Twenty-year Follow-up of Histocompatibility Leukocyte Antigen-matched Kidney and Bone Marrow Cotransplantation for Multiple Myeloma With End-stage Renal Disease: Lessons Learned.

BACKGROUND

Specific immune tolerance of transplanted organs in association with either transient or sustained lymphohematopoietic chimerism has been demonstrated in several preclinical animal models and clinically in patients who are full donor chimeras after hematopoietic stem cell transplantation and subsequently received kidney transplants from the same donor. Most recently, tolerance induction has been extended to patients in whom chimerism was intentionally induced at the time of kidney transplantation.

METHODS

Twenty years ago, we reported the first successful histocompatibility leukocyte antigen-matched sibling donor bone marrow and kidney transplant following nonmyeloablative conditioning in a patient with multiple myeloma and end-stage renal disease (ESRD). After 2 decades, she has normal renal function in the absence of ongoing systemic immunosuppressive therapy. Nine patients have subsequently undergone similar treatment for multiple myeloma with ESRD.

RESULTS

In the initial patient, hematopoietic chimerism was detectable for only 105 days after the transplant. In subsequent patients, chimerism detection ranged from 49 days to >14 years. Nevertheless, a long remission of the myeloma and long-term immunosuppression-free survival of the kidney allograft were achieved in 7 of the 10 patients, 5 of whom currently survive.

CONCLUSIONS

This initial patient demonstrated the feasibility of performing combined histocompatibility leukocyte antigen-matched, sibling donor bone marrow and kidney transplantation for ESRD due to multiple myeloma. This experience paved the way for extending the initial trial to 9 additional patients with multiple myeloma and ESRD and, more recently, to tolerance induction strategies involving combined bone marrow and kidney transplantation for patients with and without an underlying malignancy.