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


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.
Bacigalupo
Andrea
A
Divisione Ematologia e Trapianto di Midollo Osseo, Ospedale San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy. andrea.bacigalupo@hsanmarti-no.it
Socie'
Gerard
G
Lanino
Edoardo
E
Prete
Arcangelo
A
Locatelli
Franco
F
Locasciulli
Anna
A
Cesaro
Simone
S
Shimoni
Avichai
A
Marsh
Judith
J
Brune
Mats
M
Van Lint
Maria Teresa
MT
Oneto
Rosi
R
Passweg
Jacob
J
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D019172:Transplantation Conditioning / Q000379:methods; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014916:Whole-Body Irradiation / Q000379:methods; D055815:Young Adult
D000961:Antilymphocyte Serum; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine