Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia.

This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P =0.04) and was associated with lower relapse incidence (HR=0.5; P =0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P =0.002) and overall survival (HR=0.42; P =0.004), and a lower relapse incidence (HR=0.40; P =0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting. overall survival (OS), acute graft- versus -host disease (aGvHD) and chronic graft- versus -host-disease (cGvHD). Patient-related, disease-related, and transplant-related variables were compared between the 2 groups receiving or not TKI before transplantation using the χ 2 statistics for categorical variables and the Mann-Whitney test for continuous variables. Factors that dif-fered significantly between the two groups with P values less than 0.05, and all factors associated with a P value less than 0.10 by univariate analysis were included in the final models. Cumulative incidence functions (CIF) to estimate RI and NRM in a competing risk setting, because death and relapse compete with each To study cGvHD, we considered relapse and death to be competing events. Probabilities of LFS and OS were calculated using Kaplan-Meier Univariate analyses were performed using Gray’s test for CIF and the log rank test for LFS and OS. Associations of patients’ and graft characteristics with outcomes were evaluated in multivariate analysis, using Cox propor-tional hazards model. In order to assess the possible impact of acute GvHD, chronic GvHD and use of up-front prophylactic TKI after transplant on outcome, we used a Cox model with time-dependent variables. outcomes. Statistical analyses performed and (R tive factors against relapse. Two other “post transplant” factors were associated with lower RI in multivariate analysis: TKIs post transplant in prophylaxis (HR=0.40; 95%CI: 0.21-0.76; P =0.01) and aGvHD grade II or over (HR=0.45; 95%CI: 0.29-0.71; P =0.001). The use of an RIC regimen (HR=1.69; 95%CI: 1.08-2.65; P =0.02) and higher WBC at diagnosis (HR=1.003; 95%CI: 1.002-1.005; P =0.0002) remained a significant risk factor for higher RI. post-transplant no in and LFS who received an RIC regimen a regimen. that RIC is a valid option for for