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.

Biology of Blood and Marrow Transplantation(2007)

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Abstract
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/m2 (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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Key words
Hepatoxicity,High-dose therapy,Multiple myeloma,Veno-occlusive disease
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