Haploidentical stem cell transplant with post-transplantation cyclophosphamide and mini-dose methotrexate in children

Background: Haploidentical stem cell transplantation (haplo-SCT) is an option for patients without human leukocyte antigen-matched related or unrelated donor. Post-transplantation cyclophosphamide (PTCy) is an effective method of graft versus host disease (GVHD) prophylaxis and permits the use of T-cell replete grafts in settings were ex vivo manipulation is not feasible.

Methods: A retrospective study among patients younger than 18 years, with a history of hematologic malignancies who underwent haplo-SCT between 2012 and 2016. All patients received a preparative regimen of fludarabine, busulfan, and 400 cGy total body irradiation or melphalan. Post-transplant GvHD prophylaxis consisted either of PTCy (50 mg/kg on Days + 3 and + 4) and cyclosporine (CSA) plus mycophenolate (MMF) (15 mg/kg/dose, thrice daily, per os), or mini-dose methotrexate (MTX; 5 mg/m² dose) on Days + 5, +7, +10, and + 15.

Results: A total of 52 children were included, whose median age was 9 years (interquartile range, 4.9-14; range, 1.2-17 years), and 63% were males. The most common complications were cytomegalovirus reactivation (57%) and hemorrhagic cystitis (36%). The acute GVHD prophylaxis was PTCy, CSA, and mini-dose MTX in 42 (81%) patients, and 10 (19%) patients received PTCy, CSA, and MMF. The cumulative incidence of acute GvHD II-IV, acute GvHD III-IV, and chronic GvHD were 42%, 8.5%, and 19%, respectively. Grades I-IV acute GvHD occurred in 100% of the patients who received prophylaxis with CSA and MMF, and 62% who received CSA and mini-dose MTX (p = .055). The transplant-related mortality at 100 days was 18%. The 5-year overall and event-free survival were 59% and 57%, respectively.

Conclusions: Haplo-SCT with PT/Cy can be an available, safe, and feasible option for children with hematologic malignancies; meanwhile, the use of mini-dose of MTX was associated with lower rates of acute GVHD. However, our results require further support from prospective randomized studies to improve the efficacy of this prophylactic strategy.