Induction Of Kidney Allograft Tolerance After Transient Lymphohematopoietic Chimerism In Patients With Multiple Myeloma And End-Stage Renal Disease1

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Abstract
Two patients with end-stage renal disease secondary to multiple myelomas were treated with combined kidney and bone marrow transplantation in an effort to achieve donor-specific allotolerance through the induction of mixed lymphohematopoietic chimerism. Two female patients (55 and 50 years of age) with end-stage renal disease secondary to kappa light-chain multiple myelomas received a nonmyeloablative conditioning regimen that consisted of 60 mg/kg cyclophosphamide intravenously (IV) on days −5 and −4; 15 mg/kg equine anti-thymocyte globulin (ATGAM) IV on days −1, +1, and +3; and thymic irradiation (700 cGy) on day −1. On day 0, the recipients underwent kidney transplantation, followed by IV infusion of donor bone marrow (2.7×108 and 3.8×108 /kg nucleated cells, respectively) obtained from a human leukocyte antigen (HLA)-matched sibling. Cyclosporine A was administered IV at a dose of 5 mg/kg on day −1, then continued orally at 8 to 12 mg/kg per day until days +73 and +77, respectively, after which no further immunosuppression was given. Donor leukocyte infusions (1×107/kg CD3+ T cells) were administered in an attempt to enhance the graft-versus-myeloma effect (days +66 and +112 in the first patient and day +78 in the second patient). Hematopoietic chimerism was monitored weekly by microsatellite assays. Multilineage lymphohematopoietic chimerism (5%–80% donor CD3+ or CD3− cells, or both) was first detected during the second posttransplant week and was maintained for approximately 12 weeks, after which there was a gradual decline to undetectable levels (Conclusions. This nonmyeloablative regimen followed by combined HLA-matched donor bone marrow and renal allotransplantation is the first example of an intentional and clinically applicable approach to inducing renal allograft tolerance and achieving potent and sustained antitumor effects in patients with multiple myeloma.