Related HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion: observations of a single Chinese center

Abstract

The Institute of Hematology, Peking University, is the largest hematopoietic stem cell transplantation (HSCT) center in China. A total of 400 HSCTs performed in 2010 accounted for a quarter of all allogeneic HSCTs performed in China. The GIAC protocol, which uses HLA-mismatched/haploidentical blood or bone marrow transplantation without in vitro T-cell depletion, entails administration of granulocyte-colony stimulating factor (G-CSF) to all donors, intensified immunological suppression, and treatment with anti-human thymocyte immunoglobulin. The stem cell grafts are a combination of G-CSF-primed bone marrow cells and G-CSF-mobilized peripheral blood stem cells, which may be critical to the success of this protocol through the immune modulation of G-CSF. Using this protocol, more than 99% engraftment and complete donor chimerism were achieved in pediatric and adult patients with hematological malignancies. The incidence of graft-versus-host disease (GVHD) grades 3 and 4 was 13.4% and that of extensive chronic GVHD 22.6%. Comparable relapse rates were observed between patients who received unmanipulated haploidentical transplantation, and those who received HLA-identical or unrelated HSCT. Patients with confirmed minimal residual disease, (expression levels of Wilms' tumor suppressor gene 1 and flow cytometry) after HSCT received pre-emptive modified donor lymphocyte infusion to prevent relapse. Infection was the main cause of non-relapse death. Prospective studies are ongoing to investigate the mechanisms of immune reconstitution in order to refine the protocol. In 1964, a patient with severe aplastic anemia received a bone marrow infusion from her syngeneic, pregnant sister, and remained disease-free over a 40-year follow-up period. Following this success, there was a 20-year interruption in the transplantation program at our center. The hiatus ended in 1981 with the first allogeneic HSCT, which was used to treat a girl with acute lymphoblastic leukemia (ALL). In the mid-1990s, the facility performed allo-HSCTs from unrelated donors (URD) and umbilical cord blood (UCB). Then, in 2000, a patient with refractory acute leukemia received related haploidentical HSCT and achieved long-term survival without relapse over an 11-year followup period. Coincident with the rapid economic development experienced in China since 2000, the transplantation program at our Institute has been expanded to include broadened indications, multiple sources of stem cells and improved outcomes. The Institute is the largest HSCT center in China, now with 130 beds in four wards, 33 of which are laminar-flow rooms. Between 2007 and 2009, over 350 HSCTs were performed per year, rising to a total of 400 in 2010. Further, in 2010, 94% of these HSCTs were allogeneic transplants, accounting for a quarter of all allo-HSCTs performed in China. Of these, transplants from URD accounted for 6%-7%, those using UCB for less than 5%, those from identical siblings for 25%-30%, and those from the related haploidentical for 55%-65%. The most common indications for treatment with allo-HSCT are intermediate-to-high risk of acute leukemia or myelodysplastic syndrome, advanced chronic myeloid leukemia (CML), refractory lymphoma, or severe aplastic anemia.