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

被引：15

作者：

Hamilton, Betty K. ^{[1
]}

Liu, Ying ^{[2
]}

Hemmer, Michael T. ^{[2
]}

Majhail, Navneet ^{[1
]}

Ringden, Olle ^{[3
]}

Kim, Dennis ^{[4
]}

Costa, Luciano ^{[5
]}

Stuart, Robert ^{[6
]}

Alousi, Amin ^{[7
]}

Pidala, Joseph A. ^{[8
]}

Couriel, Daniel R. ^{[9
]}

Aljurf, Mahmoud ^{[10
]}

Antin, Joseph H. ^{[11
]}

Bredeson, Christopher ^{[12
,13
]}

Cahn, Jean-Yves ^{[14
]}

Cairo, Mitchell ^{[15
]}

Choi, Sung Won ^{[16
]}

Dandoy, Christopher ^{[17
]}

Gale, Robert Peter ^{[18
]}

Gergis, Usama ^{[19
]}

Hematti, Peiman ^{[20
]}

Inamoto, Yoshihiro ^{[21
]}

Kamble, Rammurti T. ^{[22
]}

MacMillan, Margaret ^{[23
]}

Marks, David, I ^{[24
]}

Nemecek, Eneida ^{[25
,26
]}

Nishihori, Taiga ^{[27
]}

Saad, Ayman ^{[28
]}

Savani, Bipin N. ^{[29
]}

Schriber, Jeff ^{[30
,31
]}

Seo, Sachiko ^{[32
]}

Socie, Gerard ^{[33
]}

Teshima, Takanori ^{[34
]}

Verdonck, Leo F. ^{[35
]}

Waller, Edmund K. ^{[36
]}

Wirk, Mona ^{[37
]}

Spellman, Stephen R. ^{[38
]}

Arora, Mukta ^{[39
]}

Chhabra, Saurabh ^{[40
,41
]}

机构：

[1] Cleveland Clin Taussig Canc Inst, Blood & Marrow Transplant Program, Cleveland, OH USA

[2] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[3] Karolinska Inst, Clin Sci Intervent & Technol, Translat Cell Therapy Grp, Stockholm, Sweden

[4] Princess Margaret Canc Ctr, BMT Program, Toronto, ON, Canada

[5] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA

[6] Med Univ South Carolina, Charleston, SC 29425 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX 77030 USA

[8] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[9] Utah Blood & Marrow Transplant Program Adults, Salt Lake City, UT USA

[10] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh, Saudi Arabia

[11] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA

[12] Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada

[13] Ottawa Hosp Res Inst, Ottawa, ON, Canada

[14] CHU Grenoble Alpes, Dept Hematol, Grenoble, France

[15] New York Med Coll, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, Valhalla, NY 10595 USA

[16] Univ Michigan, Ann Arbor, MI 48109 USA

[17] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[18] Imperial Coll London, Hematol Res Ctr, Dept Med, Div Expt Med, London, England

[19] Weill Cornell Med Ctr, Dept Med Oncol, Hematol Malignancies & Bone Marrow Transplant, New York Presbyterian Hosp, New York, NY USA

[20] Univ Wisconsin, Dept Med, Div Hematol Oncol Bone Marrow Transplantat, Madison, WI USA

[21] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan

[22] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[23] Univ Minnesota, Blood & Marrow Transplant Program Pediat Adults, Minneapolis, MN USA

[24] Univ Hosp Bristol NHS Trust, Adult Bone Marrow Transplant, Bristol, Avon, England

[25] Doernbecher Childrens Hosp, Dept Pediat, Pediat Blood & Marrow Transplant Program, Portland, OR USA

[26] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[27] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA

[28] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA

[29] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA

[30] Virginia G Piper Canc Ctr, Canc Transplant Inst, Scottsdale, AZ USA

[31] Arizona Oncol, Scottsdale, AZ USA

[32] Dokkyo Med Univ, Dept Hematol & Oncol, Mibu, Tochigi, Japan

[33] Hop St Louis, Dept Hematol, Paris, France

[34] Hokkaido Univ Hosp, Sapporo, Hokkaido, Japan

[35] Isala Clin, Dept Hematol Oncol, Zwolle, Netherlands

[36] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA

[37] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA

[38] Ctr Int Blood & Marrow Transplant Res Minneapolis, Minneapolis, MN USA

[39] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA

[40] Ctr Int Blood & Marrow Transplant Res Milwaukee, Milwaukee, WI USA

[41] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Milwaukee, WI 53226 USA

来源：

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION | 2019年 / 25卷 / 09期

关键词：

Graft-versus-host disease; Mycophenolate mofetil; Methotrexate; Myeloablative; Allogeneic hematopoietic cell transplantation; VERSUS-HOST-DISEASE; TERM-FOLLOW-UP; BONE-MARROW; GVHD PROPHYLAXIS; MINIDOSE METHOTREXATE; COMPARING METHOTREXATE; PERIPHERAL-BLOOD; ACID EXPOSURE; PHASE-III; GRAFT;

D O I：

10.1016/j.bbmt.2019.05.019

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Combination therapy with a calcineurin inhibitor (CNI), such as cyclosporine (CSA) or tacrolimus (Tac), and methotrexate (MTX) or mycophenolate mofetil (MMF) is a widely used approach to graft-versus-host disease (GVHD) prevention. Data on the comparative effectiveness of MMF compared with MTX are limited and conflicting, however. We analyzed data from the Center for International Blood and Marrow Transplant Research for adult patients undergoing first myeloablative hematopoietic cell transplantation (HCT) from an HLA-identical matched related donor (MRD; n = 3979) or matched unrelated donor (URD; n = 4163) using CSA+MMF, CSA+MTX, Tac+MMF, or Tac+MTX for GVHD prevention between 2000 and 2013. Within the MRD cohort, 2252 patients received CSA+MTX, 1391 received Tac+MTX, 114 received CSA+MMF, and 222 received Tac+MMF. Recipients of CSA+MMF had a higher incidence of acute GVHD grade II-IV (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.24 to 2.20; P < .001) and grade III-IV (HR, 1.92; 95% CI, 1.31 to 2.83; P < .001) compared with Tac+MTX. The use of CSA+MMF was also associated with inferior overall survival (OS) (HR, 2.31; 95% CI, 1.73 to 3.09; P < .001) due to higher transplantation-related mortality (TRM) (HR, 4.03; 95% CI, 2.61 to 6.23; P < .001) compared with Tac+MTX. Within the URD cohort, 974 patients received CSA+MTX, 2697 received Tac+MTX, 68 received CSA+MMF, and 424 received Tac+MMF. CSA+MMF was again significantly associated with a higher incidence of grade III-IV acute GVHD (HR, 2.31; 95% CI, 1.57 to 3.42; P <0001), worse OS (HR, 2.36; 95% CI, 1.67 to 3.35; P < .001), and higher TRM (HR, 3.09; 95% CI, 2.00 to 4.77; P < .001), compared with Tac+MTX and other regimens. Thus, this large retrospective comparison of MMF versus MTX in combination with CSA or Tac demonstrates significantly worse GVHD and survival outcomes with CSA+MMF compared with Tac+MTX. (C) 2019. Published by Elsevier Inc.

引用

页码：1744 / 1755

页数：12

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