Pediatric Malignancies

Question 1

ALL symptoms

Answer 1

• Signs and Symptoms
  
  • Pallor, fatigue, petechiae, easy bruising
  • Fever, weight loss
  • Splenomegaly (75%), hepatomegaly (50%)
• Laboratory Findings
  
  • WBC - high/low/normal - blasts usually present on differential
  • Anemia and thrombocytopenia are common
  • Tumor Lysis Syndrome- increased serum potassium, phosphorous, uric acid, creatinine; decreased serum calcium
  • Elevated lactate dehydrogenase (LDH)
• Radiographic Findings
  
  • Chest X-ray - mediastinal mass possible

Question 2

good and poor prognoses for ALL

Answer 2

Poor prognostic factors (present at diagnosis)

• Age < 1 y.o. or >= 10 y.o.
• WBC > 50,000
• Certain chromosomal abnormalities t(9;22), t(4;11), 11q23/KMT2A
• T-cell disease

Good prognostic factors

• Down’s syndrome (trisomy 21)
• Hyperdiploidy (>50 chromosomes instead of normal 46)
• ETV6-RUNX1, triple trisomies chromosome 4, 10, 11

Question 3

ALL chemotherapy options

Answer 3

Question 4

Reduced TPMT effects

Answer 4

• Myelosuppresion
• Hepatotoxicity

More prevalent in AA and Europeans

Question 5

CPIC recommendation for abnormal TPMT

Answer 5

Question 6

CPIC recommendation for abnormal NUDT15

Answer 6

Question 7

daunorubicin

Answer 7

Question 8

vincristine

Answer 8

Question 9

asparaginase

Answer 9

Question 10

methotrexate

Answer 10

Question 11

imatinib/dasatinib

Answer 11

Question 12

Wilms Tumor Clinical Findings

Answer 12

• Signs and Symptoms
  
  • Asymptomatic abdominal mass (80%)
  • Hypertension
• Laboratory Findings
  
  • Hematuria (rarely gross)
  • CBC, Chemistries, UA are rarely abnormal
• Radiographic Findings
  
  • Abdominal CT
  • Chest CT to evaluate for metastases
• Metastatic disease is uncommon, but lung is most common site of metastases

Question 13

Wilms Tumor treatment options

Answer 13

• Surgery
  
  • Essential, determines stage
  • Nephrectomy becoming less common
• Chemotherapy
  
  • Vincristine & dactinomycin ± doxorubicin ± cyclophosphamide
• Radiation
  
  • Stage III and IV
  • Tumor bed and metastases if present

Question 14

Neuroblastoma clinical findings

Answer 14

• Signs and Symptoms
  
  • Abdominal mass
  • Fever, weight loss
  • Peri-orbital ecchymosis (raccoon eyes)
  • Bluish skin nodules
• Laboratory Findings
  
  • Urine catecholamine (HVA/ VMA) elevated in 90% of patients
  • Check prior to initial surgery, then follow response to treatment
• Radiographic Findings
  
  • CT primary tumor, evaluate metastases
  • MIBG scan (metaiodobenzylguanidine)
  • Calcifications frequently seen in imaging

Question 15

neuroblastoma treatment options

Answer 15

• Surgery
  
  • Possibly curative for localized disease
  • Post-chemo for bulky tumors
• Chemotherapy:
  
  • Multi-agent Rx: doxorubicin, vincristine, cyclophosphamide, etoposide, cisplatin, topotecan
  • HD chemo with HSCT
  • Dinutuximab (Unituxan®) - anti-GD2 monoclonal antibody
  • Isotretinoin (Claravis®) cis-retinoic acid
  • Investigational: therapeutic MIBG
• Radiation
  
  • Symptomatic relief or post-op to field

Question 16

dinutuximab

Answer 16

• Immunotherapy treating minimal disease post stem cell transplant or in relapse
• Binds GD2 found on neuroblastoma cells and cells of neuroectodermal origin (pain fibers).
• Active via antibody-dependent cell mediated toxicity (ADCC) and complement-dependent cytotoxicity (CDC)
• Sargramostim (GM-CSF) is used adjunctively
• ADEs: infusion-related reactions/ hypotension, capillary leak (SIRS), pain are all common.

Question 17

osteosarcoma clinical findings

Answer 17

• Signs and Symptoms
  
  • Pain, swelling, mass (many months)
  • Systemic symptoms are rare
• Laboratory Findings
  
  • Non-specific
• Radiographic Findings
  
  • CT/ MRI of primary site
  • Bone scan
  • Chest CT

Question 18

osteosarcoma treatment options

Answer 18

• Surgery- *Essential
  
  • Limb sparing often attempted
  • Pulmonary mets must be resected
• Chemotherapy- 1 full year of treatment
  
  • “Neoadjuvant”
  • MAP: Cisplatin/doxorubicin/ HD methotrexate
  • Etoposide/ Ifosfamide
  • Intra-arterial (intra-lesional) cisplatin (not contemporary COG therapy)
• Radiation
  
  • Non-responsive

Question 19

MTX doses for osteosarcoma and ALL

Answer 19

Osteosarcoma: 12 gram/m2 over 4 hours

• High peaks achieve higher concentration within tumor
• Goal peak 1000-1500 micromolar (measure of efficacy)
• Leucovorin rescue at 24 hours

Acute lymphocytic leukemia (ALL): 1-5 gram/m2 over 24- 42 hours

• Maintain a high concentration over time, maintain levels in CNS
• Goal peak levels less than 100-150 micromolar (avoid toxicity)
• Leucovorin rescue at 42-48 hours

Question 20

MTX supportive care

Answer 20

• Hyper-hydration at 2x maintenance or higher rate
  
  • Hourly rate 125-200 ml/m2/hour
  • Goal specific gravity of urine 1.010 or below
• Alkalization to goal urine pH of 7 or above
  
  • Sodium bicarbonate or sodium acetate added to hydration fluid (30-50 mEq/L)
  • Oral sodium bicarbonate or sodium citrate/ citric acid solution
• Requires leucovorin rescue

Question 21

MTX DDIs

Answer 21

• Pertain to HIGH DOSE therapy only
• Avoid prior to, during methotrexate and until serum level is cleared below level of detection
• Septra (trimethoprim/ sulfamethoxazole)
• NSAIDs
• Salicylates
• PCN/ Amox (cephalosporins are OK)
• PPIs

Question 22

ALL CNS disease classification

Answer 22

CNS-1: WBC in CSF < 5 cells/µl and no CSF blasts
CNS-2: WBC in CSF < 5 cells/µl with CSF blasts
Neither positive or negative
CNS-3: WBC in CSF >= 5 cells/µl with CSF blasts