Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

Abstract

T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow-up was 52 months from mutation detection and 26 months from transplantation. At transplantation, 51.5% of patients with chronic myeloid leukemia were in the chronic phase and 4.5% were in advanced phases. Median overall survival after transplantation was 10.3 months (range 5.7 months to not reached [ie, still alive]) for those with chronic myeloid leukemia in the blast phase and 7.4 months (range 1.4 months to not reached [ie, still alive]) for those with Philadelphia chromosome-positive acute lymphoblastic leukemia but has not yet been reached for those in the chronic and accelerated phases of chronic myeloid leukemia. The occurrence of chronic GVHD had a positive impact on overall survival (P = .047). Transplant-related mortality rates were low. Multivariate analysis identified only blast phase at transplantation (hazard ratio 3.68, P = .0011) and unrelated stem cell donor (hazard ratio 2.98, P = .011) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors.

Figures

Figure 1

Overall survival for patients harboring T315I mutated leukemias. (A) OS analysis for patients with CML in CP (bold solid line), AP (bold dashed line), or blast crisis (thin solid line) or with de novo Ph+ ALL (thin dashed line) since T315I ABL mutation detection who underwent allogeneic SCT. (B) OS analysis for patients with CML in CP (bold solid line), AP (AccP; bold dashed line), or blast crisis (BC; thin solid line) or with de novo Ph+ ALL (thin dashed line) since T315I ABL mutation detection in the overall cohort of patients with T315I mutation (Figure 2D in Nicolini et al) compared with panel A. (C) OS analysis for patients with CML in CP (bold solid line), AP (bold dashed line), or blast crisis (thin solid line) or with de novo Ph+ ALL (thin dashed line) since allogeneic SCT according to disease status at transplantation. Median OS has not been reached for CP and AP and was 10.3 months for BP (range 5.7 months to not reached) and 7.4 months for Ph+ ALL (range 1.4 months to not reached).