Cord Blood Transplantation from Unrelated Donors for Adults with Advanced Lymphoid Malignancies - A Eurocord-Netcord Group/EBMT-LWP Study.
Authors: Rodrigues Celso A. , Brunstein Claudio , Sanz Guillermo , Renaud Marc , de Lima Marcos , Blaise Didier , Rio Bernard , Madureira Adrienne B.M. , Sureda Anna , Wagner John E. , Gluckman Eliane , Rocha Vanderson 
Published: April 2020

Abstract
Umbilical cord blood transplants (UCBT) from unrelated donors is a feasible option for adults with high-risk acute leukemia. However, little is known about the outcome of UCBT in patients with advanced lymphoid malignancies. We evaluated 93 adult patients (median age, 41 years; median weight, 67 kg) who received a single (n=73) or a double (n=20) unrelated UCBT for an advanced lymphoid malignancy. Sixty patients had non-Hodgkin lymphoma (16 diffuse large B-cell lymphoma, 9 follicular lymphoma, 8 mantle cell lymphoma, 8 peripheral T-cell lymphoma, 6 anaplastic large cell lymphoma, 6 other T-cell lymphomas, 5 other B-cell lymphomas and 2 unspecified), 22 had Hodgkin lymphoma, and 11 had B-cell chronic lymphocytic leukemia (CLL). Based on antigen-level HLA-A and B and allele-level HLA-DRB1 typing, cord blood units were matched (9%) or mismatched at 1 (26%), 2 (58%), 3 (6%) or 4 (2%) HLA antigens. The median number of total nucleated cells (TNC) infused was 2.5 × 107/kg for single transplants and 2.8 × 107/kg for double transplants. The majority of patients (85%) had advanced disease (relapse, refractory disease, partial remission or 3rd complete remission), and 45% had a prior autologous transplant. Conditioning regimen varied according to the transplant center: 60% received a reduced-intensity conditioning regimen (RIC) and 62% received total body irradiation (TBI), 73% of which low-dose (2 Gy). Median follow-up time of surviving patients was 13 months (3–67 months). The probability of engraftment at day 60 was 84%, with a median time of 17 days (3–54) for patients who received RIC and 24 days (6–48) for those who received myeloablative regimens. In a multivariate analysis, a higher cell dose (2.5×107 TNC/kg) was significantly associated with the neutrophil engraftment (p=0.01). Grade II–IV acute graft-versus-host disease (GVHD) was observed in 26% of the patients, grade III–IV in 11% and chronic GVHD in 22% of evaluable patients. Transplant-related mortality (TRM) was 35% at 1 year. In a multivariate analysis, TRM was significantly lower for patients with B-cell malignancies (B-cell non-Hodgkin lymphomas and CLL) as compared to those with Hodgkin or T-cell lymphomas (22% vs. 55%; p=0.001), patients who received TBI (23% vs. 57%; p=0.0003), and patients who received ≥2.0 × 107 TNC/kg (22% vs. 67%; p=0.001). Disease free survival (DFS) at 1 year was 40%. In a multivariate analysis, DFS was significantly better for patients with B-cell malignancies (51% vs. 17%; p=0.006), patients who received TBI (49% vs. 20%; p=0.001), and patients who received ≥2.0 × 107 TNC/kg (45% vs. 13%; p=0.003). In conclusion, UCBT is a valuable alternative for patients with advanced non-Hodgkin lymphoma and CLL who lack an HLA-matched donor. B-cell malignancies, the use of TBI and higher cell doses are associated with a significantly better outcome.