title: Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS).
abstract: Using population-based data from Sweden, we identified all multiple myeloma (MM) patients (n = 8740) and 5652 monoclonal gammopathy of undetermined significance (MGUS) patients diagnosed between 1986 and 2005. We calculated standardized incidence rates (SIRs) for all subsequent hematologic and nonhematologic malignancies for MM patients diagnosed before/after 1995 (introduction of high-dose melphalan/autologous stem cell transplantation [HDM-ASCT]) and 2000 (introduction of immunomodulatory drugs [IMiDs]), respectively. MM patients had an 11.51-fold (95% confidence interval: 8.19-15.74) increased risk of acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS); risk was very similar before/after 1995 and 2000, respectively. MGUS patients had an 8.01-fold (5.40-11.43) increased risk of AML/MDS. Risk was confined to IgG/IgA, while no IgM MGUS patients developed AML/MDS; patients with monoclonal-protein (M-protein) concentrations > 1.5 g/dL (SIR = 11.12; 3.61-25.96) had higher risk than those < 1.5 g/dL (SIR = 4.67; 1.71-10.16). An excess risk of nonmelanoma skin cancer was observed subsequent to both MM (SIR = 2.22; 1.74-2.80) and MGUS (SIR = 3.30; 2.76-3.90). Our novel observations of an excess risk for AML/MDS following IgG/IgA (but not IgM) MGUS, and the highest risk associated with M-protein concentrations > 1.5 g/dL, support a role for nontreatment-related factors in plasma cell dyscrasias. AML/MDS risk following MM was the same before/after the introduction of HDM-ASCT. Longer follow-up is needed to characterize second tumor risks in the IMiD era.
authors.affiliation: Multiple Myeloma Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Sham
authors.initials: S
authors.lastname: Mailankody
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Sigurdur Y
authors.initials: SY
authors.lastname: Kristinsson
authors.forename: Neha
authors.initials: N
authors.lastname: Korde
authors.forename: Magnus
authors.initials: M
authors.lastname: Bjorkholm
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000628:therapy; D008297:Male; D008558:Melphalan; D008875:Middle Aged; D009101:Multiple Myeloma / Q000453:epidemiology* / Q000628:therapy; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000209:etiology / Q000628:therapy; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000628:therapy; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013548:Sweden / Q000453:epidemiology; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007155:Immunologic Factors; D008558:Melphalan