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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 W. Williams, Nina Tolkoff-Rubin MD, 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 hematopoietic cell and kidney transplantation is safe and feasible with post-transplant cyclophosphamide.

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

Abstract

At Massachusetts General Hospital (MGH), we pioneered simultaneous hematopoietic cell (HCT) / kidney transplantation from HLA-identical related donors for the treatment of hematological malignancies with end-stage renal failure (ESRD). We have now extended this to HLA-haploidentical donors in a pilot trial (NCT01758042). Six recipients underwent combined HCT / kidney transplantation from haploidentical donors, five of whom were conditioned with fludarabine, cyclophosphamide and total body irradiation; graft-vs.-host disease (GVHD) prophylaxis included post-HCT cyclophosphamide, tacrolimus and mycophenolate mofetil. One patient died from complications of fludarabine neurological toxicity. No neurological toxicity was observed in subsequent patients who received lower fludarabine doses and more intense post-fludarabine dialysis. There were no cases of grades II-IV acute GVHD and one case of moderate chronic GVHD by 12 months. One patient experienced relapse of multiple myeloma at 30 months after HCT and died four years post-transplant. Overall, four of six patients remain alive, without disease relapse and with long-term renal rejection-free survival.

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