Alternative Donor Transplantation For Adults With Lymphoma: Comparison Of Umbilical Cord Blood Versus 8/8 HLA-Matched Donor (URD) Versus 7/8 URD
Authors: Bachanova Veronika , Brunstein Claudio , Burns Linda J. , Wang Tao , Carreras Jeanette , Laport Ginna G. , Smith Sonali M. , Montoto Silvia , Maloney David G. , Saber Wael 
Published: October 2019

Abstract
Allogeneic donor hematopoietic cell transplantation (HCT) is increasingly used to treat relapsed lymphoma with curative intent; however, many patients will not have a suitable matched sibling donor. Transplant centers are investigating the use of alternative stem cell sources although data comparing outcomes by stem cell source are limited.
We compared outcomes of 1593 non-Hodgkin and Hodgkin lymphoma patients who underwent alternative donor HCT from 2000-2010 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Umbilical cord blood (UCB) (n=142), 8/8 (human leukocyte antigen [HLA] –A, B, C, and DRB1) matched adult unrelated donor (URD) (n=1176) and 7/8 HLA matched URD (n=275) HCT recipients were followed for a median of 25, 57 and 65 months, respectively.
The median age in the 3 groups were UCB: 45 years (range 19-73 yrs), 8/8 URD: 50 (range 18-75 yrs) and 7/8 URD: 45 years (range 18-71yrs). Male gender and mantle cell lymphoma were more frequent in 8/8 URD recipients. 7/8 URD HCT recipients had lower Karnofsky performance scores, and UCB recipients were more likely to be non-Caucasian, have chemosensitive disease and to have undergone HCT in recent years.
UCB recipients had inferior neutrophil and platelet engraftment rates at 100 days; however they were less likely to develop acute and chronic graft versus host disease (GVHD) compared to 7/8 URD and 8/8 URD (Table). The cumulative incidence of treatment related mortality (TRM) at 3 years was higher in 7/8 URD. There were no differences among the 3 groups in the 3-year relapse/progression, progression free survival (PFS) or overall survival (OS).Table.OutcomesUCBURD 8/8URD 7/8% (95%CI)% (95%CI)%( (95%CI)P-valueTime to ANC>0.5 x 109/L at 28 days66 (57-73)94 (92-95)94 (90-96)<0.001Platelet recovery ≥ 20 x 109/L at 100 days68 (59-76)86 (84-88)85 (80-89)<0.001Acute GVHD (II-IV) at 100 days26 (19-34)37 (35-40)49 (43-55)<0.0013 years Chronic GVHD at 3 years22 (15-30)51 (48-54)48 (42-54)<0.0013 years Treatment related mortality38 (29-46)35 (32-37)46 (41-52)0.0023 years Relapse/Progression29 (22-37)32 (29-34)25 (20-31)0.1073 years Progression free survival33 (25-42)33 (31-37)29 (23-34)0.1863 years Overall survival44 (35-53)43 (40-46)34 (29-40)0.017
In multivariate analysis stratified for performance status, lymphoma histology, GVHD prophylaxis, and disease status, no significant difference in OS was detected between UCB and 8/8 URD (HR 0.87 [95% CI 0.68-1.12]; p=0.29), UCB and 7/8 URD (HR 1.04 [95% CI 0.78-1.40]; p=0.77), and 8/8 and 7/8 URD (HR 1.19 [95%CI 0.97-1.45; p=0.08). Lower risk of treatment failure (death or relapse; inverse of PFS) was observed in transplants performed after 2007 (HR 0.79 [95% CI 0.66-0.96]; p=0.01) as compared to the time periods 2000-2003. Patients' age, time from diagnosis to HCT, race, history of prior HCT, and conditioning intensity did not influence OS or PFS.
In conclusion, our results suggest that UCB and 7/8 URD grafts for patients with advanced lymphoma provide similar survival to 8/8 URD, extending allogeneic HCT to most patients with no suitable matched sibling donors. Graft source needs to be determined by availability, the clinical urgency of transplant, and transplant center experience.

Disclosures:
No relevant conflicts of interest to declare.