Haploidentical Hematopoietic Stem Cell Transplantation in Pediatric Patients: Comparison of Early Post-Transplant Outcome According to in Vitro Depletion Method

Currently, haploidentical hematopoietic cell transplantation (HHCT) is considered an established option for patients who have diseases curable with HCT but who lack a suitable donor. We compared the early post-transplant outcomes of the two transplant groups using different in vitro depletion method.

Between July 2008 and June 2014, 49 pediatric patients underwent in vitro T cell-depleted HHCT. Of 49 patients, 28 received CD3-depleted stem cells (CD3-HHCT) and 21 received TCRαβ-depleted grafts (TCRαβ-HHCT). Among 28 patients of CD3-HHCT, nine had hematologic malignancy [HM, one with ALL in non-CR, six with AML (3 CR1, 2 CR2, 1 non-CR), and two with MDS-RCMD], 18 had non-malignant disease (one with Fanconi anemia, 16 with acquired SAA, and one with CDA), and one had refractory neuroblastoma. Among 21 patients of TCRαβ-HHCT, 16 had HM [five with ALL (2 CR1, 2 CR2, 1 CR3), five with AML (2 CR1, 2 CR2, 1 non-CR), one with mixed lineage leukemia in non-CR, one with MDS-RCC, two with JMML, and two with NHL (1 CR2, 1 CR3)], two had SAA, and three had solid tumors [two with RMS (1 CR2, 1 refractory), and one with Ewing sarcoma in CR3].

Of 28 patients who received CD3-HHCT, two patients failed to achieve primary engraftment, and five patients experienced graft rejection (GR) within 28 days post-transplant. No patients of TCRαβ-HHCT experienced graft failure (GF). Early GF (primary GF and GR) was more common in CD3-HHCT compared to TCRαβ-HHCT (P=0.011). The cumulative incidence of acute GVHD ≥ grade II was comparable between two groups (33.3% for CD3-HHCT and 27.0% for TCRαβ-HHCT). Extensive chronic GVHD occurred in three patients from CD3-HHCT and one from TCRαβ-HHCT. T and T4 cell counts at 2 months post-transplant were higher in TCRαβ-HHCT than that of CD3-HHCT (P=0.007 for T and P=0.074 for T4). In CD3-HHCT, four patients died of non-relapse causes (two of CMV disease, one of encephalopathy, and one of autoimmune hemolytic anemia) and one died of leukemia. In contrast, five patients from TCRαβ-HHCT died of disease but, none died of non-relapse cause.

Of 20 patients (18 from CD3-HHCT and two from TCRαβ-HHCT) with non-malignant disease, only one patient of CD3-HHCT died of TRM. As for 29 patients (10 from CD3-HHCT and 19 from TCRαβ-HHCT) with malignant disease, the EFS at 1 year for CD3-HHCT and TCRαβ-HHCT were 60.0% and 56.6%, respectively (P>0.05).

In this study, TCRαβ-depleted HHCT showed a better early post-transplant outcome in terms of engraftment, immune recovery, and NRM, compared to CD3-HHCT. However, further study is warranted to evaluate the efficacy of TCRαβ-HHCT in preventing relapse in advanced malignancy.