Beneficial impact of low-dose rabbit anti-thymocyte globulin in unrelated hematopoietic stem cell transplantation: focusing on difference between stem cell sources

Shichijo, Takafumi; Fuji, Shigeo; Tajima, Kinuko; Kubo, Hiroyuki; Nozaki, Kengo; Honda, Takeshi; Yamaguchi, Junko; Kawashima, Ichiro; Kawajiri, Akihisa; Takemura, Tomonari; Onishi, Akio; Ito, Ayumu; Tanaka, Takashi; Inamoto, Yoshihiro; Kurosawa, Saiko; Kim, Sung-Won; Fukuda, Takahiro

doi:10.1038/s41409-017-0045-9

Cited by 11 publications

(2 citation statements)

References 15 publications

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“…ATG doses below 4.5 mg/kg were also investigated in MUD HCT patients receiving both PBSC and BM graft sources and showed benefit in reducing the incidence of cGVHD and overall disease severity while maintaining nonrelapse mortality (NRM) and overall survival (OS). 65,66 Variable ATG dosing strategies, IST, and donor sources have made assessment of therapeutic risk and toxicity difficult. Future investigations of the optimal ATG-based prophylactic dosing regimen considering GVHD risk may optimize therapeutic efficacy without significantly delaying immune reconstitution and/or increasing infection risk.…”

Section: Antithymocyte Globulinmentioning

confidence: 99%

Evolving Therapeutic Options for Chronic Graft‐versus‐Host Disease

Gonzalez

Pidala

2020

Pharmacotherapy

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Despite improvements in prevention and treatment of acute graft‐versus‐host disease (GVHD), chronic GVHD (cGVHD) remains a significant contributor to morbidity and mortality of allogeneic transplant patients. Chronic GVHD remains a leading cause of late complications posttransplant and is impacted by donor‐, patient‐, and transplant‐related (hematopoietic cell transplant [HCT]) factors. Advances in the biological understanding of cGVHD have provided opportunities to improve clinical interventions for prevention and treatment. Expansion of posttransplantation cyclophosphamide beyond haploidentical HCTs has transformed alternative donor, matched, and mismatch GVHD outcomes and is currently being investigated in two upcoming clinical trials network prophylaxis studies. Although corticosteroids remain the cornerstone therapy, several clinical trials are prospectively investigating the utility of using novel agents in combination with corticosteroids as upfront therapy to mitigate prolonged steroid exposure. Several treatment options for patients with steroid‐refractory cGVHD are currently being investigated, and advances have resulted in ibrutinib becoming the first cGVHD agent approved by the U.S. Food and Drug Administration. We review recent advances in understanding of cGVHD pathophysiology and new approaches for the prevention and treatment of cGVHD.

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Section: Antithymocyte Globulinmentioning

confidence: 99%

Evolving Therapeutic Options for Chronic Graft‐versus‐Host Disease

Gonzalez

Pidala

2020

Pharmacotherapy

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“…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][9][10][11][12][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].…”

Section: Introductionmentioning

confidence: 99%

High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease

et al. 2020

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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 lowdose 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 × 10 9 /L vs 0.06 × 10 9 /L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 10 9 /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.

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