Excessive Toxicity of Once Daily Intravenous Busulfan, Melphalan, and Thiotepa Followed by Autologous Stem Cell Transplantation On Patients with Non-Hodgkin's Lymphoma.

Abstract 4361

The busulfan, melphalan, and thiotepa (BuMelTT) regimen has shown high activity in the treatment of patient with breast cancer, ovarian cancer, aggressive lymphoma, and relapsed Hodgkin's disease. Given the limited toxicity observed with intravenous busulfan and the known activity of BuMelTT regimen in NHL, we developed a protocol utilizing once-daily intravenous busulfan/melphalan/thiotepa (ivB-MT) regimen as a conditioning for HDT in the patients with high risk or relapsed NHL.

Between March and December 2008, 13 patients with relapsed or primary refractory NHL but sensitive to salvage chemotherapy or chemo-sensitive high risk NHL underwent HDT with ivB-MT regimen followed by autologous SCT at the Soonchunhyang University Hospital, Asan Medical Center of Ulsan University, and Samsung Medical Center of Sungkyunkwan University, Seoul, Korea. The conditioning regimen consisted of busulfan 130mg/m²/day i.v. on day -8, -7, and -6, melphalan 50mg/m²/day i.v. on day -5 and -4, and thiotepa 250mg/m²/day i.v. on day -3 and -2. One patient did not recovered neutrophil and platelets and the disease relapsed on day 30 and another patient died on day 74 due to sepsis without recovery of platelets. The remaining patients achieved an ANC > 500/mm³ at a median of 10 days (range 9-30) and an unsupported platelet count of > 20,000/mm³ at a median 20 days (range 11-35) after infusion of peripheral blood stem cells(PBSC). Grade 3-4 regimen related toxicities (RRT) occurred in eight of 13 (61.5%) patients, mainly including mucositis, GI, and hepatic toxicity. Six patients (46%) developed hepatic VOD including one severe type and three patients documented infections (klebsiella pneumonia, streptococcal pneumonia, and sepsis due to MRSA and CMV bacteremia), one died of sepsis on post-transplant day 74. In all, one patient was not evaluable for response because of septic death. Four (80%) out of five patients with PR state before HDT achieved CR after HDT and one out of seven patients with CR state progressed during HDT, resulted 10 out of 12 patients achieved or maintained CR after HDT. During the follow up period (median 312 days, range 74-467), four patients were relapsed after CR and EFS were 60, 102, 104, and 203 days, respectively.

In the current study, grade 3 to 4 mucositis and liver toxicity occurred in 65% and VOD developed in 46%. It is assumed that such toxicities may be relevant to regimen with triple alkylating drugs. Despite of comparable efficacy, ivB-MT regimen was too toxic to apply to the patients with NHL undergoing HDT and autologous SCT.