title: MDS-type abnormalities within myeloma signature karyotype (MM-MDS): only 13% 1-year survival despite tandem transplants.
abstract: Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high-dose therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan-based tandem autotransplants (median follow-up, 5 years). Negative consequences for both overall survival (OS) and event-free survival (EFS) in the presence of any CA were confirmed, especially when detected within 3 months of HDT. In the context of standard prognostic factors (SPF), 'MM-MDS' (MM karyotype that contains, in addition, CA typical of MDS) imparted a poor OS and EFS, after adjusting for any CA and all individual CA. One-year mortality was also high, especially for the MM-MDS subgroup with trisomy 8 within a MM signature karyotype (87%vs 34% in its absence, P < 0.001). No patient remained event free 5 years post transplant in the presence of these baseline high-risk CA. However, certain trisomies (e.g. chromosomes 7 and 9) and del 20 had favourable clinical consequences. The higher risk that is associated with CA compared with SPF justifies routine cytogenetic studies in all patients with MM at diagnosis and whenever additional treatment decisions are considered, such as in planning HDT either for initial response consolidation, at the time of primary unresponsiveness to induction therapy, or at relapse.
authors.affiliation: Cancer Research and Biostatistics, Seattle, WA 98101-1468, USA. jothj@crab.org
authors.forename: Joth
authors.initials: J
authors.lastname: Jacobson
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: John
authors.initials: J
authors.lastname: Shaughnessy
authors.forename: Johannes
authors.initials: J
authors.lastname: Drach
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Athanasios
authors.initials: A
authors.lastname: Fassas
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Dori
authors.initials: D
authors.lastname: Giroux
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Aubrey
authors.initials: A
authors.lastname: Hough
authors.forename: Jeff
authors.initials: J
authors.lastname: Sawyer
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D020732:Cytogenetic Analysis / Q000379:methods; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D008558:Melphalan / Q000627:therapeutic use; D009006:Monosomy; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D015996:Survival Rate; D014178:Translocation, Genetic; D014182:Transplantation, Autologous; D014314:Trisomy
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan