May 06, 2022
Test your knowledge of leukemia and cellular therapies with two multiple-choice questions from the ASCO Self-Evaluation Program (ASCO-SEP) on ASCO Education.
ASCO seeks to advance the education of all oncology professionals and ultimately facilitate and support enhanced patient care. The ASCO Oncology Self-Assessment Series on ASCO Connection consists of free case-based multiple-choice practice questions, educational links, and answer rationales. Questions are developed by a group of oncology experts in multiple tumor topic areas. The self-assessment questions are aligned with the American Board of Internal Medicine (ABIM)’s Medical Oncology blueprints and ASCO’s Medical Oncology In-Training Exam (ITE) blueprints.
Review the Education Essentials for Oncology Fellows (EEOF) package, which includes the ASCO Self-Evaluation Program (ASCO-SEP), hosted on ASCO Education for more online education.
Correct answers are listed at the bottom of the page
Question 1: Leukemia
A 55-year-old man presents to the emergency department with a two-week history of worsening shortness of breath, fatigue, and bleeding gums. He has no significant comorbidities, and his Eastern Cooperative Oncology Group (ECOG) performance status is 1. A complete blood count is performed, and he is noted to have a leukocyte count of 50 x 109/L, a hemoglobin level of 5.6 g/dL, and a platelet count of 5 x 109/L with 90% circulating blasts. A bone marrow biopsy revealed acute myeloid leukemia (AML) with a normal karyotype and an FLT3-ITD mutation with an allelic ratio of 0.75. Echocardiography showed an ejection fraction of 60% and is otherwise normal.
Which of the following treatment regimens should you recommend now?
- Daunorubicin, cytarabine, and midostaurin
- Azacitidine and venetoclax
- Single-agent gilteritinib
- Liposomal daunorubicin and cytarabine
Question 2: Cellular Therapies
A 45-year-old man was recently diagnosed with acute myeloid leukemia (AML). He initially presented to the clinic with shortness of breath and excessive bruising. A complete blood count at the time revealed a leukocyte count of 30,000/mm3, a hemoglobin level of 6 g/dL, and a platelet count of 16,000/mm3. A bone marrow biopsy revealed hypercellular marrow (90% cellularity) with 80% myeloblasts. Karyotype findings were consistent with t(6;9) and inv(3). On molecular testing, FLT3 internal tandem duplication and NPM1 were absent. The patient achieved complete remission after induction therapy with cytarabine and idarubicin (“7 + 3” regimen). His Eastern Cooperative Oncology Group (ECOG) performance status is 1.
Along with consolidation therapy using high-dose cytarabine, which is the most appropriate next step in management?
- Autologous stem cell transplant
- Allogeneic stem cell transplant
- Maintenance therapy
Question 1 Rationale and References
Correct answer: A. Daunorubicin, cytarabine, and midostaurin
Rationale: The addition of the multitargeted kinase inhibitor, midostaurin, when added to the standard "7 + 3" backbone has been shown to prolong overall survival and event-free survival. Azacitidine and venetoclax are an approved first-line regimen for patients who have newly diagnosed AML and are unfit for intensive induction chemotherapy or those who are older than 75 years. This patient is 55 years old with excellent performance status and normal ejection fraction with no significant comorbidities, making him a suitable candidate for intensive induction. Gilteritinib is a highly active oral FLT3 inhibitor approved for the treatment of relapsed or refractory FLT3-positive AML, not in the upfront setting as in this case. Liposomal daunorubicin and cytarabine have been shown to improve overall survival and event-free survival in patients with secondary or treatment-related AML or AML with myelodysplasia-related changes. In this case, there is no history of prior chemotherapy exposure, and cytogenetics are normal, excluding myelodysplasia-related changes.
- Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454-64. DOI: https://doi.org/10.1056/NEJMoa1614359
Question 2 Rationale and References
Correct answer: B. Allogeneic stem cell transplant
Rationale: Genetic abnormalities are an important prognostic factor in patients with newly diagnosed AML. AML can be classified into good, intermediate, and poor prognosis groups based on cytogenetics and molecular profiling of the disease. The presence of cytogenetic abnormalities such as inv(3), t(6;9), del(5q), del(7p), abnormalities involving chromosome 17, and complex karyotype confer poor prognosis. In the first remission, allogeneic stem cell transplant has been shown to improve outcomes (overall survival and relapse-free survival) in patients with intermediate- and high-risk newly diagnosed AML. Therefore, in this patient with good performance status and high-risk AML, allogeneic stem cell transplant after consolidation therapy is the most appropriate treatment option.
- Fenwarth L, Thomas X, de Botton S, et al. A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. Blood. 2021;137(4):524-32. DOI: https://doi.org/10.1182/blood.2020005524