title: 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.
authors.affiliation: Hematology Department, Hôpital Edouard Herriot, 5 place d'Arsonval, Lyon, France. franck-emmanuel.nicolini@chu- lyon.fr
authors.forename: Franck Emmanuel
authors.initials: FE
authors.lastname: Nicolini
authors.forename: Grzegorz W
authors.initials: GW
authors.lastname: Basak
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mauro
authors.forename: Martin C
authors.initials: MC
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Charles
authors.initials: C
authors.lastname: Chuah
authors.forename: Inge H
authors.initials: IH
authors.lastname: Dufva
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rege-Cambrin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Saglio
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Hélène
authors.initials: H
authors.lastname: Labussière
authors.forename: Stéphane
authors.initials: S
authors.lastname: Morisset
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hayette
authors.forename: Gabriel
authors.initials: G
authors.lastname: Etienne
authors.forename: Eduardo
authors.initials: E
authors.lastname: Olavarria
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Senaka
authors.initials: S
authors.lastname: Peter
authors.forename: Jane F
authors.initials: JF
authors.lastname: Apperley
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006086:Graft vs Host Disease / Q000401:mortality*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012042:Registries / Q000706:statistics & numerical data; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D016044:Fusion Proteins, bcr-abl