Cord Blood Transplantation after Non Myeloablative Conditioning (Minneapolis Protocol): Impact on Transplant Outcomes in 112 Adults with Hematologic Malignancy. A French Multicentric Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and Eurocord.

The aim of this retrospective multicentric study was to assess the results of 112 consecutive umbilical cord blood transplantations (UCBT) following nonmyeloablative conditioning (NMA) performed in 20 French centres, between October 2003 and March 2007.Characteristics of the patients : Underlying disease: acute leukaemia: myeloid 60, lymphoblastic 17, lymphoma: 15, myelodysplasia: 5, myeloma: 4, Hodgkin: 4, chronic leukaemia: myeloid 3 and lymphoid 3 and 1 solid tumor. Median age at transplantation: 44 y (16–69), median weight: 62 kg (42–125), male: 49 (43%), CMV seropositivity: 64% ; 32 pts had received previous autologous and 3 allogeneic transplantation. The time between diagnosis and transplant was 19 months (3–174). Disease status at transplantation was early (31%), intermediate (37%) and advanced (32%). Median follow-up was 7 months (2–38). The original Minneapolis conditioning regimen was used in 106 (96%) pts and modified in 6 (4 or 6 Gy TBI: 4 pts; ATG: 2). Characteristics of the grafts: A single unit was infused in 77 pts (69%), two in 35 (31%). HLA compatibility was 6/6 in 6 pts, 5/6 in 36, 4/6 in 60, ≤ 3/6 in 6 ; 43 pts were ABO matched. Infused nucleated cells (NC) was 3.1×10⁷/kg (1–9): 2.9 × 10⁷/kg in single units and 3.7 × 10⁷/kg in double units. Results: Neutrophils recovery was 85±4% at a median of 19 days (0–48) ; 14% pts experienced autologous recovery; 14% had mixed and 72% full donor chimerism at D+100. Univariate analysis indicated the low weight, previous transplantation, double units and HLA compatibility as significant factors for neutrophil recovery; however multivariate analysis did not find any significant factor. Acute GVHD was observed in 34±5% of pts: 21, 12 and 5 pts had grade II, III or IV aGVHD respectively and chronic GVHD in 16%. Non relapse mortality was 12±3% at 6 months ; relapse: 22±5% ; overall survival: 72±5%. Causes of death were relapse in 17 pts, GVHD in 2 pts, venocclusive disease and multiorgan failure in 5, infections in 4 and other toxicity in 3. DFS at 6 and 24 months were 68±5% and 65±5%, respectively. By univariate analysis, risk factors for DFS were age (>44y), weight, previous transplant, HLA disparity (0+1 vs 2+3), and NC dose (<3.1× 10⁷/kg). Multivariate analysis identified 3 independent risk factors: HLA disparity, cell dose and age were still significant. This French experience of UCBT after NMA confirms the good results of the Minneapolis group (Brunstein et al. Blood 2007). Few events were observed between 6 and 24 mo and DFS remains high, however a longer follow up is needed. A prospective study of UCBT after NMA conditioning in AML is ongoing in France to identify the risk factors for DFS in a more homogeneous group of pts.