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Lymphoid Reconstitution

Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin

Abstract

Antithymocyte globulin is widely used before haematopoietic transplantation with HLA-matched unrelated donors or mismatched relatives to prevent rejection and graft-versus-host disease (GVHD). However, optimal dosage is still under debate. Thirty-one consecutive children, mainly with haematological malignancies, were transplanted in a single institution with such donors, selected by HLA-A -B compatibility by serology and DRB1* by DNA typing. Antithymocyte globulin (Thymoglobuline; Sangstat) was infused at days −3, −2, −1. Total dosage varied: 16 patients received a median of 7.5 mg/kg (2.5 to 10.5: low-dose group), and 15 a median of 15.5 mg/kg (14.4 to 19.4: high-dose group). Post-transplant GVHD prophylaxis consisted of cyclosporine, short-course methotrexate and steroids. CD3+, CD4+ and CD19+ cell reconstitution was slower in the high-dose group. Median time to reach 100 CD4+ cells was 8 months vs 4 months (P = 0.03). Median time to normal CD19+ cells was 16 months vs 8 months (P = 0.01). CD16+CD56+ and CD8+ cell reconstitution was similar. Nine patients in the high-dose group and two in the low-dose group experienced life-threatening opportunistic infections (P = 0.009). Although obtained from a limited number of patients, our data suggest that a higher pre-graft dose of antithymocyte globulin may negatively influence immune reconstitution.

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Acknowledgements

We are greatly indebted to Jacqueline Nouyrigat. Her volunteer logistic work made possible data collection, analysis and writing of this paper. We also thank Marc Dumont for statistical assistance and revising the manuscript, and Mark Bernstein for critical revision.

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Duval, M., Pédron, B., Rohrlich, P. et al. Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin. Bone Marrow Transplant 30, 421–426 (2002). https://doi.org/10.1038/sj.bmt.1703680

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