Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA Working Party.

Abstract

BACKGROUND:

We analyzed the outcome of 100 patients with acquired severe aplastic anemia undergoing an alternative donor transplant, after immune suppressive therapy had failed.

DESIGN AND METHODS:

As a conditioning regimen, patients received either a combination of fludarabine, cyclophosphamide, and antithymocyte globulin (n=52, median age 13 years) or this combination with the addition of low dose (2 Gy) total body irradiation (n=48, median age 27 years).

RESULTS:

With a median follow-up of 1665 and 765 days, the actuarial 5-year survival was 73% for the group that received fludarabine, cyclophosphamide, and antithymocyte globulin and 79% for the group given the conditioning regimen including total body irradiation. Acute graft-versus-host disease grade III-IV was seen in 18% and 7% of the groups, respectively. Graft failure was seen in 17 patients with an overall cumulative incidence of 17% in patients receiving conditioning with or without total body irradiation: 9 of these 17 patients survive in the long-term. The most significant predictor of survival was the interval between diagnosis and transplantation, with 5-year survival rates of 87% and 55% for patients grafted within 2 years of diagnosis and more than 2 years after diagnosis, respectively (P=0.0004). Major causes of death were graft failure (n=7), post-transplant-lymphoproliferative-disease (n=4) and graft-versus-host disease (n=4).

CONCLUSIONS:

This study confirms positive results of alternative donor transplants in patients with severe aplastic anemia, the best outcomes being achieved in patients grafted within 2 years of diagnosis. Prevention of rejection and Epstein-Barr virus reactivation may further improve these results.

• Authors: Andrea Bacigalupo, Gerard Socie', Edoardo Lanino, Arcangelo Prete, Franco Locatelli, Anna Locasciulli, Simone Cesaro, Avichai Shimoni, Judith Marsh, Mats Brune, Maria Teresa Van Lint, Rosi Oneto, Jacob Passweg, Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation
• Journal: Haematologica (Haematologica) Vol. 95 Issue 6 Pg. 976-82 (Jun 2010) ISSN: 1592-8721 [Electronic] Italy
• PMID: 20494932 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antilymphocyte Serum
• Cyclophosphamide
• Vidarabine
• fludarabine

Topics

• Adolescent
• Adult
• Anemia, Aplastic (drug therapy, mortality, surgery)
• Antilymphocyte Serum (therapeutic use)
• Bone Marrow Transplantation (methods)
• Child
• Child, Preschool
• Cyclophosphamide (therapeutic use)
• Europe
• Female
• Follow-Up Studies
• Graft vs Host Disease (drug therapy, mortality, prevention & control)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Living Donors
• Male
• Middle Aged
• Retrospective Studies
• Survival Rate (trends)
• Transplantation Conditioning (methods)
• Vidarabine (analogs & derivatives, therapeutic use)
• Whole-Body Irradiation (methods)
• Young Adult