Pediatric oncology group experience with modified LSA2-L2 therapy in 107 children with non-Hodgkin's lymphoma (Burkitt's lymphoma excluded)

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Abstract
From September 1976 to August 1979 the Pediatric Oncology Group accessed 145 children to study the effectiveness of modified LSA2-L2 therapy for the treatment of non-Hodgkin's lymphoma (NHL). Burkitt's lymphoma patients were ineligible; E-rosette-positive patients with ≥ 25% blasts in the marrow entered after February 1977 were reported separately. Radiotherapy could be used to treat patients with compressive mediastinal disease at diagnosis and was prescribed for those with residual abdominal disease as demonstrated by second-look surgery on completion of induction chemotherapy. Confirmation of diagnosis by the Pathology Panel and Repository Center for Lymphoma Clinical Trials was mandatory. Diagnostic tissues of 131 patients were reviewed. Among 107 evaluable patients, 91 (85%) achieved complete remission. Differences in response rates among the three major histologic groups (lymphoblastic, undifferentiated, and large cell) were of statistical significance, with response being poorest for diffuse undifferentiated lymphoma (P = 0.03). Failure-free survival did not differ significantly for the three major histologic diagnoses. While response rate was lowest for Murphy Stage III patients (79%), the differences among the stages were not significant. Stage was not a significant prognostic factor for failure-free survival (P = 0.08). The number of patients still at risk and the Kaplan-Meier estimate of percentage of patients remaining at risk after 3 years is: Stage I, 8 (100%); Stage II, 10 (67%); Stage III, 28 (57%); Stage IV, 6 (39%); and > 25% blasts, 1 (13%). Stage III failure curves for lymphoblastic disease show continuing stepwise failure through 3 years. Among patients with diffuse large cell and undifferentiated disease, most failures occurred by 8 months. M1 and M2 levels of marrow involvement were not prognostic among children with lymphoblastic disease. The presence of a mediastinal mass was a significant factor contributing to failure in children with lymphoblastic disease without marrow involvement. Leucocytosis > 10,000/1, was a significant (P = 2-L2 regimen was associated with considerable toxicity, severe or worse in 77% and life-threatening to 40% of these patients. Four died of toxicity. However, therapy was given more easily and safely as investigator experience increased. Maintenance therapy was delivered on an out patient basis without complications in most instances. This study demonstrates the ability of the LSA2-L2 regimen to produce long-term remissions, or to “cure” 60% to 70% of children among the major histologic categories of childhood NHL, excepting Burkitt's lymphoma. Long-term survival, or “cure”, occurs in 90% with Stages I and II disease and some 50% of those with Stages III and IV disease. Neither radiotherapy nor second-look surgical procedures appear to influence outcome. The continuous relapse pattern seen in lymphoblastic disease involving the mediastinum suggests the need for more intensive repetitive therapy “up-front”. The relapse pattern of non-lymphoblastic disease suggests the discontinuation of therapy after 1 year.