HEMATOLOGY-ONCOLOGY
ONCOLOGIC EMERGENCIES
FEVER AND NEUTROPENIA (FN)
Definition
• Fever: single oral temp ≥38.3°C (101°F) or ≥38°C (100.4°F) for ≥1 h
• Neutropenia: ANC <500 cells/µL or <1000 cells/µL with predicted nadir <500 cells/µL
Pathophysiology and microbiology
• Predisposing factors: catheters, skin breakdown, GI mucositis, obstruction (lymphatics, biliary tract, GI, urinary tract), immune defect a/w malignancy
• Most episodes thought to result from seeding of bloodstream by GI flora
• Neutropenic enterocolitis (typhlitis): RLQ pain, watery/bloody diarrhea, cecal wall thickening
• GNRs (esp. P. aeruginosa) were historically most common
• Gram 
infections have recently become more common (60–70% of identified organisms)
• Fungal superinfection often results from prolonged neutropenia & antibiotic use
• Infection with atypical organisms and bacterial meningitis is rare
Prevention
• Levofloxacin (500 mg qd) ↓ febrile episodes & bacterial infections in chemo-related high-risk neutropenic patients; no difference in mortality (NEJM 2005;353:977 & 988)
Diagnostic evaluation
• Exam: skin, oropharynx, lung, perirectal area, surgical & catheter sites; avoid DRE
• Labs: CBC with differential, electrolytes, BUN/Cr, LFTs, U/A
• Micro: blood (peripheral & through each indwelling catheter port), urine, & sputum cx; for localizing s/s → ✓ stool (C. difficile, cx), peritoneal fluid, CSF (rare source)
• Imaging: CXR; for localizing s/s → CNS, sinus, chest or abdomen/pelvis imaging
• Caveats: neutropenia → impaired inflammatory response → exam and radiographic findings may be subtle; absence of neutrophils by Gram stain does not r/o infection
Risk stratification (factors that predict lower risk)
• History: age <60 y, no symptoms, no major comorbidities, cancer in remission, solid tumor, no h/o fungal infection or recent antifungal Rx
• Exam: temp <39°C, no tachypnea, no hypotension, no Δ MS, no dehydration
• Studies: ANC >100 cells/µL, anticipated duration of neutropenia <10 d, normal CXR
Initial antibiotic therapy (Clin Infect Dis 2011;52:e56)
• Empiric regimens including drug w/ antipseudomonal activity; consider VRE coverage if colonized; OR 3.8 for VRE if VRE (BBMT 2010;16:1576)
• PO abx may be used in low-risk Pts (<10 d neutropenia, nl hep/renal fxn, no N/V/D, no active infxn, stable exam): cipro + amoxicillin-clavulanate (NEJM 1999;341:305)
• IV antibiotics: no clearly superior regimen; monotherapy or 2-drug regimens can be used
Monotherapy: ceftazidime, cefepime, imipenem or meropenem
2-drug therapy: aminoglycoside + antipseudomonal β-lactam
PCN-allergic: levofloxacin + aztreonam or aminoglycoside
• Vancomycin added in select cases (hypotension, indwelling catheter, severe mucositis, MRSA colonization, h/o quinolone prophylaxis), discontinue when cultures 
× 48 h
Modification to initial antibiotic regimen
• Low-risk Pts who become afebrile w/in 3–5 d can be switched to PO antibiotics
• Empiric antibiotics changed for fever >3–5 d or progressive disease (eg, add vancomycin)
• Antifungal therapy is added for neutropenic fever >5 d
liposomal amphotericin B, caspofungin, micafungin, anidulafungin, voriconazole, posaconazole all options (NEJM 2002;346:225; 2007;356:348)
Duration of therapy
• Known source: complete standard course (eg, 14 d for bacteremia)
• Unknown source: continue antibiotics until afebrile and ANC >500 cells/µL
• Less clear when to d/c abx when Pt is afebrile but prolonged neutropenia
Role of hematopoietic growth factors (NEJM 2013;368:1131)
• Granulocyte (G-CSF) and granulocyte-macrophage (GM-CSF) colony-stimulating factors can be used as 1° prophylaxis when expected FN incidence >20% or as 2° prophylaxis after FN has occurred in a previous cycle (to maintain dose-intensity for curable tumors). CSFs ↓ rate of FN but have not been shown to impact mortality.
• Colony-stimulating factors can be considered as adjuvant therapy in high-risk FN Pts
SPINAL CORD COMPRESSION
Clinical manifestations (Lancet Neuro 2008;7:459)
• Metastases located in vertebral body extend and cause epidural spinal cord compression
• Prostate, breast and lung cancers are the most common causes, followed by renal cell
carcinoma, NHL and myeloma
• Site of involvement: thoracic (60%), lumbar (25%), cervical (15%)
• Signs and symptoms: pain (>95%, precedes neuro Ds), weakness, autonomic dysfunction (urinary retention, ↓ anal sphincter tone), sensory loss
Diagnostic evaluation
• Always take back pain in Pts with solid tumors very seriously
• Do not wait for neurologic signs to develop before initiating evaluation b/c duration & severity of neurologic dysfunction before Rx are best predictors of neurologic outcome
• Urgent whole-spine MRI (Se 93%, Sp 97%); CT myelogram if unable to get MRI
Treatment
• Dexamethasone (10 mg IV × 1 stat, then 4 mg IV or PO q6h)
initiate immediately while awaiting imaging if back pain + neurologic deficits
• Emergent RT or surgical decompression if confirmed compression/neuro deficits
• Surgery + RT superior to RT alone for neuro recovery in solid tumors (Lancet 2005;366:643)
• If pathologic fracture causing compression → surgery; if not surgical candidate → RT
TUMOR LYSIS SYNDROME
Clinical manifestations (NEJM 2011;364:1844; BJH 2010;149:578)
• Large tumor burden or a rapidly proliferating tumor → spontaneous or chemotherapy-induced release of intracellular electrolytes and nucleic acids
• Most common w/ Rx of high-grade lymphomas (Burkitt’s) and leukemias (ALL, AML, CML in blast crisis); rare with solid tumors; rarely due to spontaneous necrosis
• Electrolyte abnormalities: ↑ K, ↑ uric acid, ↑ PO4 → ↓ Ca
• Renal failure (urate nephropathy)
Prophylaxis
• Allopurinol 300 mg qd to bid PO or 200–400 mg/m2 IV (adjusted for renal fxn) & aggressive hydration prior to beginning chemotherapy or RT
• Rasburicase (recombinant urate oxidase) 0.15 mg/kg or 6 mg fixed dose (except in obese Pts) & aggressive hydration prior to beginning chemotherapy or RT (see below)
Treatment
• Avoid IV contrast and NSAIDs
• Allopurinol + aggressive IV hydration ± diuretics to ↑ UOP
• Consider alkalinization of urine w/ isotonic NaHCO3 to ↑ UA solubility & ↓ risk of urate nephropathy (controversial: may cause metabolic alkalosis or Ca3(PO4)2 precipitation)
• Rasburicase (0.1–0.2 mg/kg × 1, repeat as indicated) for ↑↑ UA, esp. in aggressive malig; UA level must be drawn on ice to quench ex vivo enzyme activity (JCO 2003;21:4402; Acta Haematol2006;115:35). Avoid in G6PD deficiency as results in hemolytic anemia.
• Treat hyperkalemia, hyperphosphatemia and symptomatic hypocalcemia
• Hemodialysis may be necessary; early renal consultation for Pts w/ renal insuffic. or ARF