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Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient

From the Hôpital Henri Mondor, Créteil (SM); France Greffe de Moelle (FGM), Saint Denis (M-LB-A); Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC), Saint Denis (ZC); Hôpital Haut Lévêque, Pessac (J-MB); Hôpital Debrousse, Lyon (CG); Hôpital Robert Debré, Paris (KY); Hôpital de Brabois, Nancy (PB); Hôpital Charles Nicolle, Rouen (AM-C); Hôpital Hotel Dieu, Nantes (NM); Hôpital Hôtel Dieu, Clermont Ferrand (JK); Hôpital Necker Adultes, Paris (NM); Hôpital Saint-Louis, Paris, France (GS)

Correspondence: Sébastien Maury, M.D., Ph.D., Service d’Hématologie, Hôpital Henri, Mondor, 51, Avenue du Mal de Lattre, de Tassigny, 94010 Créteil, France. E-mail: sebastien.maury{at}hmn.aphp.fr

Background and Objectives: 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.

Design and 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 years, p<0.0001). Survival reached 78±11% at 5 years for the younger, fully HLA-matched patients.

Interpretation and 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.

Key words: aplastic anemia, volunteer donors, HLA matching, prognostic factors.

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