Fever and Neutropenia

• Often the first and only sign of serious infection. It should be evaluated immediately.
  
• Definition
  
  
  
  • Fever: Single temperature ≥38.3°C (101°F) or a temperature ≥38.0°C (100.4°F) on two occasions 1 h apart. (Note: The temperature should not be taken rectally for immunocompromised patients!)
    
  • Neutropenia: ANC <500/mm3.
  
  
• Diagnosis
  
  
  
  • History and physical exam: HR (tachycardia) and/or BP (hypotension), mental status (AMS) are ominous signs; examine sites for infection (oropharynx, respiratory tract, perianal area, CVL sites, locations of recent procedures, skin and soft tissues), abdomen (eg, typhlitis).
    
  • Evaluation: CBC, blood cultures (all lumens of CVL), UA (no catheterization), do not I & D skin lesions.
    
  • Optional studies: Urine culture (only if UA abnormal; do not catheterize immunosuppressed patients), CXR (based on signs and symptoms), abdominal US, other cultures based on clinical suspicion (stool, CSF, CVL site, wound).
  
  
• Empiric therapy: Will ↓ mortality from gram-negative infections (80% → 10 to 40%)
  
  
  
  • Low risk and patient appears well: Monotherapy with ceftazidime, piperacillin/tazobactam, imipenem/cilastatin, or meropenem (often dependent on institutional practice and/or previous infections/sensitivities).
    
  • High risk (ANC <100, infant ALL, AML, induction therapy) and/or patient with concern for sepsis: Triple therapy with vancomycin + amynoglycoside + antipseudomonal penicillin (ceftazidime, cefepime, or carbapenem) (Clin Infect Dis. 2002; 34:730).
    
  • Modifications to empiric therapy: Consider adding antifungal coverage if fever persists >5 d.

Tumor Lysis Syndrome

(J Clin Oncol 2008;26(16):2767)

• Pathophysiology: Rapid lysis of tumor cells → release of intracellular contents into bloodstream → phosphorus, potassium, uric acid → renal failure, ↓ Ca2+; typically occurs 12–72 h after therapy starts (may occur at presentation).
  
• More common in tumors with high proliferative rate, large volume, or sensitive to chemotherapy (NHL, ALL, AML, especially acute monocytic leukemia)
  
• Prevention: Aggressive hydration with or without diuresis is fundamental
  
  
  
  • High risk: Rasburicase (recombinant urate oxidase)
    
  • Intermediate risk: Allopurinol
    
  • Low risk: Watch and wait
    
  • Alkalinization is currently not recommended
  
  
• Management
  
  
  
  • Hyperuricemia: Hydration 2–3L/m2/day (200 mL/kg/day if wt <10 kg) with D5 ¼ NS + rasburicase (contraindicated in G6PD deficiency).
    
  • Hyperphosphatemia: Aluminum hydroxide, dialysis (severe case).
    
  • Hyperkalemia and hypocalcemia: See Chapter 15.

Spinal Cord Compression

(Cancer Treatment Rev 1993;19:129)

• History: Local or radicular pain in 80%, lower extremity weakness or numbness, bowel or bladder incontinence
  
• Tumors: Sarcomas, NBL, germ cell tumors, lymphoma, leukemia, leptomeningeal spread (drop metastases) from CNS tumors
  
• Evaluation: Emergent MRI of the spine (CT myelography if MRI is unavailable)
  
• Management
  
  
  
  • Rapidly progressing or exam with anatomic level of dysfunction: Dexamethasone 1–2 mg/kg IV once
    
  • Child with or possible dx of cancer: Dexamethasone 0.25–0.5 mg/kg PO Q6h
    
  • Definitive therapy: Emergent spinal decompression (laminectomy), radiation, chemotherapy (see figure below)

Anaphylaxis with Chemotherapy

Hyperleukocytosis

• Definition: WBC >100,000 (risk of clinical complications increases with ↑ WBC)
  
• Pathogenesis: ↑ Blood viscosity → leukostasis caused by ↑ adherence → causes CNS hemorrhage or thrombosis, pulmonary leukostasis, tumor lysis → sx depend on location of leukostasis
  
