Abstract
Therapy-related acute myeloid leukemia (t-AML) is a heterogeneous entity most frequently related to breast cancer or lymphoproliferative diseases (LD). Population-based studies have reported an increased risk of t-AML after treatment of lymphomas. The aim of this study was to describe the characteristics and outcome of 80 consecutive cases of t-AML following treatment of LD. t-AML accounted for 2.3% of all AML cases, occurred 60 months after LD diagnosis, and were characterized by a high frequency of FAB M6 AML and poor-risk cytogenetic abnormalities. Time to t-AML diagnosis was influenced by patient age, type of LD, and treatment. Among the 48 t-AML patients treated with intensive chemotherapy, median overall survival (OS) was 7.7 months compared to 26.1 months in de novo, 4.2 months in post-myeloproliferative neoplasm, 9.4 months in post-myelodysplastic syndrome, 8.6 months in post-chronic myelomonocytic leukemia AML, 13.4 months in t-AML secondary to the treatment of solid cancer, and 14.7 months in breast cancer only. OS of post-LD t-AML patients was significantly influenced by age, performance status, myelodysplastic syndrome prior to LD/t-AML, and treatment regimen for LD. Thus, t-AML following lymphoid malignancies treatment should be considered as very high-risk secondary AML. New treatment strategies in patients with LD/t-AML are needed urgently.
Highlights
Therapy-related acute myeloid leukemia (t-AML) is described in the WHO classification [1,2] as AML occurring after a previous cancer whose treatment comprises mainly an alkylating agent, ionizing radiation therapy – giving rise to chromosome 5 or 7 abnormalities, and/or topoisomerase II inhibitor – generating balanced translocations, including t(15;17) [3] or 11q23 [MLL] rearrangements among others
Among the 48 t-AML patients treated with intensive chemotherapy, median overall survival (OS) was 7.7 months compared to 26.1 months in de novo, 4.2 months in post-myeloproliferative neoplasm, 9.4 months in post-myelodysplastic syndrome, 8.6 months in post-chronic myelomonocytic leukemia AML, 13.4 months in t-AML secondary to the treatment of solid cancer, and 14.7 months in breast cancer only
Www.impactjournals.com/oncotarget almost all other alkylating agents have been associated with an increased risk of t-AML in patients treated for a wide spectrum of diseases [5] whereas topoisomerase II inhibitors were first associated with secondary AML in children who received epipodophyllotoxins for acute lymphoblastic leukemia [6]
Summary
Therapy-related acute myeloid leukemia (t-AML) is described in the WHO classification [1,2] as AML occurring after a previous cancer whose treatment comprises mainly an alkylating agent, ionizing radiation therapy – giving rise to chromosome 5 or 7 abnormalities, and/or topoisomerase II inhibitor – generating balanced translocations, including t(15;17) [3] or 11q23 [MLL] rearrangements among others. Www.impactjournals.com/oncotarget almost all other alkylating agents have been associated with an increased risk of t-AML in patients treated for a wide spectrum of diseases [5] whereas topoisomerase II inhibitors were first associated with secondary AML in children who received epipodophyllotoxins for acute lymphoblastic leukemia [6]. Individualization of this category of AML permitted to emphasize the distinct biological and clinical features of this entity typically characterized by an adverse outcome [7]. It has been shown that cytotoxic therapy favors the expansion of rare hematopoietic stem cells carrying TP53 mutations in a founding clone that expands preferentially after therapy and evolves to leukemia through the accumulation of chromosomal abnormalities found typically in t-AML [9]
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