Early postinduction intensification therapy improves survival for children and adolescents with high risk acute lymphoblastic leukemia: a report from the Chilren’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: 10.43). 03/2008; 111(5):2548-55. DOI: 10.1182/blood-2007-02-070342
Source: PubMed

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 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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Available from: Charles M Rubin, Aug 25, 2015
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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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    Statistics in Biosciences 12/2010; 2(2):154-179. DOI:10.1007/s12561-010-9026-x
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    • "In the past, the prognosis for paediatric T-ALL patients was inferior compared with the outcome of T-LBL patients, and this despite treatment with comparably intensive chemotherapy protocols (Pullen et al, 1999; Schrappe et al, 2000; Vilmer et al, 2000; Ballerini et al, 2008). Sufficient tools for risk stratification, identification of highly effective protocol elements and the reduced mortality of stem cell transplantation in high risk patients improved the outcome of children with T-ALL to 75–83% event-free survival (EFS) (Goldberg et al, 2003; Pui et al, 2004; Moricke et al, 2008; Seibel et al, 2008). These results are similar or only a little less than the EFS of 78–90% achieved for T-LBL in recent trials (Reiter et al, 2000; Burkhardt et al, 2006a; Sun et al, 2008; Uyttebroeck et al, 2008; Sandlund et al, 2009) as summarized in Table II. "
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    British Journal of Haematology 11/2009; 149(5):653-68. DOI:10.1111/j.1365-2141.2009.08006.x · 4.96 Impact Factor
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    • "However, concerns about late adverse effects of CRT, including lifelong secondary brain tumours, endocrinopathies, increased mortality and morbidity, and neurocognitive deficits (Jankovic et al, 1994; Löning et al, 2000; Reddick et al, 2006; Spiegler et al, 2006; Goshen et al, 2007; Hijiya et al, 2007; Waber et al, 2007; Mody et al, 2008) led to the development of alternative CNS-directed strategies (Clarke et al, 2003), including reduced-dose radiotherapy (Reiter et al, 1994; Schrappe et al, 2000a,b; Möricke et al, 2008) or its replacement with additional IT injections and effective systemic chemotherapy. By the 1990s, most of the large cooperative groups no used preventive CRT (pCRT) for the majority of non-very-high-risk patients with B-cell-lineage ALL (Tubergen et al, 1993; Reiter et al, 1994; Nachman et al, 1998; Gaynon et al, 2000; Maloney et al, 2000; Manera et al, 2000; Schrappe et al, 2000a,b; Stark et al, 2000; Vilmer et al, 2000; Kamps et al, 2002; Clarke et al, 2003; Hill et al, 2004; Pui et al, 2004; Saarinen-Pihkala et al, 2004; Matloub et al, 2006; Nathan et al, 2006; Moghrabi et al, 2007; Möricke et al, 2008; Seibel et al, 2008). Triple intrathecal therapy (TIT), consisting of cytarabine and steroids in addition to MTX, was administered by some groups (Pullen et al, 1993; Maloney et al, 2000; Manera et al, 2000; Stark et al, 2000; Pui et al, 2004; Moghrabi et al, 2007) and found to be more effective for isolated CNS control than IT MTX; however, no advantage in EFS was ultimately proven (Matloub et al, 2006). "
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