Last Updated: 2009-01-28 14:54:02 -0400 (Reuters Health)

By Scott Baltic

NEW YORK (Reuters Health) - Pediatric-inspired chemotherapy markedly improves the outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL), at least up to the age of 45 years. This finding comes from a multicenter phase II study by the Group for Research on Adult Acute Lymphoblastic Leukemia, a French/Swiss/Belgian consortium, and is published online by the Journal of Clinical Oncology.

The authors note that several earlier studies had found that patients age 15-20 years "markedly benefited from a pediatric approach." The purpose of this study was to examine whether a pediatric-inspired strategy could also help adults over 20.

Dr. Herve Dombret of the Hopital Saint-Louis, Paris, told Reuters Health that pediatric and adult approaches to treating ALL have progressively diverged over the last 30 years, with chemotherapy emphasized in children and stem cell transplantation (SCT) favored for adults.

Children better tolerate the higher cumulative chemotherapy doses, he explained, while the greater prevalence of chemotherapy-resistant ALL subtypes in adults led many hematologists to believe that SCT following a non-intensive course of chemotherapy was the only practical option in adults.

The study enrolled 225 adult patients (median age 31 years, range 15-60) between November 2003 and November 2005. One hundred forty-nine patients had B-cell precursor ALL, and the others had T-lineage ALL.

In the course of all phases of treatment (induction, salvage, consolidation, intensification and maintenance), patients in the trial received 16-fold more L-asparaginase, 3.7-fold more vincristine, and 8.6-fold more prednisone than had the patients in the France-Belgium Group for Lymphoblastic Acute Leukemia in Adults 94 (LALA-94) study. In addition to the pediatric-style chemotherapy protocol, the study retained treatment options generally used in adults, such as cranial irradiation, early intensive administration of growth factors, and allogeneic SCT in first complete remission.

The authors retrospectively compared their results to those from the LALA-94 trial, which had included 712 patients age 15-55. The complete remission rate, event-free survival, and overall survival in the current study were significantly better than the LALA-94 results.

Older age "remained an important bad prognostic factor," the team reports, with 45 years the best cutoff for benefit.

"Currently, we propose using unmodified pediatric protocols in teenagers and adapted pediatric-inspired protocols in younger adults," the researchers write. "To reduce treatment-related toxicity in patients older than 45 years, we are currently recommending systemic anti-infectious prophylaxis during induction and delayed intensification."

J Clin Oncol 2009;27.