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.
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
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
16.
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
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…
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)
34.
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
Hinweis der Redaktion
Multinational Association of Supportive Care in Cancer