scholarly journals Immunological effects of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or philadelphia chromosome-positive acute lymphoblastic leukemia

Oncotarget ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 418-429 ◽  
Author(s):  
Nira Varda-Bloom ◽  
Ivetta Danylesko ◽  
Roni Shouval ◽  
Shiran Eldror ◽  
Atar Lev ◽  
...  
Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5697-5700 ◽  
Author(s):  
Franck Emmanuel Nicolini ◽  
Grzegorz W. Basak ◽  
Simona Soverini ◽  
Giovanni Martinelli ◽  
Michael J. Mauro ◽  
...  

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-ABLT315I 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-ABLT315I mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6533-6533
Author(s):  
Satoshi Nishiwaki ◽  
Koichi Miyamura ◽  
Kazuteru Ohashi ◽  
Mineo Kurokawa ◽  
Shuichi Taniguchi ◽  
...  

6533 Background: Although allogeneic stem cell transplantation (allo-SCT) could improve the outcome of adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source, particularly the position of cord blood (CB) transplantation, is still uncertain. Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients transplanted at the first time between 1998 and 2009 with myeloablative preparative regimens who were registered in the Japan Society for Hematopoietic Cell Transplantation database. Two hundred and thirty-three received CB transplantation [first complete remission (CR1): 95, subsequent CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor (URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR: 207). Results: Overall survival (OS) in patients after CB transplantation in CR1 was comparable with that after allo-SCT from URD or RD [57% in CB, 64% in URD, and 65% in RD at 4 years, respectively, P=0.11]. Donor source was not a significant risk factor for OS in multivariate analysis. Although URD was a favorable factor for relapse and an unfavorable factor for non-relapse mortality (NRM), CB was not a significant factor for them [Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively (P=0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years, respectively (P=0.0001)]. Among CB recipients in CR1, age at allo-SCT (45 years or older) was solely a significant adverse prognostic factor in multivariate analysis. Among patients younger than 45 years who received allo-SCT in CR1, OS after CB transplantation was significantly better than that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%, P=0.04). Similarly, OS was not different by donor source in subsequent CR or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD, P=0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P=0.20 at 4 years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes as either RD or URD in any disease status. CB transplantation is a good alternative for adult Ph(-) ALL patients without a suitable RD or URD.


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