High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease
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ORIGINAL ARTICLE
High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease Souichi Shiratori 1 & Hiroyuki Ohigashi 1 & Takahide Ara 1 & Atsushi Yasumoto 1 & Hideki Goto 1 & Masao Nakagawa 1 & Junichi Sugita 1 & Masahiro Onozawa 1 & Kaoru Kahata 1 & Tomoyuki Endo 1 & Daigo Hashimoto 1 & Takanori Teshima 1 Received: 1 September 2020 / Accepted: 11 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 × 109/L vs 0.06 × 109/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD. Keywords Allogeneic hematopoietic stem cell transplantation . Peripheral blood stem cell transplantation . Antithymocyte globulin . Graft-versus-host disease . Absolute lymphocyte count
Introduction Graft-versus-host disease (GVHD) is one of the main causes of transplant-associated morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). For prophylaxis of GVHD, antithymocyte globulin (ATG) is recommended, particularly in HSCT from unrelated donor or peripheral blood stem cell transplantation (PBSCT) [1], based on the results of a series of prospective randomized phase III studies [2–7]. However, the appropriate dose of ATG remains to be determined. Because a higher dose of ATG is a risk factor for infection or posttransplant lymphoproliferative disorder, a few recent studies have utilized lower doses of ATG [8–13]. Our
previous pilot study showed that a total of 2 mg/kg of rabbit ATG (thymoglobulin) was sufficient to reduce naive T cells at day 28 after PBSCT [14]. In a prospective, multicenter, phase II study evaluating the safety and efficacy of low-dose ATG in HLA-matched PBSCT, we showed that 2 mg/kg of thymoglobulin efficiently prevented severe acute and chronic GVHD, with 1.4% grade III to IV acute GVHD and 5.6% moderate to severe chronic G
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