Impact of Induction Regimen and of Allogeneic Hematopoietic Cell Transplantation on Outcome in Younger Adults Patients with Acute Myeloid Leukemia with a Monosomal Karyotype

Monosomal karyotype (MK) confers a poor prognosis in patients with acute myeloid leukemia (AML). Here, we determined the impact of the type of remission-induction chemotherapy and the impact of having a donor in younger AML patients with a MK included in two phase III trials. In the first trial, patients were randomized to receive either daunorubicin (DNR), mitoxantrone (MTX), or idarubicin (IDA) in addition to standard-dose cytarabine (SDAC) and etoposide for induction chemotherapy. In the second trial, patients were randomized between either SDAC or high dose cytarabine (HiDAC) induction, both with DNR and etoposide. In both trials, patients who achieved a complete remission with (CR) or without (CRi) complete hematological recovery received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) if they had a donor or an autologous HSCT (auto-HSCT) otherwise. In comparison to patients with intermediate risk cytogenetics without MK (n=1584) and with adverse cytogenetics without MK (n=218), MK+ patients (n=188) were more likely not to achieve a CR/CRi (odds ratio=2.85, 95% confidence interval, CI: 2.10-3.88) and had shorter overall survival (OS) (hazard ratio, HR=2.44, 95% CI: 2.08-2.88) and OS from CR/CRi (HR=2.73, 95% CI: 2.17-3.45). There was no impact of the type of anthracycline or of SDAC vs HiDAC on outcomes in MK+ patients. Among MK+ patients who achieved a CR/CRi, HLA-identical related donor availability was associated with longer survival from CR/CRi (HR=0.59, 95% CI: 0.37-0.95). In summary, these data suggest no benefit of HiDAC in MK+ patients but better OS associated with allo-HSCT.