1. Neutropenic fever and tumor lysis syndrome are hematologic oncologic emergencies that require prompt assessment and treatment to prevent complications and death. 2. Patients at high risk for complications from neutropenic fever should receive inpatient empiric antibiotics targeting pseudomonas such as an antipseudomonal beta-lactam with vancomycin. 3. For persistent fevers, the treatment regimen should be modified based on cultures and the patient should be reassessed for new infections, including invasive fungal infections if fevers persist for more than 4 days. Catheter-related bloodstream infections also require prompt management.

1. HEMATOLOGIC-ONCOLOGIC
EMERGENCIES
Neutropenic Fever andTumor Lysis Syndrome

2.  Tumor Lysis Syndrome
 Neutropenic Fever
 Leukostasis (pulm and neurotoxicity)
 Hypercalcemia
 Spinal Cord Compression
 SuperiorVena Cava Syndrome

3. TLS: bags breaking open

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