Reduced Intensity Conditioning Regimen for Unrelated Cord Blood Transplantation in Adults. A Multicentric Phase I-II Trial.

Curative potential of allogeneic transplantation from related or unrelated donors is limited by tranplant related mortality (TRM) and donor compatibility. After reduced intensity conditioning regimens (RIC) transplantation can be extended to older patients, those with poor performance status, organ dysfunction or intensive prior therapy. In absence of HLA-matched donor, unrelated cord blood transplant (UCBT) is a possible source of hematopoietic stem cells. In order to confirm previous report of RIC after UCBT in adults we conducted a phase I–II trial. Primary endpoint was neutrophil recovery and chimerism. Secondary endpoints were early TRM, acute GVHD incidence, early relapse and survival. Between October 2003 and March 2005, 18 patients (pts) were enrolled: median age: 46y (19–64), weight: 62.5 kg(45–90), gender: 13 females and 5 males, CMV serpositivity in 8 pts, ABO major incompatibility in 8 pts. The median of follow-up was 4.5 mo (0.5–16). Disease status were 2 ALL (CR1: 1; CR2: 1), 10 AML (CR1: 3, CR2: 6, CR3: 1), 1 AP CML, 1 CLL, 1 Waldenström disease, 3 follicular lymphoma relapsed after autologous transplantation. Infused nucleated and CD34+ cells number were respectively: 2.3x107/kg (1.7–3.7) and 0.7x105/kg (0.4–1.2). Only a single cord blood was used. HLA disparity was 0/6 in 1, 1/6 in 6 and 2/6 in 11. RIC regimen consisted of cyclophosphamide 50 mg/kg D-6, fludarabine 200 mg/m² and 2Gy TBI at D-1. CsA and MMF from D-3 were used in GVHD prophylaxis. Pts received GCSF until 5 G ANC/l.

Results: Median day for 0.5 G/l ANC recovery was 14 days (0–28) and for 20 G/l platelets was 28 days (0–48). Mixt chimerism was present until D+56 and full chimerism at D+80/100 in all pts except 2 who relapsed. Mucositis was not observed, CMV reactivation in 2 pts, bacteremia in 3, SRV pneumonitis in 1 pt, bone aspergillosis in 1 pt. Regressive limbic encephalitis in 2 pts. Two pts recovered normal ovarian function 5 mo and 12 mo after UCBT. Grade 2 acute GVHD was observed in 2 pts and limited chronic GVHD in 3 out of 8 pts at risk. TRM was 0%. Two pts relapsed and died at D+100 and D+171. EFS was 80+/−13%. In conclusion, in spite of the short follow-up and few patients enrolled in this trial, these results confirm those reported by Barker J et al. Importantly there was a rapid neutrophil recovery with acquired late full chimerism and absence of early TRM. The encouraging results justify the use of cord blood cells in RIC and prospective trials in order to compare phenoidentical peripheral blood stem cell transplantation and UCBT with the same RIC regimen.