Effective T‐cell replete haploidentical stem cell transplantation for pediatric patients with high‐risk hematologic disorders

Abstract

Objectives Patients with high‐risk hematologic diseases require intensive modalities, including high‐dose chemotherapy and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Haploidentical T‐cell–replete transplantation is a logical choice because of the limited availability of matched sibling donors and the prolonged time needed to identify matched unrelated donors in Thailand. Methods The clinical outcomes data of 43 patients undergoing allo‐HSCT were reviewed. All patients had high‐risk hematologic malignancies, were younger than 20 years, and were in complete cytological remission at the time of allo‐HSCT. We used two different conditioning regimens: total body irradiation (TBI) combined with cyclophosphamide, fludarabine, and melphalan (n = 23) and thiotepa combined with fludarabine and busulfan (n = 20). All patients received a graft‐versus‐host disease prophylaxis regimen consisting of cyclophosphamide, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. Results There was no difference in engraftment between patients receiving either of the regimens. After a median follow‐up of 35.8 (range, 0.6–106.2) months, the overall survival (OS) and event‐free survival (EFS) rates were 62.4% and 54.7%, respectively. OS and EFS were comparable between the respective regimens. Conclusions We conclude that thiotepa‐based conditioning has similar efficacy and tolerability as TBI‐based conditioning for haploidentical HSCT with post‐transplant cyclophosphamide.

Haploidentical HSCT in the Treatment of Pediatric Hematological Disorders

“…Tannumsaeung et al aimed to determine the results of haplo-HSCT with PTCy preceded by either TBI- or thiotepa-based conditioning regimens. The percentage of graft-related complications and infections was comparable in both groups of patients [ 105 ].…”

“…Apart from the above-mentioned trials or retrospective analyses, the available literature discussing haplo-HSCT in pediatric patients with hematologic malignancies contains a couple of single-institution reports (Table 3). TT regimen 20% 3-year OS 62.4% [105] aGVHD-acute graft-versus-host disease, Ara-C-cytarabine, ATG-anti-thymocyte globulin, Bu-busulfan, CAR-T-chimeric antigen receptor T-cells, cGVHD-chronic graftversus-host disease, CIR-cumulative incidence of relapse/progression, CSA-cyclosporin A, Cy-cyclophosphamide, Flu-fludarabine, G-CSF-granulocyte colony-stimulating factor, haplo-HSCT-haploidentical hematopoietic stem cell transplantation, ISD-HSCT-identical sibling donor hematopoietic stem cell transplantation, L-PAM-melphalan, Me-CCNU-methyl chloride hexamethylene urea nitrate (semustine), MMF-mycophenolate mofetil, MP-methylprednisolone, MUD-matched unrelated donor, MSDT-matched sibling donor transplant, MTX-methotrexate, NRM-non-relapse mortality, OS-overall survival, PTCy-post-transplant cyclophosphamide, TAC-tacrolimus, TBI-total body irradiation, TKi-tyrosine kinase inhibitor, TT-thiotepa, UCB-unrelated cord blood. Currently, novel studies aim to test a new graft manipulation involving ꭤ β T-cell removal, while retaining both NK and 𝛾𝛿 T-cells in the graft [35].…”

An analysis of the efficacy of graft-versus-host disease prophylaxis with post-transplant cyclophosphamide in children with acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation from HLA-matched and partially-matched unrelated donors

“…Накопившиеся за последние несколько лет данные свидетельствуют о том, что эта стратегия может быть успешно применена к детям. Однако представленные результаты единичны, большинство опубликованных исследований на педиатрической когорте пациентов [29][30][31][32][33][34] [35,36], морфоло гический вариант -на основании FAB-классификации [37,38]. Кариотипы пациентов интерпретировали в соответствии с Международной системой номенкла туры цитогенетики человека [39][40][41].…”