Combined Simultaneous Kidney/Bone Marrow Transplantation1

Abstract

On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.

Kidney transplantation with bone marrow augmentation: five-year outcomes

“…This analysis confirms earlier reports suggesting that bone marrow augmentation in renal transplant recipients is associated with reasonable patient and graft survival, 5,6,7,9,10 and extends these findings, with 5-year actuarial patient and graft survival rates of 85% and 76%, respectively. As in previous analyses, no significant improvement was noted in graft survival, when compared with control patients not receiving bone marrow.…”

“…As in previous analyses, no significant improvement was noted in graft survival, when compared with control patients not receiving bone marrow. 6,7,10 However, there is a suggestion that bone marrow augmentation had some immunomodulatory effect, with a trend toward a progressive decrease in the incidence of chronic allograft nephropathy. This observation has also been made by the Miami group.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] In this report, we present our experience with bone marrow augmentation in renal transplantation over the past 7 years. …”

Microchimerism, Donor Dendritic Cells, and Alloimmune Reactivity in Recipients of Flt3 Ligand-Mobilized Hemopoietic Cells: Modulation by Tacrolimus

“…The observation of Starzl et al (1,2) that multilineage microchimerism could be detected in long-surviving recipients of organ allografts, and the argument that chimerism was an essential prerequisite for tolerance induction (1,44) prompted studies to augment natural microchimerism in an effort to promote tolerance induction in humans and reduce or eliminate dependence on immunosuppressive therapy. Recent efforts to enhance natural microchimerism in clinical organ transplantation have centered on the infusion of unmodified donor BM cells, usually at the time of transplantation (16,45,46). In principle, an alternative/additional approach is the use of specific growth factors to promote hemopoiesis, as in BM transplantation (47).…”

Bone Marrow Augmentation in Renal Transplant Recipients

“…Thus, bone marrow augmentation without recipient preconditioning was begun in December 1992, and has been done with all of the transplantable organs (kidney, pancreas, islets, liver, heart, lung, and intestine). [28][29][30][31][32] As with all of the other reported experiences, the logistic difficulties of bone marrow procurement have militated against a randomized trial, and in fact the only randomized trial of bone marrow augmentation is being performed in Miami, in liver recipients. 33 Between December 1992 and October 1996, 86 cases of bone marrow augmentation were accrued among the nearly 800 kidney transplantations at our center.…”