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Biol Blood Marrow Transplant. 2019 Jan;25(1):73-85. doi: 10.1016/j.bbmt.2018.08.018. Epub 2018 Aug 25.

Comparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation.

Author information

1
Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: schhabra@mcw.edu.
2
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Institute for Health and Society, Department of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin.
3
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
4
Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
5
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
6
Division of Hematology and Hematologic Malignancies, Utah Blood and Marrow Transplant Program, Salt Lake City, Utah.
7
Department of Stem Cell Transplantation, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
8
Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
9
Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.
10
Department of Medical Oncology & Hematology, Princess Margaret Cancer Center, Toronto, Canada.
11
Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
12
Department of Hematology, IDIBAPS, Institute of Research Josep Carreras, Hospital Clínic, University of Barcelona, Barcelona, Spain.
13
Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
14
Department of Medicine-Hematology and Oncology, University Hospitals Case Medical Center, Cleveland, Ohio.
15
Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, United Kingdom.
16
Department of Hematology, Hôpital Saint Louis, Paris, France.
17
Department of Hematology, Academische Ziekenhuis, Maastricht, the Netherlands.
18
Department of Hematology, 26-Department of Pediatrics, University Hospital of Leuven, Leuven, Belgium.
19
Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California.
20
Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland.
21
Department of Hematology, CHU Grenoble Alpes, Grenoble, France.
22
Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
23
Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
24
Departmentt of Hematology/Oncology, Isala Clinic, Zwolle, the Netherlands.
25
Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
26
University of Minnesota Blood and Marrow Transplant Program, Minneapolis, Minnesota.
27
Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, Minnesota.
28
Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, Georgia.
29
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
30
Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, Wisconsin.
31
Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas.
32
Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri.
33
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, Missouri.
34
Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, United Kingdom.
35
Divison of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
36
Department of Hematology & Oncology, National Cancer Research Center East, Chiba, Japan.
37
Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia; Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, Minnesota.
38
Department of Hematology Kyushu University Hospital, Sapporo, Japan.
39
Hematolgic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, New York.
40
Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
41
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, Minnesota.
42
Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota. Electronic address: arora005@umn.edu.

Abstract

The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). The study divided the patient population into 4 cohorts based on regimen: MMF-TAC, MMF-CYSP, MTX-TAC, and MTX-CYSP. In the URD group, MMF-CYSP was associated with increased risk of grade II to IV acute GVHD (relative risk [RR], 1.78; P < .001) and grade III to IV acute GVHD (RR, 1.93; P = .006) compared with MTX-TAC. In the URD group, use of MMF-TAC (versus MTX-TAC) lead to higher nonrelapse mortality. (hazard ratio, 1.48; P = .008). In either group, no there was no difference in chronic GVHD, disease-free survival, and OS among the GVHD prophylaxis regimens. For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.

KEYWORDS:

Allogeneic hematopoietic cell transplantation; Calcineurin inhibitor Tacrolimus; Cyclosporine; Graft-versus-host disease prophylaxis; Methotrexate; Mycophenolate mofetil; Reduced-intensity conditioning

PMID:
30153491
PMCID:
PMC6355336
DOI:
10.1016/j.bbmt.2018.08.018
[Indexed for MEDLINE]
Free PMC Article

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