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.

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

SAGLIO, Giuseppe;
2011-01-01

Abstract

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.
2011
118
20
5697
5700
http://bloodjournal.hematologylibrary.org/content/118/20/5697.full.pdf+html
Adolescent; Adult; Aged; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Fusion Proteins, bcr-abl; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Prognosis; Registries; Transplantation, Homologous; Young Adult; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematology; Biochemistry; Cell Biology; Immunology
Nicolini FE; Basak GW; Soverini S; Martinelli G; Mauro MJ; Müller MC; Hochhaus A; Chuah C; Dufva IH; Rege-Cambrin G; Saglio G; Michallet M; Labussière http://www.ncbi.nlm.nih.gov/pubmed 7 di 24 30/11/14 17:17 H; Morisset S; Hayette S; Etienne G; Olavarria E; Zhou W; Peter S; Apperley JF; Cortes J.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/157518
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