Haploidentical Hematopoietic Stem Cell Transplantation and Immunotherapy: The Experience of AP-HP Pitié Salpétrière hospital

Allogeneic hematopoietic stem cell transplant (HSCT) remains theonly potentially curative option for a variety of hematologic disorders.Haploidentical BMT has been associated with significant risks of graftrejection and severe graft-versus-host disease (GvHD) but over the pastdecade, haploidentical donors have emerged as a viable alternate graftsource for patients without an HLA-matched donor. Initially, the risk ofsevere GvHD has been reduced in intensively conditioned recipientsby grafts that have been rigorously depleted of mature T cells, but therisks of relapse, serious infection and death in these severely immunecompromisedpatients was high. In our experience of CD34+ selectedand CD3/CD19 depleted haploidentical HSCT, in high-risk acuteleukemia patients, 45%, 24% and 22% of patients respectively died fromrelapse, infection and GVHD. In the last 10 years, different methods toselectively inhibit alloreactivity while preserving immunity to infectionand malignancy have been proposed. Among them, post-transplantationimmunosuppression with high-dose Cyclophosphamide (PT-Cy), wasassociated with an acceptably low incidence of graft rejection, severeaGvHD, and extensive cGvHD, while allowing prompt engraftment.In more of 100 haploidentical hematopoietic stem cell transplantationusing high-dose cyclophosphamide, we observed an incidence of fetalGvHD less than 20%, similar to that reported in others studies; in thissetting, the major causes of death were a high incidence of severeopportunistic infections (53%) and relapse (29%). Thus, it remains toboost both graft anti-leukemia and anti-pathogens effects to improve theoutcomes of haploidentical hematopoietic stem cell transplant and wewill report major clinical trials and our own experience of T and NK cellsmanipulation strategies.

کلیدواژه ها:

Allogeneic hematopoietic stem cell transplant ، Graft-versushost disease ، NK cells manipulation