Unmanipulated haploidentical blood and marrow transplantation: where we are.

ABSTRACT

Human leukocyte antigen (HLA)-mismatched/haploidentical blood and marrow transplants (haplo-BMT) from family donors have been intensively studied because of the decreasing family size in mainland China, and also because the Chinese Marrow Donor Program is still not big enough. The protocol for unmanipulated haplo-BMT has been designated as 'GIAC' by Dr DP Lu--'G' represents granulocyte colony-stimulating factor mobilisation; 'I' stands for immunosuppression during pre-conditioning being prolonged and intensified; 'A' stands for the use of antithymocyte globulin; 'C' means combined use of bone marrow and peripheral blood as the graft. Haplo-BMT with GIAC regimen has been shown to be feasible for many applications as reported in 2004. Under this protocol, haplo-BMT has achieved comparable outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality (TRM), disease-free survival (DFS), and overall survival with HLA-identical sibling transplantation. The probabilities of DFS at 2 years in haplo-BMT setting were 70.7%, 49.6%, 22.2% in standard-risk, high-risk, advanced disease groups, respectively. As the third party cells, cord blood co-infusion could significantly reduce the incidence and severity of acute GVHD, and also 100-day TRM. The majority of refractory cytomegalovirus, Epstein-Barr virus and aspergillus infections can be controlled by adoptive cellular therapy. Many patients who early relapsed after BMT and failed, or are ineligible for standard therapy, have been salvaged with dendritic cell-primed cytokine-induced killer cells. With these new strategies, the lower TRM and improved DFS have been attained. Therefore, it is better to consider haplo-BMT for the patients with otherwise incurable haematological malignancies at earlier stage, when matched sibling or unrelated donors are not available.