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

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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.

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Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Hematology, Hokkaido University Faculty of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan

    Souichi Shiratori, Hiroyuki Ohigashi, Takahide Ara, Atsushi Yasumoto, Hideki Goto, Masao Nakagawa, Junichi Sugita, Masahiro Onozawa, Kaoru Kahata, Tomoyuki Endo, Daigo Hashimoto & Takanori Teshima

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  1. Souichi Shiratori
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Correspondence to Souichi Shiratori.

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This work was supported by grants from North Japan Hematology Study Group and the Japan Agency for Medical Research and Development (AMED, 20ek0510025h0003).

TT has received research funds from Sanofi.

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Supplementary Information

Supplemental Fig. 1

The cumulative incidence of grade II to IV (solid lines) and grades III to IV (dashed lines) acute GVHD (a), all-grade chronic GVHD (solid lines) and moderate to severe (dashed lines) chronic GVHD (b), relapse (c), NRM (d), Kaplan-Meier plots of OS (e) and PFS (f) after PBSCT using low-dose ATG (JPG 81 kb)

Supplemental Fig. 2

ALC (a) and WBC (b) before the administration of ATG; ALC (c), and WBC (d) before conditioning in patients with or without grade II to IV acute GVHD. ALC before ATG in patients with grade II to IV acute GVHD was significantly higher compared to those without it (median, 0.18 × 109/L vs. 0.63 × 109/L, P = 0.01). The other indices were equivalent between the groups (WBC before ATG; median, 2.50 × 109/L vs. 2.00 × 109/L, P = 0.42, ATG before conditioning; median, 0.75 × 109/L vs. 0.67 × 109/L, P = 0.32, WBC before conditioning; median, 2.70 × 109/L vs 3.30 × 109/L, P = 0.67). The cumulative incidence of grade II to IV acute GVHD in patients with high ALC before ATG (≥ 0.15 × 109/L, dashed lines, n = 13) or low ALC before ATG (solid lines, n = 40) (e), high WBC before ATG (≥ 1.50 × 109/L, dashed lines, n = 31) or low WBC before ATG (solid lines, n = 22) (f), high ALC before the conditioning (≥ 1.00 × 109/L, dashed lines, n = 12) or low ALC before conditioning (solid lines, n = 41) (g), and high WBC before conditioning (≥ 2.90 × 109/L, dashed lines, n = 27) or low WBC before conditioning (solid lines, n = 26) (h). The cumulative incidence of grade II to IV acute GVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (≥ 0.15 × 109/L: 53.8% vs. < 0.15 × 109/L: 5.0%, P < 0.01). The other indices were not associated with the incidence of grade II to IV acute GVHD (WBC before ATG; ≥ 1.50 × 109/L: 22.6% vs. < 1.50 × 109/L: 9.1%, P = 0.18, ATG before conditioning; ≥ 1.00 × 109/L: 33.3% vs. < 1.00 × 109/L: 12.2%, P = 0.08, WBC before the conditioning; ≥ 2.90 × 109/L: 14.8% vs. < 2.90 × 109/L: 19.2%, P = 0.64) (JPG 63 kb)

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Shiratori, S., Ohigashi, H., Ara, T. et al. High lymphocyte counts before antithymocyte globulin administration predict acute graft-versus-host disease. Ann Hematol 100, 1321–1328 (2021). https://doi.org/10.1007/s00277-020-04347-1

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