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HEMATOLOGIC-ONCOLOGIC
EMERGENCIES
Neutropenic Fever andTumor Lysis Syndrome
 Tumor Lysis Syndrome
 Neutropenic Fever
 Leukostasis (pulm and neurotoxicity)
 Hypercalcemia
 Spinal Cord Compression
 SuperiorVena Cava Syndrome
TLS: bags breaking open
TLS: bags breaking open
 Hyperkalemia
 High uric acid
 Hyperphosphatemia
 Hypocalcemia
 (LDH)
LaboratoryTLS
 Hyperkalemia :  25% or ≥ 6.0
mmol/L
 Hyperuricemia:  25% or ≥ 8mg/dL
 Hyperphosphatemia :  25% or ≥ 4.5
mg/dL
 Hypocalcemia:  25% or < 7.0 mg/dL
ClinicalTLS: end-organ damage
 Renal Failure
 Arrythmias
 Seizures
 Death: 5-20% of cancer patients
To optimize opportunity
and therapy for patients
 identify high-risk pts
 recognizeTLS early
Ideally,Goalis PREVENTION
TLS: Risk factors
 Rapidly growing or bulky tumors (LDH)
 Hematologic malignancies (AML w/WBC >50K,
Burkitt’s, aggressive BCL)
- Ki-67: protein cell marker for proliferation
 Solid tumors that are advanced or metastatic
(lung, breast, GYN, GI, sarcoma, brain)
- mortality is 35%
- rare
 Aggressive poly-chemotherapeutic regimems
- cisplatin, cytosine arabinoside, etoposide,
methotrexate
TLS: Risk factors
 Renal dysfunction/disease (DM2)
 Decreased po intake
 Nephrotoxic agents (NSAIDs)
 First 48-72h
 First exposure to a regimen
TLS-Hyperkalemia
 ECG: peakedT’s, QT interval abnlities
 IVF
 **Kayexalate, Lasix
If >6.0, then:
 Insulin (and D50)
 Albuterol
 Avoid Ca++gluconate
 NaHCO3
Hyperuricemia
 Renal Failure: direct tubular damage by uric
acid crystallization in kidneys
Hyperuricemia: low risk IVF
and prophylaxis
 Hydration: IVF
- goal urine o/p: 100ml/hr
- ideally 48h before chemo
 Prophylaxis: Allopurinol
- blocks xanthine-oxidase
 Alkalinization
-encourages conversion to urate salt but also Ca++phos
product and ppt of urinary xanthine crystals
Hyperuricemia: High risk 
IVF and treatment (also ppx)
 Treatment: Rasburicase
- recombinant urate-oxidase  allantoin
- 5-10 x more soluble
 History: in pediatric population
- recommended dose: 0.15 or 0.2 mg/kg daily for 3-5
days
- we use: 3 mg flat dose ($850/1.5mg)
 Precautions:
- check g6PD: deficiency is a contraindication
- antibody formation: it is a foreign protein. Cloned
from Aspergillus
- recombinant form: low incidence (pruritis, edema,
wheezing), less in nonrecombinant product.
Hyperphosphatemia/hypocalcem
ia
 Calcium x Phosphate product  calciphylaxis
 Goal < 60
 Prevention is all
 Sevelemer, not Ca++acetate
 No Ca++ repletion unless symptomatic (tetany,
ms change, arrythmias)
- generally if <6.0
Is there a role for HD in
TLS? Yes, and they are the
same ones you already know
 Acidosis, severe metabolic
 Electrolyte Abnormalities, persistent
 Oliguria/Anuria
 Uremia, pericarditis and
encephalopathy
Nf and tls
Neutropenia and Fever
 ANC <500 cells/mm3 or 1000 and
trending down
 Fever >101 °F (38.3°C) or >100.4
(38.0°C) x 1 hour
- oral measurement
Neutrophils = inflammation
 FEVER may be only symptom
 Even afebrile patients with si/sx of infection
should be considered high-risk
 Empiric therapy saves lives
(culprits)?
