Autologous Hematopoietic Cell Transplantation (HCT) Is Superior To Allogeneic Transplantation For Acute Promyelocytic Leukemia In Second Complete Remission (CR2)

Abstract

Acute promyelocytic leukemia (APL) is often curable in adults. However, in 10-20% of patients with initial remission, leukemic relapse occurs. For these patients extended disease free survival is possible following stem cell infusion during second complete remission (CR2). The choice between allogeneic and autologous transplantion is dependent on the availability of suitable donors, the presence of minimal residual disease (MRD) and comorbid illnesses. The risks of treatment related mortality (TRM) associated with allografts must be balanced against a possible higher recurrence rate when autografts are used. To compare the utility of allogeneic and autologous transplantation in the arsenic era, we reviewed 294 patients with APL undergoing HCT in CR2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2006. Outcomes included overall survival (OS), disease free survival (DFS), relapse incidence, and TRM following either allogeneic or autologous HCT. The influence of pre-HCT molecular MRD status on outcome was examined in 114/232 allogeneic grafts and 41/62 autologous grafts. As summarized in Table 1, OS significantly favored autologous transplant, largely related to differences in TRM. Multivariate analysis confirmed that treatment failure was increased with age >40 years (HR=2.30, 95% CI 1.44-3.67, p= 0.0005), and after allogeneic HCT (HR=1.88, 95% CI=1.16-3.06, p=0.011). OS was significantly worse with allogeneic vs. autologous HCT (HR= 2.66, 95%CI 1.52-4.65, p=0.0006; age >40 (HR=3.29, 95% CI 1.95-5.54, p<0.001) and short CR1 (HR=1.56 95% CI 1.07-2.26, p=0.021). Relapse rates (RR) at 5 years were similar after autologous 30% (95% CI 19-42%) vs. allogeneic HCT (18% (95% CI 14-24%); adjusted HR=0.71, 95%CI 0.4-1.28, p=0.26). As expected, TRM in allogeneic was significantly higher at 31% (25-37) compared to autologous 7 % (2-17) with a HR of 7.07(2.56-19.57) P=0.0002. These results are summarized in Table 1. In patients with pre-HCT positive molecular or cytogenetic MRD, the allogeneic group (n=17) had a 5 year relapse rate of 27%, DFS 60%, and OS 65%. Notably, in MRD+ autologous group (n=6), only 1 relapsed at 6 months and died; 5 remain alive and disease-free at 47, 60, 61, 72, and 129 months after HCT. Surprisingly, pre-HCT molecular status did not influence relapse, treatment failure or OS in either group. Although the mechanism is not clear, this observation suggests effective eradication of residual disease in vivo. In this diverse cohort of patients, this retrospective study identifies that autologous transplantation offers superior overall survival when compared to allogeneic transplantation. The finding of long term survival in autologous transplanted patients with MRD+ grafting remains an important subject for further study.Table 1Outcome of Patients with APL Undergoing HCT in C2OutcomeAutoAlloP-valueOS54%(48-61)75%(68-85)0.02TRM31%(25-37)7%(2-17)<0.0001DFS50%(44-57)63%(49-75)0.10RR18%(14-24)30%(19-42)0.40 [Display omitted] Disclosures:No relevant conflicts of interest to declare.