Haploidentical HCT using an αβ T-cell-depleted graft with targeted αβ+ cells by add-back after a reduced intensity preparative regimen containing low-dose TBI

• Published in: Bone marrow transplantation (Basingstoke) Vol. 51; no. 9; pp. 1217 - 1222
• Main Authors: Im, H J, Koh, K N, Suh, J K, Lee, S W, Choi, E S, Jang, S, Kwon, S W, Park, C-J, Seo, J J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2016; Nature Publishing Group
• Subjects: 631/532/1542; 692/699/1541; Adolescent; Antilymphocyte Serum - administration & dosage; Bone marrow; Cell Biology; Child; Child, Preschool; Cyclophosphamide; Cyclophosphamide - administration & dosage; Depletion; Dosage; Failure rates; Fatalities; Female; Fludarabine; Follow-Up Studies; Globulins; Graft rejection; Graft vs Host Disease - pathology; Graft-versus-host reaction; Grafting; Grafts; Hematologic Neoplasms - therapy; Hematology; Humans; Infant; Internal Medicine; Leukocytes (neutrophilic); Lymphocyte Depletion - methods; Lymphocytes; Lymphocytes T; Male; Malignancy; Medicine; Medicine & Public Health; Neoplasms - therapy; original-article; Patients; Pediatrics; Public Health; Receptors, Antigen, T-Cell, alpha-beta; Solid tumors; Stem cell transplantation; Stem Cells; Survival Analysis; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Thymocytes; Transplantation; Transplantation Conditioning - methods; Transplantation, Haploidentical - adverse effects; Transplantation, Haploidentical - methods; Transplantation, Haploidentical - mortality; Transplants & implants; Treatment Outcome; Tumors; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Whole-Body Irradiation - methods; Young Adult
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2016.114

Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ + T-cell-depleted graft with targeted αβ cells at 1–5 × 10 5 /kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾grade II and ⩾grade III acute GvHD were 31±7.1% (SE) and 12±5.0%, respectively, and 1-year CI of chronic GvHD was 15±5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6±2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5–43 months), the estimated 2-year event-free survival for NM and HM were 88±11.7 and 50±10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ + T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor.