Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group

Author:

Seibel Nita L.1,Steinherz Peter G.2,Sather Harland N.3,Nachman James B.4,DeLaat Cynthia5,Ettinger Lawrence J.6,Freyer David R.7,Mattano Leonard A.8,Hastings Caroline A.9,Rubin Charles M.4,Bertolone Kathy10,Franklin Janet L.11,Heerema Nyla A.12,Mitchell Torrey L.13,Pyesmany Allan F.14,La Mei K.3,Edens Cheryl15,Gaynon Paul S.11

Affiliation:

1. Hematology/Oncology, Children's National Medical Center and George Washington University School of Medicine and Public Health, Washington, DC;

2. Memorial Sloan Kettering Cancer Center, New York, NY;

3. Group Operations Center, Children's Oncology Group, Arcadia, CA;

4. University of Chicago Comer Children's Hospital, IL;

5. Cincinnati Children's Hospital Medical Center, OH;

6. St Peter's University Hospital, New Brunswick, NJ;

7. DeVos Children's Hospital, Grand Rapids, MI;

8. Kalamazoo Center for Medical Studies, MI;

9. Children's Hospital and Research Center Oakland, CA;

10. Kosair Children's Hospital, Louisville, KY;

11. Children's Hospital of Los Angeles, CA;

12. Ohio State University College of Medicine, Columbus;

13. Raymond Blank Children's Hospital, Des Moines, IA;

14. Izaak Walton Killam (IWK) Health Center, Halifax, NS; and

15. Department of Hematology/Oncology, Vanderbilt University, Nashville, TN

Abstract

Longer and more intensive postinduction intensification (PII) improved the outcome of children and adolescents with “higher risk” acute lymphoblastic leukemia (ALL) and a slow marrow response to induction therapy. In the Children's Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using a 2 × 2 factorial design for children with higher risk ALL and a rapid marrow response to induction therapy. Between November 1996 and May 2002, 2078 children and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count 50 000/ or more, or 10 years of age or older with any white blood count) were enrolled. After induction, 1299 patients with marrow blasts less than or equal to 25% on day 7 of induction (rapid early responders) were randomized to standard or longer duration (n = 651 + 648) and standard or increased intensity (n = 649 + 650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P < .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most apparent after 2 years from diagnosis. Longer duration PII provided no benefit. Stronger intensity but not prolonged duration PII improved outcome for patients with higher-risk ALL. This study is registered at http://clinicaltrials.gov as NCT00002812.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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