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Blood, 15 July 2006, Vol. 108, No. 2, pp. 441-451.
Prepublished online as a Blood First Edition Paper on March 23, 2006; DOI 10.1182/blood-2005-07-3011.
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Submitted July 27, 2005
Accepted March 3, 2006
CCG 1953: acute lymphoblastic leukemia in infants: analysis of prognostic factors. A report from the Children's Oncology Group
Joanne M Hilden*, Patricia A Dinndorf, Sharon O Meerbaum, Harland Sather, Doojduen Villaluna, Nyla A Heerema, Ron McGlennen, Franklin O Smith, William G Woods, Wanda L Salzer, Helen S Johnstone, Zoann Dreyer, and Gregory H Reaman
The Children's Hospital at The Cleveland Clinic, Cleveland, OH, USA
Children's National Medical Center, Washington, DC, USA
Children's Oncology Group Operations Center, Arcadia, CA, USA
Columbus Children's Hospital, Columbus, OH, USA
University of Minnesota, Minneapolis, MN, USA
Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH, USA
Children's Healthcare of Atlanta, Atlanta, GA, USA
Keesler Medical Center, Keesler AFB (Biloxi), MS, USA
University of Illinois, Chicago, IL, USA
Texas Children's Cancer Center at Baylor College of Medicine, Houston, TX, USA
Children's National Medical Center, Washington, DC, USA; Children's Oncology Group Operations Center, Arcadia, CA, USA
* Corresponding author; email: hildenj{at}ccf.org.
Infant ALL has a poor therapeutic outcome despite attempts to treat it based on prognostic factor-guided therapy. This is the first cooperative group trial characterizing all infants at the molecular level for MLL/11q23 rearrangement. All infants enrolled on CCG 1953 were tested for MLL rearrangement by Southern Blot, and the 11q23 translocation partner identified (4;11, 9;11, 11;19, or "other") by reverse-transcriptase PCR. 115 infants enrolled; overall event-free survival (EFS) was 41.7% (SD = 9.2%) and overall survival (OS) was 44.8% at 5 years. Five-year EFS for MLL rearranged cases was 33.6%, and for MLL non-rearranged cases was 60.3%. The difference in EFS between the three major MLL rearrangements did not reach statistical significance. Multivariate Cox regression analyses showed a rank order of significance for negative impact on prognosis of CD10 negativity, age less than 6 months, and MLL rearrangement, in that order. Toxicity was the most frequent cause of death. Relapse as a first event in 1953 was later (median 295 days) compared to 1883 historical control (median 207 days). MLL/11q23 rearrangement, CD10 expression, and age are important prognostic factors in infant ALL, but molecular 11q23 translocation partners do not predict outcome.
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