Mixed lymphohaemopoietic chimerism and graft-ver suslymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation
M Sykes, F Preffer, S McAfee, SL Saidman… - The Lancet, 1999 - thelancet.com
M Sykes, F Preffer, S McAfee, SL Saidman, D Weymouth, DM Andrews, C Colby…
The Lancet, 1999•thelancet.comBackground 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 failure. We tested a new approach to
find out whether lymphohaemopoietic graft-versus-host reactions could occur without
excessive GVHD in mixed haemopoietic chimeras produced across HLA barriers with
nonmyeloablative conditioning. Methods Five patients with refractory non-Hodgkin …
myeloablative conditioning therapy for haematological malignant disorders has been limited
by severe graft-versus-host disease (GVHD) and graft failure. We tested a new approach to
find out whether lymphohaemopoietic graft-versus-host reactions could occur without
excessive GVHD in mixed haemopoietic chimeras produced across HLA barriers with
nonmyeloablative conditioning. Methods Five patients with refractory non-Hodgkin …
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 failure. We tested a new approach to find out whether lymphohaemopoietic graft-versus-host reactions could occur without excessive GVHD in mixed haemopoietic chimeras produced across HLA barriers with nonmyeloablative conditioning.
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 included cyclophosphamide and thymic irradiation before transplantation, and antithymocyte globulin before and after transplantation. The only other GVHD prophylaxis was cyclosporin.
Findings
Four of five patients were evaluable and showed engraftment. Mixed haemopoietic chimerism was established, with a predominance of donor lymphoid 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-mismatched bone-marrow transplantation by a non-myeloablative conditioning regimen. The antilymphoma responses seen in two patients suggest that allogeneic bone-marrow transplantation without myeloablative conditioning might have potent immunotherapeutic benefits.
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