• Management: Hydration, monitor WBC, monitor and tx for tumor lysis; initiate definitive tx for tumor; consider exchange transfusion or leukapheresis for the following groups:
  
  
  
  • Age < 2yr: WBC >100,000 cells/mm3
    
  • Child with ALL: WBC >200,000 cells/mm3 with symptoms or >400,000 cells/mm3 without symptoms
    
  • Child with AML (M4/M5): WBC >150,000 cells/mm3
    
  • Child with all other AML: WBC >200,000 cells/mm3 with symptoms or >300,000 cells/mm3 without symptoms

• Etiology: Chemotherapy induced (anticipatory also common), radiation induced, disease induced (eg, brain tumors, CNS leukemia, constipation), drug induced (Cancer J 2008;14(2):85)

• Treatment: Antiemetic drugs and nonpharmacologic approach (see table below)

• Etiology: r/o viral stomatitis; cytotoxic damage by chemotherapy or radiation of oral mucosa or GI tract; local immune activity and bacterial colonization may be associated.
  
• Clinical presentation: Pain and ulceration, which lead to infection and ↓ oral intake.

• Prevention and treatment (Cancer 2007; 109:820)
  
  
  
  • If untreated, mucositis may lead to significant malnutrition and overwhelming infection
    
  • Early detection by regular assessment of oral pain and hygiene
    
  • Use of soft toothbrush
    
  • Various mouthwashes have been used traditionally (without strong evidence) (eg, chlorhexidine, topical anesthetics [benadryl:maalox:lidocaine mixture ratio for swish and spit], carafate)
    
  • Aggressive pain management (eg, morphine PCA)
    
  • Consider nutrition support based on grade of mucositis and nourishment status (eg, TPN).
    
  • Consider antimicrobials when infection is suspected

• Definition: Uncontrolled proliferation of immature lymphocytes; by convention >25% lymphoblasts on BMA
  
• Epidemiology: 30% of childhood cancers; ∼2500–3500 cases/yr; peak incidence 2–5 yr of age; Risk is ↑ 14-fold in children with Down syndrome; minor risk ↑ in siblings with ALL and in children with immunodeficiencies
  
• Diagnosis
  
  
  
  • History and physical exam: ↓ Energy, fever (60%), bone pain (25%), night sweats, weight loss, pallor, petechiae or bruising (50%), HSM (66%), lymphadenopathy (50%; definition: epitrochlear or supraclavicular LN >5 mm, inguinal LN >15 mm, and >10 mm for all other LN; malignant LN are typically rubbery, firm, and nontender). May also have headache, nausea or vomiting, AMS, testicular enlargement (2%–5%). Older children may have wheezing, cough, or SVC syndrome caused by a mediastinal mass.
  
  
• Labs/evaluation:
  
  
  
  • CBC (hyperleukocytosis; ∼50% with a WBC >10,000 and ∼20% >50,000); 95% present with ≥1 cell line down (∼90% with a Hb <11 g/dL, ∼45% <7 g/dL), ∼75% with platelets <100,000/mm3
    
  • Chem 10: May be normal or ↓ Ca2+, but with tumor lysis ↑ Ca2+, ↑ K+, ↑PO4–
    
  • PT, PTT, liver panel (↑PT/PTT, ↑ transaminases), ↑ LDH, ↑ uric acid if tumor lysis
    
  • CXR: Evaluate for mediastinal mass
    
  • BMA (>25% lymphoblasts) and LP (∼5% with CNS involvement) for definitive dx
  
  
• Differential dx: JRA, osteomyelitis, ITP, pertussis, EBV, aplastic anemia, other malignancies (eg, neuroblastoma, EWS, RMS).
  
• Classification: Multiple systems exist for describing ALL variants: morphologic, immunologic, cytogenetic (see tables below).
  
  
  
  • Cytogenetic: Karyotype and FISH; results are taken into account with other factors and used to confer a designation of low, standard, high, or very high risk.

• Treatment: Consists of four or five phases; total duration of therapy ∼2 yr for girls and 3 yr for boys. The drug regimen and duration of therapy are based on risk designation as shown in tables below (Pediatr Clin North Am 2008;55:1).

(Blood 2007;109:926)