title: Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient.
abstract: OBJECTIVE
  Severe acquired aplastic anemia (SAA) is a potentially fatal bone marrow failure syndrome occurring mainly in children and young adults. Immunosuppressive regimens and hematopoietic stem cell transplantation (HSCT) are the only two available curative treatments. Patients who lack an HLA-identical sibling donor may receive HSCT from an unrelated donor, a strategy historically associated with high mortality rates. Thus, for patients refractory to immunosuppressive regimens, the decision to transplant stem cells from unrelated donors is weighed against supportive care and often represents a dilemma for physicians. We aimed to determine whether outcome after unrelated HSCT has improved in recent years and, if so, to determine the factors responsible for the improvement.
  
  
  METHODS
  We analyzed the outcome of 89 patients (median age 17 years, range 0-52) with acquired SAA undergoing HSCT from an unrelated donor between 1989 and 2004. Cases were consecutively reported to the French Registry (SFGM-TC) by 25 centers.
  
  
  RESULTS
  Patients transplanted during two successive time-periods (1989-1998 and 1999-2004) had different 5-year survival probabilities (+/-95% confidence interval): 29%+/-7% and 50%+/-7%, respectively (p<0.01). The main difference between the two cohorts concerned HLA matching between donors and recipients at the allelic level for the ten HLA-A, -B, -C, -DRB1 and -DQB1 antigens, which was more frequent in 1999-2004 than in the former period (p=0.0004). In multivariate analysis, the only two factors affecting survival were HLA allelic matching (p<0.01) and younger age of recipient (17 pounds sterling years, p<0.0001). Survival reached 78%+/-11% at 5 years for the younger, fully HLA-matched patients.
  
  
  CONCLUSIONS
  Survival after unrelated HSCT for SAA has improved significantly over the past 15 years, mainly due to better HLA matching. Results for young patients who are fully HLA-matched at the allelic level with their donor are comparable to those observed after HSCT from a related donor.
authors.affiliation: Service d'Hématologie, Hôpital Henri Mondor, Créteil, France. sebastien.maury@hmn.aphp.fr
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
authors.forename: Marie-Lorraine
authors.initials: ML
authors.lastname: Balère-Appert
authors.forename: Zina
authors.initials: Z
authors.lastname: Chir
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Boiron
authors.forename: Claire
authors.initials: C
authors.lastname: Galambrun
authors.forename: Karima
authors.initials: K
authors.lastname: Yakouben
authors.forename: Pierre
authors.initials: P
authors.lastname: Bordigoni
authors.forename: Aude
authors.initials: A
authors.lastname: Marie-Cardine
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.forename: Judith
authors.initials: J
authors.lastname: Kanold
authors.forename: Natacha
authors.initials: N
authors.lastname: Maillard
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000209:etiology / Q000401:mortality / Q000601:surgery*; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002423:Cause of Death; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data*; D006457:Hemoglobinuria, Paroxysmal / Q000150:complications; D006505:Hepatitis / Q000150:complications; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D019520:Living Donors; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012086:Reoperation; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D015996:Survival Rate; D013601:T-Lymphocytes; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000961:Antilymphocyte Serum; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine