Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy

Treatment-related myelodysplastic syndrome/acute myeloid leukemia in survivors of childhood cancer – An update

“…In a study of adults with t-MDS/t-AML previously treated with mitoxantrone (topoisomerase II inhibitor) for ALL, abnormalities involving chromosome arms 7q, 20q, 1q and 13q were found. In that study, no patient developed an abnormality of 11q23 [50], a contrast to findings of most pediatric studies where 11q23 abnormalities are relatively common. Most children with t-MDS/t-AML have cytogenetic abnormalities, perhaps related to the reluctance to diagnose refractory anemia without evidence of a clonal abnormality.…”

“…In addition, blood and bone marrow of some patients following stem cell transplantation may have dysplastic features [47,48] without evolution to fulfil the diagnostic criteria for MDS/AML [41,48]. Such patients may have evidence of transient abnormal clonal hematopoiesis [49,50]. These changes compound the difficulty of diagnosing treatment-related leukemia following a primary (de novo) MDS/AML.…”

Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML

“…Interestingly, studies have reported cases of AML relapsing with a karyotype incompatible with the AML present at diagnosis, suggesting that, in some cases, relapsed AML may arise from a hematopoietic cell unrelated to the initial AML. [20][21][22][23][24] Given the sensitivity limitations of next-generation sequencing and the difficulty in distinguishing rising clones from coexisting persistent leukemia-related populations, this study likely underestimates the genetic complexity of patients with AML after induction therapy. Additional patients and longer follow-up are needed to define the extent and prognostic implications of nonleukemic clonal expansion following AML therapy.…”

Toxicity of the topoisomerase II inhibitors

“…In recent reports, chromosomal changes that are more typical following alkylating agents (-5 and -7) were noted in patients who had received topoisomerase II inhibitors without alkylating agents [100].…”