Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath

Br J Haematol. 2001 Sep;114(3):701-5. doi: 10.1046/j.1365-2141.2001.02993.x.

Abstract

The increasing success of human leucocyte antigen (HLA)-matched sibling donor (MSD) transplants and combination immunosuppressive treatments have dramatically improved the prognosis of severe aplastic anaemia (SAA) in children and young adults. For patients who lack a MSD there is a significant minority who fail immunosuppressive therapy or suffer from a severe constitutional aplastic anaemia in which immunosuppression would be ineffective. Alternative donor bone marrow transplantation (AD-BMT) has only had limited success in this context. We report the successful outcome of AD-BMT in eight consecutive patients aged 7 months to 15 years, six of whom had acquired aplastic anaemia who had previously failed to respond to immunosuppression, and two of whom had a severe (non-Fanconi) constitutional aplastic anaemia. All eight patients had received multiple red cell and platelet transfusions. We used a new combination of agents for pretransplant conditioning aiming to maximize immunosuppression and minimize toxicity, consisting of Campath-1G or -1H, cyclophosphamide and low-dose total body irradiation (LD TBI) or fludarabine. Toxicity was minimal and all eight children are alive, well and free of disease at a median follow-up of 32 months. We suggest that this approach could facilitate the successful treatment of children with SAA in whom immunosuppressive therapy has failed or is not appropriate.

Publication types

  • Multicenter Study

MeSH terms

  • Alemtuzumab
  • Anemia, Aplastic / immunology
  • Anemia, Aplastic / therapy*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Bone Marrow Transplantation / methods*
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Infant
  • Male
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Treatment Outcome
  • Whole-Body Irradiation

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • Immunosuppressive Agents
  • Alemtuzumab
  • Cyclophosphamide