HLA Haploidentical Stem Cell Transplant with Pretransplant Immunosuppression for Patients with Sickle Cell Disease

Biol Blood Marrow Transplant. 2018 Jan;24(1):185-189. doi: 10.1016/j.bbmt.2017.08.039. Epub 2017 Sep 20.

Abstract

Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD), but a significant number of patients lack an HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report we describe a favorable haploidentical HCT approach in a limited cohort of SCD patients with significant comorbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit antithymocyte globulin, busulfan, and fludarabine preceded with 2 courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine and dexamethasone. Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil starting on day +5. Four patients (ages 13, 19, 19, and 23 years) received T cell-replete haploidentical stem cell infusion. All patients engrafted with 99.9% to 100% donor chimerism, and all patients continued with stable engraftment at the last follow-up (5 to 11 months post-transplant). Time to neutrophil engraftment was 14 to 26 days. Two patients had high levels of donor-specific anti-HLA antibodies, which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26, respectively. One patient developed grade I acute GVHD, which resolved. Three patients developed mild, limited skin GVHD that responded to conventional immunosuppressive therapy. Human herpesvirus-6 viremia was detected in 3 patients but resolved without treatment. One patient developed asymptomatic cytomegalovirus viremia that responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for patients with SCD.

Keywords: Haploidentical stem cell transplantation; Hematopoietic stem cell transplantation; Post-transplant cytoxan; Sickle cell disease.

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / therapy*
  • Antilymphocyte Serum / therapeutic use
  • Busulfan / therapeutic use
  • Cohort Studies
  • Dexamethasone / therapeutic use
  • Graft Survival
  • Humans
  • Immunosuppression Therapy / methods*
  • Immunosuppressive Agents / therapeutic use
  • Transplantation, Haploidentical / methods*
  • Transplantation, Homologous / methods
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Dexamethasone
  • thymoglobulin
  • Vidarabine
  • Busulfan
  • fludarabine