D, Zimran A. Review of the safety and efficacy of imiglucerase treatment of Gaucher disease. Biologics 2009;3:407-17.

10.

Greenwood A, Altarescu G, Zimran A, Elstein D. Vitamin D Receptor (VDR) Polymorphisms
in the Cardiac Variant of Gaucher Disease. Pediatr Cardiol 2010 ;31(1):30-2.


48

11.

Altarescu G, Seror-Bukris O, Zimran A, Elstein D. Proteinase-activated receptor (PAR1)
polymorphic variant correlates with thrombocytopenia in Gaucher disease. Blood Cells
Mol Dis 2010;44(2):79-81.

12.

Hollak CE, vom Dahl S, Aerts JM, Belmatoug N, Bembi B, Cohen Y, Collin-Histed T,
Deegan P, van Dussen L, Giraldo P, Mengel E, Michelakakis H, Manuel J, Hrebicek M,
Parini R, Reinke J, di Rocco M, Pocovi M, Sa Miranda MC, Tylki-Szymanska A, Zimran A,
Cox TM. Force majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis 2010;44(1):417.

13.

Weinreb NJ, Cappellini MD, Cox TM, Giannini EH, Grabowski GA, Hwu WL, Mankin H,
Martins AM, Sawyer C, vom Dahl S, Yeh MS, Zimran A. A validated disease severity scoring system for adults with type 1 Gaucher disease. Genet Med 2010;12(1):44-51

14.

Hollak CE, Aerts JM, Belmatoug N, Bembi B, Bodamer O, Cappellini D, Collin-Histed T,
Cox TM, Deegan P, Giraldo P, Hughes D, Lukina E, Manuel J, Michelakakis H, Di Rocco
M, Vellodi A, Zimran A. Guidelines for the restart of imiglucerase in patients with Gaucher
disease: recommendations from the European Working Group on Gaucher disease. Blood
Cells Mol Dis 2010;44(2):86-7.

15.

Elstein D, Gellman A, Altarescu G, Abrahamov A, Hadas-Halpern I, Phillips M, Margalit
M, Lebel E, Itzchaki M, Zimran A. Disease severity in sibling pairs with type 1 Gaucher
disease. J Inherit Metab Dis 2010;33(1):79-83.

16.

Hadas-Halpern I, Deeb M, Abrahamov A, Zimran A, Elstein D. Gaucher disease: spectrum
of sonographic findings in the liver. J Ultrasound Med 2010;29(5):727-33.

17.

Greenwood A, Elstein D, Zimran A, Altarescu G. Effect of vitamin D receptor (VDR)
genotypes on the risk for osteoporosis in type 1 Gaucher disease. Clin Rheumatol
2010;29(9):1037-41.

18.

Zimran A, Altarescu G, Phillips M, Attias D, Jmoudiak M, Deeb M, Wang N, Bhirangi K,
Cohn GM, Elstein D. Phase I/II and extension study of velaglucerase alfa (Gene-ActivatedTM human glucocerebrosidase) replacement therapy in adults with type 1 Gaucher
disease: 48-month experience. Blood 2010; 115(23):4651-6.

19.

Hadas-Halpern I, Deeb M, Abrahamov A, Zimran A, Elstein D. Gaucher disease: spectrum
of sonographic findings in the liver. J Ultrasound Med 2010;29(5):727-33.

49

Gaucher

20.

Zimran A, Altarescu G, Elstein D. Nonprecipitous changes upon withdrawal from imiglucerase for Gaucher disease because of a shortage in supply. Blood Cells Mol Dis 2010;
;46(1):111-4.

21.

Shemesh T, Whybra C, Delgado-Sanchez S, Beck M, Elstein D, Altarescu G. Paraoxonase
(PON1) Gene Polymorphisms in Fabry Disease: Correlation with Renal Disease. Nephron
Clin Pract 2010;116(4):c289-c293.

22.

Eitan Y, Abrahamov A, Phillips M, Elstein D, Zimran A. Sixteen years of prenatal consultations for the N370S/N370S Gaucher disease genotype: what have we learned? Prenat
Diagn 2010;30(10):924-7.

23.

Marks A, Greenstein J, Berger MT, Shapiro J, Elstein D, Ioscovich A. Peripartum anesthesia in grand-grand multiparous women (≥10 births). Health Care Women Int 2010;
31(10):938-45.

24.

