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.
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.
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.
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.
1 Bone Marrow Transplant Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.
2 Massachusetts General Hospital, Boston, MA.
3 Renal Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.
4 Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Boston, MA.
5 Center for Translational Immunology, Columbia University Medical Center.
6 Center for Transplant Science, Department of Surgery, Massachusetts General Hospital, Boston, MA.
Received 12 October 2018. Revision received 28 December 2018.
Accepted 27 January 2019.
This research was performed with the support of the Immune Tolerance Network (NIH Contract #N01 AI15416), an international clinical research consortium headquartered at the University of California San Francisco and supported by the National Institute of Allergy and Infectious Diseases and the Juvenile Diabetes Research Foundation.2
www.clinicaltrials.gov # NCT00854139
T.R.S., N.T.-R., A.B.C., S.M., M.S., D.H.S., and T.K. participated in research design, writing of the article, the performance of the research, and in data analysis. B.R.D. participated in the writing of the article, the performance of the research, and in data analysis. Y.-B.C. participated in the writing of the article and in the performance of the research. F.D. participated in the performance of the research and in data analysis.
T.R.S., M.S., and D.H.S. are with ITBMed Biopharmaceuticals. The other authors declare no conflicts of interest.
Correspondence: Thomas R. Spitzer, MD, Bone Marrow Transplant Program, Massachusetts General Hospital, Zero Emerson Place, Boston, MA 02114. (firstname.lastname@example.org).