Unrelated stem cell transplantation (SCT) for fanconi anemia(FA) using cyclophosphamide(CY)+ fludarabine(FLU)+ thymoglobuline(THYMO): Consecutive analysis of 20 patients treated at the same instituition

Abstract

Background: From 1983 until September 2004, 147 patients received a SCT for FA in our BMT center and most of them were in aplastic phase. In this study we selected 20 consecutive patients who received an unrelated SCT for this disease using the same preparative regimen. Patients and Methods: Period: 02/2000 to 09/2004; median age: 8 years (range, 4–14 years); sex: 13 females and 7 males; median disease duration, 36 month (range, 7–67 months); previous transfusions: 1–65 UI(median, 12 UI); aplastic phase: 20 patients; stem cell source: bone marrow (BM), 6 patients, cord blood (CB), 14 patients; HLA disparities in 12 patients; preparative regimen: CY 60mg/kg+ FLU125 mg/m2+ THYMO(rabbit) 4 mg/kg; GVHD prophylaxis: cyclosporine (Csa)+ MTX, 6 patients (BM) or Csa+ steroids, 14 patients(CB). Allpatients received prophylactic antibiotics according to commonpractice. Results: Eleven patients (55%) are alive and well 55–566 days after transplant (M:169d). Median time to reach PMN> 500/μl was 23 days and that to reach platelets> 20.000/μl was 25 days after transplantation. Seventeen patients were evaluable for engraftment (3 patients died before day 28), and 14 patients achieved complete hematologic recovery. Three patientshad only neutrophil engraftment, and they all died early aftertransplantation (on day +32, +34, and +58) due to infectioncomplications. Nine patients died in the entire cohort betweenday +7 and +120 (median, 34 days), and in 8 patients infection was the main cause of death. Acute GVHD grade II-IV developed in 5 of 17 evaluable patients; chronic GVHD, in 1 of 10 evaluable patients. Mucositis grade III-IV occurred in 9 patients. Due to delayed immune reconstitution, EBV lymphoproliferative disease occurred in 3 patients, and in 1 of them it was the main cause of death. Two patients treated with rituximab are alive and well 6 and 10 months after EBV infection. There was no significant difference in survival for patients receiving BM or CB (67% vs 50%; P= .52). Patients receiving BM had a higher incidence of mucositis grade III-IV (83%) compared with CB (29%). Acute GVHD was the same in both groups and we did not observe chronic GVHD in patients receiving BM. Conclusions: The use of CY+ FLU+ THYMO as a preparative regimen in patients with FA provided rapid and sustained engraftment for most patients. However, transplantation-related mortality is still very high, and opportunistic infections occurring in the first 100 days remain the major causes of morbidity and mortality in this group of patients.