Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium (HAPLO2016), San Diego, California, December 1, 2016

Abstract

The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34 cell selection, "megadoses" of purified CD34 cells, or selective depletion of T cells) or newer platforms of in vivo depletion of T cells, with either post-transplantation high-dose cyclophosphamide or intensified immune suppression, have contributed to better outcomes, with survival similar to that in HLA-matched donor transplantation. Further efforts are underway to control viral reactivation using modified T cells, improve immunologic reconstitution, and decrease the relapse rate post-transplantation using donor-derived cellular therapy products, such as genetically modified donor lymphocytes and natural killer cells. Improvements in treatment-related mortality have allowed the extension of haploidentical donor transplants to patients with hemoglobinopathies, such as thalassemia and sickle cell disease, and the possible development of platforms for immunotherapy in solid tumors. Moreover, combining HSCT from a related donor with solid organ transplantation could allow early tapering of immunosuppression in recipients of solid organ transplants and hopefully prevent organ rejection in this setting. This symposium summarizes some of the most important recent advances in HaploSCT and provides a glimpse in the future of fast growing field.

Comparison of haploidentical and umbilical cord blood transplantation after myeloablative conditioning

“…Haploidentical hematopoietic stem cell transplantation (haplo HSCT) has emerged as an important alternative donor source. 1,2 Historically, the successful use of haplo HSCT was limited by high risks of severe graft-versus-host disease (GVHD), graft failure and mortality. [3][4][5] In order to ameliorate these risks, more intensive conditioning regimens were often coupled with complex T cell depletion procedures, [6][7][8][9][10][11][12][13] often leading to increased risks of opportunistic infections because of delayed immune recovery as well as conditioning-related toxicities.…”

“…It provides significant protection from GVHD and is associated with a low incidence of non-relapse mortality (NRM) particularly in adults with hematological malignancies treated with in a reduced intensity conditioning (RIC). 1,2,16,17 In the absence of an HLA matched related or unrelated donor, haploidentical relatives and banked umbilical cord blood (UCB) offer access to a potentially lifesaving treatment as well as rapid availability of a donor and greater flexibility in timing of transplantation. 18 To-date most comparisons between haplo and UCB HSCT for hematologic malignancy have either been restricted to patients treated with non-myeloablative or reduced intensity conditioning regimens.…”

T-cell deplete versus T-cell replete haploidentical hematopoietic stem cell transplantation for sickle cell disease: where are we?

“…While this approach now achieves stable donor engraftment with limited acute and chronic graft versus host disease (GvHD), its application is restricted by donor availability and regimenrelated toxicities [7]. To address these limitations, alternative donor platforms such as related haploidentical hematopoietic cell transplantation (haplo-HCT) with potential for near-universal donor availability and reduced toxicity are being developed [8][9][10][11][12][13][14][15].…”

Allodepleted T‐cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft‐versus‐host disease (GVHD) in the absence of GVHD prophylaxis

“…Although the feasibility of haploidentical stem cell transplantation has been questioned over the decades due to lethal graft‐versus‐host disease (GVHD), developments have led to a rapid increase in the use of haploidentical HSCT in recent years, challenging even matched unrelated donor as standard of care (Sureda et al , ; Passweg et al , ). Today's haploidentical transplants usually involve different ex vivo or in vivo T‐cell depletion strategies to avoid severe acute GVHD (Locatelli et al , ; Zeiser & Blazar, ; Al Malki et al , ), a major complication of T‐replete allogeneic HSCT (Sureda et al , ). Importantly, early trials of ex vivo T‐cell depletion could achieve complete engraftment without causing GVHD (Aversa et al , ; Martelli & Aversa, ).…”

“…However, the reduction of T cells results in delayed immune reconstitution and may lead to lethal opportunistic infections and disease relapse in a high number of patients (Aversa et al , ; Di Stasi et al , ). Therefore, ex vivo strategies, such as selective graft depletion of alpha‐beta‐T cells or insertion of suicide genes to donor lymphocytes, have been developed to facilitate the transfer of haploidentical lymphocytes while diminishing the challenges of life‐threatening infections, GVHD, and relapse (Al Malki et al , ). In vivo T‐cell depletion using cyclophosphamide is an extremely simple and effective approach to facilitating haploidentical transplantation, but it is also associated with the occurrence of graft failures and higher relapse rates after reduced‐intensity conditioning (Luznik et al , ; Brunstein et al , ; Ciurea et al , ; Byrne & Savani, ; Bashey et al , ; McCurdy et al , ).…”