Discontinuation of immunosuppression for prevention of kidney graft rejection after receiving a bone marrow transplant from the same HLA identical sibling donor

Gajewski, James; Ippoliti, Cindy; Ma, Yan; Champlin, Richard E.

doi:10.1002/ajh.10206

Cited by 11 publications

(7 citation statements)

References 17 publications

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“…Sayegh et al (10), have demonstrated that persons who have successful BMT and who develop ESRD may be specifically tolerant and may safely receive a kidney from the same donor without immunosuppression. These findings have subsequently been confirmed (3, 12, 13, 16, 17). It has been stressed that recipients should be carefully followed for symptoms and signs of GVHD (10) (Table 2).…”

Section: Discussionmentioning

confidence: 68%

Successful renal transplantation following prior bone marrow transplantation in pediatric patients

Thomas

Hutchinson²,

DebRoy

et al. 2004

Pediatric Transplantation

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Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system impairment and bone marrow function should be taken into consideration when weighing different immunosuppressive agents for renal transplantation. Patients who have undergone renal transplantation following BMT are at high risk for opportunistic infections and malignancy, and need life-long medical surveillance.

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Section: Discussionmentioning

confidence: 68%

Successful renal transplantation following prior bone marrow transplantation in pediatric patients

Thomas

Hutchinson²,

DebRoy

et al. 2004

Pediatric Transplantation

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“…This may suggest that the state of mixed chimerism that we observe in this allograft, which has been the subject of both animal and human studies, may provide a benefit. In human studies, tolerance has succeeded in patients who undergo a kidney or liver transplant combined with bone marrow transplantation, a state where the donor hemopoietic cells engraft the recipient's bone marrow 20,21 . However, the role of epithelial chimerism is less clear.…”

Section: Discussionmentioning

confidence: 99%

“…In human studies, tolerance has succeeded in patients who undergo a kidney or liver transplant combined with bone marrow transplantation, a state where the donor hemopoietic cells engraft the recipient's bone marrow. 20,21 However, the role of epithelial chimerism is less clear. In lung transplantation, there is longitudinal evidence of recipient-derived epithelial cells in transplanted lungs 22 however the implications of this finding are unclear.…”

Section: Discussionmentioning

confidence: 99%

Vascularized Tracheal Transplantation: A Twenty Month Follow Up

et al. 2022

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Background: Tracheal transplantation has been considered the ideal option for the reconstruction of long-segment circumferential tracheal defects. Our group developed a technique for vascularized single-staged tracheal transplantation. Twenty months ago, we performed the first-in-human tracheal transplantation. Herein, we report a twenty-month follow-up.Methods: The recipient presented with a 9.0 cm airway tracheal stenosis and complete cricoid stenosis. The patient previously failed six major conventional surgical procedures. Prior to transplantation, the patient's airway was maintained with an extended tracheostomy and stent. The patient experienced repeated life-threatening airway obstruction because of mucous plugging and obstructive granulation tissue. In January 2020 the patient underwent a single-staged tracheal transplantation treated with triple-therapy immunosuppression. Organ rejection was monitored with endoscopic tracheoscopy, narrow-band imaging, free-cell DNA assessment, and histological and cytogenetic analysis of tracheal biopsies. Mucociliary function was assessed with dye motility studies.Results: Twenty months following transplantation, there has been no evidence of acute or chronic rejection. Since day 60, there has been no detectable free cell DNA, a surrogate marker for immune-mediated allograft rejection. Fluorescence in situ hybridization (FISH) cytogenetics demonstrated that the donor trachea was repopulated with recipient epithelium establishing a chimeric allograft. Narrow-band imaging demonstrates a well-vascularized epithelial mucosa and bronchoscopic biopsies demonstrate normal ciliated epithelial architecture and viable epithelial lining with functional ciliated epithelium. The patient has resumed a normal life without a stent or tracheostomy and has returned to work.Conclusions: Twenty months after single-staged vascularized tracheal transplantation, the trachea is functional and the patient breathes without the need for a tracheostomy or stent. Single-staged long-segment tracheal transplantation is a viable option for tracheal defects that are not amenable to conventional reconstructive techniques.

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“…Subsequently, several small studies reported similar findings for kidney [25–30], lung [31] and liver [32] transplantation. Interestingly, three recent case reports showed that tolerance can also be achieved when an organ transplant is followed by BMT from the same donor [33–35]. Eight additional patients receiving BM after solid organ transplant from the same donor have been summarized [36].…”

Section: General Introductionmentioning

confidence: 99%

Clinical experience with mixed chimerism to induce transplantation tolerance

Fehr

Sykes

2008

Transplant International

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Summary Lymphohematopoietic chimerism was first shown to be associated with donor‐specific allograft tolerance more than 60 years ago. However, early clinical experience with bone marrow transplantation soon revealed that conventional, myeloablative approaches were far too toxic and the risk of graft‐versus‐host disease too great to justify using this technology for the purpose of organ allograft tolerance induction in the absence of malignant disease. In this review, we discuss a step‐wise approach that has been applied by several centers to establish less toxic approaches to using hematopoietic cell transplantation (HCT) for tolerance induction. These steps include (i) feasibility and efficacy data for tolerance induction in large animal models; (ii) safety data in clinical trials for patients with hematologic malignancies; and (iii) pilot trials of combined HCT and kidney transplantation for tolerance induction. Thus far, only one published trial conducted at the Massachusetts General Hospital in Boston has achieved long‐term acceptance of human leukocyte antigen‐mismatched kidney allografts without chronic immunosuppressive therapy. Alternative protocols have been successful in large animals, but long‐term organ allograft tolerance has not been reported in patients. Thus, proof‐of‐principle that nonmyeloablative induction of mixed chimerism can be used intentionally to induce organ allograft tolerance has now been achieved. Directions for further research to make this approach applicable for a broader patient population are discussed.

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Discontinuation of immunosuppression for prevention of kidney graft rejection after receiving a bone marrow transplant from the same HLA identical sibling donor

Cited by 11 publications

References 17 publications

Successful renal transplantation following prior bone marrow transplantation in pediatric patients

Successful renal transplantation following prior bone marrow transplantation in pediatric patients

Vascularized Tracheal Transplantation: A Twenty Month Follow Up

Clinical experience with mixed chimerism to induce transplantation tolerance

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