Chronic Graft Versus Host Disease Burden and Relapse Rates Are Lower with Comparable Overall Survival and Graft Versus Host Disease Free, Relapse Free Survival Following Adult Umbilical Cord Blood Compared to Matched Sibling Peripheral Blood Stem Cell Transplantation

Abstract

Abstract Background: Although matched related donors (MRD) are the preferred source of stem cells for allogeneic hematopoietic cell transplantation, umbilical cord blood (UCB) is a well-established donor source in patients without a MRD or matched unrelated donor (MUD). Prior studies (Eapen et al, Lancet Oncology 2010; Rocha et al, NEJM 2004) have shown similar overall survival and relapse rates after umbilical cord blood transplant (UCBT), and our group (Gutman et al, BMT 2016) has shown lower chronic graft-versus-host-disease (GVHD) when compared to MUD transplant. Based on these data, our preferred donor source is MRD followed by UCB. Here, we evaluate our data comparing transplant outcomes in UCBT recipients versus MRD recipients. Methods: We compared outcomes in all consecutive adult patients undergoing first MRD transplant versus first double UCBT from January 2010 to December 2017. Patient selection, graft-versus-host disease prophylaxis and transfusions were per institutional standards. Graft-versus-host-disease free, relapse free survival (GRFS) was defined by events that includedgrade 3-4 acute GVHD, moderate to severe chronic GVHD, relapse or any death. Results: Of the 296 patients studied, 187 underwent UCBT and 109 received MRD transplant. Graft failure occurred in 6 (3%) UCBT recipients (5 of whom received reduced intensity conditioning) and did not occur in any MRD transplant recipients. While the incidence of grade 2-4 acute GVHD was higher in UCBT recipients (p= 0.006), grade 3-4 acute GVHD was comparable (p= 0.36) between the two groups. Any chronic GVHD (p= 0.0000001) and moderate to severe chronic GVHD (p= 0.00011) was significantly higher in MRD transplant recipients (figure 1a and 1b). There were significantly lower disease relapses in UCBT recipients (n= 51, 27% versus n= 46, 42%; p= 0.0036) compared to MRD transplant recipients. Transplant related mortality was higher in UCBT recipients (n= 33, 42% versus n= 11, 23% in MRD transplant recipients; p= 0.03). There was no difference in GRFS (p=0.15, figure 1c) and overall survival (OS) in the 2 study cohorts (p=0.31, figure 1d). Conclusions: UCBT recipients as compared to MRD recipients had lower chronic GVHD and lower relapse rates with no difference in OS and the composite endpoint of GRFS. Based on these results, UCB remains an appropriate alternative donor source for hematopoietic cell transplantation and might result in improved quality of life by virtue of lower incidence of chronic GVHD in long-term transplant survivors. Disclosures Haverkos: Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Pollyea:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Curis: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding. Kamdar:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Mark:Janssen, Takeda, Celgene, Amgen: Consultancy; BMS, Celgene: Research Funding; Celgene: Honoraria.