Lieblich M, Altarescu G, Zimran A, Elstein D. Vitamin D Receptor (VDR) polymorphic variants in patients with cancer and Gaucher disease. Blood Cells Mol Dis 2011;46(1):92-4.

25.

Altarescu G, Renbaum P, Eldar-Geva T, Varshower I, Brooks B, Beeri R, Margalioth EJ,
Levy-Lahad E, Elstein D, Zimran A. Preimplantation genetic diagnosis (PGD) for a treatable disorder: Gaucher disease type 1 as a model. Blood Cells Mol Dis 2011;46(1):15-8.

26.

Fadeev A, Ioscovitch A, Rivlis A, Grisaru-Granovsky S, Samueloff A, Schimmel MS, Elstein D. Prospective study of maternal and neonatal outcome in great-grand multiparous
women (≥10 births) and in aged-matched women with lesser parity. Arch Gynecol Obstet
2011;284(4):799-805.

27.

Elstein D, Cohn GM, Wang N, Djordjevic M, Brutaru C, Zimran A. Early achievement and
maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease.
Blood Cells Mol Dis 2011;46(1):119-23.

28.

Lebel E, Ioscovich A, Itzchaki M, Zimran A, Elstein D. Hip arthroplasty in patients with
Gaucher disease. Blood Cells Mol Dis 2011;46(1):60-5.

29.

Hughes DA, Al-Sayed M, Belmatoug N, Bodamer O, Böttcher T, Cappellini M, Cohen IJ, Eagleton T, Elstein D, Giraldo P, Jones S, Kaplinsky C, Lund A, Machaczka M, Mengel E, Pastores GM, Rosenbaum H, Sjo M, Tiling N, Tsaftaridis P, Zimran A, Weinreb N. Early access experience with VPRIV(®): Recommendations


50

for ‘core data’ collection. Blood Cells Mol Dis 2011 ;47(2):140-2.
30.

Rosenbloom B, Balwani M, Bronstein JM, Kolodny E, Sathe S, Gwosdow AR, Taylor JS,
Cole JA, Zimran A, Weinreb NJ. The incidence of Parkinsonism in patients with type 1 Gaucher disease: data from the ICGG Gaucher Registry.Blood Cells Mol Dis 2011;46(1):95102.

31.

Granovsky-Grisaru S, Belmatoug N, vom Dahl S, Mengel E, Morris E, Zimran A. The
management of pregnancy in Gaucher disease. Eur J Obstet Gynecol Reprod Biol
2011;156(1):3-8.

32.

Zimran A. Velaglucerase alfa: a new option for Gaucher disease treatment. Drugs Today
(Barc) 2011;47(7):515-29.

33.

Zimran A. How I treat Gaucher disease. Blood. 2011 Aug 11;118(6):1463-71.

34.

Segel R, Anikster Y, Zevin S, Steinberg A, Gahl WA, Fisher D, Staretz-Chacham O, Zimran
A, Altarescu G. A safety trial of high dose glyceryl triacetate for Canavan disease. Mol
Genet Metab 2011;103(3):203-6.

35.

Osher E, Fattal-Valevski A, Sagie L, Urshanski N, Amir-Levi Y, Katzburg S, Peleg L, Lerman-Sagie T, Zimran A, Elstein D, Navon R, Stern N, Valevski A. Pyrimethamine increases
β-hexosaminidase A activity in patients with Late Onset Tay Sachs. Mol Genet Metab. Mol
Genet Metab 2011;102(3):356-63.

36.

Elstein D. Recent Advances in Treatment Approaches to Gaucher Disease. Curr Pharm
Biotechnol 2011;12(6):854-60.

37.

Svobodová E, Mrázová L, Lukšan O, Elstein D, Zimran A, Stolnaya L, Minks J, Eberová J,
Dvořáková L, Jirsa M, Hřebíček M. Glucocerebrosidase gene has an alternative upstream
promoter, which has features and expression characteristic of housekeeping genes. Blood
Cells Mol Dis 2011;46(3):239-45.

38.

Simchen MJ, Oz R, Shenkman B, Zimran A, Elstein D, Kenet G. Impaired platelet function and peripartum bleeding in women with Gaucher disease. Thromb Haemost
2011;105(3):509-514.

39.

