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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2736-2743.
Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-07-036665.
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Submitted July 20, 2006
Accepted November 22, 2006
Results of a randomized international study of high risk central nervous system B-non-Hodgkin's lymphoma and B-acute lymphoblastic leukemia in children and adolescents
Mitchell S. Cairo*, Mary Gerrard, Richard Sposto, Anne Auperin, C. Ross Pinkerton, Jean Michon, Claire Weston, Sherrie L. Perkins, Martine Raphael, Keith McCarthy, and Catherine Patte
Morgan Stanley Childrens Hospital of NewYork-Presbyterian, Columbia University, New York, NY
Sheffield Children's Hospital, Sheffield, United Kingdom
Keck School of Medicine, University of Southern California, Los Angeles, CA
Institut Gustave Roussy, Paris, France
Royal Marsden Hospital, Surrey, United Kingdom
Institut Curie, Villejuif, France
University of Leicester, Leicester, United Kingdom
University of Utah Health Sciences Center, Salt Lake City, UT
CHU Bicetre AP-HP, Paris, France
Gloucestershire Hospitals, NHS Foundation Trust, Gloucestershire, United Kingdom
* Corresponding author; email: mc1310{at}columbia.edu.
The prognosis for higher risk childhood B-non-Hodgkin's lymphoma has improved over the past twenty years but the optimal intensity of treatment has yet to be determined. Children  21 years with newly-diagnosed B-NHL/B-ALL with higher risk factors (BM ± CNS) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine + etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 gm/m2) + extra intrathecal therapy. Fifty-one percents had BM involvement, 20% had CNS involvement, and 29% had BM + CNS. One hundred ninety patients were randomized. The probability of 4-year EFS and S was 79 ± 2.7% and 82 ± 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced intensity therapy, the 4-year EFS after randomization was 90 ± 3.1 versus 80 ± 4.2% (one-sided P=0.064) and survival (S) was 93 ± 2.7% versus 83 ± 4.0% (one-sided P=0.032). Patients with either combined BM/CNS disease at diagnosis and/or poor response to COP reduction therapy had a significantly inferior EFS and S (P<0.001). Standard intensity FAB/LMB therapy is recommended for children with high risk B-NHL (B-ALL ± CNS).
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