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

被引:43
作者
Nicolini, Franck Emmanuel [1 ,2 ,3 ,4 ]
Basak, Grzegorz W. [4 ,5 ]
Soverini, Simona [6 ]
Martinelli, Giovanni [6 ]
Mauro, Michael J. [7 ]
Mueller, Martin C. [8 ]
Hochhaus, Andreas [9 ]
Chuah, Charles [10 ,11 ]
Dufva, Inge H. [12 ]
Rege-Cambrin, Giovanna [13 ]
Saglio, Giuseppe [4 ,13 ]
Michallet, Mauricette [1 ,2 ,3 ,4 ]
Labussiere, Helene [1 ,3 ]
Morisset, Stephane [1 ]
Hayette, Sandrine [2 ,14 ,15 ]
Etienne, Gabriel [2 ,16 ]
Olavarria, Eduardo [17 ]
Zhou, Wei [18 ]
Peter, Senaka [18 ]
Apperley, Jane F. [4 ,19 ]
Cortes, Jorge [20 ]
机构
[1] Hop Edouard Herriot, Dept Hematol, F-69437 Lyon 03, France
[2] Fi LMC Grp, French Grp CML, Poitiers, France
[3] SFGM TC, Bordeaux, France
[4] European Grp Blood & Marrow Transplantat, Leiden, Netherlands
[5] Med Univ Warsaw, Dept Hematol Oncol & Internal Dis, Warsaw, Poland
[6] Univ Bologna, Mol Biol Unit, Bologna, Italy
[7] Oregon Hlth & Sci Univ, Knight Canc Inst, Ctr Hematol Malignancies, Portland, OR 97201 USA
[8] Heidelberg Univ, Univ Med Mannheim, Med Klin 3, D-6800 Mannheim, Germany
[9] Univ Klinikum Jena, Jena, Germany
[10] Singapore Gen Hosp, Dept Hematol, Singapore 0316, Singapore
[11] Duke NUS Grad Med Sch, Canc & Stem Cell Biol Program, Singapore, Singapore
[12] Univ Copenhagen, Herlev Hosp, Dept Hematol, DK-2730 Herlev, Denmark
[13] Univ Turin, San Luigi Gonzaga Hosp, Turin, Italy
[14] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Hematol Lab, Pierre Benite, France
[15] UMR5239, Pierre Benite, France
[16] Inst Bergonie, Bordeaux, France
[17] Hosp Navarra Irunlarrea Sn, Serv Hematol, Pamplona, Spain
[18] Merck Res Labs, Dept Epidemiol, N Wales, PA USA
[19] Univ London Imperial Coll Sci Technol & Med, Ctr Haematol, London, England
[20] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
关键词
CHRONIC MYELOID-LEUKEMIA; RESISTANT; CML; HOMOHARRINGTONINE; INTERFERON; INHIBITORS; MUTATIONS;
D O I
10.1182/blood-2011-07-367326
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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). Trans-plant-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. (Blood. 2011;118(20):5697-5700)
引用
收藏
页码:5697 / 5700
页数:4
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