Volume 106, Issue 2 pp. 205-212
ORIGINAL ARTICLE

Weight-based mycophenolate mofetil dosing predicts acute GVHD and relapse after allogeneic hematopoietic cell transplantation

Nelli Bejanyan

Nelli Bejanyan

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

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John Rogosheske

John Rogosheske

Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA

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Qing Cao

Qing Cao

Biostatistics Core, Masonic Cancer Center. Adult and Pediatric Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA

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Aleksandr Lazaryan

Aleksandr Lazaryan

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

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Shernan Holtan

Shernan Holtan

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

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Celalettin Ustun

Celalettin Ustun

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

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Pamala Jacobson

Pamala Jacobson

Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA

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Margaret MacMillan

Margaret MacMillan

Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

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Daniel J. Weisdorf

Daniel J. Weisdorf

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

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John Wagner

John Wagner

Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

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Mukta Arora

Mukta Arora

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

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Claudio G. Brunstein

Corresponding Author

Claudio G. Brunstein

Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

Correspondence

Claudio G. Brunstein, Blood and Marrow Transplant Program, University of Minnesota Medical Center, Mayo Mail Code 480, 420 Delaware Street SE, Minneapolis, MN 55455, USA

Email: [email protected]

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First published: 21 October 2020
Citations: 2

Abstract

Objectives

Higher MMF dose can reduce acute GVHD risk after allogeneic hematopoietic cell transplantation (HCT). We examined the effect of MMF dose, relative to patient actual body weight (mg/kg/day), on outcomes of 680 adults after HCT.

Methods

MMF was combined with cyclosporine (n = 599) or sirolimus (n = 81). We divided MMF dose/kg/day in quartiles.

Results

The median time to grade II-IV acute GVHD was 32 days. The incidence of grade II-IV acute GVHD at day 30 was 30% in 1st (<29), 20% in 2nd (29-34), 16% in 3rd (35-41), and 19% in 4th (≥42) quartile (P < .01). Corresponding relapse incidence at 1 year was 16%, 25%, 27%, and 31%, respectively (P = .01). In multivariate analysis, as compared to 1st quartile, higher dose of weight-based MMF reduced grade II-IV acute GVHD (HR = 0.64 for 2nd, HR = 0.48 for 3rd, and HR = 0.55 for 4th quartile), but increased the risk of relapse (HR = 1.63 for 2nd, HR = 1.75 for 3rd, and HR = 2.31 for 4th quartile).

Conclusions

Weight-based MMF dose had no significant impact on engraftment, chronic GVHD, or survival. These data suggest that higher weight-based MMF dose reduces the risk of acute GVHD at the expense of increased relapse and supports conducting prospective studies to optimize MMF dosing after HCT.

CONFLICT OF INTEREST

The authors declare no competing financial interests.

DATA AVAILABILITY STATEMENT

Data available on request from the authors. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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