Unrelated Donor Allogeneic Transplantation after Failure of Autologous Transplantation for Acute Myelogenous Leukemia: A Study from the Center for International Blood and Marrow Transplantation Research

Abstract

The survival of relapsed acute myeloid leukemia (AML) after autologous hematopoietic stem cell transplantation (Autologous HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (Allo-HCT) from an unrelated donor (URD) using either myeloablative (n=242) or reduced-intensity conditioning regimens (RIC, n=60) reported to CIBMTR. After a median follow-up of 58 months (range 2–160), the probability of treatment-related mortality (TRM) was 44% (95%CI 38–50) at 1-year. The 5-year incidence of relapse and overall survival (OS) was 32% (95%CI 27–38) and 22% (95%CI 18–27), respectively. In multivariate analysis significantly better OS was observed with RIC regimens (Hazard Ratio (HR) 0.51, 95%CI 0.35–0.75, p<0.001), with Karnofsky performance status (KPS) ≥90% (HR 0.62, 95%CI 0.47–0.82, p=0.001) and in CMV-negative recipients (HR 0.64, 95%CI 0.44–0.94, p=0.022). Longer interval (>18 months) from Autologous HCT to URD Allo-HCT was associated with significantly lower Relapse risk (HR 0.19, 95%CI 0.09–0.38, p<0.001) and improved LFS (HR 0.53, 95%CI 0.34–0.84, p=0.006). URD Allo-HCT after Autologous HCT relapse results in 20% long-term leukemia-free survival, with best results with longer interval to secondary URD transplantation, KPS ≥90%, in complete remission, and using RIC regimens. Further efforts to reduce TRM and relapse are still needed.

Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia

“…Similarly, the current study showed that HCT-CI 3 was extracted as a dependent prognostic factor for poor OS and NRM within multivariate analysis. On the other hand, the current study indicated that poor KPS was associated with worse OS and higher incidence of relapse, as previously reported [23]. Results from the current study suggest that older age is not a contraindication for RIC allo-HSCT.…”

Comparison of Reduced-Intensity and Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: A Meta-Analysis

“…Moreover, this study included patients transplanted before 2005 (total patients 878) that has been mostly included in Martino 2006 (total patients 868). Foran, 2013 [60] This study included patients under the age of 13 years old. …”

Second reduced intensity conditioning allogeneic transplant as a rescue strategy for acute leukaemia patients who relapse after an initial RIC allogeneic transplantation: analysis of risk factors and treatment outcomes

“…3,5 However, because of its relatively low toxicity, a second RIC allogeneic stem cell transplantation (RIC2) is often the only feasible treatment option, and might be a valuable rescue strategy for a selected group of patients. Namely, a RIC2 HSCT has been shown to be associated with a low and acceptable non-relapse mortality (NRM) in patients who have undergone a previous autologous transplantation, 6,7 as well as in those who relapse after a previous allogeneic HSCT. 8 A retrospective study of the European Society for Blood and Marrow Transplantation (EBMT) registry data was performed to evaluate the outcome of RIC2 in terms of NRM and overall-and leukaemia-free survival (LFS), as well as to identify prognostic factors that determine the outcome of RIC2 in acute leukaemia patients.…”