Therapy-related myelodysplastic syndrome–acute myelogenous leukemia in patients treated for acute promyelocytic leukemia: an emerging problem

Abstract

The use of all-trans retinoic acid (ATRA) in combination with chemotherapy has markedly improved the prognosis for patients with acute promyelocytic leukemia (APL); the higher complete remission (CR) and survival rates now reported in this disease almost approach those obtained for other highly curable hematologic malignancies. Of 77 patients with APL who were consecutively treated at a single institution and who achieved CR after induction and consolidation therapy, 5 (6.5%) acquired therapy-related myelodysplasia (tMDS), acute myelogenous leukemia (AML), or both (tMDS-AML). Of these,

Severe Aplastic Anemia Manifesting After Complete Remission of Acute Promyelocytic Leukemia: Is it a Fortuitous Association?

“…Moreover, Nabhan and Radhakrishnan, [13] in their review article emphasized the fact that no published literature exists till date implicating 6-MP or methotrexate in causing severe AA even when these agents were employed for therapy of other disorders. Also Latagliata and co-authors in their report of five cases of t-MDS-AML following APL treatment in a cohort of 77 patients who achieved CR, suggested that APL treatment is not relevant in inducing the onset of secondary non-hematological malignancies [14].…”

“…The evolution of other clonal disorders such as PNH, MDS and AML in AA patients treated with immunosuppressive therapy has since been well recognized [3,4,6]. Similarly secondary MDS or AML developing following treatment of APL is also documented in the literature [10,14]. A primary insult to the bone marrow could simultaneously lead to several abnormal hematopoietic cell clones, with one dominating and others present below the threshold of detection.…”

Chronic Myeloid Leukemia Developing After Successful Treatment of Acute Promyelocytic Leukemia

“…In APL patients, t-MDS and t-AML are sporadically reported [1,2], which were observed in about 6.5 % patients [3]. Patients usually developed t-MDS or t-AML with a latency ranging from 22 to 46 months after receiving chemotherapy [3].…”

“…Patients usually developed t-MDS or t-AML with a latency ranging from 22 to 46 months after receiving chemotherapy [3]. Cytogenetic abnormalities such as losses or deletions of chromosome 7 and/or 5 and recurrent balanced translocations involving 11q23 and 21q22 are frequently observed in t-AML and t-MDS, and are regarded as important hallmarks for the diagnosis of these two entities [4].…”

Loss of response to azacitidine is associated with deletion 12p13 in a patient with myelodysplastic syndrome with unique translocation t(13;17)(q12;q25) after prior breast cancer and acute promyelocytic leukemia

“…With increasingly successful treatment of malignancies, therapy-related leukemia (TRL) and myelodysplastic syndrome (MDS) are increasingly observed, especially in association with prior radiotherapy, use of alkylating agents or topoisomerase-II inhibitors [1,2]. They are characterized by lesions of chromosomes 5 and 7 and poor survival (median 7-10 months) [3,4].…”