Standard conditioning regimens for autologous
stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose
melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90 -
Ibritumomab tiuxetan (Y90 -IT) is well tolerated and feasible in the
transplantation setting. We therefore investigated the combination of high-dose
melphalan and Y90 -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive
lymphoma in remission after salvage
chemotherapy could be enrolled. High-dose
therapy consisted of standard dose Y90 -IT (0.4-mCi/kg
body weight) followed by
melphalan at escalating doses (100, 140, 170 and 200 mg/m2 ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after
transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3
dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after
transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were
infection (n = 6), including 2 cases of
febrile neutropenia,
diarrhea (n = 3),
mucositis,
anorexia, viral
hepatitis,
hypokalemia,
dehydration, and multiorgan failure (n = 1 for each). The combination of Y90 -IT and high-dose
melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity.