αβ T-cell graft depletion for allogeneic HSCT in adults with hematological malignancies

• Published in: Blood advances 2021-01, Vol.5 (1), p.240-249
• Main Authors: 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, Jürgen
• Format: Article
• Language: English
• Subjects: Adult; Clinical Trials and Observations; Graft vs Host Disease - etiology; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; T-Lymphocytes
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020002444

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 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. •The incidence of aGVHD grade 2-4 after αβ T-cell depletion is 26% at day 100, allowing prophylactic DLI in the majority of patients.•The incidence of moderate and severe cGVHD at 2 years is 17% and 0%, respectively, comparing favorably to T-cell–replete allo-HSCT. [Display omitted]