Thalidomide maintenance following high-dose melphalan with autologous stem cell support in myeloma.

BACKGROUND: Recent experience with thalidomide maintenance after high-dose chemotherapy with autologous stem cell support has demonstrated improvement in progression-free survival (PFS) and overall survival (OS). We further explored the tolerability and efficacy of lower doses of maintenance thalidomide in this single-institution study. PATIENTS AND METHODS: Thirty-eight patients with myeloma were enrolled and treated with melphalan 200 mg/m(2) followed by autologous stem cell transplantation. Thalidomide 50 mg per day was started on day > or = 60 after recovery of blood counts and was escalated to a maximum dose of 200 mg per day. Responses were assessed at 2 months, 1 year, and 2 years after transplantation. RESULTS: Of the 38 enrolled patients, 7 patients never received thalidomide. Among 31 patients receiving thalidomide, complete or very good partial responses were observed in 65% and 42% of patients at 1 and 2 years, respectively. Tolerability was a major issue, with only 17 patients completing 1 year of thalidomide. The goal of dosing 200 mg per day was achieved in just 17 of 31 patients, and the median tolerated thalidomide dose was 100 mg per day. Sensory neuropathy was the primary reason for dose modification and discontinuation. No thromboembolic events were observed. The median PFS was 20.8 months, and the median OS was > 60 months. CONCLUSION: Thalidomide maintenance at a goal dose of 200 mg per day was not feasible in this population, with our data suggesting that 100 mg per day is a more reasonable maintenance dose.

Excessive toxicity of the high dose thiotepa and etoposide regimen when combined with radiation: Long-term autologous transplantation experience in follicular and mantle cell lymphoma.

We recently described a novel thiotepa plus etoposide high-dose therapy (HDT) conditioning regimen for aggressive histology non-Hodgkin's lymphoma (NHL) that had low regimen-related toxicity (RRT) and an efficacy rate comparable to other NHL HDT regimens. In this report, we describe the UW experience with the addition of total body irradiation (TBI) and pre-transplant involved-field radiation (IFRT) to the thiotepa + etoposide HDT regimen. Between 1992 and 1999, 28 patients with indolent or mantle cell lymphoma were treated on this protocol. With a median follow-up of 64 mo, the median event-free survival (EFS) was 24 months, and the median overall survival (OS) had not been reached. The median number of grade 3 - 4 non-hematologic toxicities was five. There were five deaths (18%) in the first three months after HDT due to RRT. In contrast, the thiotepa + etoposide conditioning regimen (without TBI or IFRT) given to 65 intermediate grade NHL patients resulted in only one treatment-related death and considerably fewer grade 3 - 4 toxicities. Given the relatively short EFS in this cohort of indolent NHL patients, we conclude that the combination of IFRT and TBI plus thiotepa and etoposide resulted in a HDT regimen with excessive toxicity and this protocol was closed at our institution.