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MK in EORTC/GIMEMA AML-10&12
donor for an allogeneic HSCT prolonged OS.7,23 Interestingly, we made similar findings in patients with MK+, suggesting a positive impact of allogeneic HSCT in this population of patients with a generally poor outcome. To our knowledge, our study is the first to investigate the impact of allogeneic HSCT in MK+ patients using a donor versus no donor comparison (which is considered as the gold-standard technique to address this question when donor availability is prospectively collected). These results were further confirmed in a Cox model handling allogeneic HSCT as a time-varying covariate and by comparing patients who received an allogeneic transplant from an HLA-matched related donor with those who received an autologous transplant. The three approaches, which are based on different assumptions, consistently indicated a positive impact of allogeneic HSCT. Among 20 patients who underwent allogeneic HSCT from an HLA-matched related donor, two were still alive and in follow-up 10 years after reaching CR, indicating a curative potential of the treatment. Importantly, our results are concordant with prior results from Kayser et al., who observed that allo-
AB
geneic HSCT prolonged OS in younger (18-60 years of age) MK+ AML patients (using Mantel-Byar analysis)13, as well as with a recent publication by Cornelissen et al., who demonstrated better leukemia-free survival in younger MK+ AML patients offered allogeneic HSCT (using a time- dependent Cox analysis).18 This is also concordant with previous studies showing that, although the prognosis of MK+ patients remains worse than that of MK– patients after transplantation, they have a 3-4 year OS probability rang- ing from 25% to 34%.24,25 Interestingly, a study by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation observed relatively comparable relapse incidence (HR=1.3, 95% CI: 0.7-2.6) and OS (HR=0.9, 95% CI: 0.5-1.6) in MK+ patients given grafts after reduced-intensity or myeloablative condition- ing.25 This suggests that cure of MK+ patients after allogene- ic HSCT might depend on immune-mediated graft-versus- tumor effects rather than on the intensity of the condition- ing regimen.26
In summary, this retrospective analysis of two large prospective phase III trials confirmed the poor outcome of
CD
Figure 2. Impact of cytogenetic risk on overall survival and impact of randomization in patients with a monosomal karyotype. (A) Overall survival (OS) according to cytogenetic risk group. (B) OS from complete remission/complete remission with incomplete blood count recovery according to cytogenetic risk group. (C) OS according to randomized induction therapy in the AML-10 trial among patients with a monosomal karyotype. (D) OS according to randomized induction therapy in the AML-12 trial among patients with a monosomal karyotype. MK: monosomal karyotype; 95% CI: 95% confidence interval; NotAdvMK–: not adverse cytogenetics excluding a monosomal karyotype; AdvMK–: adverse cytogenetics excluding a monosomal karyotype; MK+: monosomal karyotype.; DNR: daunorubicin; IDA: idaru- bicin; MTX: Methotrexate.
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