AML-248: Clinico-Pathological Profile of Therapy-Related Acute Myeloid Leukemia

Abstract

<h3>Context:</h3> Secondary acute myeloid leukemia (sAML) may arise from a previous clonal disorder of hematopoiesis, usually from myelodysplastic syndrome, chronic myeloproliferative neoplasm, or as a complication in patients receiving chemotherapy or radiotherapy for a primary malignancy, including hematological and non-hematological/solid malignancies (therapy-related AML [t-AML]). Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. It is associated with specific clinical features with a uniformly poor prognosis. <h3>Objective:</h3> To study patients of t-AML with respect to clinical presentation, laboratory parameters (including flow cytometry immunophenotyping), cytogenetic and molecular studies, and clinical outcome. <h3>Design:</h3> This study was a retrospective analysis of patients of t-AML from January 2011 to December 2019. <h3>Patients:</h3> The patients underwent a detailed hematological work up: peripheral blood smear, bone marrow examination along with flow cytometric immunophenotyping, and karyotyping and molecular studies (NPM1, FLT3ITD/TKD, BCR/ABL, PML/RARA, INV16, AML-ETO). Outcomes of the patients were also reviewed. <h3>Results:</h3> A total of 20 cases of therapy-related AML were diagnosed in patients treated for various malignancies of the breast (9 cases), prostate (3 cases), and pancreas (2 cases), as well as lymphomas (NHL: 4 cases and HL: 2 cases). There were 7 males and 13 females (M:F: 1:1.85) with a median age of 63 years (range 35–82 years). Median latency period to t-AML was 3.5 years (range 0.5–11.0 years). Median haemoglobin was 72.5 g/L (61–151 g/L), WBC count 3.7× 10⁹/L (1.02–169.1×10⁹/L), platelet count 40 × 10⁹/L (12–257 ×10⁹/L, peripheral blood and bone marrow blast percentage 48% (5-98%) and 76% (20–98%), respectively. AML with monocytic differentiation was the most common morphological and flow cytometric subtype (50% cases). Complex karyotype was seen in 50% cases. Molecular studies for NPM, FLT3ITD/TKD, PML/RARA, AML-ETO, and INV16 showed 8 cases with NPM1 positivity and 4 case with FLT3ITD positivity. Only 4 patients (20%) achieved complete remission but relapsed within 1 year of duration. Ten patients succumbed to their disease, the majority within 1 year of t-AML diagnosis. <h3>Conclusion:</h3> The study highlights the development of therapy-related AML following chemotherapy and/or radiotherapy as an important therapy-related complication. The latency period and clinical manifestations may differ depending on the type of cytotoxic drug, cumulative dose, and dose intensity. A close hematological follow-up should always be done for an accurate and timely diagnosis.