Ifosfamide- and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma

Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves t he prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and si multaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatm ent. Twenty-seven patients with NHL received MINE chemotherapy (mesna and i fosfamide 1330 mg/m(2) and etoposide 65 mg/m(2) i.v, days 1-3, and mitoxant rone S mg/m(2) i.v. day 1). The same schedule, but higher doses were used f or PBSC stimulation (mesna, ifosfamide 1700 mg/m(2), etoposide 175 mg/m(2), mitoxantrone 10 mg/m(2)). Forty-six patients with HD received VIM chemothe rapy (mesna, ifosfamide 1200 mg/m(2) i.v. days 1-5, etoposide 90 mg/m(2) i. v. days 1, 3, and 5, methotrexate 30 mg/m(2) i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy fur mobilization was followed by G-CS F administered at a dose 5-16 mug/kg/day depending on the clinicians judgem ent of the patient's pretreatment. Complete response after VIM and MINE wer e 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups. patients with relapsing disease had better responses than did those with primary pro gressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n=62, 85%). The median yields were 10.6 x 10(6) CD34(+) cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34(+) cells/kg and 54.5 x 10( 4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34(+) cells/kg i n all but six patients (8%), and the harvested amount of CD34(+) cells was less than 1.0 x 10(6/)kg in only two patients (3%). The toxicity of VIM and MINE was miminal and chemotherapy-induced trombocytopenia did not occur wi th PBSC collection.