Alternative Donors (Umbilical Cord Blood and Haploidentical Donors) for Allogeneic Stem Cell Transplantation in Relapsed / Refractory Hodgkin Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party and the Spanish Group of Stem Cell Transplantation (GETH)

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL.

Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases.

Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS.

Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up.

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