Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects afternon-myeloablative therapy and HLA-mismatched bone-marrow transplantation

Background. HLA-mismatched donor bone-marrow transplantation after standard myeloablative conditioning therapy for haematological malignant disorders has been limited by severe graft-versus-host disease (GVHD) and graft failu re. We tested a new approach to find out whether lymphohaemopoietic graft-v ersus-host reactions could occur without excessive GVHD in mixed haemopoiet ic chimeras produced across HLA barriers with non-myeloablative conditionin g. Methods. Five patients with refractory non-Hodgkin lymphoma underwent bone- marrow transplantation from haploidentical related donors sharing at least one HLA A, B, or DR allele on the mismatched haplotype. Conditioning includ ed cyclophosphamide and thymic irradiation before transplantation, and anti thymocyte globulin before and after transplantation. The only other GVHD pr ophylaxis was cyclosporin. Findings. Four of five patients were evaluable and showed engraftment. Mixe d haemopoietic chimerism was established, with a predominance of donor lymp hoid tissue and varying degrees of myeloid chimerism. Two patients were in GVHD-free states of complete and partial clinical remission at 460 and 103 days after bone-marrow transplantation. Interpretation. Mixed chimerism can be induced in adult recipients of HLA-m ismatched bone-marrow transplantation by a non-myeloablative conditioning r egimen. The antilymphoma responses seen in two patients suggest that alloge neic bone-marrow transplantation without myeloablative conditioning might h ave potent immunotherapeutic benefits.