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.
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/m(2) 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/m(2); 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. (Blood. 2001;97:3370-3379)
Patte
C
C
Pediatrics Department, Institut Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif Cedex, France. patte@igr.fr
Auperin
A
A
Michon
J
J
Behrendt
H
H
Leverger
G
G
Frappaz
D
D
Lutz
P
P
Coze
C
C
Perel
Y
Y
Raphaël
M
M
Terrier-Lacombe
M J
MJ
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D009367:Neoplasm Staging; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use*
D003561:Cytarabine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D006854:Hydrocortisone; D008727:Methotrexate