Transplant Cell Ther. 2022 Jan 9:S2666-6367(22)00002-1. doi: 10.1016/j.jtct.2022.01.002. Online ahead of print.
ABSTRACT
Haploidentical related donor (HRD) is a common alternative donor strategy used when matched sibling or unrelated donors are not available for hematopoietic stem cell transplantation (HSCT). However, there have been no studies comparing HRD HSCT with post-transplant cyclophosphamide (PTCy) and matched unrelated donor (MUD) HSCT with antithymocyte globulin, using similar busulfan-based myeloablative conditioning regimen in pediatric acute leukemia. Here, we compared the outcomes in children and adolescents with high-risk acute leukemia after HRD HSCT with PTCy (n=35) and MUD HSCT (n=45) after targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring. The median follow-up times of the HRD and MUD groups were 3.7 and 4.6 years, respectively. No engraftment failure was observed in both groups. The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV (34.3% versus 48.9%, p=0.142), grades III-IV (2.9% vs. 8.9%, p=0.272), moderate to severe chronic GVHD (11.4% vs. 18.3%, p=0.417), relapse (25.6% vs. 28.0%, p=0.832), and non-relapse mortality (0% vs. 2.2%, p=0.420) were not significantly different between the two groups. The 3-year severe chronic GVHD-free/relapse-free (GRFS), leukemia-free (LFS) and overall survival (OS) rates in the HRD and MUD groups were 62.9% (95% confidence intervals [CI], 45.8%, 80.0%) versus 49.8% (95% CI, 34.9%, 64.7%; p=0.318), 74.4% (95% CI, 58.7%, 90.1%) versus 67.5% (95% CI, 53.4%, 81.6%; p=0.585), and 88.6% (95% CI, 78.0%, 99.2%) versus 83.7% (95% CI, 72.5%, 94.9%; p=0.968), respectively. In a subgroup analysis of acute lymphoblastic leukemia patients (HRD, n=17; MUD, n=26), the 3-year GRFS, LFS, and OS rates of the HRD and MUD groups were 49.4% (95% CI, 24.3%, 74.5%) versus 39.5% (95% CI, 19.7%, 59.3%; p=0.601), 61.8% (95% CI, 37.5%, 86.1%) versus 63.6% (95% CI, 44.4%, 82.8%; p=0.872), and 82.4% (95% CI, 64.4%, 100%) versus 84.2% (95% CI, 70.1%, 98.3%; p=0.445), respectively. In acute myeloid leukemia patients (HRD, n=16; MUD, n=16), the 3-year GRFS, LFS, and OS rates of the HRD and MUD groups were 80.8% (95% CI, 61.2%, 100%) versus 61.9% (95% CI, 37.8%, 86.0%; p=0.326), 87.1% (95% CI, 70.2%, 100%) versus 73.9% (95% CI, 51.8%, 96.0%; p=0.478), and 93.8% (95% CI, 81.8%, 100%) versus 85.6% (95% CI, 67.0%, 100%; p=0.628), respectively. Although the difference was not statistically significant and the number of patients was small, the promising outcomes of HRD HSCT in AML patients were encouraging. Our results demonstrated that HRD HSCT with PTCy using a targeted busulfan-based myeloablative conditioning shows outcomes similar to those of MUD HSCT with antithymocyte globulin. HRD HSCT with PTCy could be a feasible option for pediatric high-risk acute leukemia patients who lack an HLA-matched related or unrelated donor.
PMID:35021131 | DOI:10.1016/j.jtct.2022.01.002
