Hematological Malignancies (Leukemias, Lymphoma, Myeloma, Myeloproliferative) MCQs

Medicine · 159 free questions with answers & explanations.

1. A 65-year-old man is found incidentally to have lymphocytosis of 28,000/μL. Peripheral smear shows mature small lymphocytes and smudge cells. Flow cytometry reveals CD5+, CD19+, CD23+, surface Ig (dim), CD10−. He is asymptomatic with no lymphadenopathy or splenomegaly. What is the most appropriate management?
2. A 72-year-old man presents with back pain, fatigue, and hypercalcemia. Serum protein electrophoresis shows an M-spike of 4.2 g/dL (IgG kappa). Bone marrow biopsy reveals 35% plasma cells. Serum creatinine is 2.1 mg/dL. X-rays show lytic lesions in the skull and vertebral bodies. Which criteria best establishes the diagnosis of multiple myeloma requiring therapy (symptomatic myeloma)?
3. A 38-year-old woman presents with painless cervical lymphadenopathy, night sweats, and 8 kg weight loss over 3 months. CT shows mediastinal and cervical lymphadenopathy. Lymph node biopsy shows large binucleated cells with prominent 'owl-eye' nucleoli surrounded by a clear space, in a background of lymphocytes, eosinophils, and plasma cells. What is the most likely diagnosis?
4. A 50-year-old man presents with splenomegaly, leukocytosis (WBC 95,000/μL with myelocytes, metamyelocytes, and basophilia), and a Philadelphia chromosome (t(9;22)/BCR-ABL1 fusion) on karyotype. His blast count is 4%. Which of the following is the most appropriate first-line therapy?
5. A 72-year-old man with multiple myeloma on lenalidomide-bortezomib-dexamethasone (RVD) regimen has achieved a very good partial response (VGPR). After 4 cycles, serum protein electrophoresis shows a residual M-spike of 0.3 g/dL. Bone marrow shows 3% plasma cells by flow cytometry but immunofixation is still positive. Which response category does this meet?
6. A 28-year-old woman presents with fever, fatigue, and lymphadenopathy. Biopsy of an enlarged cervical node shows large Reed-Sternberg cells staining positive for CD15 and CD30, negative for CD20 and CD45. PET-CT reveals supra- and infra-diaphragmatic nodal disease with splenic involvement, no extranodal disease. What stage is this Hodgkin lymphoma?
7. A 64-year-old man presents with fatigue and splenomegaly. CBC: Hb 10.2 g/dL, WBC 78,000/μL with a left shift (blasts 3%, myelocytes 18%, basophils 8%), platelets 450,000/μL. JAK2 V617F mutation is NEGATIVE. BCR-ABL1 fusion gene by RT-PCR is POSITIVE. The karyotype shows a small marker chromosome at 22. What is the most likely diagnosis?
8. A 55-year-old man with IgG kappa multiple myeloma on third-line therapy develops severe neuropathic pain, bilateral foot drop, and autonomic dysfunction (orthostatic hypotension, bladder retention). He had previously received bortezomib and thalidomide. Which toxicity is most likely responsible?
9. A 30-year-old woman presents with mediastinal mass, fever, night sweats, and 12 kg weight loss over 4 months. Biopsy of a cervical node shows Reed-Sternberg cells in a cellular background of eosinophils, plasma cells, and lymphocytes with fibrotic bands. What subtype of Hodgkin's lymphoma is this?
10. A 68-year-old man with multiple myeloma has received lenalidomide + bortezomib + dexamethasone (RVD) induction with excellent response. He is ineligible for autologous stem cell transplantation (ASCT) due to age and comorbidities. Which maintenance strategy has been shown to prolong progression-free survival in transplant-ineligible myeloma?
11. A 22-year-old woman presents with BCR-ABL1-positive acute lymphoblastic leukaemia (Ph+ ALL). Apart from induction chemotherapy, which targeted therapy is incorporated into first-line treatment to significantly improve outcomes?
12. In polycythaemia vera (PV), which mutation is found in nearly 95% of patients, and what signalling pathway does it constitutively activate?
13. The SOKAL score in chronic myeloid leukaemia (CML) was traditionally used to stratify patients. With TKI therapy, which mutation in the BCR-ABL kinase domain confers resistance to imatinib, dasatinib, and nilotinib but is sensitive to ponatinib?
14. Richter transformation in CLL refers to transformation into which histological subtype and is associated with which prognostic gene mutation?
15. In multiple myeloma, the International Staging System (ISS) uses serum beta-2 microglobulin and albumin. The Revised ISS (R-ISS) adds two additional prognostic parameters. Which pair?
16. Calreticulin (CALR) exon 9 mutations are found in approximately 25% of essential thrombocythaemia and myelofibrosis patients. How do CALR mutations drive myeloproliferation?
17. A 72-year-old man with CLL has Rai stage III disease (with anemia, Hb 9.2 g/dL). FISH cytogenetics show 17p deletion (TP53 mutation). According to current CLL management guidelines, the preferred first-line therapy for this patient is:
18. A 58-year-old man is diagnosed with primary myelofibrosis. He has a leukocyte count of 22,000/µL, massive splenomegaly (18 cm), symptomatic anemia (Hb 8.5 g/dL), and DIPSS-Plus score of intermediate-2. JAK2 V617F mutation is positive. Which agent targets the JAK-STAT pathway and is the standard of care for symptomatic disease in this condition?
19. A 66-year-old woman with newly diagnosed multiple myeloma has t(4;14) chromosomal translocation, del(17p), and plasma cell percentage of 60% on bone marrow biopsy. She is not a transplant candidate. According to the R-ISS (Revised International Staging System) staging for myeloma, which combination of factors places her in Stage III (worst prognosis)?
