Intensive Chemotherapy for High-Risk Patients with High-Grade Malignant Non-Hodgkin Lymphomas: A Pilot Study Using Adriamycin, Cyclophosphamide, Vincristine, Methotrexate, Etoposide, and Dexamethasone (ACOMED Protocol)

Abstract

<i>Background</i>: In high-grade malignant non-Hodgkin lymphomas (NHL), prognostic risk is assessable by a series of initial parameters but adequate treatment approaches to high-risk patients remain to be established. The aim of the present study was therefore to evaluate the feasibility and efficiency of the intensified induction chemotherapy regimen ACOMED for poor prognosis patients. <i>Patients and Methods</i>: Unpretreated patients with high-grade malignant NHL (Kiel classification) presenting with Ann Arbor stage Il-IV disease and at least one prognostic risk factor (stage III/IV, serum LDH > normal, performance status ECOG > 2, bulky disease > 10 cm) were treated with the ACOMED regimen consisting of four courses of adriamycin 25 mg/m2 i.v. days 4-5, cyclophosphamide 250 mg/m2 i.v. days 1-5, vincristine 2 mg i.v. absolute day 1, methotrexate 500 mg/m2 i.v. day 1 with leucovorin-rescue, etoposide 100 mg/m2 i.v. days 1-5, dexamethasone 10 mg/m2 p.o. days 1-5, supported by G-CSF and repeated on day 21. <i>Results</i>: Of 44 patients recruited to the study, 31 have already completed treatment and are thus fully evaluable. Complete remissions were obtained in 25/31 (81%) of the patients; 4/25 (16%) relapsed, median observation time for all is 12 (3-18) months. The major side effect was mucositis occurring as WHO grade 4 in 30% of the patients in cycle 1, gradually decreasing in incidence and severity in further cycles but leading to an early discontinuation of the protocol and a switch to COP-BLAM or CHOP in 8/31 patients after 2 (1-3) cycles. Infections were rarely severe and myelotoxicity of WHO grade 4, though observed in one-third of the cycles, was only of short duration. <i>Conclusions</i>: ACOMED thus presents a highly effective regimen for remission induction in NHL poor-risk patients with longer observation periods required for the final judgement on remission stability. However, modifications of supportive care to ameliorate mucositis do seem to be desirable.