Hematology and Oncology Flashcards

A 58-year-old man with newly diagnosed acute promyelocytic leukemia (APL) is started on ATRA and arsenic trioxide. On day 4, he develops fever to 39.2°C, weight gain of 3 kg, and new bilateral pulmonary infiltrates. His WBC has risen from 2,000 to 18,000/µL. Which of the following is the most appropriate next step?

Answer: Add dexamethasone 10 mg IV twice daily and continue ATRA

This presentation is classic differentiation syndrome (formerly retinoic acid syndrome), which occurs in APL patients receiving ATRA or arsenic trioxide due to rapid differentiation and cytokine release from maturing promyelocytes. Management is high-dose corticosteroids (dexamethasone 10 mg IV BID) while continuing ATRA unless severe respiratory compromise requires temporary interruption. Discontinuing ATRA outright without steroids is incorrect; the syndrome is not infectious in origin, making antibiotics alone insufficient; and delaying treatment for bronchoscopy would be dangerous.

A 45-year-old woman with stage IIIA Hodgkin lymphoma achieves complete remission after ABVD chemotherapy. A PET scan performed after cycle 2 shows a Deauville score of 3. What is the most appropriate management?

Answer: Continue standard ABVD for the planned total course

A Deauville score of 3 on interim PET (after 2 cycles of ABVD) is considered a negative scan per the Lugano criteria and indicates an adequate early response. Current evidence (RATHL trial) supports continuing standard ABVD without escalation for interim PET-negative patients with classic Hodgkin lymphoma. Escalation to BEACOPPescalated is reserved for PET-positive patients (Deauville 4–5). ASCT is for relapsed/refractory disease. Rituximab is not active in Hodgkin lymphoma (which is CD20-negative on Reed-Sternberg cells).

A 67-year-old man with CLL develops sudden onset of anemia (Hgb 6.8 g/dL), elevated indirect bilirubin, LDH 920 U/L, and a positive direct antiglobulin test (DAT) with IgG and complement positivity. His peripheral smear shows spherocytes. His CLL has been managed with ibrutinib for 14 months. What is the most likely diagnosis and appropriate initial therapy?

Answer: Warm autoimmune hemolytic anemia; initiate corticosteroids

Warm AIHA (IgG-mediated, complement-activating) is a well-recognized complication of CLL and can occur even during BTK inhibitor therapy. The DAT positivity with IgG and complement, spherocytes, and indirect hyperbilirubinemia confirm warm AIHA. First-line treatment is systemic corticosteroids (prednisone 1 mg/kg/day). Cold agglutinin disease typically shows IgM on DAT and is exacerbated by cold. Richter transformation presents as rapidly enlarging nodes, B symptoms, and elevated LDH disproportionate to anemia. Ibrutinib does not directly cause DAT-positive hemolysis.

A 72-year-old woman with a history of breast cancer treated 8 years ago presents with back pain and a serum protein electrophoresis showing an M-spike of 1.1 g/dL (IgG kappa). Bone marrow biopsy shows 7% plasma cells. Serum free light chain ratio is 2.4 (normal). She has no lytic lesions, anemia, hypercalcemia, or renal insufficiency. What is the correct diagnosis and initial management?

Answer: Smoldering multiple myeloma; observation with monitoring every 3–6 months

This patient meets criteria for smoldering multiple myeloma (SMM): M-spike ≥1 g/dL (IgG), bone marrow plasma cells 10–59% or M-spike meeting threshold, but ABSENCE of CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions) or SLiM criteria. Note: 7% plasma cells technically falls below the 10% SMM threshold, making this a borderline case; however, the M-spike of 1.1 g/dL IgG satisfies SMM M-protein criterion per IMWG 2014. Standard care is observation. Lenalidomide was studied in QUIREDEX trial for high-risk SMM only, and is not standard of care. MGUS requires M-spike <3 g/dL AND <10% plasma cells AND no end-organ damage — the M-spike threshold alone can differentiate.

A 55-year-old man with metastatic non-small cell lung adenocarcinoma is found to have an EGFR exon 20 insertion mutation. His oncologist initially considers osimertinib. Which of the following statements is most accurate regarding this mutation?

Answer: EGFR exon 20 insertions are generally resistant to first-, second-, and third-generation EGFR TKIs including osimertinib

EGFR exon 20 insertion mutations represent approximately 4–10% of EGFR mutations and are notably resistant to standard EGFR TKIs (erlotinib, afatinib, dacomitinib, and osimertinib) due to steric hindrance preventing drug binding at the active site. FDA-approved agents specifically for exon 20 insertions include amivantamab (EGFR/MET bispecific antibody) and mobocertinib, both approved for platinum-pretreated patients (not first-line). Osimertinib is the standard of care for exon 19 deletions and exon 21 L858R mutations, NOT for exon 20 insertions.

A 38-year-old woman with essential thrombocythemia (ET) and a JAK2 V617F mutation (platelet count 1,200 × 10⁹/L) develops a transient ischemic attack. She is currently on aspirin 81 mg daily. Which of the following is the most appropriate next step in management?

Answer: Add cytoreductive therapy with hydroxyurea

This patient has high-risk ET (age <60 is not high-risk by age alone, but a prior thrombotic event — TIA — makes her high-risk regardless of age or JAK2 status). Per NCCN and ELN guidelines, high-risk ET requires cytoreductive therapy to reduce thrombotic recurrence. Hydroxyurea is first-line cytoreduction. Aspirin alone is insufficient after a thrombotic event in high-risk ET. Switching to clopidogrel alone does not address the thrombocytosis. Anticoagulation with warfarin is not routinely indicated in ET unless concurrent atrial fibrillation or VTE is present. Thrombocytapheresis is reserved for emergent, acute thrombosis with extreme thrombocytosis, not for chronic management.