20. A 45-year-old man presents with fever, night sweats, weight loss, and mediastinal mass. Biopsy shows large cells with bilobed nuclei, prominent eosinophilic nucleoli (owl-eye cells), and CD30+, CD15+, CD20−, CD45− immunophenotype. This is classic Hodgkin's lymphoma. The Reed-Sternberg cell surface antigen targeted by the antibody-drug conjugate brentuximab vedotin is:
21. A 70-year-old man presents with fatigue and splenomegaly. CBC: WBC 22,000/μL with left shift, Hb 10 g/dL, platelets 650,000/μL. JAK2 V617F mutation is positive. LDH is mildly elevated, no blast cells on smear. Bone marrow shows hypercellularity with megakaryocyte clustering. Which myeloproliferative neoplasm does this best represent?
22. A 52-year-old woman is diagnosed with Waldenström's macroglobulinemia. She has hyperviscosity symptoms (blurred vision, headache). IgM level is 6,200 mg/dL. Bone marrow shows lymphoplasmacytic lymphoma. MYD88 L265P mutation is detected. Which is the most appropriate immediate therapy?
23. In multiple myeloma, International Staging System (ISS) Stage III is defined by which combination?
24. A 45-year-old woman has CML in chronic phase confirmed by BCR-ABL t(9;22). She is started on imatinib. After 12 months of therapy, BCR-ABL IS (International Scale) is 0.8% (>1 log reduction from baseline but not complete). By European LeukemiaNet (ELN) 2020 criteria, what is this response classified as?
25. A 35-year-old woman with chronic myeloid leukaemia (CML) in chronic phase on imatinib 400 mg/day achieves complete cytogenetic response at 12 months but fails to achieve major molecular response (BCR-ABL IS >0.1%) at 18 months. What is the recommended management per ELN 2020 guidelines?
26. A 70-year-old man is diagnosed with multiple myeloma with CRAB features. ISS stage III based on β2-microglobulin 6.2 mg/L and albumin 2.8 g/dL. FISH reveals deletion 17p. Which statement about this patient's risk stratification and treatment approach is correct?
27. A 65-year-old man presents with splenomegaly, constitutional symptoms, and JAK2 V617F mutation positive. Peripheral blood shows leukoerythroblastic picture; bone marrow biopsy shows grade 2 fibrosis. DIPSS-Plus score categorizes him as intermediate-2 risk. Which is the most appropriate disease-modifying therapy?
28. A 55-year-old woman with CML on imatinib for 3 years achieves complete hematologic and cytogenetic response but BCR-ABL transcript level by PCR is 0.15% IS (MR3.0, major molecular response). After 6 months, BCR-ABL rises to 2% IS confirmed on repeat testing. The most appropriate next step is:
29. A 67-year-old man is diagnosed with diffuse large B-cell lymphoma (DLBCL), stage II bulky, germinal center B-cell (GCB) subtype by Hans algorithm. PET-CT shows SUVmax 18. IPI score is 2 (intermediate risk). According to current NCCN guidelines, the standard first-line therapy is:
30. A 63-year-old man with newly diagnosed multiple myeloma has del(17p) and t(4;14) on FISH, LDH elevated, and beta-2 microglobulin 5.8 mg/L with albumin 3.2 g/dL. By the R-ISS staging system, this patient is stage:
31. A 48-year-old man is found to have JAK2 V617F mutation positive polycythemia vera. Hematocrit is 56%, platelet count 680 × 10⁹/L. He is a heavy smoker with one prior TIA. According to current ELN high-risk PV management guidelines, the appropriate treatment is:
32. A 35-year-old man presents with fever, bone pain, and fatigue. CBC shows WBC 45,000/µL with 80% blasts; blasts are MPO-negative, PAS-positive, and express CD10, CD19, CD22. Cytogenetics reveal t(9;22)(q34;q11). The prognosis of this B-ALL is primarily determined by:
33. A 68-year-old man with multiple myeloma on lenalidomide-dexamethasone develops deep vein thrombosis. Serum M-protein is 1.8 g/dL; calcium 11.2 mg/dL; creatinine 1.6 mg/dL; hemoglobin 9.4 g/dL. His ISS stage (International Staging System) is determined by which TWO parameters?
34. A 72-year-old woman is found to have absolute lymphocytosis of 28,000/µL on a routine CBC. She is asymptomatic with no lymphadenopathy or splenomegaly. Flow cytometry shows CD5+/CD19+/CD23+/CD20(dim) B-cells with kappa light chain restriction. Fluorescence in situ hybridization (FISH) shows del(13q14) as the sole abnormality. Rai stage is 0. Management is:
35. A 55-year-old man has JAK2 V617F mutation, splenomegaly, and hemoglobin 20.5 g/dL, hematocrit 63%. He is at high risk for thrombosis (age >60). Which agent reduces thrombotic risk AND controls erythrocytosis in this polycythemia vera patient?
36. A 70-year-old man is incidentally found to have a lymphocyte count of 22,000/µL. Peripheral smear shows smudge cells. Flow cytometry shows CD5+, CD19+, CD23+, CD20 (dim), surface IgM (dim). Bone marrow biopsy shows 40% infiltration. He is asymptomatic with no lymphadenopathy or organomegaly and haemoglobin 13.2 g/dL. According to Rai staging and current CLL guidelines, what is the appropriate management?
37. A 25-year-old man presents with painless cervical lymphadenopathy. Biopsy shows large lacunar cells in a background of eosinophils, plasma cells, and lymphocytes. Which subtype of Hodgkin lymphoma does this represent and what is its most common presentation pattern?
