Interleukin-7 Levels Predict GVHD in Transplant Patients

Roxanne Nelson

December 20, 2007

December 20, 2007 (Atlanta) — Increased levels of serum interleukin (IL)-7 appear to precede the development of acute graft-vs-host disease (aGVHD) in patients who have undergone allogeneic hematopoietic stem-cell transplantation, researchers reported.

"Before patients even showed signs of graft-vs-host disease, we were able to predict which patients would develop it and which patients would not, using IL-7 levels," lead author Robert M. Dean, MD, from the Cleveland Clinic in Ohio, told Medscape Oncology during a poster presentation here at the American Society of Hematology 49th Annual Meeting and Exposition. "IL-7 has a high degree of sensitivity and specificity, and we're hopeful that further work will confirm our results and that it can potentially be used as a predictive test."

Dr. Dean also pointed out that there are no validated clinical disease markers for an increased risk for aGVHD or for disease progression to potentially fatal stages.

GVHD is the major complication associated with allogeneic hematopoietic stem-cell transplantation, despite advances that have been made in transplantation immunology. The acute form of the disease generally develops within 100 days of transplantation and causes significant morbidity and mortality.

Results of experimental studies showed that the incidence of aGVHD is promoted by the homeostatic cytokine IL-7, and Dr. Dean and colleagues hypothesized that levels of serum IL-7 might be associated with the development of aGVHD in patients undergoing allogeneic hematopoietic stem-cell transplantation.

In a prospective trial, they evaluated this hypothesis using serum samples obtained from 31 patients who underwent allogeneic transplantation using human leukocyte antigen (HLA)-identical siblings as donors. All patients in the cohort received 1 to 3 pretransplant chemotherapy cycles to induce uniform host lymphopenia, which was followed by fludarabine-based reduced-intensity conditioning. Cyclosporine methotrexate was administered as prophylaxis against the development of GVHD.

The researchers measured levels of serum IL-7 at baseline and then at multiple time points during the first posttransplant year, beginning on the day of the transplant. Levels of IL-7 levels were analyzed for associations with blood lymphocyte counts, the development of aGVHD, and patient survival. They also looked at factors including patient and donor age, CD3+ and CD34+ cell doses, donor gender, donor-recipient gender mismatch, donor or recipient cytomegalovirus status, previous rituximab therapy, donor lymphoid or myeloid chimerism of more than 95% at day 14 and beyond, serum IL-15 levels, and levels of soluble tumor necrosis factor-receptors (sTNFR) 1 and 2 and their possible association with aGVHD. A total of 45% of patients developed aGVHD: 3% were grade 1, 23% were grade 2, 19% were grade 3, and none were grade 4.

The median IL-7 levels increased from 12.1 pg/mL at baseline to 37 pg/mL on day 0 and then dropped to 12.0 pg/mL on day 14 after allografting. They noted that the changes in IL-7 levels correlated inversely with absolute lymphocyte counts and with CD3, CD4, and CD8 counts both at baseline and day 7. Compared with patients who did not develop aGVHD, higher levels of IL-7 were observed at day 7 and day 14 posttransplant. Patients with higher levels of IL-7 at day 14 correlated with more severe grades of aGVHD.

"We feel it is very important to try to determine who is going to develop graft-vs-host disease ahead of time, and then we can make a decision about prophylactic treatment," said Dr. Dean.

Overall, elevated serum IL-7 levels in the early posttransplant period were able to accurately predict the risk of developing aGVHD after allogeneic transplantation. "It has the potential to be developed into a simple, reproducible, and relatively inexpensive test that can help us predict which patients are at a higher risk," he said.

American Society of Hematology 49th Annual Meeting and Exposition: Abstract 1064. Presented December 8, 2007.

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