Impact of Cytogenetics Risk on Outcome after Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) from An HLA Identical Sibling for Patients with Acute Myeloid Leukemia (AML) in First Complete Remission (CR1)

Abstract

Allo-SCT is a well established therapy for adult patients with AML. In the setting of standard myeloablative allo-SCT, the fear of early death as a result of the procedure led to the restriction of allo-SCT in CR1 to patients who presented with high risk AML features, especially taking into account the impact of cytogenetics risk on outcome determining standard (good)-, intermediate-, and poor-risk populations. In the last decade, RIC allo-SCT has emerged as an attractive modality to decrease toxicity and widen the spectrum of AML patients who are candidate to allo-SCT. However, the issue of possible higher relapse rates after RIC allo-SCT, and continuous improvements in non-allo-SCT strategies, raise concern about the utility of this approach in AML patients in CR1 (e.g. in comparison to intensive chemotherapy and new drugs). Of note, no large studies have yet assessed the impact of cytogenetics risk on outcome in the context of RIC allo-SCT. This report describes the results of 378 AML patients (185 males) transplanted in CR1 using a RIC regimen and reported to the EBMT registry between 2000 and 2007, and for whom detailed cytogenetics data were available. All patients received RIC allo-SCT from an HLA identical sibling. RIC was defined as Busulfan conditioning regimens containing < 8mg/kg total dose, or TBI <6 Gy: The median age at time of allo-SCT was 55 (range, 18–74) y. The median intervals from AML diagnosis to CR1 and from CR1 to RIC allo- SCT were 45 and 155 days respectively. In this series, 21 patients (6%) belonged to the good cytogenetics risk group, while 304 patients (80%) and 53 patients (14%) belonged to the intermediate and poor cytogenetics risk groups respectively. Age, year of transplant, WBC at diagnosis, gender, CMV serostatus, stem cell source, and RIC regimen type were comparable between all three groups. The M5-6-7 FAB subgroup was significantly higher in the poor risk group (30% vs. 20% in the intermediate group). With a median follow-up of 24 (range, 1–93) months, the KM estimates of 2 years leukemia-free survival (LFS) were 64+/−4, 57+/-3 and 38+/−7% in the good-, intermediate-, and poor-risk subgroups respectively (P=0.003). In multivariate analysis, cytogenetics was not significantly associated with non-relapse mortality. However, relapse incidence was significantly influenced by the cytogenetics risk groups (P=0.0001) and a higher WBC at diagnosis (P=0.001). Finally, LFS was significantly influenced by the cytogenetics risk groups (P=0.004), a higher WBC at diagnosis (P=0.006), and year of transplant (P=0.04). Despite its retrospective nature, results from this large study strongly suggest that RIC allo-SCT from an HLA-matched sibling donor is a valid option for AML patients in CR1 not eligible for standard allo-SCT. As it has been shown in the setting of myeloablative conditioning allo-SCT, patients from the poor cytogenetics risk group had increased relapse incidence and decreased LFS rate after RIC allo-SCT. Therefore, prospective strategies such as use of new drugs, intensification of conditioning regimen, post HST immunotherapy should be investigate to improve current results in this group.