Faculty Collaboration Database

Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation. Biol Blood Marrow Transplant 2017 Aug;23(8):1295-1302

Date

04/17/2017

Pubmed ID

28412518

DOI

10.1016/j.bbmt.2017.04.009

Scopus ID

2-s2.0-85019639994 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in randomized trials.

Author List

Kanate AS, Hari PN, Pasquini MC, Visotcky A, Ahn KW, Boyd J, Guru Murthy GS, Rizzo JD, Saber W, Drobyski W, Michaelis L, Atallah E, Carlson KS, D'Souza A, Fenske TS, Cumpston A, Bunner P, Craig M, Horowitz MM, Hamadani M

Authors

Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Ehab L. Atallah MD Professor in the Medicine department at Medical College of Wisconsin
Karen-Sue B. Carlson MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Anita D'Souza MD Associate Professor in the Medicine department at Medical College of Wisconsin
William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Timothy Fenske MD Professor in the Medicine department at Medical College of Wisconsin
Guru Subramanian Guru Murthy MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Laura Michaelis MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
J. Douglas Rizzo MD, MS Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin
Alexis M. Visotcky Biostatistician III in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Allografts
Disease-Free Survival
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunologic Factors
Male
Methotrexate
Middle Aged
Prospective Studies
Survival Rate
Tacrolimus