Outcomes of Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Severe Sickle Cell Disease With Myeloablative Conditioning and Intermediate-Dose of Rabbit Anti-Thymocyte Globulin

Pediatr Blood Cancer. 2014 Sep;61(9):1685-9. doi: 10.1002/pbc.25059. Epub 2014 Apr 17.

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for sickle cell disease (SCD) in children. Despite excellent outcomes of matched sibling donor (MSD) HSCT, there is still 5-10% chance of rejection and transplant related mortality (TRM) with 12-23% incidence of graft versus host disease (GVHD). We postulated that an intermediate dose of rabbit anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in preventing both rejection and GVHD.

Patients and methods: Fifteen patients, median age 5 (range 1.5-18) years, underwent MSD HSCT using busulfan (≥ 12.8 mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r-ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given for GVHD prophylaxis.

Results: All patients achieved donor engraftment and there was no TRM. One patient rejected donor cells at 2 months post-transplant. Majority of the patients had high and sustained level of donor chimerism. None of the patients developed ≥ Grade II GVHD. Incidence of CMV (10%) and EBV (9%) reactivations was low with rapid immune-reconstitution. Overall survival was 100% with event free survival of 93%.

Conclusions: Eliminating the risks of TRM and GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD.

Keywords: blood and marrow transplant; sibling donor; sickle cell disease; stem cell transplant.

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / therapy*
  • Animals
  • Antilymphocyte Serum / therapeutic use*
  • Busulfan / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Male
  • Myeloablative Agonists / therapeutic use*
  • Prospective Studies
  • Rabbits
  • Siblings*
  • Tissue Donors*
  • Transplantation Conditioning*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Busulfan