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Title: Imatinib Improves Survival in Pediatric Ph-Positive ALL: Presented at ASH
URL: http://www.pslgroup.com/dg/218D2E.htm
Doctor's Guide
December 11, 2007


By John Gever

ATLANTA, GA -- December 11, 2007 -- Children with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL) showed improved 2-year event-free survival when imatinib was added to chemotherapy.

The results were presented here on December 9 in a plenary session at the 49th American Society of Hematology (ASH) Annual Meeting and Exposition by Kirk Schultz, MD, Associate Professor of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.

Continuous treatment with 340 mg/day of imatinib, along with conventional chemotherapy, produced a 2-year event-free survival of 85%. Patients treated with a similar regimen without imatinib in an earlier trial had a 2-year event-free survival of 38%.

Ph-positive ALL is rare in children, accounting for about 2% to 4% of pediatric ALL cases, Dr. Schultz said. The prognosis has been poor.

The regimen tested in this study began with two 3-week cycles of consolidation therapy followed by a reinduction cycle, an intensification cycle, another reinduction cycle, and finally, long-term maintenance. Dr. Schultz's group tried several different imatinib-dosing schedules on top of this regimen.

They settled on continuous imatinib throughout the entire treatment period when patients showed clearly improved response over intermittent imatinib dosing.

Fifty patients received 280 days of continuous imatinib, out of 93 patients in the entire study, prior to long-term maintenance.

Thirty-two patients received bone marrow transplant instead of the full chemotherapy regimen. Those patients tended toward poorer 2-year event-free survival relative to those treated with chemotherapy alone (64% for matched sibling donors, 70% for unmatched related donors, 81% for chemotherapy alone), but the difference was not statistically significant.

Imatinib also seemed to help reduce residual disease following the initial consolidation cycles. Fewer than 20% of patients receiving continuous imatinib had greater than 0.01% residual disease following consolidation, compared with about 80% when imatinib was omitted from the consolidation cycles (P =.01).

Dr. Schultz said the study design calls for stopping imatinib after 2.5 years. "I have to say I have big concerns that we may see an increase in relapse rates after that," he said. "We will know within 1 year whether that phenomenon is or is not occurring."

Future studies should examine the effects of starting imatinib or similar agents during induction therapy, he said, and whether longer therapy after bone marrow transplant will improve outcomes.

Ph-positive ALL is more common in adults, Dr. Schultz said, comprising about one quarter of all ALL cases. While the regimens in this study were extremely intensive, pediatric therapies can often be applied to young adults. Other groups are now investigating the addition of imatinib to treatments for adult Ph-positive ALL.


[Presentation title: Improved Early Event Free Survival (EFS) in Children With Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) With Intensive Imatinib in Combination With High Dose Chemotherapy: Children's Oncology Group (COG) Study AALL0031. Abstract 4]

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