38. A 65-year-old man with multiple myeloma has serum creatinine 2.1 mg/dL, calcium 11.4 mg/dL, and bone marrow plasmacytosis of 25%. His serum free light chain ratio is markedly abnormal. He is deemed ineligible for autologous stem cell transplant due to cardiac comorbidities. Which regimen is the current standard of care for transplant-ineligible NDMM based on MAIA trial data?
39. A 34-year-old woman is found to have JAK2 V617F mutation positive polycythaemia vera. Her haematocrit is 54%, she has splenomegaly, and a history of one episode of deep vein thrombosis. What is the most appropriate cytoreductive treatment choice in this high-risk PV patient?
40. A 70-year-old man has fatigue, bone pain, and serum protein electrophoresis showing an IgG-kappa M-spike of 4.2 g/dL. Bone marrow biopsy shows 35% plasma cells. Serum calcium is 11.1 mg/dL and creatinine is 2.4 mg/dL. Skeletal survey reveals lytic lesions in skull and spine. According to IMWG 2014 criteria, this patient has:
41. The BCR-ABL1 fusion gene in chronic myeloid leukaemia (CML) results from the translocation t(9;22). The preferred FIRST-LINE tyrosine kinase inhibitor for newly diagnosed chronic-phase CML with SOKAL high-risk score and desire for treatment-free remission is:
42. A 55-year-old man has splenomegaly, pruritus after bathing (aquagenic), plethora, and Hb 19.5 g/dL, haematocrit 62%. JAK2 V617F mutation is positive. Serum erythropoietin is low. The diagnostic condition is polycythaemia vera (PV). The MOST important initial therapy to prevent thrombosis is:
43. In Hodgkin lymphoma, which subtype is associated with LP (lymphocyte predominant) cells (popcorn cells), CD20 positive, CD15 negative, CD30 negative, and an indolent clinical course distinct from classical HL?
44. Polycythemia vera (PV) is distinguished from secondary polycythemia by the presence of which molecular mutation in >95% of cases?
45. A 70-year-old patient with multiple myeloma is being started on bortezomib-based therapy. Which prophylactic measure is specifically required with bortezomib that is not routinely needed with lenalidomide-based regimens?
46. Richter's transformation in CLL is characterized by transformation to which aggressive lymphoma in most cases?
47. A 52-year-old patient with newly diagnosed Philadelphia chromosome-positive ALL is being evaluated for treatment. Per current evidence, which agent should be added to chemotherapy induction?
48. A 28-year-old man presents with fever, fatigue, lymphadenopathy, and mediastinal widening on CXR. Biopsy shows Reed-Sternberg cells in a lymphocyte-rich background with scattered plasma cells and eosinophils. Immunophenotype: CD15+, CD30+, CD20–. What is the most likely diagnosis?
49. A 65-year-old man is found to have WBC 145 × 10⁹/L with 92% mature lymphocytes. Flow cytometry shows CD5+, CD19+, CD23+, CD20(dim), sIg(dim), FMC7–. The MOST likely diagnosis is:
50. A 58-year-old woman with multiple myeloma is started on bortezomib-based therapy. She develops painful burning paresthesias in a stocking distribution. The MOST likely culprit agent and the recommended modification is:
51. A 45-year-old woman with Philadelphia chromosome-positive CML in chronic phase is started on imatinib. After 12 months, BCR-ABL1 transcript level by PCR is 1.2% (IS). According to ELN 2020 response criteria, this response at 12 months is:
52. A 70-year-old man presents with lytic bone lesions, serum protein electrophoresis showing an M-spike of 3.8 g/dL (IgG kappa), hemoglobin 8 g/dL, serum calcium 11.2 mg/dL, and creatinine 2.1 mg/dL. Bone marrow shows 35% plasma cells. Using the ISS staging system, which parameter combination defines Stage III?
53. A 68-year-old man has leukocytosis (WBC 85,000/µL) with 92% lymphocytes on differential. Lymphocytes are small, mature-appearing, with smear cells. Flow cytometry shows CD5+, CD19+, CD23+, CD20 (dim), surface Ig (dim), FMC7−. What is the diagnosis?
54. A 55-year-old man with newly diagnosed multiple myeloma has renal impairment (creatinine 2.4 mg/dL), bone pain, and calcium 11.8 mg/dL. Bone marrow biopsy shows 40% plasma cells. FISH reveals t(4;14) translocation. He is eligible for autologous stem cell transplantation. What is the standard induction regimen?
55. A 35-year-old woman presents with mediastinal mass, B symptoms, and cervical lymphadenopathy. Biopsy shows binucleate giant cells with prominent owl-eye nucleoli in a background of lymphocytes, eosinophils, and plasma cells. CD15+, CD30+, CD45−. What is the most common histological subtype of this condition?
56. A 50-year-old woman with polycythemia vera is started on hydroxyurea. After 6 months, her WBC is 14,000/µL, hematocrit 48%, but she develops painful leg ulcers. Which alternative cytoreductive agent is most appropriate?
57. A 68-year-old man presents with fatigue, night sweats and a mediastinal mass on CT. Biopsy shows large lacunar cells with a background of eosinophils, plasma cells and lymphocytes in a nodular sclerotic pattern. CD15+, CD30+, CD45−. Staging PET-CT shows disease in mediastinum and left axilla only. Ann Arbor stage and recommended treatment are:
58. A 72-year-old woman has multiple myeloma with t(4;14) translocation, del(17p) and bone marrow plasma cells 60%. She is ineligible for stem cell transplant. Which cytogenetic finding confers the HIGHEST risk and poorest prognosis?
