Poor-risk non-lymphoblastic lymphoma of childhood: results of an intensive pilot study.

Children with "poor-risk" nonlymphoblastic lymphoma, especially those with marrow or nervous system (CNS) involvement at presentation, have fared poorly even on aggressive chemotherapy regimens. We report here the results of a pilot study of 30 children treated with a highly intensive chemotherapy regimen. This regimen includes an intensive Induction Phase consisting of three cycles of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and corticosteroids) as well as intensive intrathecal therapy with each cycle. This is followed by a CNS Consolidation Phase consisting of a single cycle of CHOP therapy with five intrathecal doses of "triple" chemotherapy (methotrexate, cytosine arabinoside, and hydrocortisone). Thereafter, a Maintenance Phase consists of alternating cycles of 1) cytosine arabinoside and 6-thioguanine, 2) oral methotrexate and VP-16, and 3) CHOP, for a duration that varied from 36 to 72 wk. Neither debulking surgery nor radiation therapy were recommended. There were 20 patients with Stage III disease (St. Jude's Staging System) and an additional ten patients with bone marrow and/or CNS involvement. The latter group included six patients with B-cell leukemia, three of whom also had CNS disease at presentation. Two additional patients had CNS disease without marrow involvement. Twenty-nine of 30 patients achieved a complete response. Six patients died with recurrent or progressive disease. Twenty-three patients are alive without any adverse events between 21 and 65 mo after diagnosis, with the median time of survival not yet reached (at least 32 mo). All seven adverse events occurred within 7 mo of diagnosis. Event-free survival for all patients is 77%, for Stage III patients is 80%, and for patients with marrow and/or CNS involvement is 70%. This pilot study offers encouragement for improvement in the prognosis of children with "poor-risk" nonlymphoblastic lymphoma and merits evaluation in a Phase III randomized trial in the multicenter cooperative group setting.