CLINICAL TRIAL
COMPARATIVE STUDY
JOURNAL ARTICLE
RANDOMIZED CONTROLLED TRIAL
RESEARCH SUPPORT, NON-U.S. GOV'T
RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
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Studies on the pathology of non-Hodgkin's lymphoma of childhood. I. The role of routine histopathology as a prognostic factor. A report from the Children's Cancer Study Group.

Cancer 1984 April 16
Between April 1977, and August 1980, the Children's Cancer Study Group (CCSG) conducted a clinical trial of childhood non-Hodgkin's lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4-drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP] ) was compared with a 10-drug regimen (regimen 2, modified LSA2-L2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitt's tumor (BT), 40; "undifferentiated" non-Burkitt's type (NB), 67; large cell or "histiocytic" lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.

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