1. BY DR.ANIRUDH J SHETTY
PROF.DR.G.ELANGOVAN’S UNIT

2. 28 yr male patient came with c/o
abdominal pain-1 week in duration
involving predominantly
the left upper and
centre of the abdomen
vague dragging pain
assoc with fullness of abd
no h/o any aggravating or
relieving factors

3.  h/o early satiety +
 h/o loss of appetite +
 No h/o loss of weight
 No h/o jaundice
 No h/o haematemesis
 No h/o altered bowel habits
 No h/o bleeding tendencies

4.  PAST h/o -> No h/o Tb/HTN/DM
 PERSONAL h/o -> consumes alcohol
occasionally
not a smoker

5.  O/E – Pt conscious
oriented
afebrile
anemic
no Cyanosis,clubbing,icterus,
lymphadenopathy
B.P-110/70 mmHG
P.R -80 min

6.  P/A –mild distention of abdomen+
no dialated viens,scars or sinuses
massive spleenomegaly(+) crossing
the umbilicus
no hepatomegaly
no FF+

7.  CVS – S1S2(+)
NO murmurs
RS – NVBS+
no added sounds
CNS - NFND

8. CBC
 Hb – 14
 TC – 9300
 P69,L31
 ESR – 15
 PLATLETS – 1,50,000
RFT
 RBS -152
 UREA – 32
 CREAT – 1.0
 SODIUM; 135
 K+ - 6.0
 CL – 105
 HCO- 19

9.  ECG – WNL
 CHEST X – RAY - WNL

12. CBC
TC – 1,60,000
SHIFT TO LEFT
BLAST 1%
HB – 9.2
PLATLET -1,80,000
Chronic phase of CML
 P/S
Markedly increased TC,
showsMYELOBLAST,PR
OMYELOCYTE,METAMY
ELOCYTE,BAND FORMS

15.  BONE MARROW FRAGMENT
SHOWING A DENSLLY CELLULAR MARROW
FRAGMENT WITH ABSENT FAT CELLS

17.  LOW POWER MICROSCOPE:
MYELOID HYPERPLASIA WITH RELATIVELY
REDUCED ERYTHROID PROGENITORS

21.  Patient was started on Imatinib mesylate
400mg 1-0-0

24.  CML accounts for 15% of all cases of
leukemia.
 More common in men
 Peak incidence : fourth and fifth decade

26.  In CML the c-ABL gene is translocated from
its normal abode on chromosone 9 to
chromosone 22,where it fuses with bcr gene.
 As a consequence of the fusion, c-ABL loses a
region that controls tyrosine kinase activity.
Thus the BCR-ABL protien,the product of the
fusion gene has potent and constitutive
tyrosine kinase activity.

28. 1. CHRONIC PHASE
2. ACCELARATED PHASE
3. BLAST CRISIS

29.  EASY FATIGABILITY
 DECREASE TOLERANCE TO EXERTION
 ABDOMINAL DISCOMFORT AND EARLY
SATIETY( DUE TO SPLENIC ENLARGEMENT)
 WIEGHT LOSS AND EXCESSIVE SWEATING
The symptoms are vague, nonspecific and
gradual in onset

30.  A physical examination may detect pallor and
splenomegaly.The latter was present in 90%
of patients.
UNCOMMON PRESENTATIONS :
 Dramatic hypermetabolism(night sweats,wt
loss,heat intolerance)
 Acute gouty arthritis(due to hyperurecemia)
 Priapism,tinnitus
 Lt upper quadrant n lt shoulder pain due to
splenic infarction and perisplenitis.

31.  CML is often suspected on the basis on
the complete blood count, which shows
increased granulocytes of all types, typically
including maturemyeloid cells.
 Basophils and eosinophils are almost universally
increased; this feature may help differentiate
CML from a leukemoid reaction.
 A bone marrow biopsy is often performed as
part of the evaluation for CML, and CML is
diagnosed by detecting the Philadelphia
chromosome.

32.  10–19% myeloblasts in the blood or bone
marrow.
 >20% basophils in the blood or bone marrow
 Platelet count <100,000, unrelated to therapy
 Cytogenetic evolution with new abnormalities in
addition to the Philadelphia chromosome
 Increasing splenomegaly or white blood cell
count, unresponsive to therapy

33.  Blast crisis is the final phase in the evolution of CML, and
behaves like an acute leukemia, with rapid progression
and short survival.
 Blast crisis is diagnosed if any of the following are present
in a patient with CML:
 >20% myeloblasts or lymphoblasts in the blood or bone
marrow.
 Large clusters of blasts in the bone marrow on biopsy.
 Development of a chloroma (solid focus of leukemia
outside the bone marrow)

34.  IMATINIB MESYLATE
 STEM CELL TRANSPLANTATION
 IFN-ALPHA
 HYDROXYUREA
 SECOND GENERATION TK INHIBITOR-
DASATINIB AND NILOTINIB

35.  IMTINIB NOW IS USED AS INITIAL THERAPY IN
ALMOST ALL PATIENTS WITH CML.
 IN CASES WHERE WBC COUNT IS MARKEDLY
ELEVATED HYDROXYUREA CAN BE USED TO
PREVENT HYPERLEUKOCYTIC SYNDROME.

36.  The bcr abl oncoprotien
with a molecule of ATP in
d kinase pocket.
 Phosphorylation - >
substrate .Activates
downstream molecules
 Imatinib occcupies d
kinase pocket preventing
phosphorylation of its
substrates

38. HAEMATOLOGIC
RESPONSE
CYTOGENETIC
RESPONSE
MOLECULAR
RESPONSE(BCR
ABL TO
CONTROL GENE
RATIO
ACCORDING TO
IS SCALE)
FREQUENCY .Every 2 weeks
until a complete
response has been
achieved and
confirmed.
every 3 months
unless othwise
required
every 6 months
until a complete
response has
been achieved
and confirmed.
then every 12
months
EVERY 3
MONTHS
METHOD complete blood
count (CBC) with
differential
Conventional
cytogenetic
examination
.FISH
(fluorescene in
situ
hybridisation)
(only before
treatment)
.RQ-PCR
(Reverse
transcription
quantitative
polymerase
chain reaction)

39. SMENT METHOD
SUBOPTIMAL RESPONSE FAILURE
tologic No Complete hematologic
response(CHR) within 3
months
No hematologic response
within 3 months
Loss of CHR at any time
enetic No MCyR (Major cytogenetic
response )within 6 months
No CCyR(Complete
cytogenetic response) within
18 months
.No cytogenetic response
within 6 months
No MCyR within 12 mont
No CCyR within 18 mont
Loss of CCyR at any time
Not applicable.
CULAR No MMR(Major molecular
response) within 8 months
Loss of MMR at any time

41.  Second generation TKI like
DASATINIB
NILOTINIB
 Allogenic human stem cell transplant

42.  Well tolerated compared to other treatment
options in CML
 Superficial edema
 Nausea,muscle cramps
 Rash,Diarrhea
 Uncommon side effects:tumour lysis in
accelerated phase,splenic rupture,cerebral
edema,Varicella Zoster infections

43.  Imatinib is not recommended during
pregnancy.
 Hydroxyurea has the lowest mutagenic
potential among the cytotoxic agents.
 IFN can also be safely used during pregnancy.

44.  Patients who are younger than 65 yrs and
who have a identical twin or a
histocompatible sibling can be transplanted
after intensive therapy usually with
cyclophosphamide.
 GVHD is common.

45. THANK YOU