Long-Term Outcome and Prognostic Factors after Single-Unit Umbilical Cord-Blood Transplantation (UCBT) for Adults with Hematologic Malignancies.
Authors: Sanz Guillermo , Cantero Susana , Larrea Luis , Planelles Dolores , Lorenzo Ignacio , Banlloch Barbara , Banlloch Luis , Senent Leonor , Montesinos Pau , Cervera Jose , Jimenez Carmen , Martin Guillermo , Martinez Jesus , Jarque Isidro , De la Rubia Javier , Sanz Miguel A. 
Published: October 2019

The major aim of this study was to update our preliminary report on the results of single-unit UCBT for adults with hematologic malignancies (Sanz GF et al, Blood2001; 98:2332). From May 1997 to June 2006, 92 patients underwent single-unit UCBT with a myeloablative conditioning that included thiotepa (TT), busulfan (BU; oral, 43; iv, 49 - iv single daily dose, 20), cyclophosphamide (72) or fludarabine (FLU; 20), and antithymocyte globulin (Lymphoglobulin, 32; Thymoglobulin [THY], 60). All received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis and filgrastim to fasten engraftment. Diagnoses were acute lymphoblastic leukemia in 34, acute myeloblastic leukemia in 25, chronic myelogenous leukemia (CML) in 21, myelodysplastic syndrome in 5 and lymphoid malignanices in 7. The stage of the disease at transplant was advanced in 32 cases (35%). Median age and weight were 31 yr (range, 16–47) and 71 kg (range, 41–112). HLA match (HLA-A and -B at antigen and -DRB1 at allelic level) was 6/6 in 5 (5%), 5/6 in 33 (34%), and 4/6 in 54 cases (59%). The median number of nucleated cells (NCs) and CD34+ cells infused was 2.1 x 107/kg (range, 0.9–4.9) and 1 x 105/kg (range, 0.1–5.7) respectively. Median time to neutrophils > 0.5 × 109/L and platelets > 20 × 109/L was 22 days (range, 11–57) and 88 days (range, 27–188), and the cumulative incidence of myeloid and platelet engraftment was 90% at 60 days and 64% at 180 days, respectively. The cumulative incidence of grade II–IV acute GVHD was 36% (grade III–IV, 18%) and 28 of 55 patients at risk (51%) developed chronic GVHD (extensive in 19). The cumulative incidence of non-relapse mortality (NRM) at 30 days, 100 days, and 3 years was 8%, 25%, and 40% respectively. With a median follow-up of 26 months (range, 2–111), the cumulative incidence of relapse and the probability of disease-free survival (DFS) at 3 years were 21% and 39% (95% CI, 27–51%). Multivariate analyses showed that the absolute number of CD34+ cells in the UCB unit was the most important predictor of myeloid and platelet engraftment (P < 0.0001). The use of THY was related to faster platelet engraftment (P < 0.01) and lower incidence of acute GVHD (P < 0.0001). The development of grade II–IV acute GVHD was associated with slower platelet engraftment (P < 0.01) and greater NRM (P = 0.03). A higher age predicted for greater NRM (P = 0.005) whereas conditioning with TT, FLU, iv BU as a single daily dose, and THY (P = 0.004) and higher numbers of CD3+ cells infused (P = 0.0024) were associated with a lower NRM. Risk of relapse was lower for patients with CML (P = 0.02) and higher for those transplanted in advanced disease stage (P = 0.02). The only variable independently associated with DFS was the stage of the disease at transplant (P = 0.001). For patients transplanted in early stages DFS at 3 years was 52% (95% CI, 37–67%). The number of NCs and HLA mismatches did not impact any outcome. These results confirm that single-unit UCBT is a clear alternative for adults with high-risk hematologic malignancies, especially if transplanted in early stages. They also show that the universally accepted criteria for selecting the best UCB unit for transplantation in adults need to be modified.