αβ T-cell graft depletion for allogeneic HSCT in adults with hematological malignancies
De Witte, Moniek A.; Janssen, Anke; Nijssen, Klaartje; Karaiskaki, Froso; Swanenberg, Luuk; van Rhenen, Anna; Admiraal, Rick; van der Wagen, Lotte; Minnema, Monique C.; Petersen, Eefke; Raymakers, Reinier A.P.; Westinga, Kasper; Straetemans, Trudy; Halkes, Constantijn J.M.; Boelens, Jaap Jan; Kuball, Jurgen
(2021) Blood Advances, volume 5, issue 1, pp. 240 - 249
(Article)
Abstract
We conducted a multicenter prospective single-arm phase 1/2 study that assesses the outcome of αβ T-cell depleted allogeneic hematopoietic stem cell transplantation (allo-HSCT) of peripheral blood derived stem cells from matched related, or unrelated donors (10/10 and 9/10) in adults, with the incidence of acute graft-versus-host disease (aGVHD) as the
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primary end point at day 100. Thirty-five adults (median age, 59; range, 19-69 years) were enrolled. Conditioning consisted of antithymocyte globulin, busulfan, and fludarabine, followed by 28 days of mycophenolic acid after allo-HSCT. The minimal follow-up time was 24 months. The median number of infused CD34+ cells and αβ T cells were 6.1 × 106 and 16.3 × 103 cells per kg, respectively. The cumulative incidence (CI) of aGVHD grades 2-4 and 3-4 at day 100 was 26% and 14%. One secondary graft failure was observed. A prophylactic donor lymphocyte infusion (DLI) (1 × 105 CD3+ T cells per kg) was administered to 54% of the subjects, resulting in a CI of aGVHD grades 2-4 and 3-4 to 37% and 17% at 2 years. Immune monitoring revealed an early reconstitution of natural killer (NK) and γδ T cells. Cytomegalovirus reactivation associated with expansion of memory-like NK cells. The CI of relapse was 29%, and the nonrelapse mortality 32% at 2 years. The 2-year CI of chronic GVHD (cGVHD) was 23%, of which 17% was moderate. We conclude that only 26% of patients developed aGVHD 2-4 after αβ T-cell-depleted allo-HSCT within 100 days and was associated with a low incidence of cGVHD after 2 years. This trial was registered at www.trialregister.nl as #NL4767.
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Keywords: Adult, Graft vs Host Disease/etiology, Hematologic Neoplasms/therapy, Hematopoietic Stem Cell Transplantation/adverse effects, Humans, Middle Aged, Neoplasm Recurrence, Local, Prospective Studies, T-Lymphocytes, Hematology, Journal Article, Research Support, Non-U.S. Gov't, Clinical Trial, Phase I, Multicenter Study, Clinical Trial, Phase II
ISSN: 2473-9529
Publisher: The American Society of Hematology
Note: Funding Information: Funding for this study was provided by the Dutch Cancer Society (KWF; UU 2015-7553) (M.A.d.W.) and Netherlands Organisation for Health Research and Development (ZonMW; 43400003), Experienced Researchers (VIDI)-ZonMW 917.11.337, KWF UU 2010-4669, UU 2013-6426, UU 2014-6790, UU 2015-7601, UU 2018-11393, UU 2018-11979, UU 2020-12586, UU 2021-13043, Vrienden van het UMCU (Friends UMC Utrecht), Association for International Cancer Research (AICR; grants 10-0736, and 15-0049) (J.K.). Publisher Copyright: © 2021 by The American Society of Hematology. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
(Peer reviewed)