Spectre G, Roth B, Ronen G, Rosengarten D, Elstein D, Zimran A, Varon D, Revel-Vilk S. Platelet adhesion defect in type I Gaucher Disease is associated with

51

Gaucher

a risk of mucosal bleeding. Br J Haematol. 2011 May;153(3):372-8.
40.

Altarescu G, Elstein D. Fabry disease in an oligosymptomatic male. Isr Med Assoc J
2011;13(3):191-2.

41.

Elstein D, Foldes AJ, Zahrieh D, Cohn GM, Djordjevic M, Brutaru C, Zimran A. Significant
and continuous improvement in bone mineral density among type 1 Gaucher disease
patients treated with velaglucerase alfa: 69-month experience, including dose reduction.
Blood Cells Mol Dis 2011;47(1):56-61.

42.

Ribner A, Altarescu G, Zimran A, Elstein D. Osteopontin polymorphic susceptibility factor for
Parkinson’s disease among patients with Gaucher disease. Mov Disord 2011;26(7):13413.

43.

Altarescu G, Renbaum P, Eldar-Geva T, Brooks B, Varshaver I, Avitzour M, Margalioth EJ,
Levy-Lahad E, Elstein D, Epsztejn-Litman S, Eiges R. Preventing mucopolysaccharidosis
type II (Hunter syndrome): PGD and establishing a Hunter (46, XX) stem cell line. Prenat
Diagn 2011. [Epub ahead of print]

44.

Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Terreros Muñoz E,
Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta
A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D. Pivotal
trial with plant-cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel
enzyme replacement therapy for Gaucher disease. Blood 2011;118(22):5767-73.

45.

Michaelson-Cohen R, Elstein D, Ioscovich A, Armon S, Schimmel MS, Butnaru A, Samueloff A, Grisaru-Granovsky S. Severe heart disease complicating pregnancy does not preclude a favourable pregnancy outcome: 15 years’ experience in a single centre. J Obstet
Gynaecol 2011;31(7):597-602.

46.

Ioscovich A, Fadeev A, Rivilis A, Elstein D. Requests and usage of epidural analgesia in
grand-grand multiparous and similar-aged women with lesser parity: prospective observational study. J Perinat Med 2011;39(6):697-700.

47.

Elstein D, Tiomkin M, Hadas-Halpern I, Zimran A. Organ volume by computed tomography correlates with longitudinal axis on ultrasound in patients with Gaucher disease.
Ultrasound Q 2011;27(4):25-8.

48.

Elstein D, Altarescu G, Maayan H, Phillips M, Abrahamov A, Hadas-Halpern I, Tiomkin M,


52

Zimran A. Booster-effect with velaglucerase alfa in patients with Gaucher disease switched
from long-term imiglucerase therapy: Early Access Program results from Jerusalem. Blood
Cells Mol Dis 2012;48(1):45-50.
49.

Givol N, Goldstein G, Peleg O, Shenkman B, Zimran A, Elstein D, Kenet G. Thrombocytopenia and bleeding in dental procedures of patients with Gaucher disease. Haemophilia
2012;18(1):117-21.

50.

Saranjam H, Sidransky E, Levine W, Zimran A, Elstein D. Mandibular and dental manifestations of Gaucher disease. Oral Dis 2012;18(5):421-9.

51.

Samuels N, Elstein D, Lebel E, Zimran A, Oberbaum M. Acupuncture for symptoms of
Gaucher disease. Complement Ther Med 2012;20(3):131-4.

52.

Elstein D, Schachamorov E, Beeri R, Altarescu G. X-inactivation in Fabry disease. Gene
2012 [Epub ahead of print]

53.

Chetrit EB, Alcalay RN, Steiner-Birmanns B, Altarescu G, Phillips M, Elstein D, Zimran A.
Phenotype in patients with Gaucher disease and Parkinson disease. Blood Cells Mol Dis.
2012.

54.

Altarescu G, Beeri R, Eiges R, Epsztejn-Litman S, Eldar-Geva T, Elstein D, Zimran A,
Margalioth EJ, Levy-Lahad E, Renbaum P. Prevention of lysosomal storage diseases and
derivation of mutant stem cell lines by preimplantation genetic diagnosis. Mol Biol Int.
2012;2012:797342.

55.

