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

Hematology/Oncology, Children's National Medical Center and George Washington University School of Medicine and Public Health, 111 Michigan Avenue NW, Washington, DC 20010, USA.
Blood (Impact Factor: 10.45). 03/2008; 111(5):2548-55. DOI: 10.1182/blood-2007-02-070342
Source: PubMed


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 x 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/mm3 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 as NCT00002812.

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    • "7 Data Application: Children's Oncology Group Study 1961 7.1 Is there evidence of correlation between the survival times of patients within the same institution? We applied our method to a Children's Oncology Group (COG) study (protocol number 1961) (Seibel et al, 2008 "
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    • "It appeared that POG9411 consolidation helped achieve a greater reduction of leukemia. A recent study of CCG1961 indicated that longer post-induction intensification failed to prolong EFS, while an early aggressive post-induction intensification resulted in better EFS and OS for patients with newly diagnosed high-risk ALL [18]. Many studies have reported that the presence of minimal residual disease (MRD) prior to allogeneic transplantation is predictive of subsequent treatment failure [19, 20]. "
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    • "We subsequently determined the expression levels of the genes in the 5-GC by qRT-PCR in diagnostic bone marrow specimens from 34 pediatric T-ALL patients from a completely independent Validation Cohort. Most of these patients were treated on COG 1882 or 1901, while the patients in the Training Cohort were treated on COG 1961 [4]. In the Validation Cohort the 5-GC yielded an overall prediction accuracy of 79% (Table 4). "
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