High-dose posttransplantation cyclophosphamide after haploidentical stem cell transplantation in a child with recurrent neuroblastoma: a step forward to separate GVT from GVH

Abstract

Allogeneic HSCT with graft versus tumor (GVT) effect is an accepted therapeutic option in pediatric solid tumors. Due to donor availability and logistic reasons, unmanipulated family haploidentical transplants are becoming increasingly used in patients lacking an HLA identical family donor, or a well matched unrelated donor. Recently nonmyeloablative, haplo-identical T-cell replete bone marrow transplantation using high-dose cyclophosphamide post-HSCT (PTCy) to control GVHD and prevent graft rejection by inducing bi-directional tolerance was described. The objective of this report is an analysis of case of a child treated for relapsed neuroblastoma with haploidentical HSCT with PTCy. In this case following therapeutic modalities were combined: haploidentical HSCT in pediatric solid tumor relapsing after autologous HSCT, non-myeloablative haploidentical HSCT with unmanipulated T-repleted graft, and post-transplant use of high-dose cyclophosphamide as GVHD prophylaxis. This strategy was safe and efficient, as we observed low toxicity, relatively fast hematological engraftment, and hyperacute GVHD followed by mild GVHD. Patient stayed in remission for 12 months. Based on published data, it seems possible, that PTCy selectively depletes T cells that react against host allo-antigens, yet preserves tumor-specific and pathogen reactive T cells.