Zimran A, Pastores GM, Tylki-Szymanska A, Hughes DA, Elstein D, Mardach R, Eng C,
Smith L, Heisel-Kurth M, Charrow J, Harmatz P, Fernhoff P, Rhead W, Longo N, Giraldo P,
Ruiz JA, Zahrieh D, Crombez E, Grabowski GA. Safety and efficacy of velaglucerase alfa
in Gaucher disease type 1 patients previously treated with imiglucerase. Am J Hematol.
2012.

53

Gaucher

Medical Genetics
Institute

T

he Medical Genetics Institute was established in 1996.
It is directed by Prof. Ephrat Levy-Lahad, and includes
three board certified specialists in Medical Genetics:
Prof. Gheona Altarescu, whose is also a specialist in Internal
Medicine and is Head of the Zohar Preimplantation Diagnosis Unit (PGD), Dr. Reeval Segel, who is also a specialist in
Pediatrics and directs the Cytogenetics and microarray service, and Dr. Rachel Michaelson-Cohen, who is also a specialist in Obstetrics and Gynecology. Genetics impacts all areas of
medicine and the diverse medical backgrounds of the senior
physicians in the Institute ensures expertise in a broad range
of fields.
The Institute provides services through various clinics, which
in addition to the physicians are staffed by M.Sc. and Ph.D.
genetic counselors. The major clinics include: Cancer Genetics, which was one of the first of its kind in Israel, Pediatric
Genetics, for evaluation of children with intellectual disabilities or congenital malformations and Prenatal Genetics, for
the evaluation of pregnancies at risk for genetic disease or fetal malformations. The Institute also coordinates a number of
multidisciplinary clinics: 1) The Neurofibromatosis clinic for
both children and adults with this common, complex disease,
operates in collaboration with the Pediatric Neurology Unit,
Adult Neurology Dept., Pediatric Ophthalmology Unit , Pediatric Orthopedics Unit, Plastic Surgery, all at Shaare Zedek,
and Pediatric Neurosurgery at Dana Hospital in Tel Aviv; 2)
The Neurogenetics Clinic, in collaboration with the Pediatric
Neurology Unit, diagnoses and treats children with combined


54

neurological and genetic issues, e.g. Prader Willi disease; 3) The Noga clinic, which offers follow-up and surveillance for female BRCA1/BRCA2 carriers who are at high risk of breast and
ovarian cancer, operates in collaboration with the Gynecology service and the Breast Surgery
Unit; 4) The Fetal Malformation clinic operates in collaboration with the Prenatal Ultrasound
service, the Neonatal Intensive Care Unit and all subspecialties of the Pediatrics Department.
The multidisciplinary clinics are national referral centers, and serve patients from all over the
country.
The diagnostic Medical Genetics Laboratory is directed by Paul Renbaum, Ph.D. and includes
a Molecular Genetics laboratory headed by Rachel Beeri, Ph.D., a Cytogenetics and microarray
laboratory headed by Dr. Reeval Segel, and a Molecular Pathology Laboratory headed by Dr. Eli
Golomb, a specialist in Pathology. The laboratories provide genetic testing in all these areas.
In addition to the clinical laboratories, there are research laboratories within the molecular
laboratory, and a stem-cell research lab, headed by Rachel Eiges, Ph.D.. Research is performed
by graduate students and post-doctoral fellows through our affiliation with the Medical Research Institute at the Hebrew University Faculty of Medicine.

Research is a major focus of the Medical Genetics Institute, and reflects the research interests
of its senior personnel.
• Cancer Genetics. The Shaare Zedek teams have been studying risks of cancer associated
with inherited mutations, in particular mutations in the BRCA1 and BRCA2 genes. Women
who inherit mutations in these genes have a much higher risk of breast and ovarian cancer,
and these mutations are particularly common in Ashkenazi Jewish women. We are studying genetic and environmental factors that influence this risk. For example, we have found
that variations in other genes are important, and that risk is increasing in women today
compared to carriers in previous generations. We have recently completed a study providing
evidence for population screening of these mutations in Jewish women. We are also collaborating with Palestinian colleagues to determine inherited mutations that affect breast
cancer risk in Arab women.
• Inherited diseases in children. A major focus is identifying the mutations responsible for
genetic diseases in children. In Jerusalem, marriage between relatives or within a small
ethnic group is still common, and combined with large family size, this results in a higher
frequency of genetic diseases in children. Some diseases are common, e.g. Tay Sachs, which
is now prevented by prior testing, but many of these often devastating diseases are specific

55

Medical Genetics

Medical Research Report 2013

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