59. A 35-year-old man is diagnosed with Philadelphia chromosome-positive CML in chronic phase. He is started on imatinib 400 mg daily. After 3 months of therapy, BCR-ABL transcript level is 45% (IS). By 12 months, BCR-ABL is 2% (IS). Which term correctly describes the 12-month response and what should be done?
60. A 70-year-old man with polycythemia vera (JAK2 V617F positive) has a hematocrit of 58%, platelet count 850 × 10⁹/L and has had a prior thrombotic event (DVT). He is classified as high-risk. Which cytoreductive agent is first-line for high-risk PV?
61. A 55-year-old man presents with fatigue, splenomegaly 18 cm, WBC 2.4 × 10⁹/L, Hb 8.2 g/dL, platelet count 68 × 10⁹/L and a leukoerythroblastic blood film. Bone marrow biopsy shows dry tap with reticulin grade MF-3. JAK2 V617F is positive. The diagnosis and its DIPSS-plus classification are being determined. Which factor is NOT included in the DIPSS-plus scoring for primary myelofibrosis?
62. A 68-year-old man is diagnosed with chronic lymphocytic leukemia (CLL). His lymph node biopsy shows diffuse infiltration by prolymphocytes and the Ki-67 proliferation index is >30%. FISH shows del(17p) affecting TP53. Which treatment regimen is most appropriate for this high-risk CLL?
63. A 55-year-old woman is diagnosed with Philadelphia chromosome-positive ALL (Ph+ ALL). She receives standard induction chemotherapy. Which addition to the induction regimen has significantly improved outcomes and is now standard of care?
64. A 62-year-old man presents with fatigue, bone pain, hypercalcemia, and a serum protein electrophoresis showing a monoclonal (M) protein spike of 4.2 g/dL (IgG lambda). Bone marrow biopsy shows 35% plasma cells. Serum free light chain ratio is abnormal. CRAB criteria are met. What is the current first-line triplet regimen for transplant-eligible newly diagnosed multiple myeloma?
65. A 45-year-old man presents with splenomegaly, leukocytosis (WBC 120 × 10⁹/L with basophilia and eosinophilia on differential), low LAP score, and the Philadelphia chromosome is detected by cytogenetics. He is in chronic phase CML. According to current guidelines, what is the first-line treatment?
66. A 70-year-old man presents with fatigue and splenomegaly. CBC shows WBC 80,000/µL with a left shift (many myelocytes and metamyelocytes), Hb 10 g/dL, platelets 650,000/µL. BCR-ABL1 fusion transcript (p210) is detected by RT-PCR. He is in chronic phase CML. Per ELN guidelines, first-line treatment is:
67. A 55-year-old woman presents with constitutional symptoms, cervical and inguinal lymphadenopathy, and splenomegaly. PET-CT shows diffuse nodal disease. Biopsy shows a neoplasm positive for CD20, CD10, BCL-2, and BCL-6, with a t(14;18) translocation and a Ki-67 of 30%. The diagnosis is:
68. A 65-year-old man with multiple myeloma is being considered for treatment. He has 60% plasma cells on bone marrow biopsy, serum M-protein of 4.8 g/dL, serum calcium 2.7 mmol/L, creatinine 180 µmol/L, and lytic bone lesions on skeletal survey. He is considered transplant-ineligible. The preferred induction regimen per current guidelines is:
69. A 45-year-old man presents with pruritis, night sweats, and a mediastinal mass on CXR. Biopsy shows Reed-Sternberg cells positive for CD15 and CD30, negative for CD45. The neoplastic cells are admixed with a mixed inflammatory infiltrate. This represents which histological subtype of Hodgkin lymphoma with the best prognosis?
70. A 68-year-old man presents with splenomegaly, leucocytosis of 85,000/μL with full myeloid spectrum, basophilia, and a Philadelphia chromosome (t(9;22)) on cytogenetics. He is started on imatinib. What is the mechanism of action of imatinib?
71. A 72-year-old man has IgG kappa monoclonal protein of 4.8 g/dL, serum free light chain ratio 145, bone marrow plasma cells 18%, multiple lytic bone lesions, and serum calcium 11.6 mg/dL. He is considered transplant-ineligible. Which induction regimen is preferred per IMWG guidelines?
72. A 35-year-old woman presents with mediastinal mass, fever, night sweats, and weight loss >10% over 6 months. Biopsy shows Reed-Sternberg cells with CD15+, CD30+, CD45−, CD20− immunophenotype. CT staging reveals disease above and below the diaphragm with splenic involvement but no extranodal disease. What is the Ann Arbor stage?
73. A 66-year-old man with CLL (Rai Stage III) has del(17p) detected on FISH. He requires treatment. Which statement BEST describes the impact of del(17p) on therapy selection?
74. A 65-year-old man presents with splenomegaly, leucocytosis (WBC 120×10⁹/L) with a myeloid spectrum on smear, basophilia, and low leucocyte alkaline phosphatase (LAP) score. BCR-ABL1 translocation is confirmed. He is started on imatinib. What is the target of molecular response that defines 'deep molecular response' (MR4.5) used to consider treatment-free remission eligibility?
75. A 72-year-old man presents with fatigue, weight loss, splenomegaly, and a WBC of 48×10⁹/L. Smear shows predominantly mature small lymphocytes. Flow cytometry shows CD5+, CD19+, CD23+, CD20 dim, FMC7 negative, sIg dim. What is the diagnosis and first-line treatment for symptomatic disease?
76. A 58-year-old woman is diagnosed with multiple myeloma (MM): serum M-protein IgG kappa 4.2 g/dL, plasma cells 35% on bone marrow biopsy, multiple lytic lesions. She is transplant-eligible. According to current guidelines, what is the preferred induction regimen?
