Principles and Practice Of Pediatric Oncology. 6th ed. Philadelphia, PA: LWW; 2011;1190–1242)
Fever and Neutropenia (Clin Infect Dis 2011;52:e56)
• Definition for purposes of Rx: ANC < 500 & temp 101 (or 100.5–101 × 2 in <24 hr).*
• Background: High risk of bacterial infection w/ overwhelming sepsis. Need to treat empirically with broad-spectrum antibiotics
• Higher-risk pts: ANC < 100, prolonged neutropenia (>1 wk), comorbidities
• Evaluation:
• Hx: Sx, prior infxns, most recent chemo agents and timing, exposures
• Exam: Vital signs w/ O2 sat & attention to oropharynx, lungs, abdomen, skin including nailbeds, central line site & perineal area
• Dx studies: CBC w/ diff, CMP, blood cx from all lumens CVL (+/− peripheral), blood bank sample, U/A & Ucx. Consider: Coags if toxic, CXR/throat cx/viral panel depending on signs and symptoms
• Rx w/ broad-spectrum IV abx w/i 1 hr of presentation, after blood cx obtained (do not delay rx for other studies such as urine cx)
• Cefepime is reasonable mono-Rx. Add AG for additional GN coverage for toxic patients, vancomycin empirically after high-dose AraC for α-hemolytic strep or if cellulitis. Consider anti-fungal rx if prolonged F&N >5–7 d
• Usually managed as inpts until afeb with evident neutrophil recovery
• For lower-risk patients consider IV or oral rx and outpatient management
Superior Vena Cava (SVC) Syndrome (Pediatr Clin North Am 1997;44:809)
• Definition: Signs and sx from compression &/or obstruction of SVC
• Etiology: Often a presenting feature of intrathoracic malignancies
• Malignancies p/w mediastinal mass most commonly include NHL, T-cell ALL, and Hodgkin dz. Less common: Teratoma, sarcoma, neuroblastoma, thymoma
• Pathophysiology: Mediastinal mass compresses SVC causing venous stasis
• Compression &/or clotting of SVC → ↓ venous return from head, neck, & upper thorax
• Tracheal compression may also be present, esp with anterior masses
• Presentation: Cough, dyspnea, dysphagia, orthopnea, stridor, “wheeze,” & hoarseness
• Later sx of anxiety, confusion, lethargy, HA, Δ vision, and syncope may = CO2 retention; can also see facial +/− UE swelling, plethora, chest pain, pleural effusions
• Sx worse when patient is supine; should raise suspicion for mediastinal mass
• Diagnostic studies: CXR; typically will show anter mediastinal mass; trach deviation, and narrowing on lateral view. CT neck/chest crucial to assess airway patency
• CBC, Chem10, LDH, and uric acid; obtain dx tissue sample before Rx if possible
• Anesthesia may be contraindicated if tracheal compression
• Treatment: Depends on underlying malignancy
• If significant CV or resp compromise, emergent XRT and/or IV methylprednisolone/dexamethasone treatment may be indicated
Tumor Lysis Syndrome (TLS) (Nat Clin Pract Oncol 2006;3:438)
• Definition: Metabolic abn 2/2 cell death and subsequent release cell contents into circ
• Metabolic disturbances can result in severe end-organ impairment, esp renal
• Etiology/risk factors
• Occurs in tumors w/ ↑ growth fraction and large tumor burden/volume
• Malignancies most commonly assoc w/ TLS include Burkitt lymphoma, ALL (particularly T-cell variant), and lymphoblastic lymphoma; TLS rare in AML
• Can occur before onset of Rx but typically occurs w/i 12–72 hr of initiation of Rx
• Risk factors: WBC > 50,000, ↑ LDH, ↑ uric acid on admit, Cr > 1.6 or ↓ GFR
• Diagnostic studies: Elevated uric acid (>10) – caused by breakdown of nucleic acids
• Hyperphosphatemia and secondary hypocalcemia; hyperkalemia
• Consequences of TLS
