title: Abnormalities of chromosome 1p/q are highly associated with chromosome 13/13q deletions and are an adverse prognostic factor for the outcome of high-dose chemotherapy in patients with multiple myeloma.
abstract: The prognostic value of chromosomal abnormalities was studied in untreated multiple myeloma patients who were registered into a prospective randomised multicentre phase 3 study for intensified treatment (HOVON24). A total of 453 patients aged less than 66 years with stage II and III A/B disease were registered in the clinical study. Cytogenetic analysis was introduced as a standard diagnostic assay in 1998. It was performed at diagnosis in 160 patients and was successful in 137/160 patients (86%). An abnormal karyotype was observed in 53/137 (39%) of the patients. Abnormalities of chromosome 1p and 1q were found in 19 (36% of patients with an abnormal karyotype) and 21 patients (40%). There was a strong association between chromosome 1p and/or 1q abnormalities and deletion of chromosome 13 or 13q (n = 27, P < 0.001). Patients with karyotypic abnormalities had a significantly shorter overall survival (OS) than patients with normal karyotypes. Complex abnormalities, hypodiploidy, chromosome 1p abnormalities, chromosome 1q abnormalities, and chromosome 13 abnormalities were associated with inferior OS on univariate analysis, as well as after adjustment for other prognostic factors. In conclusion, chromosome 13 abnormalities and chromosome 1p and/or 1q abnormalities were highly associated, and are risk factors for poor outcome after intensive therapy in multiple myeloma.
authors.affiliation: Erasmus MC, Department of Haematology, Rotterdam, the Netherlands.
authors.forename: Ka Lung
authors.initials: KL
authors.lastname: Wu
authors.forename: Berna
authors.initials: B
authors.lastname: Beverloo
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
authors.forename: Christine M
authors.initials: CM
authors.lastname: Segeren
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Monique M
authors.initials: MM
authors.lastname: Steijaert
authors.forename: Petra H
authors.initials: PH
authors.lastname: Westveer
authors.forename: Pino J
authors.initials: PJ
authors.lastname: Poddighe
authors.forename: Gregor E
authors.initials: GE
authors.lastname: Verhoef
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan