Faculty Collaboration Database

Sibling donor and recipient immune modulation with atorvastatin for the prophylaxis of acute graft-versus-host disease. J Clin Oncol 2013 Dec 10;31(35):4416-23

Date

10/30/2013

Pubmed ID

24166529

Pubmed Central ID

PMC3842909

DOI

10.1200/JCO.2013.50.8747

Scopus ID

2-s2.0-84894066201 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

PURPOSE: Graft-versus-host disease (GVHD) is major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Atorvastatin is a potent immunomodulatory agent that holds promise as a novel and safe agent for acute GVHD prophylaxis.

PATIENTS AND METHODS: We conducted a phase II trial to evaluate the safety and efficacy of atorvastatin administration for GVHD prophylaxis in both adult donors and recipients of matched sibling allogeneic HCT. Atorvastatin (40 mg per day orally) was administered to sibling donors, starting 14 to 28 days before the anticipated first day of stem-cell collection. In HCT recipients (n = 30), GVHD prophylaxis consisted of tacrolimus, short-course methotrexate, and atorvastatin (40 mg per day orally).

RESULTS: Atorvastatin administration in healthy donors and recipients was not associated with any grade 3 to 4 adverse events. Cumulative incidence rates of grade 2 to 4 acute GVHD at days +100 and +180 were 3.3% (95% CI, 0.2% to 14.8%) and 11.1% (95% CI, 2.7% to 26.4%), respectively. One-year cumulative incidence of chronic GVHD was 52.3% (95% CI, 27.6% to 72.1%). Viral and fungal infections were infrequent. One-year cumulative incidences of nonrelapse mortality and relapse were 9.8% (95% CI, 1.4% to 28%) and 25.4% (95% CI, 10.9% to 42.9%), respectively. One-year overall survival and progression-free survival were 74% (95% CI, 58% to 96%) and 65% (95% CI, 48% to 87%), respectively. Compared with baseline, atorvastatin administration in sibling donors was associated with a trend toward increased mean plasma interleukin-10 concentrations (5.6 v 7.1 pg/mL; P = .06).

CONCLUSION: A novel two-pronged strategy of atorvastatin administration in both donors and recipients of matched sibling allogeneic HCT seems to be a feasible, safe, and potentially effective strategy to prevent acute GVHD.

Author List

Hamadani M, Gibson LF, Remick SC, Wen S, Petros W, Tse W, Brundage KM, Vos JA, Cumpston A, Bunner P, Craig MD

Author

Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin

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

Administration, Oral
Adult
Aged
Bacterial Infections
Cytokines
Feasibility Studies
Female
Graft vs Host Disease
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Heptanoic Acids
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Male
Middle Aged
Pyrroles
Siblings
Survival Analysis
Tissue Donors
Transplantation Immunology
Transplantation, Homologous
Treatment Outcome
Virus Diseases
Young Adult