title: Characteristics and outcomes of patients with multiple myeloma who develop therapy-related myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia.
abstract: BACKGROUND
  Patients with multiple myeloma (MM) have had significant improvements in outcomes. An increased risk of therapy-related myeloid neoplasms (t-MNs) has also developed. Little is known about the characteristics and outcomes of these patients.
  
  
  METHODS
  Patients with MM treated at our institution from 1993 to 2011 were reviewed. Forty-seven patients were diagnosed with t-MN. Our primary objective was to evaluate the interval to t-MN, response to treatment, and overall survival (OS).
  
  
  RESULTS
  The median patient age at the MM diagnosis was 65 years. Of the 47 patients, 32 (68.0%) initially received conventional chemotherapeutic agents, 7 (14.9%), novel agents (eg, lenalidomide, thalidomide, bortezomib), and 8 (17.0%), a combination. Twenty patients (42.6%) underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation. The median interval from the MM diagnosis to t-MN was 7 years (95% CI, 5.0-28.0). Of the 47 patients, 33 (70.2%) developed therapy-related myelodysplastic syndrome (t-MDS), 11 (23.4%) acute myeloid leukemia (t-AML), and 3 (6.4%) chronic myelomonocytic leukemia (t-CMML). The median age at the t-MN diagnosis was 65 years. Of the 47 patients, 26 (78.8%) with t-MDS, 9 (81.8%) with t-AML, and 1 (33.3%) with t-CMML had complex/high-risk cytogenetics. The median OS for all 47 patients after the t-MN diagnosis was 6.3 months (95% CI, 4.0-8.7).
  
  
  CONCLUSIONS
  The development of t-MN in patients with MM is associated with poor outcomes. These patients, in general, have complex cytogenetic abnormalities and short complete remission and OS times. A better understanding of the disease biology and novel therapeutic approaches are warranted.
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: npemmaraju@mdanderson.org.
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Shah
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Graciela M
authors.initials: GM
authors.lastname: Nogueras González
authors.affiliation: Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Veera
authors.initials: V
authors.lastname: Baladandayuthapani
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Verena
authors.initials: V
authors.lastname: Wagner
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Lymphoma/Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Jatin
authors.initials: J
authors.lastname: Shah
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Naval
authors.initials: N
authors.lastname: Daver
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Aziz
authors.initials: A
authors.lastname: Nazha
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Stem Cell Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Marcos
authors.initials: M
authors.lastname: De Lima
authors.affiliation: Department of Hematology and Oncology, Case Western Reserve University, Cleveland, OH.
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Hematology and Oncology, Case Western Reserve University, Cleveland, OH.
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology* / Q000628:therapy*; D009190:Myelodysplastic Syndromes / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Novel therapeutic agents; Overall survival; Second primary neoplasm; Therapy-related myeloid neoplasm
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