NF: Epidemiology and
Etiology
 Neutropenic Sepsis Mortality: 18-40% (largely
due to Pseudomonas)
 Bacteremia ~25%
-GPC >GNR but latter higher mortality
 Negative ID w/u in >50%
 Etiology: gut translocation, because of
integumentary compromise
NeutropenicFever
1. **WHO: High-Risk groups
2. WHAT: Empiric Antibiotics
3. Antibiotic Modification
4. Antibiotic Duration
5. **WHEN: Antibiotic prophylaxis
6. **WHEN: Empiric Antifungals
7. WHEN: Antiviral prophylaxis
8. WHAT: CSF?
9. **WHAT: Catheter-related infections
NF: Identifyhigh-risk
1. Inpt vs. Outpt
2. Intravenous vs. oral
3. Duration of therapy
4. Hospital access and home
support
WHO: High Risk Inpatient
1. Cancer type:AML,ALL, HSCT, hematologic
2. Chemo: induction, consolidation
3. Duration: Neutropenic ≥ 7 days
4. Severity:ANC ≤ 100 cells/mm3
5. Clinical common sense: Hypotension, pna,
ms change, new abdominal pain,
uncontrolled cancer, s/p mult chemo
regimens, advanced age, poor PS
6. Liver or Kidney dysfunction
MASCC score: High risk < 21
NF: WHAT  intravenous
 Anti-Pseudomonal
- what abx?
 Vancomycin
-When?
Modifications: h/o ESBL (carbapenem), KPC
(tigecycline, polymyxin-colistin),VRE (linezolid,
dapto)
Low-risk = NOT high-risk
 Ciprofloxacin and amoxicillin-clavulanate
 4th-generation floroquinolone
Afterstartingempiricantibiotics…
1. When do you stop?
2. When do you change?
3. How long do you treat?
If fevers resolve
- Continue abx until ANC ≥ 500
cells/mm3
- Modify regimen according to
culture data
- D/c empiric vanco if no positive
culture after 48h
If persistent fever
If stable, continue current regimen
Continue to assess for new infection
If persistent fever >48-72h or
unstable:
re-image (CT, MRI, PET)
Reculture and consider viral and fungal
pathogens
Broaden anti-bacterial coverage (MRSA, ESBL),
anaerobes
Add anti-fungal if >4-7 days
If persistent fever
 Mucositis: consider antiviral (HSV) and
antifungal (Candida) treatment w/ acylovir
and fluconazole, respectively
 Typhlitis: GNR (inc Pseudomonas) and
anerobic coverage >> antifungal
- Surgery consult
 Non-infectious…
PersistentFever:non-infectiousddx
 Drug-fever
 Thrombophlebitis
 Tumor/Cancer
 Hematoma
 PE/thrombus
 G-CSF
WHEN: Antifungals
 Empiric: consider when
1. fever persistent >4 days
2. CT sinus and chest
3. BDG and AG, PCP DFA and PCR
4. High risk
- h/o intensive chemo
- s/p HSCT
- neutropenic >10 days
WHAT: Antifungals – no
particular regimen
 If not on ppx: azole, most likely Candida
- Candida glabarata and kruseii
- amphoterecin B, vori- or itraconazole
 If on ppx: usually h/o Aspergillus or at risk
(AML pts)
- echinocandin, i.e. micafungin
- something different from ppx antifungal
~25% given antifungals by these criteria and 4%
have invasive fungal infection. [NEJM 2007; 356; 348-59]
WHEN: CSF
1. Prophylaxis when incidence of neutropenia
>20%
2. Not generally recommended for treatment
of established fever and neutropenia
- days of neutropenia, fever, LOS
decreased
- no mortality benefit
* expensive ($350 vs >$5K)
