• Enric Carreras, Laura Rosiñol, Maria José Terol, Adrián Alegre, Felipe de Arriba, José García-Laraña, José Luis Bello, Raimundo García, Angel León, Rafael Martínez, M Jesús Peñarrubia, Concha Poderós, Paz Ribas, Josep Maria Ribera, Jesús San Miguel, Joan Bladé, Juan José Lahuerta, and Spanish Myeloma Group/PETHEMA.
• Haematology Department of Hospital Clínic, Barcelona, Spain. carreras@clinic.ub.es
• Biol. Blood Marrow Transplant. 2007 Dec 1; 13 (12): 1448-54.

AbstractVeno-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.

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