Alternative donor peripheral blood stem cell transplantation for the treatment of high-risk refractory and/or relapsed childhood acute leukemia: a randomized trial

BACKGROUND: The high-risk refractory and/or relapsed (R/R) childhood acute leukemia prognosis is poor, and allogeneic stem cell transplantation (allo-HSCT) is the most prudent treatment modality. However, there are limited matched sibling donors (MSDs), and alternative donors (ADs) are the main source for allo-HSCT. Thus, we evaluated the clinical efficacy of AD peripheral allo-HSCT for treating high-risk R/R childhood acute leukemia. METHODS: We assessed 111 children who underwent allo-HSCT at the Affiliated Cancer Hospital of Zhengzhou University between October 2006 and July 2019. The patients were divided in the MSD and AD groups, and their clinical characteristics, complications, and survival rates were compared. RESULTS: The cumulative incidences of Epstein–Barr virus and cytomegalovirus infections were significantly higher in the AD than in the MSD group (P < 0.001); however, the recurrence and mortality rates were significantly higher in the MSD than in the AD group (P < 0.05). Furthermore, the 5-year disease-free (DFS) (65.2% vs. 43.3%, P = 0.033) and overall survival (OS) rates (71.6% vs. 53.8%, P = 0.053) were significantly higher in the AD than in the MSD group. In the AD group, the grade II–IV acute graft-versus-host disease (aGVHD), donor-recipient ABO compatibility, conditioning regimen, and CMV infection affected the 5-year OS. The grade II–IV aGVHD also affected the 5-year DFS; however, only the donor-recipient ABO compatibility affected the 5-year DFS. The donor MSD (HR: 2.035, 95% confidence interval [CI] 1.057–3.920, P = 0.034) and the grade II–IV aGVHD (HR: 2.914, 95% CI 1.261–6.736, P = 0.012) affected the 5-year DFS of childhood acute leukemia after allo-HSCT, and the grade II–IV aGVHD (HR: 3.016, 95% CI 1.217–7.473, P = 0.017) affected the 5-year OS. Moreover, the donor source (HR: 2.836, 95% CI 1.179–6.823, P = 0.020) and grade II–IV aGVHD (HR: 3.731, 95% CI 1.332–10.454, P = 0.012) were independent predictors of the 5-year DFS, while the latter (HR: 3.524, 95% CI 1.310–10.988, P = 0.030) was an independent predictor of the 5-year OS. CONCLUSIONS: AD-PBSCT was effective for high-risk R/R childhood leukemia and may have better clinical outcomes than MSD-PBSCT; thus, it can be used as first-line treatment for high-risk R/R childhood leukemia.