Nf and tls
CLABSI
1. If GPC or Pseudomonas, remove catheter.
Replace after 48h of negative surveillance
cultures
2. if persistently + cultures > 72h
3. Complications: pocket infection, septic
thromboses
4. Duration: at least 14d from first negative
blood culture
5. Linezolid – can suppress bm, Daptomycin – can
raise CPK
Summary
1. Assess Risk
- fever may be only symptom
- early empiric antibiotics can save lives
1. Persistent fever requires careful and
continued reassessment
2. Consider antifungals if fevers >4 days (or
new sx, esp. respiratory)
3. CLABSI – Do not pass GO
Nf and tls

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Nf and tls

  • 2.  Tumor Lysis Syndrome  Neutropenic Fever  Leukostasis (pulm and neurotoxicity)  Hypercalcemia  Spinal Cord Compression  SuperiorVena Cava Syndrome
  • 4. TLS: bags breaking open  Hyperkalemia  High uric acid  Hyperphosphatemia  Hypocalcemia  (LDH)
  • 5. LaboratoryTLS  Hyperkalemia :  25% or ≥ 6.0 mmol/L  Hyperuricemia:  25% or ≥ 8mg/dL  Hyperphosphatemia :  25% or ≥ 4.5 mg/dL  Hypocalcemia:  25% or < 7.0 mg/dL
  • 6. ClinicalTLS: end-organ damage  Renal Failure  Arrythmias  Seizures  Death: 5-20% of cancer patients
  • 7. To optimize opportunity and therapy for patients  identify high-risk pts  recognizeTLS early Ideally,Goalis PREVENTION
  • 8. TLS: Risk factors  Rapidly growing or bulky tumors (LDH)  Hematologic malignancies (AML w/WBC >50K, Burkitt’s, aggressive BCL) - Ki-67: protein cell marker for proliferation  Solid tumors that are advanced or metastatic (lung, breast, GYN, GI, sarcoma, brain) - mortality is 35% - rare  Aggressive poly-chemotherapeutic regimems - cisplatin, cytosine arabinoside, etoposide, methotrexate
  • 9. TLS: Risk factors  Renal dysfunction/disease (DM2)  Decreased po intake  Nephrotoxic agents (NSAIDs)  First 48-72h  First exposure to a regimen
  • 10. TLS-Hyperkalemia  ECG: peakedT’s, QT interval abnlities  IVF  **Kayexalate, Lasix If >6.0, then:  Insulin (and D50)  Albuterol  Avoid Ca++gluconate  NaHCO3
  • 11. Hyperuricemia  Renal Failure: direct tubular damage by uric acid crystallization in kidneys
  • 12. Hyperuricemia: low risk IVF and prophylaxis  Hydration: IVF - goal urine o/p: 100ml/hr - ideally 48h before chemo  Prophylaxis: Allopurinol - blocks xanthine-oxidase  Alkalinization -encourages conversion to urate salt but also Ca++phos product and ppt of urinary xanthine crystals
  • 13. Hyperuricemia: High risk  IVF and treatment (also ppx)  Treatment: Rasburicase - recombinant urate-oxidase  allantoin - 5-10 x more soluble  History: in pediatric population - recommended dose: 0.15 or 0.2 mg/kg daily for 3-5 days - we use: 3 mg flat dose ($850/1.5mg)  Precautions: - check g6PD: deficiency is a contraindication - antibody formation: it is a foreign protein. Cloned from Aspergillus - recombinant form: low incidence (pruritis, edema, wheezing), less in nonrecombinant product.
  • 14. Hyperphosphatemia/hypocalcem ia  Calcium x Phosphate product  calciphylaxis  Goal < 60  Prevention is all  Sevelemer, not Ca++acetate  No Ca++ repletion unless symptomatic (tetany, ms change, arrythmias) - generally if <6.0
  • 15. Is there a role for HD in TLS? Yes, and they are the same ones you already know  Acidosis, severe metabolic  Electrolyte Abnormalities, persistent  Oliguria/Anuria  Uremia, pericarditis and encephalopathy
  • 17. Neutropenia and Fever  ANC <500 cells/mm3 or 1000 and trending down  Fever >101 °F (38.3°C) or >100.4 (38.0°C) x 1 hour - oral measurement
  • 18. Neutrophils = inflammation  FEVER may be only symptom  Even afebrile patients with si/sx of infection should be considered high-risk  Empiric therapy saves lives (culprits)?
