title: 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.
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/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.
authors.affiliation: Haematology Department of Hospital Clínic, Barcelona, Spain. carreras@clinic.ub.es
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Terol
authors.forename: Adrián
authors.initials: A
authors.lastname: Alegre
authors.forename: Felipe
authors.initials: F
authors.lastname: de Arriba
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bello
authors.forename: Raimundo
authors.initials: R
authors.lastname: García
authors.forename: Angel
authors.initials: A
authors.lastname: León
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez
authors.forename: M Jesús
authors.initials: MJ
authors.lastname: Peñarrubia
authors.forename: Concha
authors.initials: C
authors.lastname: Poderós
authors.forename: Paz
authors.initials: P
authors.lastname: Ribas
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Ribera
authors.forename: Jesús
authors.initials: J
authors.lastname: San Miguel
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lahuerta
mesh_terms: D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D019653:Myeloablative Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D013030:Spain; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014182:Transplantation, Autologous / Q000009:adverse effects
chemical_list: D019653:Myeloablative Agonists; D002066:Busulfan; D008558:Melphalan