77. A 35-year-old man presents with fever, night sweats, pruritus, and cervical lymphadenopathy. Biopsy shows Reed-Sternberg cells with a background of eosinophils and plasma cells. CD15+ and CD30+ by IHC. PET-CT shows stage IIA disease (above the diaphragm, no B symptoms, ESR 38). What is the current preferred treatment?
78. Which of the following myeloproliferative neoplasms is associated with a JAK2 V617F mutation in nearly 100% of cases?
79. A 66-year-old man presents with fatigue, night sweats, and splenomegaly. Blood counts show WBC 210,000/µL with a left shift, basophilia 8%, eosinophilia, normocytic anaemia, and platelets 650,000/µL. Cytogenetics reveal t(9;22). The BCR-ABL1 fusion creates an abnormal tyrosine kinase with constitutive activity. The first-line treatment according to current ELN 2020 guidelines is:
80. A 72-year-old man is diagnosed with multiple myeloma with 60% plasma cells in bone marrow, serum calcium 11.8 mg/dL, creatinine 1.9 mg/dL, and haemoglobin 8.2 g/dL. FISH shows del(17p) and t(4;14). He is not a transplant candidate. According to IMWG 2023 guidance, the preferred induction regimen is:
81. A 58-year-old man presents with painless cervical lymphadenopathy. Biopsy shows diffuse proliferation of large B cells with CD20+, CD10+, BCL6+, MYC+ expression, and Ki-67 of 90%. FISH reveals MYC rearrangement AND BCL2 rearrangement. The specific diagnosis and prognosis is:
82. The JAK2 V617F mutation is present in the majority of patients with polycythaemia vera (PV). According to ELN 2018 criteria, a diagnosis of PV requires which major criterion in addition to bone marrow findings?
83. A 72-year-old man presents with fatigue, night sweats, and splenomegaly. CBC shows WBC 280,000/µL with myeloid predominance across all stages, basophilia, and a Philadelphia chromosome on cytogenetics. He is treatment-naive. According to current guidelines, the first-line treatment is:
84. A 65-year-old woman is diagnosed with stage IV follicular lymphoma (FLIPI score 3, high risk). She is asymptomatic, has a small-volume disease, and normal organ function. According to current ESMO guidelines, what is the most appropriate initial approach?
85. A 58-year-old man is diagnosed with multiple myeloma. He is transplant-eligible with good performance status. Which initial finding would shift the prognosis to high-risk myeloma requiring more aggressive therapy per the R-ISS staging system?
86. Which JAK2 V617F mutation-positive myeloproliferative neoplasm is most likely to present with splenic vein thrombosis or Budd-Chiari syndrome?
87. A 70-year-old man has multiple myeloma with serum creatinine 3.2 mg/dL. He is not a transplant candidate. Which triplet regimen is the current standard of care for newly diagnosed transplant-ineligible myeloma per IMWG?
88. A 45-year-old man with CML is on imatinib and achieves complete cytogenetic response but NOT major molecular response at 12 months. BCR-ABL1 PCR shows 1.2% IS. According to ELN 2020 guidelines, this response is classified as:
89. A 65-year-old woman with follicular lymphoma (grade 1–2, stage III, FLIPI score 3) is asymptomatic, with no B symptoms, and has stable low-volume disease. Which approach is most appropriate at initial presentation?
90. A 55-year-old man presents with plethora, splenomegaly, and elevated haemoglobin of 20 g/dL. JAK2 V617F mutation is detected. He has a prior history of DVT. His Hct is 62%. What is the most important initial treatment goal in polycythaemia vera?
91. A 68-year-old man presents with pallor, bone pain, and hypercalcemia. Serum protein electrophoresis shows an M-spike of 4.2 g/dL (IgG kappa). Bone marrow biopsy shows 40% plasma cells. Serum creatinine is 2.4 mg/dL. According to CRAB criteria for multiple myeloma requiring therapy, how many CRAB features does this patient have?
92. A 55-year-old woman is diagnosed with diffuse large B-cell lymphoma (DLBCL), stage IIIA, with an IPI score of 3. PET-CT shows FDG-avid lymphadenopathy. The standard first-line treatment is:
93. A 45-year-old man with CML on imatinib for 18 months achieves complete cytogenetic response but fails to achieve a major molecular response (MMR, BCR-ABL1 IS >0.1%). Mutation analysis shows a T315I mutation in BCR-ABL1. Which TKI is appropriate?
94. An 18-year-old man is diagnosed with acute promyelocytic leukemia (APL, AML-M3). He develops bleeding and his coagulation profile shows PT 22s, APTT 48s, fibrinogen 80 mg/dL, D-dimer markedly elevated. The pathognomonic cytogenetic abnormality in APL is:
95. A 72-year-old woman with CLL (Binet stage C) requires treatment. She has del(17p) detected by FISH. Her renal function is reduced (CrCl 38 mL/min). The preferred treatment based on current guidelines (NCCN/ESMO) is:
96. A 68-year-old man has CLL with del(17p) detected by FISH, TP53 mutation on sequencing, and Rai stage III disease. He requires treatment. Which frontline regimen is recommended?
97. A 72-year-old woman is diagnosed with multiple myeloma: IgG kappa, serum M-protein 4.8 g/dL, bone marrow plasma cells 45%, creatinine 1.3 mg/dL, haemoglobin 9.2 g/dL, and calcium 10.8 mg/dL. She is not a transplant candidate. Which triplet regimen is the current standard of care for frontline treatment?
98. A 35-year-old woman is diagnosed with Philadelphia-positive ALL. After induction with hyper-CVAD plus imatinib achieving complete remission, what is the preferred consolidation strategy?
