Browsing by Author "Hwang, William YK"

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    Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015-04) Ballen, Karen K; Logan, Brent R; Laughlin, Mary J; He, Wensheng; Ambruso, Daniel R; Armitage, Susan E; Beddard, Rachel L; Bhatla, Deepika; Hwang, William YK; Kiss, Joseph E; Koegler, Gesine; Kurtzberg, Joanne; Nagler, Arnon; Oh, David; Petz, Lawrence D; Price, Thomas H; Quinones, Ralph R; Ratanatharathorn, Voravit; Rizzo, J Douglas; Sazama, Kathleen; Scaradavou, Andromachi; Schuster, Michael W; Sender, Leonard S; Shpall, Elizabeth J; Spellman, Stephen R; Sutton, Millicent; Weitekamp, Lee Ann; Wingard, John R; Eapen, Mary
    Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.
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    Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide.
    (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019-02) Horwitz, Mitchell E; Wease, Stephen; Blackwell, Beth; Valcarcel, David; Frassoni, Francesco; Boelens, Jaap Jan; Nierkens, Stefan; Jagasia, Madan; Wagner, John E; Kuball, Jurgen; Koh, Liang Piu; Majhail, Navneet S; Stiff, Patrick J; Hanna, Rabi; Hwang, William YK; Kurtzberg, Joanne; Cilloni, Daniela; Freedman, Laurence S; Montesinos, Pau; Sanz, Guillermo

    Purpose

    Increasing the number of hematopoietic stem and progenitor cells within an umbilical cord blood (UCB) graft shortens the time to hematopoietic recovery after UCB transplantation. In this study, we assessed the safety and efficacy of a UCB graft that was expanded ex vivo in the presence of nicotinamide and transplanted after myeloablative conditioning as a stand-alone hematopoietic stem-cell graft.

    Methods

    Thirty-six patients with hematologic malignancies underwent transplantation at 11 sites.

    Results

    The cumulative incidence of neutrophil engraftment at day 42 was 94%. Two patients experienced secondary graft failure attributable to viral infections. Hematopoietic recovery was compared with that observed in recipients of standard UCB transplantation as reported to the Center for International Blood and Marrow Transplant Research (n = 146). The median time to neutrophil recovery was 11.5 days (95% CI, 9 to 14 days) for recipients of nicotinamide-expanded UCB and 21 days (95% CI, 20 to 23 days) for the comparator ( P < .001). The median time to platelet recovery was 34 days (95% CI, 32 to 42 days) and 46 days (95% CI, 42 to 50 days) for the expanded and the comparator cohorts, respectively ( P < .001). The cumulative incidence of grade 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 44%, and grade 3 and 4 acute GVHD at day 100 was 11%. The cumulative incidence at 2 years of all chronic GVHD was 40%, and moderate/severe chronic GVHD was 10%. The 2-year cumulative incidences of nonrelapse mortality and relapse were 24% and 33%, respectively. The 2-year probabilities of overall and disease-free survival were 51% and 43%, respectively.

    Conclusion

    UCB expanded ex vivo with nicotinamide shortens median neutrophil recovery by 9.5 days (95% CI, 7 to 12 days) and median platelet recovery by 12 days (95% CI, 3 to 16.5 days). This trial establishes feasibility, safety, and efficacy of an ex vivo expanded UCB unit as a stand-alone graft.