T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

• Published in: Bone marrow transplantation (Basingstoke) Vol. 49; no. 8; pp. 999 - 1008
• Main Authors: Bashey, A, Solomon, S R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2014; Nature Publishing Group
• Subjects: 631/250/1854; 692/700/565/545/576/1955; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Availability; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Care and treatment; Cell Biology; Clinical trials; Clinical Trials as Topic; Cord blood; Cord Blood Stem Cell Transplantation; Depletion; Evaluation; Female; Graft rejection; Graft Rejection - prevention & control; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Grafting; Granulocyte colony-stimulating factor; Hematology; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histocompatibility antigen HLA; Histocompatibility Testing; Humans; Immune response; Immunological memory; Immunoproliferative diseases; Immunosuppression; Infections; Internal Medicine; Living Donors; Lymphocyte Depletion; Lymphocytes; Lymphocytes T; Lymphoproliferative Disorders - therapy; Male; Medical sciences; Medicine; Medicine & Public Health; Memory cells; Mud; Patients; Posttransplant lymphoproliferative disorders; Public Health; Rejection; review; Risk analysis; Risk factors; Siblings; Standard of care; Stem cell transplantation; Stem Cells; T-Lymphocytes; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplants; Transplants & implants; Umbilical cord; Unrelated Donors; Human; Haploidentical graft; Hematology; Histocompatibility; Related donor; T-Lymphocyte
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2014.62

Availability of an HLA-identical sibling (MRD) or suitably matched unrelated donor (MUD) has historically been a limiting factor in the application of allogeneic hematopoietic transplantation. Although almost all patients have an HLA-haploidentical family donor, prior attempts at transplantation from such donors using T-cell replete grafts and conventional immunosuppression were associated with unacceptable rates of GVHD, and when stringent ex vivo T-cell depletion was used to control GVHD, rates of graft rejection and post-transplant infections were prohibitive. The recent approach to HLA-haploidentical donor transplantation developed in Baltimore that uses T-cell replete grafts and post-transplant CY (Haplo-post-HCT-CY) to control post-transplant allo-reactivity appears to have overcome many of the obstacles historically associated with haploidentical donor transplantation. In particular, TRM rates of <10% are usual and rapid reconstitution of immunity leads to a low rate of post-transplant infections and no post-tranplant lymphoproliferative disorders (PTLD), consistent with the hypothesis that post-transplant CY selectively depletes proliferating alloreactive T cells responsible for GVHD and graft rejection while preserving resting memory T cells essential for post-transplant immunologic recovery. In parallel trials using similar non-myeloablative conditioning regimens, Haplo-post-HCT-CY produced similar overall survival to double umbilical cord blood transplantation(DUCBT) in adult patients (62% vs 54%), with low rates of TRM (7% vs 24%), severe acute GVHD (0% vs 21%) and chronic GVHD (13% vs 25%). Furthermore, recent non-randomized comparisons adjusted for risk factors show that Haplo-post-HCT-CY achieve at least equivalent outcomes to conventional MRD and MUD transplants. Although most experience has been obtained using BM, emerging data suggest that a G-CSF mobilized PBSC graft can also safely be used for Haplo-post-HCT-CY. Haplo-post-HCT-CY also avoids the graft acquisition costs of DUCBT and MUDs and the cost of cell selection associated with T-depleted grafts. Although randomized comparisons will be forthcoming, Haplo-post-HCT-CY can already be considered a valid standard-of-care in patients who lack conventional donors thus extending the availability of allogeneic transplants to almost all patients. This donor source may also challenge the routine preference for a MUD in patients lacking an MRD.