99. A 55-year-old man with polycythaemia vera and JAK2 V617F mutation has a haematocrit persistently above 45% despite phlebotomy and low-dose aspirin. He has had one prior venous thromboembolic event. What is the next appropriate cytoreductive agent?
100. A 68-year-old man has multiple myeloma. Bone marrow biopsy shows 35% plasma cells. He has serum M-protein (IgG kappa) of 4.2 g/dL, calcium 11.5 mg/dL, creatinine 2.8 mg/dL, and multiple osteolytic lesions. Which translocation most commonly found in IgH-associated myeloma and confers poor prognosis is best treated with bortezomib-containing regimens?
101. A 45-year-old woman with CML on imatinib 400 mg/day has a complete cytogenetic response but fails to achieve a major molecular response (BCR-ABL > 0.1% IS at 12 months). BCR-ABL kinase domain mutation analysis reveals T315I. What is the most appropriate next step?
102. A 72-year-old man is found to have enlarged lymph nodes on CT (cervical, axillary, abdominal). Biopsy shows a follicular lymphoma (Grade 1-2), FLIPI score 3. He is asymptomatic with no B symptoms, no bulky disease, normal LDH. What is the preferred initial management?
103. Polycythemia vera (PV) is distinguished from secondary polycythemia by which finding?
104. A 65-year-old man has polycythaemia vera (PV) with JAK2 V617F mutation, haematocrit 58%, and a history of transient ischaemic attack. According to ELN 2018 risk stratification and management guidelines, the MOST appropriate treatment is:
105. A 72-year-old man presents with bone pain, serum calcium 12.4 mg/dL, total protein 10.2 g/dL, IgG kappa M-protein 4.2 g/dL on SPEP, and 38% plasma cells on bone marrow biopsy. FISH shows t(4;14). Which of the following is the MOST appropriate initial treatment for this transplant-ineligible patient?
106. A 30-year-old woman presents with fever, painless cervical lymphadenopathy, night sweats, and weight loss >10% over 3 months. Biopsy shows Reed-Sternberg cells with CD15+, CD30+, CD45−, EBV LMP-1+. She is staged as IIA (no B symptoms at staging but had constitutional symptoms before). PET/CT shows FDG-avid mediastinal and bilateral cervical nodes only. The MOST appropriate first-line treatment is:
107. Which translocation in CML results in a constitutively active tyrosine kinase and is the direct molecular target of imatinib?
108. A 68-year-old man is found to have serum protein electrophoresis showing an M-protein of 3.2 g/dL (IgG kappa), bone marrow plasma cells 12%, but NO lytic lesions, no anaemia, and no renal insufficiency. Urine SFLC ratio is 4 (normal). This best fits which diagnosis and what is the appropriate management?
109. A 25-year-old man presents with mediastinal mass, fever, and night sweats. Biopsy shows Reed-Sternberg cells positive for CD15, CD30, and EBV-LMP1, with background mixed cellularity pattern. Which genetic alteration is CHARACTERISTICALLY seen in the Reed-Sternberg cells of classic Hodgkin lymphoma?
110. A 72-year-old woman with previously treated CLL (fludarabine, cyclophosphamide, rituximab - FCR) relapses with progressive lymphocytosis and lymphadenopathy at 24 months. TP53 mutation is confirmed. The MOST appropriate salvage therapy is:
111. A 58-year-old man is found to have Hb 19.8 g/dL, PCV 61%, WBC 13,500/µL, and spleen +6 cm below costal margin. JAK2 V617F mutation is positive. He has a history of a deep vein thrombosis 2 years prior. According to revised WHO/ELN criteria for polycythaemia vera, what is the MOST appropriate treatment?
112. In a patient presenting with fever, petechiae, and microangiopathic haemolytic anaemia, the pentad of TTP includes all of the following EXCEPT:
113. A 70-year-old man is diagnosed with chronic lymphocytic leukemia (CLL). FISH shows del(17p) with TP53 mutation. IgHV mutation status is unmutated. He has symptomatic disease (Rai Stage III). According to current guidelines, what is the preferred first-line therapy?
114. A 68-year-old man with multiple myeloma on lenalidomide maintenance develops new bone pain. X-ray shows lytic lesions in T8 vertebra. Serum M protein rises from 0.3 to 1.8 g/dL over 2 months. He was previously treated with bortezomib-lenalidomide-dexamethasone (VRd). Per IMWG 2016 criteria for progression, what is the minimum requirement to define biochemical relapse requiring treatment?
115. A 42-year-old woman with Hodgkin lymphoma (nodular sclerosis, stage IIA, no bulk) achieves complete metabolic response (PET-CT Deauville score 1) after 2 cycles of ABVD. What is the current preferred management strategy?
116. A 55-year-old man is diagnosed with polycythemia vera (PV). JAK2 V617F positive. Hematocrit is 58%, spleen is palpable 5 cm below costal margin. He has a history of stroke 3 years ago. According to current ELN guidelines, what is the appropriate management?
117. A 35-year-old man with AML (de novo, normal cytogenetics) achieves CR1 after 7+3 induction. Molecular testing reveals NPM1 mutation with FLT3-ITD low allele burden. He has a matched sibling donor available. According to ELN 2022 risk stratification, what is his risk category and recommended post-remission strategy?
118. A 68-year-old man is found to have an absolute lymphocyte count of 18,000/μL with smudge cells on peripheral smear. Flow cytometry shows CD5+, CD19+, CD23+, CD20 dim, FMC7-. Fluorescence in situ hybridisation (FISH) reveals del(17p). Per current CLL guidelines, this genetic finding influences treatment by:
119. A 35-year-old man with Philadelphia chromosome-positive ALL is in complete haematological remission after induction with ponatinib plus mini-hyper-CVD. Measurable residual disease (MRD) by flow cytometry remains detectable at 10^−3. Which statement regarding subsequent management is MOST accurate?
