Originally published as JCO Early Release 10.1200/JCO.2008.17.1314 on November 10 2008

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dean, R. M. Articles by Bishop, M. R. Search for Related Content PubMed PubMed Citation Articles by Dean, R. M. Articles by Bishop, M. R. Social Bookmarking                            What's this?

Association of Serum Interleukin-7 Levels With the Development of Acute Graft-Versus-Host Disease

Robert M. Dean, Terry Fry, Crystal Mackall, Seth M. Steinberg, Fran Hakim, Daniel Fowler, Jeanne Odom, Jason Foley, Ronald Gress, Michael R. Bishop

From the Experimental Transplantation and Immunology Branch; Pediatric Oncology Branch; Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD; and the Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH

Corresponding author: Michael R. Bishop, MD, Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10/CRC, Room 4-3152, 10 Center Drive, Bethesda, MD 20892; e-mail: mbishop{at}mail.nih.gov

Purpose Morbidity from acute graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic stem-cell transplantation (HSCT) to treat malignancy. Interleukin-7 (IL-7), the principal homeostatic cytokine for T cells, is required for acute GVHD in murine models. In contrast to inflammatory cytokines (eg, IL-2, tumor necrosis factor ), IL-7 has not been studied extensively in the clinical transplant setting relative to its relationship with acute GVHD.

Patients and Methods We evaluated the association of serum IL-7 levels with acute GVHD in 31 patients who were uniformly treated in a prospective clinical trial with reduced-intensity allogeneic HSCT from human leukocyte antigen–identical siblings. GVHD prophylaxis consisted of cyclosporine and methotrexate. Serum IL-7 levels and lymphocyte populations were determined at enrollment, the day of transplantation before the allograft infusion, and at specified intervals through 12 months post-transplantation.

Results As expected, IL-7 levels were inversely correlated with T-cell populations (P < .00001). Acute GVHD was significantly associated with higher IL-7 levels at day +7 (P = .01) and day +14 (P = .00003) post-transplantation as well as with the allograft CD34⁺ cell dose (P = .01). IL-7 levels at day +14 also correlated with the severity of acute GVHD (P < .0001). In logistic regression models, these factors were highly sensitive (up to 86%) and specific (100%) for classifying whether patients developed acute GVHD.

Conclusion These data support preclinical observations that IL-7 plays a critical role in inducing acute GVHD and provide a rational basis for novel approaches to prevent and treat acute GVHD through modulation of the IL-7 pathway.

published online ahead of print at www.jco.org on November 10, 2008.

Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00055744 [ClinicalTrials.gov] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?