HEMATOLOGICAL SUPPORT OF HIGH-DOSE SEQUENTIAL CHEMOTHERAPY - CLINICAL-EVIDENCE FOR REDUCTION OF TOXICITY AND HIGH RESPONSE RATES IN POOR-RISK LYMPHOMAS

The toxicity and feasibility of a high-dose sequential (HDS) chemother apy programme delivered with growth factor support were evaluated in p atients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) or with progressive Hodgkin's disease. The scheme includes the sequent ial administration of single cytotoxic drugs at very high doses follow ed by intensified treatment with circulating progenitor autograft. In some instances, the original HDS scheme, initially designed at the Mil an Cancer Center, was partially modified and intensified with a prelim inary debulking phase. The use of G-CSF (filgrastim) made toxicity in the high-dose phase acceptable and allowed good harvests of peripheral blood progenitor cells (PBPC); the use of PBPC in the final autograft ing phase resulted in low haematological toxicity. Of 71 patients with NHL treated at our institution with either the original or the intens ified HDS version, the overall toxicity-related mortality was 5.6%, th us comparable to lethal toxicity commonly associated with conventional chemotherapy Adequate PBPC harvests are crucial for good tolerability of the programme. Optimal harvests are generally obtained in patients without neoplastic marrow infiltration, while patients with marrow di sease often have a poorer mobilisation. However, an optimally time-spa ced chemotherapy debulking might also restore sufficient mobilisation in these latter patients. In terms of therapeutic efficacy, HDS has pr oduced promising results since the initial experience in relapsed pati ents. More recently, HDS was evaluated as first-line treatment in a se ries of 22 consecutive patients, presenting with advanced-stage, inter mediate-grade NHL other than diffuse large cell subtype. A CR rate of 82% was obtained following HDS, with a projected survival of 86% at fi ve years. Thus, delivery of an intensive high-dose chemotherapy progra mme with haematopoietic growth factor support was found to be feasible and reasonably, safe. The high antitumour efficacy of such a scheme m akes it suitable for wider applicability in all those chemosensitive t umours where a dose increase might enhance the chance of cure.