120. A 72-year-old woman with multiple myeloma on lenalidomide maintenance develops a new IgG M-protein of 0.4 g/dL, different isotype from her original IgA myeloma. Bone marrow biopsy confirms a second plasma cell clone. This scenario best represents:
121. A 48-year-old man with polycythaemia vera (PV) has haematocrit >65%, platelet count 900 × 10^9/L, splenomegaly, and pruritus. He has the JAK2 V617F mutation. His 10-year cardiovascular risk is high. Beyond phlebotomy and aspirin, which cytoreductive agent is NOW preferred over hydroxyurea as FIRST-LINE for high-risk PV?
122. A 32-year-old woman is diagnosed with Philadelphia chromosome-positive ALL (Ph+ ALL). Current treatment guidelines recommend adding which tyrosine kinase inhibitor to the chemotherapy backbone to improve outcomes?
123. In multiple myeloma, which molecular event defines 'high-risk' cytogenetics that predicts poor prognosis regardless of treatment?
124. A patient with polycythaemia vera (PV) has not responded to phlebotomy and low-dose aspirin and has recurrent thrombotic events. According to WHO/ELN guidelines, the MOST appropriate cytoreductive therapy is:
125. The Ann Arbor staging system for Hodgkin lymphoma is supplemented by which suffix designating systemic B symptoms (fever >38°C, drenching night sweats, unexplained weight loss >10% in 6 months)?
126. A 72-year-old man is diagnosed with CLL. His Rai stage is IV (haemoglobin 9.2 g/dL, platelets 88 × 10⁹/L). FISH analysis shows del(17p) and TP53 mutation. Which treatment approach is preferred according to current guidelines?
127. A 55-year-old man with multiple myeloma has hypercalcaemia, renal failure (creatinine 3.1 mg/dL), anaemia, and more than 10% plasma cells on bone marrow biopsy. FISH shows t(4;14). Serum free light chain ratio is 200. How is this patient's disease risk classified under the R-ISS staging?
128. A patient with polycythaemia vera (PV) has a haematocrit of 62%, splenomegaly, and pruritus. JAK2 V617F mutation is confirmed. His cardiovascular risk is high (age 65, prior DVT). Which management is most appropriate?
129. A 67-year-old man has serum protein electrophoresis showing an M-spike of 4.2 g/dL (IgG kappa), bone marrow biopsy with 38% plasma cells, serum free light chain ratio of 320, and lytic bone lesions on whole-body PET-CT. Revised ISS (R-ISS) staging is used in myeloma. Which combination correctly identifies Stage III R-ISS?
130. A 72-year-old man has been on ibrutinib for CLL for 14 months. He now develops a new atrial fibrillation, hypertension, and grade 3 bleeding. The mechanism of ibrutinib causing these adverse effects is:
131. A 28-year-old woman is diagnosed with Hodgkin lymphoma, nodular sclerosis type, stage IIA with bulky mediastinal disease (mass > 1/3 chest diameter). Current standard of care per GHSG HD17 trial principles favours:
132. A 55-year-old man with polycythaemia vera (JAK2 V617F mutation, Hct 58%, splenomegaly, platelets 780 × 10⁹/L) had a prior deep vein thrombosis. Risk stratification places him in high-risk category. Which agent, beyond phlebotomy and low-dose aspirin, has shown myelosuppressive benefit and reduction in thrombotic events specifically in PV?
133. A 50-year-old man presents with splenomegaly, WBC 120,000/µL with a left shift, basophilia, and Philadelphia chromosome positive (BCR-ABL1). He is started on imatinib. After 12 months, PCR for BCR-ABL1 remains detectable at 1% IS. What is the NEXT best step?
134. A 70-year-old man has IgG myeloma with revised ISS (R-ISS) Stage III. He is transplant-ineligible. Current NCCN preferred induction regimen is:
135. A 45-year-old woman presents with polycythemia vera (JAK2 V617F positive). She has no prior thrombosis. She is 42 years old. Her initial cytoreductive therapy should be:
136. A 28-year-old man with Hodgkin lymphoma (nodular sclerosis, Stage IIA) achieves complete metabolic response (Deauville score 1–2) after 2 cycles of ABVD on interim PET-CT. According to response-adapted strategy (RATHL trial), what should be the next step?
137. A 72-year-old man presents with fatigue. CBC shows WBC 85,000/µL with 78% small mature-appearing lymphocytes, Hb 10.2 g/dL, platelets 98,000/µL. Peripheral smear shows smudge cells. Flow cytometry: CD5+, CD19+, CD20 (dim)+, CD23+, FMC7−, CD79b (dim)+, surface Ig (dim)+. What is the CLL/SLL score for this patient, and what prognosis does the score imply?
138. A 58-year-old man with multiple myeloma is being evaluated for autologous stem cell transplant eligibility. He has no significant comorbidities. Serum M-protein is 3.8 g/dL (IgG kappa), bone marrow plasma cells 55%, and serum free light chain ratio is abnormal. LDH is normal. Serum beta-2 microglobulin is 5.2 mg/L and albumin is 3.0 g/dL. FISH shows t(4;14) translocation. According to the Revised ISS (R-ISS), what stage is this myeloma?
139. A 45-year-old woman with diffuse large B-cell lymphoma (DLBCL) completes 6 cycles of R-CHOP. PET-CT shows a Deauville score of 4 at the previously involved sites. What is the appropriate next step per NCCN guidelines?
