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Haploidentical hematopoietic cell and kidney transplantation for hematological malignancies and end-stage renal failure

Yi-Bin Chen, Nahel Elias, Eliot Heher, Jeannine S. McCune, Kerry Collier, Shuli Li, Candice Del Rio, Areej El-Jawahri, Winfred Williams, Nina Tolkoff-Rubin, Jay A. Fishman, Steven McAfee, Bimalangshu R. Dey, Zachariah DeFilipp, Paul V. O’Donnell, A. Benedict Cosimi, David Sachs, Tatsuo Kawai and Thomas R. Spitzer

Key Points

  • Combined haploidentical HCT/kidney transplantation is safe and feasible with posttransplantation cyclophosphamide.

  • Fludarabine can be used for conditioning in patients with end-stage renal disease if proper dose adjustments and dialysis are used.

Abstract

At Massachusetts General Hospital, we pioneered simultaneous hematopoietic cell (HCT)/kidney transplantation from HLA-identical related donors for the treatment of hematological malignancies with end-stage renal failure. We have now extended this to HLA-haploidentical donors in a pilot trial. Six recipients, 5 of whom were conditioned with fludarabine, cyclophosphamide, and total-body irradiation, underwent combined HCT/kidney transplantation from haploidentical donors; graft-versus-host disease (GVHD) prophylaxis included post-HCT cyclophosphamide, tacrolimus, and mycophenolate mofetil. One patient died as a result of complications of fludarabine neurological toxicity. No neurological toxicity was observed in subsequent patients who received lower fludarabine doses and more intense postfludarabine dialysis. There were no cases of grade 2 to 4 acute GVHD and 1 case of moderate chronic GVHD by 12 months. One patient experienced relapse of multiple myeloma at 30 months after HCT and died 4 years posttransplantation. Overall, 4 of 6 patients remain alive, without disease relapse and with long-term renal rejection–free survival. This trial was registered at www.clinicaltrials.gov as #NCT01758042.

  • Submitted March 25, 2019.
  • Accepted May 22, 2019.
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