Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

Haematologica. 2012 May;97(5):710-6. doi: 10.3324/haematol.2011.050096. Epub 2011 Dec 16.

Abstract

Background: Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen.

Design and methods: We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days).

Results: Median age was 21 years (range 4-43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV graft-versus-host disease was 23% (95%CI 13-34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20-46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P = 0.017). With a median follow up of 73 months (range 8-233), the estimated 6-year overall survival was 87% (95% CI 78-97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin's lymphoma) during follow up.

Conclusions: Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Aplastic / etiology
  • Anemia, Aplastic / mortality
  • Anemia, Aplastic / prevention & control*
  • Antilymphocyte Serum / therapeutic use*
  • Child
  • Child, Preschool
  • Cyclophosphamide / therapeutic use*
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Prognosis
  • Survival Rate
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Cyclophosphamide