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Low mean post-transplantation tacrolimus levels in weeks 2–3 correlate with acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation from related and unrelated donors

Bone Marrow Transplantation volume 54, pages 155–158 (2019)Cite this article

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Despite refinement of conditioning regimens for allogeneic stem cell transplantation (allo-SCT), non-relapse mortality (NRM) continues to be problematic with acute graft-versus-host disease (aGVHD) the leading cause [1]. Since the mid-1980s, a short course of methotrexate with a calcineurin inhibitor is the standard approach to prevent aGVHD [2], although modifications have been introduced [3]. Tacrolimus, a potent macrolide lactone immunosuppressant produced by Streptomyces tsukubaensis and highly effective in vitro [4], has activity resembling cyclosporine (CSA). While several randomized phase II/III trials comparing tacrolimus to CSA as the backbone for GVHD prophylaxis demonstrated less aGVHD for tacrolimus, this did not translate into a consistent improvement in overall survival (OS) or relapse [5, 6].

Recommendations on the optimal blood levels of tacrolimus to prevent aGVHD are mixed, with some studies showing no correlation between trough levels and aGVHD while others indicate trough levels between 7 and 15 ng/mL are ideal [7,8,9,10,11]. Due to this inconsistency, we retrospectively evaluated the relationship between trough or mean tacrolimus blood concentration in a 'real world' setting and the incidence of aGVHD in a large cohort of adult patients following allo-SCT. We hypothesized that lower trough and or mean tacrolimus levels in the immediate post-transplant period will translate to increased incidence of grade II–IV and III–IV aGVHD [12].

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Authors and Affiliations

  1. Loyola University Medical Center, Internal Medicine, Maywood, IL, USA

    Patrick A. Hagen

  2. Loyola University Chicago, Clinical Research Office Biostatistics Core, Maywood, IL, USA

    William Adams

  3. Loyola University Medical Center, Hematology/Oncology, Maywood, IL, USA

    Scott Smith

  4. Loyola University Medical Center, Internal Medicine, Maywood, IL, USA

    Stephanie Tsai

  5. loyola University Medical Center, hematology/Oncology, maywood, IL, USA

    Patrick Stiff

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  1. Patrick A. Hagen
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Correspondence to Patrick A. Hagen.

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Hagen, P.A., Adams, W., Smith, S. et al. Low mean post-transplantation tacrolimus levels in weeks 2–3 correlate with acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation from related and unrelated donors. Bone Marrow Transplant 54, 155–158 (2019). https://doi.org/10.1038/s41409-018-0267-5

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