  • 19. NF: Epidemiology and Etiology  Neutropenic Sepsis Mortality: 18-40% (largely due to Pseudomonas)  Bacteremia ~25% -GPC >GNR but latter higher mortality  Negative ID w/u in >50%  Etiology: gut translocation, because of integumentary compromise
  • 20. NeutropenicFever 1. **WHO: High-Risk groups 2. WHAT: Empiric Antibiotics 3. Antibiotic Modification 4. Antibiotic Duration 5. **WHEN: Antibiotic prophylaxis 6. **WHEN: Empiric Antifungals 7. WHEN: Antiviral prophylaxis 8. WHAT: CSF? 9. **WHAT: Catheter-related infections
  • 21. NF: Identifyhigh-risk 1. Inpt vs. Outpt 2. Intravenous vs. oral 3. Duration of therapy 4. Hospital access and home support
  • 22. WHO: High Risk Inpatient 1. Cancer type:AML,ALL, HSCT, hematologic 2. Chemo: induction, consolidation 3. Duration: Neutropenic ≥ 7 days 4. Severity:ANC ≤ 100 cells/mm3 5. Clinical common sense: Hypotension, pna, ms change, new abdominal pain, uncontrolled cancer, s/p mult chemo regimens, advanced age, poor PS 6. Liver or Kidney dysfunction
  • 23. MASCC score: High risk < 21
  • 24. NF: WHAT  intravenous  Anti-Pseudomonal - what abx?  Vancomycin -When? Modifications: h/o ESBL (carbapenem), KPC (tigecycline, polymyxin-colistin),VRE (linezolid, dapto)
  • 25. Low-risk = NOT high-risk  Ciprofloxacin and amoxicillin-clavulanate  4th-generation floroquinolone
  • 26. Afterstartingempiricantibiotics… 1. When do you stop? 2. When do you change? 3. How long do you treat?
  • 27. If fevers resolve - Continue abx until ANC ≥ 500 cells/mm3 - Modify regimen according to culture data - D/c empiric vanco if no positive culture after 48h
  • 28. If persistent fever If stable, continue current regimen Continue to assess for new infection If persistent fever >48-72h or unstable: re-image (CT, MRI, PET) Reculture and consider viral and fungal pathogens Broaden anti-bacterial coverage (MRSA, ESBL), anaerobes Add anti-fungal if >4-7 days
  • 29. If persistent fever  Mucositis: consider antiviral (HSV) and antifungal (Candida) treatment w/ acylovir and fluconazole, respectively  Typhlitis: GNR (inc Pseudomonas) and anerobic coverage >> antifungal - Surgery consult  Non-infectious…
  • 30. PersistentFever:non-infectiousddx  Drug-fever  Thrombophlebitis  Tumor/Cancer  Hematoma  PE/thrombus  G-CSF
  • 31. WHEN: Antifungals  Empiric: consider when 1. fever persistent >4 days 2. CT sinus and chest 3. BDG and AG, PCP DFA and PCR 4. High risk - h/o intensive chemo - s/p HSCT - neutropenic >10 days
  • 32. WHAT: Antifungals – no particular regimen  If not on ppx: azole, most likely Candida - Candida glabarata and kruseii - amphoterecin B, vori- or itraconazole  If on ppx: usually h/o Aspergillus or at risk (AML pts) - echinocandin, i.e. micafungin - something different from ppx antifungal ~25% given antifungals by these criteria and 4% have invasive fungal infection. [NEJM 2007; 356; 348-59]
  • 33. WHEN: CSF 1. Prophylaxis when incidence of neutropenia >20% 2. Not generally recommended for treatment of established fever and neutropenia - days of neutropenia, fever, LOS decreased - no mortality benefit * expensive ($350 vs >$5K)
  • 35. CLABSI 1. If GPC or Pseudomonas, remove catheter. Replace after 48h of negative surveillance cultures 2. if persistently + cultures > 72h 3. Complications: pocket infection, septic thromboses 4. Duration: at least 14d from first negative blood culture 5. Linezolid – can suppress bm, Daptomycin – can raise CPK
  • 36. Summary 1. Assess Risk - fever may be only symptom - early empiric antibiotics can save lives 1. Persistent fever requires careful and continued reassessment 2. Consider antifungals if fevers >4 days (or new sx, esp. respiratory) 3. CLABSI – Do not pass GO

Notes de l'éditeur

  1. Multinational Association of Supportive Care in Cancer
  2. - h/o MRSA, CLABSI, skin or soft tissue infection, PNA, hemodynamic instability