Single UM171 Expanded Cord Blood Transplant Is Feasible, Safe, and Permits Transplantation of Better HLA Matched Cords with Very Low Transplant Related Mortality

Autor: Sandra Cohen, Jean Roy, Silvy Lachance, Anne Marinier, Denis-Claude Roy, Jean-Sébastien Delisle, Lambert Busque, Pierre Caudrelier, Fannie Larochelle, Philippe Bouchard, Nadia M. Bambace, Léa Bernard, Thomas L Kiss, Sébastien Lemieux, Peter W. Zandstra, Guy Sauvageau
Rok vydání: 2017
Předmět:
Zdroj: Blood. 130:658-658
ISSN: 1528-0020
0006-4971
Popis: Cord blood (CB) transplants are hampered by low cell dose and high transplant related mortality (TRM). UM171, a novel and potent agonist of hematopoietic stem cell (HSC) self-renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. Hence, we initiated a clinical trial to test the safety and efficacy of UM171 expanded CB (eCB). The procedure was designed to be non-labor intensive and of short duration for it to be clinically viable. Patients (pts) received a myeloablative conditioning regimen. On day(D)-7 of transplant, CB was thawed and CD34+ selected. The CD34- lymphocyte containing fraction was cryopreserved and infused on day of transplant. The CD34+ component was placed in a closed culture system with UM171 and media was injected once a day until D0, when cells were washed and infused. The first 3 pts also received a 2nd nonmanipulated CB (neCB) to permit documentation of eCB engraftment. This fed-batch culture system allowed for small culture volumes, saving cost and labor. Between 6/16-7/17, 16 adults with a median weight and age of 77 kg and 44 years, respectively, were transplanted with a single eCB (13 pts) or with an eCB and a neCB (3 pts). Median final culture volume was 609 mL. The median net viable (v)CD34 fold expansion was 36. Median 1st day of 100 and 500 neutrophils were D+10 and D+19, respectively. Achieving 100 neutrophils was faster than expected and cell dose independent, suggesting that clinically meaningful expansion of an early repopulating myeloid progenitor is at saturation even with smaller CBs. In contrast, attaining 500 neutrophils was accelerated but dependent on infused vCD34+ cell dose. More importantly, patients appeared to derive clinical benefit beyond neutrophil engraftment defined as the 1st of 3 consecutive days of 500 neutrophils. Patients' last day of fever prior to neutrophil engraftment was Day +7, which occurred much earlier than D+19 of engraftment. We offer 2 hypotheses as explanation: i) 100 neutrophils, which are attained much earlier at D+10, provide significant defence against infection, ii) the graft contains a significant proportion of dendritic cell precursors (>25%) which offer protection during severe neutropenia. When compared to our pts who have received the same conditioning regimen with peripheral blood or marrow, eCB pts were free of fever much earlier (D+7 vs D+15 p Despite preliminary data, it appears that a 7 day UM171 single eCB protocol is feasible and provides clinical benefit beyond faster engraftment with fewer infectious complications, better HLA matching and low TRM, all the while saving production and hospitalization costs. In conclusion, this 1st trial documents the potency of UM171 and positions UM171-expanded CB as a viable HSC source. Disclosures Cohen: University of Montreal: Patents & Royalties: royalties. Marinier: ExCellThera: Equity Ownership. Busque: Novartis Canada Inc.: Honoraria; Bristol Myer Squibb: Honoraria; Pfizer: Honoraria; Paladin: Honoraria. Caudrelier: ExCellThera: Employment. Kiss: Otsuka: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance support, Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding. Zandstra: ExCellThera: Equity Ownership. Sauvageau: ExCellThera: Equity Ownership, Patents & Royalties: royalties.
Databáze: OpenAIRE
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