Hematology and Oncology Flashcards

A 58-year-old man with newly diagnosed acute myeloid leukemia (AML) with FLT3-ITD mutation begins induction chemotherapy with 7+3 (cytarabine + daunorubicin). On day 14 bone marrow biopsy, there is aplasia with no residual blasts. Which maintenance strategy is most appropriate following complete remission and consolidation with high-dose cytarabine?

Answer: Allogeneic hematopoietic stem cell transplantation in first complete remission

FLT3-ITD mutation in AML confers high risk of relapse, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission is the preferred consolidation/curative strategy for eligible patients. While midostaurin is used as part of induction (with 7+3) and as maintenance post-transplant (per some protocols), it does not replace allo-HSCT as definitive therapy. Autologous SCT is generally reserved for AML patients without a suitable donor or with favorable-risk cytogenetics. Observation alone is insufficient for FLT3-ITD AML given the high relapse risk.

A 45-year-old woman presents with progressive fatigue, splenomegaly, and a WBC of 185,000/µL with a left shift. BCR-ABL1 is detected by FISH. She is started on imatinib 400 mg daily. After 3 months, her BCR-ABL1 transcript level by quantitative PCR is 15% (IS). After 6 months, it is 12% (IS). According to ELN 2022 guidelines, what is the most appropriate next step?

Answer: Perform ABL kinase domain mutation analysis and switch to a second-generation TKI

ELN 2022 guidelines define BCR-ABL1 >10% (IS) at 6 months as treatment failure (not just warning). At 6 months, the target is BCR-ABL1 ≤10% (IS) — achieving major molecular response milestone. This patient at 12% at 6 months has failed the 6-month milestone. The appropriate next step is ABL kinase domain mutation testing to guide TKI selection, followed by switching to a second-generation TKI (dasatinib, nilotinib, or bosutinib). Simply continuing imatinib without change is inadequate for a failure response.

A 72-year-old man with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after two prior lines of therapy achieves complete remission following CAR-T cell therapy (axicabtagene ciloleucel). Three weeks post-infusion, he develops fever (39.2°C), hypotension requiring vasopressors, and neurological symptoms including confusion and seizures. Ferritin is 42,000 ng/mL. What is the most appropriate immediate management?

Answer: Tocilizumab plus dexamethasone, with anakinra considered for refractory disease

This patient has concurrent severe CRS (Grade 3–4: hypotension requiring vasopressors) and severe ICANS (Grade 3–4: seizures, confusion). Per ASTCT consensus guidelines, severe CRS requires tocilizumab; however, tocilizumab has limited CNS penetrance and may worsen ICANS by shifting cytokines centrally. For concurrent severe CRS and ICANS, the standard approach is tocilizumab (for CRS) PLUS dexamethasone (for ICANS, given its CNS penetrance). Anakinra (IL-1 blockade) is considered for steroid-refractory cases. Tocilizumab alone is insufficient when ICANS is severe. Rituximab would deplete CAR-T cells and eliminate any therapeutic benefit.

A 68-year-old woman with IgG kappa multiple myeloma on maintenance lenalidomide after autologous stem cell transplantation develops new-onset dyspnea and bilateral lower extremity edema 18 months post-transplant. Echocardiogram reveals a thickened interventricular septum (14 mm), diastolic dysfunction, and a 'sparkling' appearance. Serum protein electrophoresis shows no M-spike. What is the most likely diagnosis and appropriate next step?

Answer: AL amyloidosis from plasma cell dyscrasia; perform fat pad biopsy and bone marrow biopsy with Congo red staining

The clinical picture — diastolic dysfunction, thickened interventricular septum with 'sparkling' or 'granular' echocardiographic appearance, and bilateral edema in the context of a plasma cell dyscrasia — is classic for cardiac AL amyloidosis. The absence of an M-spike does not exclude AL amyloidosis, as the paraprotein may be below detection threshold, particularly after SCT. Fat pad biopsy (sensitivity ~70–80%) and bone marrow biopsy with Congo red staining are the preferred initial diagnostic steps. Lenalidomide-induced cardiotoxicity is not a recognized entity. Cardiac plasmacytoma would appear as a mass lesion, not diffuse thickening with diastolic dysfunction.

A 55-year-old man with metastatic melanoma is started on combination ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). After cycle 2, he develops severe diarrhea (>7 stools/day above baseline) with abdominal cramping. Colonoscopy reveals ulcerations throughout the colon. He is started on high-dose methylprednisolone 2 mg/kg/day IV but shows no improvement after 72 hours. What is the next most appropriate therapy?

Answer: Add infliximab 5 mg/kg IV; if contraindicated, use vedolizumab

This patient has Grade 4 immune-related colitis (>7 stools/day, endoscopic ulcerations) refractory to high-dose corticosteroids after 72 hours. Per ASCO/NCCN guidelines for steroid-refractory immune-related colitis, infliximab (anti-TNF) 5 mg/kg IV is the preferred second-line agent. Vedolizumab (gut-selective anti-integrin) is the alternative if infliximab is contraindicated (e.g., prior TB exposure, demyelinating disease, CHF). Escalating corticosteroid dose beyond 2 mg/kg is not guideline-supported and increases toxicity without evidence of benefit. FMT is investigational and not standard of care. Rechallenge decisions should be deferred until the acute episode resolves.

A 62-year-old woman with polycythemia vera (JAK2 V617F positive) controlled on hydroxyurea presents with a 3-month history of increasing spleen size, constitutional symptoms, and worsening anemia requiring transfusions (hemoglobin 7.8 g/dL). Bone marrow biopsy shows >20% blasts. Cytogenetics reveal del(17p) and complex karyotype. What is the most appropriate diagnosis and management strategy?

Answer: Blast-phase transformation of PV (secondary AML); consider venetoclax + azacitidine and evaluate for allogeneic SCT

Blast phase (blast crisis) of polycythemia vera — defined as ≥20% blasts in bone marrow or peripheral blood — represents transformation to secondary AML, a recognized complication of MPN. This is distinct from post-PV myelofibrosis or accelerated phase (10–19% blasts). The complex karyotype including del(17p) (TP53 locus) confers very high-risk cytogenetics. Standard AML induction has poor outcomes; venetoclax + azacitidine (HMA/ven) is increasingly used for TP53-mutated or complex-karyotype secondary AML in older/unfit patients, with allo-HSCT in CR1 as the only potentially curative option. Ruxolitinib addresses myelofibrosis symptoms but is not appropriate for blast-phase disease. The blast count of >20% definitively excludes the MF accelerated phase designation.