An in vivo purging with intensive debulking chemotherapy prior to peripheral blood progenitor cell (PBPC) collection may reduce the risk of tumor contamination of the harvest products; however, it is usually associated with a marked reduction in PBPC mobilization. These issues have been considered while designing an adapted version of the high-dose sequential regimen for patients with lymphoid malignancies and bone marrow involvement. To reduce tumor contamination risks, PBPC collection was postponed to the end of the high-dose phase; however, in order to enhance progenitor cell mobilization, a chemotherapy-free lag period was introduced prior to the final mobilizing course. Thirty-nine patients (median age 47 years, range 26-62) with previously untreated indolent lymphoma entered this pilot study; all had advanced-stage disease, and 29 had overt marrow involvement. Sufficient numbers of PBPC to perform autograft with safety were harvested in 34 patients, with a median of 3 (range 2-5) leukaphereses. A median of 14.8 x 10(6) (range 2-51) CD34+/kg and 32.6 x 10(4) (range 1.77-250) colony forming units-granulocyte/macrophage/kg were collected per patient. In univariate analysis, the duration of the chemotherapy-free interval prior to the final mobilizing course, i.e. > or <65 days, was the most significant variable influencing progenitor mobilization. These data suggest that extensive in vivo tumor debulking is feasible provided that a sufficient chemotherapy-free period preceding the mobilizing course is allowed in order to allow a full recovery of marrow functions.