Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism.
BACKGROUND
Experimental and clinical evidence has demonstrated that the establishment of allogeneic chimerism after bone marrow transplantation may provide donor-specific tolerance for solid organ allografts.


METHODS
Based on the preliminary results of a clinical trial using nonmyeloablative preparative therapy for the induction of mixed lymphohematopoietic chimerism, we treated a 55-year-old woman with end stage renal disease secondary to multiple myeloma with a combined histocompatibility leukocyte antigen-matched bone marrow and renal transplant after conditioning with cyclophosphamide, antithymocyte globulin, and thymic irradiation.


RESULTS
The posttransplant course was notable for early normalization of renal function, the absence of acute graft-versus-host disease, and the establishment of mixed lymphohematopoietic chimerism. Cyclosporine, which was the only posttransplant immunosuppressive therapy, was tapered and discontinued on day +73 posttransplant. No rejection episodes occurred, and renal function remains normal on day + 170 posttransplant (14 weeks after discontinuing cyclosporine). Although there is presently no evidence of donor hematopoiesis, there is evidence of an ongoing antitumor response with a recent staging evaluation showing no measurable urine kappa light chains. The patient remains clinically well and is off all immunosuppressive therapy.


CONCLUSIONS
This is the first report of the deliberate induction of mixed lymphohematopoietic chimerism after a nonmyeloablative preparative regimen to treat a hematological malignancy and to provide allotolerance for a solid organ transplant.
Spitzer
T R
TR
Bone Marrow Transplantation Program/Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Delmonico
F
F
Tolkoff-Rubin
N
N
McAfee
S
S
Sackstein
R
R
Saidman
S
S
Colby
C
C
Sykes
M
M
Sachs
D H
DH
Cosimi
A B
AB
D016026:Bone Marrow Transplantation; D002678:Chimera / Q000276:immunology; D005260:Female; D006680:HLA Antigens; D006801:Humans; D007108:Immune Tolerance; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000601:surgery*; D016030:Kidney Transplantation; D019520:Living Donors; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000628:therapy*; D014184:Transplantation, Homologous
D006680:HLA Antigens