Allogeneic stem cell transplantation for children and adolescents/young adults with de novo blastic phase chronic myeloid leukemia in the tyrosine kinase inhibitor era

Abstract

Chronic myeloid leukemia (CML) incidence increases with age, thus the disease is rare during childhood, comprising 2%-3% of childhood leukemia. 1 At diagnosis, the vast majority of children with CML present in chronic phase (CP); thus, children or adolescents/young adults (AYAs) diagnosed with blastic phase CML (de novo CML-BP) are extremely rare. 2 While tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with CML, hematopoietic stem cell transplantation (HSCT) still plays an important role for some high-risk patients.However, few studies have investigated prognostic factors related to HSCT outcomes for children with CML in the TKI era, 3,4 and those focusing on de novo CML-BP are even more limited.Here, we investigated the characteristics and outcomes of 165 patients diagnosed with de novo CML-BP under 40 years old who received TKI treatment and their first HSCT between 2000 and 2019 in Japan. Details for methods are provided in Supplementary Methods S1.Characteristics of patients included in this study are presented in Table S1. The median follow-up period of survivors was 5.0 years after HSCT (range, 0.2-15.9 years). Comparison of the characteristics of children (0-17 years old) and AYA patients (18-39 years old) demonstrated that the former received donor-recipient sex mismatched HSCT more frequently and were more likely to undergo HSCT with better disease status. Median time from diagnosis to HSCT did not differ significantly between the two age. Among the 165 patients, 17 received reduced-intensity conditioning (RIC) before HSCT, and information on reasons for choosing a RIC regimen was available for 9 patients. The most frequent reason was patient complications present at the time of HSCT (n = 6), and the second most common reason was to avoid future long-term complications (n = 3).Five-year event-free survival (EFS) of all included patients was 64.1% (95% confidence interval [CI], 55.9%-71.2%), and 5-year overall survival (OS) was 70.3% (95% CI, 62.0%-77.1%). Cumulative incidence of relapse at 5 years was 21.2% (95% CI, 15.2%-27.9%), and cumulative incidence of non-relapse mortality at 5 years was 14.7% (95% CI, 9.5%-20.9%). These outcomes did not differ significantly between children and AYA patients as the 5-year EFS of children was 72.6% (95% CI, 55.1%-84.2%), and that of AYA patients was 61.7% (95% CI, 52.2%-69.9%; p = .226; Figure 1A), and the 5-year OS did not differ between them ( p = .507; Figure 1B). Causes of death were