• Hyperuricemia → precipitation of uric acid in collecting ducts of renal tubules, causing resultant nephropathy and acute renal failure
• Hyperkalemia → cardiac arrhythmias and sudden death
• Hypocalcemia → hypotension, EKG changes, tetany, and seizures
• Hyperphosphatemia → renal precipitation; exacerbate nephropathy and renal failure
• Management/prevention of TLS: Electrolyte abn managed acutely as indicated
• Upon dx of malignancy and before starting Rx, aggressive mgmt to prevent TLS
• Aggressive hydration (2–4× maintenance) to ↑ GFR and ↑ urinary outflow
• Urinary alkalization w/ D51/4NS w/NaHCO3 (40–80 mEq/L) to urine pH ≥ 7 to prevent uric acid precipitation
• Allopurinol (250–500 mg/m2/d) inhibits xanthine oxidase; ↓ uric acid formation
• Alternatively, rasburicase (recombinant urate oxidase) in place of allopurinol. More effective & 1st choice in high-risk cases
• Alkalinization not necessary after uric acid level falls
• Close observation of electrolytes, Ca, Mg, Ph, LDH, and uric acid (q6–12h upon initiation of Rx) essential to monitor for development of TLS
Spinal Cord Compression (SCC) (Pediatr Clin North Am 1997;44:809)
• Definition/etiology: Occurs in 2.7–5% of children w/ cancer
• Most cases 2/2 epidural compression from extension of paravertebral tumor
• ↑ risk w/ neuroblastoma, Ewing sarcoma, non-Hodgkin lymphoma, and Hodgkin lymphoma
• Osteosarcoma and rhabdomyosarcoma typically cause SCC only w/ recurrence
• Clinical manifestations: Back pain present in 80% pedi pts w/ cord compression
• Sx typically present for an avg of 2 wk before dx is made
• Weakness, sensory loss, and incontinence are later and more concern-causing findings
• Evaluation/treatment
• Detailed neuro exam in any pt p/w suspected malign; rectal exam for sphincter tone
• Plain radiographs often performed but only show findings in ½ of affected patients
• MRI w/ contrast is study of choice to assess presence and extent of SCC
• Children w/ neuro findings and/or rapidly progressing spinal cord dysfxn should receive dexamethasone 1 mg/kg IV and have emergent spinal MRI
• Surgery, XRT, and chemo are other emergent Rx options depending on tumor type
Hyperleukocytosis (Pediatr Clin North Am 1997;44:809)
• Definition/etiology: WBC >100,000; presence of high # of circ leukemic blast cells
• Clinically signif hyperleukocytosis >200,000 in AML, >300,000 in ALL and CML
• Occurs in 9–13% of patients with ALL and 5–22% of patients with AML
• Pathogenesis: Excessive leukocytes obstruct circulation in brain, lung, and other organs forming aggregates and white thrombi in small veins
• Excessive leukocytes also compete for oxygen and damage vessel walls
• Morbidity is directly related to blood viscosity
• Myeloblasts and monoblasts are larger (AML) and more likely to cause obstruction
• Clinical manifestations
• Pulmonary leukostasis → dyspnea, hypoxia, and right ventricular failure
• Intracerebral leukostasis → Δ mental status, frontal HA, szr, and papilledema
• Other possible complications include priapism, renal failure, and dactylitis
• Major complications of hyperleukocytosis in ALL usually result of TLS
• Complications of hyperleukocytosis in AML usually are result of intracerebral leukostasis and include stroke and hemorrhage
• Treatment: Aggressive hydration, alkalize, & rasburicase or allopurinol (to ↓ risk of TLS)
• Maintain platelet count >20,000 minimize RBC xfusion to prevent further ↑ in viscosity
• Correct coagulopathy w/ FFP and vitamin K as indicated
• Exchange xfusion and leukophoresis also used to help rapidly ↓ leukocyte count Prompt initiation of chemotherapy (or ATRA for acute promyelocytic leukemia)