Complex karyotype, older age, and reduced first‐line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long‐term follow‐up

Abstract

Approximately 40% of patients affected by core binding factor (CBF) acute myeloid leukemia (AML) ultimately die from the disease. Few prognostic markers have been identified. We reviewed 192 patients with CBF AML, treated with curative intent (age, 15-79 years) in 11 Italian institutions. Overall, 10-year overall survival (OS), disease-free survival (DFS), and event-free survival were 63.9%, 54.8%, and 49.9%, respectively; patients with the t(8;21) and inv(16) chromosomal rearrangements exhibited significant differences at diagnosis. Despite similar high complete remission (CR) rate, patients with inv(16) experienced superior DFS and a high chance of achieving a second CR, often leading to prolonged OS also after relapse. We found that a complex karyotype (i.e., 4 cytogenetic anomalies) affected survival, even if only in univariate analysis; the KIT D816 mutation predicted worse prognosis, but only in patients with the t(8;21) rearrangement, whereas FLT3 mutations had no prognostic impact. We then observed increasingly better survival with more intense first-line therapy, in some high-risk patients including autologous or allogeneic hematopoietic stem cell transplantation. In multivariate analysis, age, severe thrombocytopenia, elevated lactate dehydrogenase levels, and failure to achieve CR after induction independently predicted longer OS, whereas complex karyotype predicted shorter OS only in univariate analysis. The achievement of minimal residual disease negativity predicted better OS and DFS. Long-term survival was observed also in a minority of elderly patients who received intensive consolidation. All considered, we identified among CBF AML patients a subgroup with poorer prognosis who might benefit from more intense first-line treatment.

Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT

“…There is evidence indicating that auto-HSCT is able to significantly reduce relapse risk in AML with favorable cytogenetics, which still carry disease recurrence rates up to 35–40 % following conventional chemotherapy, with a particular risk for core-binding factor (CBF) AML with adverse prognostic features [39] or positive MRD after consolidation chemotherapy [40]. Further, there is data suggesting that in NPM1-mutated and CEBPA double-mutated (CEBPAdm) AML, the high chemosensitivity of the disease might be exploited with auto-HSCT intensification [41, 42].…”

Results of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia with t(8;21)(q22;q22)/RUNX1-RUNX1T1 and Additional Cytogenetic Abnormalities

“…К настоящему времени к прогностически неблагоприятным факторам относятся наличие дополнительных хромосомных нарушений, прежде всего делеции del(9)(q22), трисомии некоторых хромосом, а также сложные нарушения кариотипа [2,3,[10][11][12][13][14]. Что же касается молекулярных маркеров, то про-гностически неблагоприятными являются мутации генов ASXL, BAALC, c-KIT, FLT3 [3,13].…”

Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia

“…Complex cytogenetic abnormalities are also found in CBF-AML and have been shown to adversely affect long-term survival in some studies. 33,34 Interestingly, we observed that among our CBF-AML patients (n=27), lower HLTF expressors also had more secondary chromosome abnormalities (1.46 vs. 0.5) and higher chances of carrying a complex karyotype (23% vs. 0%) involving three or more additional aberrations than higher HLTF expressors. These observations suggest broad impacts of HLTF reduction on chromosomal instability across AML subtypes.…”