Multiple cycles of aggressive chemotherapy prior to autologous peripheral stem cell transplantation for lymphoma

Based on in vitro evidence of synergy between certain chemotherapeutic agents and of improved efficacy of cytotoxics administered as continuous infusions we devised a novel chemotherapy regimen for use in patients with lymphoma.

To assess the efficacy and tolerability of this regimen alone and in combination with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory lymphoma.

The regimen consisted of cytosine arabinoside and etoposide given as five day continuous infusions, bolus doses of methotrexate and cyclophosphamide and four days of oral dexamethasone (MADEC), together with prophylactic G-CSF. Fifty-one patients aged 17 to 65 years (median 43) were treated; 34 had intermediate or high grade non-Hodgkin's lymphoma and 17 had Hodgkin's disease. Patients with responsive disease received a second cycle.

Eleven patients (22%) achieved a complete response and 19 patients (38%) achieved a partial response, eight of whom were gallium negative. Previous chemosensitivity was highly predictive for response; minimal response was seen in patients with primary refractory disease. The probability of survival and event-free survival at 40 months for the entire group is 46% (+/- 8% SEM) and 26 +/- 8% respectively. Thirty-one patients proceeded to ASCT; the probability of survival of the transplanted group is 65 +/- 11% at 40 months. The regimen caused significant myelosuppression. The majority of cycles were complicated by febrile neutropenia and the requirement for platelet and red cell transfusions. Non-haematological toxicity was predominantly mucositis and was generally mild.

MADEC is a highly active regimen in patients with relapsed lymphoma. Patients responding to MADEC who proceed to ASCT have a good chance of achieving a durable remission.