140. A 62-year-old man with polycythemia vera (PV) is on hydroxyurea. Despite hydroxyurea at 2g/day, haematocrit remains > 45%, platelet count is 900,000/µL, and he develops new splenomegaly. He has JAK2 V617F mutation. Per ELN 2018 criteria, what defines 'resistance/intolerance' to hydroxyurea in PV?
141. A 68-year-old woman presents with fatigue and is found to have haemoglobin 8.5 g/dL, normal WBC, platelets 650,000/µL, and serum ferritin 8 ng/mL. Peripheral smear shows microcytic hypochromic cells. Colonoscopy is negative. Bone marrow biopsy shows hypercellularity with increased megakaryocytes and absent iron stores. JAK2 V617F mutation is positive. The MOST likely diagnosis is:
142. A 55-year-old man has multiple myeloma with del(17p) and t(4;14) detected on FISH. Serum creatinine is 2.8 mg/dL. Per current myeloma risk stratification, he is classified as:
143. In chronic myeloid leukaemia (CML), a patient achieves complete cytogenetic response (CCyR) on imatinib but loses major molecular response (MMR). BCR-ABL kinase domain mutation testing reveals T315I mutation. Which is the ONLY TKI active against this mutation?
144. Richter's transformation in CLL is best characterised by:
145. A 68-year-old man presents with bone pain, serum calcium 11.8 mg/dL, creatinine 2.1 mg/dL, and haemoglobin 8.2 g/dL. Serum protein electrophoresis shows an M-protein of 4.2 g/dL. Bone marrow shows 35% plasma cells. Which WHO criterion is MET to define multiple myeloma over smouldering myeloma?
146. A 45-year-old woman is diagnosed with chronic myeloid leukaemia (CML) in chronic phase. BCR-ABL transcript is detected. She has no prior TKI treatment. Sokal score is intermediate. Which FIRST-LINE treatment is preferred per current guidelines?
147. A 70-year-old man with diffuse large B-cell lymphoma (DLBCL) completes 6 cycles of R-CHOP and achieves complete metabolic response on PET-CT. What is the MOST important prognostic marker that was assessed at diagnosis to guide initial intensity of therapy in DLBCL?
148. A 55-year-old man is found to have polycythaemia vera. JAK2 V617F mutation is confirmed. Haematocrit is 56%, and he has no prior thrombosis. He is 55 years old (high-risk based on age). What is the CORRECT target haematocrit and preferred cytoreductive agent?
149. A 55-year-old presents with fatigue, splenomegaly, and leukocytosis (WBC 180 × 10⁹/L) with basophilia. BCR-ABL1 fusion gene (Philadelphia chromosome) is detected. He is started on imatinib 400 mg daily. At 3 months, BCR-ABL1 transcript on quantitative PCR is 12% IS (international scale). According to ELN 2020 response criteria, this represents:
150. A 70-year-old presents with bone pain, serum protein electrophoresis showing an M-protein spike of 4.2 g/dL (IgG kappa), serum free light chain ratio of 85, bone marrow plasma cells 65%, and lytic lesions on PET-CT. The International Staging System (R-ISS) staging uses which combination of parameters?
151. A patient with JAK2 V617F-positive polycythaemia vera (PV) has haematocrit persistently >55% despite weekly phlebotomy. The patient is 68 years old. The MOST appropriate cytoreductive agent is:
152. The Ann Arbor staging system for Hodgkin lymphoma is modified by the 'Cotswolds modification'. The suffix 'E' in staging denotes:
153. A 58-year-old man is diagnosed with CML in chronic phase. BCR-ABL p210 fusion is confirmed. He is started on imatinib 400 mg/day. At 3 months, BCR-ABL transcript level by RT-PCR is 12% IS. What does this indicate and what is the next step?
154. A 72-year-old woman presents with fatigue, weight loss, and massive splenomegaly. Blood film shows teardrop cells, giant platelets, and circulating CD34+ blasts. Bone marrow trephine shows dry tap. JAK2 V617F mutation is positive. Fibrosis grade MF-2 on WHO grading. IPSS score is intermediate-2. What is the most appropriate disease-modifying therapy?
155. A 65-year-old patient with multiple myeloma has achieved VGPR after VRd (bortezomib, lenalidomide, dexamethasone) induction. He is transplant-eligible. Serum free light chain ratio is abnormal. What is the next most appropriate step?
156. A 45-year-old woman presents with mediastinal mass, fever, night sweats, and pruritus. Biopsy shows Reed-Sternberg cells in a background of eosinophils, plasma cells, and lymphocytes — mixed cellularity subtype. LDH is elevated, stage IIIB. Which prognostic scoring system is used to determine treatment intensity in advanced classical Hodgkin lymphoma?
157. A 70-year-old man with CLL has del(17p) on FISH and TP53 mutation. He requires treatment for bulky lymphadenopathy. Which treatment regimen is most appropriate given the high-risk cytogenetics?
158. A 60-year-old man presents with constitutional symptoms and a left supraclavicular node biopsy showing large cells with bi-lobed nuclei, prominent eosinophilic 'owl eye' nucleoli, and a CD30+/CD15+ immunophenotype with CD45 negativity. PET-CT shows disease above and below the diaphragm without extranodal involvement, 4 nodal sites. Ann Arbor stage III. Bulk disease is absent. The standard chemotherapy regimen is:
159. A 55-year-old woman presents with anemia (Hb 7.2 g/dL), thrombocytopenia (platelets 48,000), and hepatosplenomegaly. Bone marrow biopsy shows 'dry tap' on aspiration. Trephine biopsy shows hypercellular marrow with reticulin fibrosis (grade MF-2) and abnormal megakaryocytes with cloud-like nuclei. JAK2 V617F is positive. The Dynamic International Prognostic Scoring System (DIPSS) category is determined by which parameters?