Results of Unrelated Cord Blood Transplants in Fanconi Anemia.

Background: allogeneic hematopoietic stem cell transplant (HSC) is the only chance of cure in patients with Fanconi anemia (FA). Unrelated cord blood transplant is a possible alternative source of HSC. We report here a worldwide experience of unrelated cord blood transplant (UCBT) in a series of 72 patients with FA.

Patients and transplant characteristics : This is a retrospective multicenter analysis of 72 patients (62 children, 12 adults) with FA complicated by severe aplastic anemia or leukemia/MDS. Median age was 8 years ( 1–45), median follow-up after UCBT 23 months. The unrelated CB was HLA identical for A, B DRB1 in 9 cases, had 1 HLA difference in 29 cases and 2 or 3 HLA differences in 33 cases. The median number of nucleated cells (NC) infused was 4.4x107/kg, of CD34+ 2.1x105/kg. Conditioning varied: 24 patients received low dose cyclophosphamide with low dose TBI/TLI, 33 Fludarabine with cyclophosphamide and TBI or Busulfan, 55 patients received ATG. GVH prophylaxis consisted of cyclosporine alone (16) or with prednisone (37).

Results: CI of engraftment was 54%. In multivariate analysis: unfavourable factors were nb of HLA differences>2 (p .007) and NC infused <4.4x107/kg (p.04) CI of GVH> II was 32% and of cGVH 11%. Overall survival was 36%. In multivariate analysis, favourable factors were negative recipient CMV serology ( p.001), nb of NC infused> 4.4x107/kg (p.007) and use of Fludarabine (p.035). Causes of death were non engraftment :10 pts, GVH: 4 pts, infections: 15 pts and toxicity:15 pts. These results are quite similar to our current results of matched unrelated bone marrow transplant.

Conclusion: results of unrelated cord blood transplants could be improved by better patient and cord blood selection with units closely HLA matched and high number of cells, Conditioning with Fludarabine seems to improve results. In FA, use of cord blood might be beneficial because of the reduction of the risk of GVH which might decrease the risk of long term cancers.