Low Transplant-Related Mortality in Patients with Hematologic Malignancies Undergoing Umbilical Cord Blood Transplantation (UCBT) with Thiotepa (TT), Once-Daily Intravenous (IV) Busulfan (BU), Fludarabine (FLU) and Anti-Thymocyte Globulin (ATG).

High transplant-related mortality (TRM) is of major concern after myeloablative conditioning for UCBT. The use of once-daily IV BU and FLU has recently shown to reduce TRM and prolong disease-free survival (DFS) in patients with myeloid malignancies undergoing transplantation from HLA-identical siblings and marrow unrelated donors. The aim of this study of the GETH cooperative group was to evaluate the short term outcome of single-unit UCBT for the treatment of patients with high-risk hematologic malignancies after conditioning with TT, once-daily IV BU, FLU and rabbit ATG. Seventy-three consecutive patients (37 males, 36 females) with a median age of 31 yr (range, 1–54; 67 adults) who underwent transplantation from March 2005 to March 2007 were included. Conditioning consisted of TT (5 mg/kg/d on days -7 and -6), FLU (50 mg/m²/d on days −5, −4, and −3), once-daily IV BU (3.2 mg/kg on days −5, −4, and −3) and Thymoglobulin (2 mg/kg/d on days −5, −4, −3, and −2). Cyclosporine and prednisone were used for graft-versus-host disease (GVHD) prophylaxis. Most patients (92%) received an HLA-mismatched UCB unit with 1 (36%) or 2 (56%) HLA disparities. The median number of nucleated and CD34+ cells infused was 2.5 x 10⁷/kg and 1.4 x 10⁵/kg respectively. Baseline diagnosis was AML (32 pts), ALL (29), MDS (4), Hodgkin’s disease (4), NHL (3), and CML (1). Fifty-three patients (73%) were on early disease stage at transplant (acute leukemia and lymphoma in CR1 or CR2, MDS untreated or in CR, and CML in CP) and 15 (20%) had failed a previous autologous stem cell transplant (ASCT). Cumulative incidence (CI) of myeloid and platelet engraftment was 89% and 64% (Kaplan-Meier cumulative probability, 100% and 75%) at a median time of 22 (range, 11–52) and 41 (range, 24–115) days respectively. CI of grades II-IV and III-IV acute GVHD was 16% and 6% respectively. With a median follow-up of 7 months (range, 2–24) TRM at 100 and 180 days was 14% and 20% respectively, and was significantly increased in patients > 30 yrs (25% vs 14%; p = 0.05) and in those with a previous ASCT (51% vs 13%; p < 0.01). Causes of death (22 pts) were infection (11; 3 aspergillosis, 2 bacterial blood stream infections, 2 tuberculosis, 2 pneumonia, 1 CMV disease and 1 toxoplasmosis), relapse (5), GVHD (1), graft failure (1), veno-occlusive disease (1), post-transplant lymphoproliferative disorder (1), microangiopathic hemolytic anemia (1), and multiorgan failure (1).These results suggest that the present myeloablative conditioning regimen for single-unit UCBT offers a high and fast engraftment rate and a low incidence of both acute GVHD and TRM in patients with hematologic malignancies. Longer follow-up is required to assess its impact on relapse risk and DFS.