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

E Brissot, M Labopin, MM Beckers, G Socie, A Rambaldi, L Volin, J Finke, S Lenhoff, N Kroger, GJ Ossenkoppele, CF Craddock, I Yakoub-Agha, G Gurman, NH Russell, M Aljurf, MN Potter, A Nagler, O Ottmann, Jan Cornelissen, J EsteveM Mohty

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Abstract

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 leukemiafree 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.
Original languageUndefined/Unknown
Pages (from-to)392-399
Number of pages8
JournalHaematologica
Volume100
Issue number3
DOIs
Publication statusPublished - 2015

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