Veno-occlusive disease of the liver after high-dose cytoreductive therapy with Busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients

Veno-occlusive disease of the liver (VOD) is a potentially severe complication of high-dose cytoreductive therapy (HDT) used for stem cell transplantation (SCT). This complication is uncommon after HDT for autologous SCT (ASCT) in patients with multiple myeloma (MM). The Spanish Myeloma Group/PETHEMA conducted a study (MM2000) for patients with newly diagnosed MM consisting of induction with alternating VBMCP/VBAD chemotherapy followed by intensification with busulfan/melphalan (Bu/MEL) with a second high-dose therapy procedure in patients not achieving at least near-complete remission with the first procedure. After 2 years of the trial, a number of episodes resembling classical VOD but with a late onset were recognized. Consequently, the protocol was modified, and Bu/MEL was replaced by melphalan 200 mg/m(2) (MEL-200). Three years later, after a total of 734 patients had undergone first autologous SCT, the incidence and characteristics of VOD episodes were analyzed in the whole series. Nineteen cases of VOD (8%) were observed among the first 240 patients receiving Bu/MEL, whereas only 2 (0.4%) were observed among the 494 patients treated with MEL-200 (P < .0001). VOD manifestations in the Bu/MEL group appeared at a median of 29 days (range, 3-57 days) after ASCT. Mortality directly attributable to VOD was 2% in the Bu/MEL group and 0.2% in the MEL-200 group (P = .026). This high incidence of severe VOD probably had a multifactorial origin (busulfan followed by melphalan and previous use of BCNU). This observation should be kept in mind when designing future trials for the treatment of MM. (c) 2007 American Society for Blood and Marrow Transplantation.