Allogeneic Transplantation In Chronic Myeloid Leukemia And The Effect Of Tyrosine Kinase Inhibitors On Survival, A Quasi-Experimental Study

Abstract

Objective: Tyrosine kinase inhibitors (TKIs) have changed the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia (CML). Therefore, we aimed to evaluate the effect of TKIs on allo-HSCT in CML. Materials and Methods: In this quasi-experimental study, we compared patient, disease, and transplantation characteristics as well as allo-HSCT outcomes between the pre-TKI era (before 2002) and the post-TKI era (2002 and later) in patients with CML. A total of 193 allo- HSCTs were performed between 1989 and 2012. Results: Patients in the post-TKI era had more advanced disease (>chronic phase 1) at the time of transplant and more frequently received reduced-intensity conditioning compared to patients in the pre-TKI era. Relapse/progression occurred more frequently in the year ≥2002 group than in the year <2002 group (48% vs. 32% at 5 years, p=0.01); however, overall survival (OS) was similar in these two groups (5-year survival was 50.8% vs. 59.5%, respectively; p=0.3). TKIs (with donor lymphocyte infusions or alone) for treatment of relapse after allo-HSCT were available in the post-TKI era and were associated with improved OS. While the rates of hematologic remission at 3 months after allo-HSCT were similar between TKI eras, patients having remission had better disease-free survival (DFS) [relative risk (RR): 0.15, confidence interval (CI) 95%: 0.09-0.24, p<0.001] and OS (RR: 0.14, CI 95%: 0.09-0.23, p<0.001). Male allo-HSCT recipients had worse DFS (RR: 1.7, CI 95%: 1.2-2.5, p=0.007) and OS (RR: 1.7, CI 95%: 1.1-2.6, p=0.02) than females. Conclusion: TKIs are an effective option for the treatment of relapse after allo-HSCT in CML. Hematologic remission after allo-HSCT is also an important factor for survival in CML patients.