Inferior Outcomes with Cyclosporine and Mycophenolate mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation

Authors

Betty K. Hamilton
Ying Liu
Michael T. Hemmer
Navneet Majhail
Olle Ringden
Dennis Kim
Luciano Costa
Robert Stuart
Amin Alousi
Joseph A. Pidala
Daniel R. Couriel
Mahmoud AljurfFollow
Joseph H. Antin
Christopher Bredeson
Jean-Yves Cahn
Mitchell CairoFollow
Saurabh Chhabra

DOI

10.1016/j.bbmt.2019.05.019

Journal Title

Biology of Blood and Marrow Transplantation

First Page

1744

Last Page

1755

Document Type

Article

Publication Date

September 2019

Department

Pediatrics

Abstract

The combination of a calcineurin inhibitor (cyclosporine [CSA] or tacrolimus [Tac]) and methotrexate (MTX) or mycophenolate mofetil (MMF) are widely used approaches to graft-versus-host disease (GVHD) prevention. There is limited and conflicting data, however, on the comparative effectiveness of MMF compared to MTX. We analyzed data from the CIBMTR for adult patients undergoing first myeloablative hematopoietic cell transplant (HCT) from an HLA-identical matched related (MRD) (N=3979) or matched unrelated donor (URD) (N=4163) using CSA+MMF, CSA+MTX, Tac+MMF or Tac+MTX for GVHD prevention from 2000-2013. Within the MRD cohort, 2252 received CSA+MTX, 1391 Tac+MTX, 114 CSA+MMF, and 222 Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute grade 2-4 (HR 1.65, 95% CI 1.24-2.20, P<0.001) and grade 3-4 (HR 1.92, 95% CI 1.31-2.83, P<0.001) GVHD compared to Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR 2.31, 95% CI 1.73-3.09, P<0.001) due to higher transplant-related mortality (TRM) (HR 4.03, 95% CI 2.61-6.23, P<0.001) versus Tac+MTX. Within the URD cohort, 974 received CSA+MTX, 2697 Tac+MTX, 68 CSA+MMF, and 424 Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade 3-4 acute GVHD (HR 2.31, 95% CI 1.57-3.42, P<0001), worse OS (HR 2.36, 95% CI 1.67-3.35, P<0.001), and higher TRM (HR 3.09, 95% CI 2.00-4.77, P<0.001), compared to Tac+MTX, and other regimens. This large retrospective comparison of MMF versus MTX in combination with CSA or Tac thus demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared to Tac+MTX.

Comments

Please see the work itself for the complete list of authors.

Recommended Citation

Hamilton, B., Liu, Y., Hemmer, M., Majhail, N., Ringden, O., Kim, D., Costa, L., Stuart, R., Alousi, A., Pidala, J., Couriel, D., Aljurf, M., Antin, J., Bredeson, C., Cahn, J., Cairo, M., & Chhabra, S. (2019). Inferior Outcomes with Cyclosporine and Mycophenolate mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 25 (9), 1744-1755. https://doi.org/10.1016/j.bbmt.2019.05.019