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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3370-3379
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
The Société Française d'Oncologie
Pédiatrique LMB89 protocol: highly effective multiagent
chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia
Catherine Patte,
Anne Auperin,
Jean Michon,
Henk Behrendt,
Guy Leverger,
Didier Frappaz,
Patrick Lutz,
Carole Coze,
Yves Perel,
Martine Raphaël, and
Marie-Josée Terrier-Lacombe on behalf of the Société
Française d'Oncologie Pédiatrique
From the Pediatrics Department, Statistics
Department, and Pathology Department, Institut Gustave Roussy,
Villejuif, France; Pediatrics Department, Institut Curie, Paris,
France; Emma Kinder Ziekenhuis, AMC Amsterdam, The Netherlands;
Onco-Hematology Department, Hopital Trousseau, Paris, France;
Pediatrics Department, Centre Léon Berard, Lyon, France;
Onco-Hematology Department, Institut de Puériculture, Strasbourg,
France; Pediatric Oncology Department, La Timone, Marseille, France;
Onco-Hematology Department, CHU, Bordeaux, France; and Biologic
Hematology Department, Hopital Avicenne, Bobigny, France.
This study was undertaken to show that a high survival rate can be
obtained in B-cell (Burkitt and large B-cell) lymphoma and L3 leukemia
with multiagent chemotherapy adapted to the tumor burden (stage,
resection status, percentage of blasts in bone marrow, and central
nervous system [CNS] involvement) and early response to chemotherapy,
to investigate actual prognostic factors, and to see if large B-cell
lymphoma can be treated with the same regimen as Burkitt lymphoma.
Patients were classified into 3 risk groups. Group A (resected stage I
and abdominal stage II) received 2 courses of vincristine,
cyclophosphamide, doxorubicin, and prednisone. Group B (patients not
eligible for groups A or C) received 5 courses of chemotherapy with, in
addition, high-dose methotrexate, 3 g/m2 over 3 hours;
infusional cytarabine; and intrathecal (IT) methotrexate. Group C
(patients with CNS involvement and acute lymphoblastic leukemia with at least 70% of blasts in bone marrow) received 8 courses with, in addition, high-dose methotrexate, 8 g/m2; high-dose cytarabine; etoposide; and triple IT.
Except in group A, treatment started with a prephase (COP, low-dose
vincristine and cyclophosphamide). It was intensified for patients who
did not respond to COP in group B and any patient with residual viable cells after the consolidation phase. A total of 561 patients were enrolled in the SFOP LMB89 protocol (July 1989-June 1996). Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and event-free survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI,
77%-90%) for group A, B, and C, respectively. In group B,
multivariate analysis of prognostic factors showed that a lactate
dehydrogenase level more than 2-fold the normal value, no response
after COP, and age of at least 15 years were associated with a lower
EFS. CNS involvement was the only prognostic factor in group C.
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