Grant Funds Acute Lymphoblastic Leukemia Research


Relapsed acute lymphoblastic leukemia (ALL) is a common pediatric cancer with a poor prognosis. The primary treatment for relapsed ALL is hematopoietic (blood-forming) stem cell transplant (HSCT), but stem cell transplant is successful in half or fewer cases, usually because the leukemia returns after the transplant.

HSCT treatment can fail if the chemotherapy or radiation therapy does not eradicate the leukemia, leaving minimal residual disease, or if the transplanted immune system does not successfully attack the disease.

Stephan Grupp, M.D., Ph.D., and coworkers in the Division of Oncology have performed laboratory and translational studies supporting a new concept in ALL therapy — the use of a signal transduction inhibitor to decrease risk of ALL relapse following HSCT. This work has led to pilot clinical trials performed by Nancy Bunin, M.D., and Susan Rheingold, M.D., both in the Division of Oncology, and now a nationwide Phase III trial for patients with relapsed ALL. Dr. Grupp was recently awarded a grant from the National Cancer Institute to study ALL biology in patient specimens collected on this clinical trial. The five-year, $2 million study provides a unique opportunity to study mechanisms of this new therapy in the context of the trial, bringing the initial concept full circle from the lab, to phase III trial, and back to the lab.

Dr. Grupp will study the anti-leukemic effect of sirolimus, a signal transduction inhibitor widely used as an immunosuppressive agent, and evaluate its impact on residual ALL after HSCT. The use of sirolimus to limit the risk of ALL relapse after HSCT is a novel approach, and a method to improve HSCT outcome using sirolimus would be a major advance in antileukemia therapy and transplantation.

Investigators will compare standard post-HSCT treatment with the same treatment plus sirolimus, determining the impact of the new treatment on clinical success. Using samples collected from children on the trial who have relapsed ALL, Dr. Grupp and his colleagues will demonstrate the impact of sirolimus treatment on patient ALL cells, study the immune reactions of the donor immune system against the ALL cells, and study measurements of minimal residual disease in each patient.

The clinical trial is a major area of emphasis for the Children's Oncology Group, a National Institutes of Health-funded multicenter clinical research organization that supports clinical trials for pediatric cancer patients. The trial is now open nationwide.