Tyrosine kinase inhibitors: relapse prophylaxis after allogeneic hematopoietic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia

Cellular Therapy and Transplantation

article

Kseniia S. Afanaseva¹  Olga V. Pirogova¹  Evgeny A. Bakin¹  Anna G. Smirnova¹  Elena V. Morozova¹  Yulia Yu.Vlasova¹  Ildar M. Barkhatov¹  Tatiana L. Gindina¹  Ivan S. Moiseev¹  Sergey N. Bondarenko¹ 

[1] RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University

关键词: Acute lymphoblastic leukemia;    Ph-positive;    BCR-ABL1;    tyrosine kinase inhibitor;    allogeneic hematopoietic stem cell transplantation;    relapse;    minimal residual disease;    chronic GvHD.;   

DOI  :  10.18620/ctt-1866-8836-2022-11-3-4-45-59

学科分类：肿瘤学

来源: Universitaetsklinikum Hamburg - Eppendorf / University Medical Center Hamburg - Eppendorf

【 摘 要 】

The role of prophylactic TKIs after allogeneic stem cell transplantation in Ph-positive acute lymphoblastic leukemia (ALL) remains controversial. We performed a retrospective study in 106 adult patients subjected to allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched related donors (MRD, 26%), matched unrelated donors (MUD/MMUD, 60%), and haploidentical donors (14%) in complete remission (CR1, 59%), CR2 (14%), and advanced disease (27%). Among them, 60 (57%), received 1st- or 2nd-generation TKIs as prophylaxis after allo-HSCT. In multivariate analysis of RFS, the following factors were associated with reduced risk of relapse or death: allo-HSCT after 2012 (HR=0.46, 95%CI 0.26-0.83, p=0.009), any MRD status of the disease before allo-HSCT except active disease with relatively similar HR in the context of post-transplant TKI prophylaxis. Allo-HSCT from haploidentical donor was associated with increased risk of relapse or death (HR=2.71, 95% CI 1.20-6.13 p=0.016). We were unable to demonstrate the significance of chronic GvHD when performing landmark analysis on day+180 and day+270, as based on available data (HR=0.43, 95% CI 0.13-1.45, p=0.17 and HR=0.5, 95% CI 0.19-1.32; p=0.161, respectively), under the conditions of maintaining TKI therapy after allo-HSCT. This relatively large study in unfavorable group of patients confirms an importance of TKIs prophylaxis for adult patients with Ph-positive ALL after allo-HSCT. A larger group of patients is required to formulate strong clinical recommendations in this cohort.

【 授权许可】

CC BY