title: Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma.
abstract: Lenalidomide has been linked to myelodysplastic syndrome (MDS) after autotransplants for myeloma. Total therapy trials (TT; TT2(-/+) thalidomide) and TT3 (TT3a with bortezomib, thalidomide; TT3b with additional lenalidomide) offered the opportunity to examine the contribution of these immune-modulatory agents to MDS-associated cytogenetic abnormalities (MDS-CA) and clinical MDS or acute leukemia ("clinical MDS/AL"). Of 1080 patients with serial cytogenetic studies, MDS-CA occurred in 11% and clinical MDS/AL in 3%. Risk features of MDS-CA included TT3b, age ≥65 years, male gender, levels of β-2-microglobulin >5.5 mg/L, and multiple myeloma relapse. Clinical MDS/AL occurred less frequently in the control arm of TT2 and more often with TT3a and TT3b. Since MDS-CA often antedated clinical disease, periodic cytogenetic monitoring is recommended. Larger CD34 quantities should be collected upfront as the risk of MDS could be reduced by applying higher CD34 doses with transplant. Thus, treatment, host, and myeloma features could be linked to MDS development after therapy for this malignancy. This trial was registered at www.clinicaltrials.gov: TT3A: NCT00081939, TT3B: NCT00572169.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA. susmani@uams.edu
authors.forename: Saad Z
authors.initials: SZ
authors.lastname: Usmani
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sawyer
authors.forename: Adam
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Michele
authors.initials: M
authors.lastname: Cottler-Fox
authors.forename: Joshua
authors.initials: J
authors.lastname: Epstein
authors.forename: Shmuel
authors.initials: S
authors.lastname: Yaccoby
authors.forename: Rachael
authors.initials: R
authors.lastname: Sexton
authors.forename: Antje
authors.initials: A
authors.lastname: Hoering
authors.forename: Zeba
authors.initials: Z
authors.lastname: Singh
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Heuck
authors.forename: Sarah
authors.initials: S
authors.lastname: Waheed
authors.forename: Nabeel
authors.initials: N
authors.lastname: Chauhan
authors.forename: Donald
authors.initials: D
authors.lastname: Johann
authors.forename: Al-Ola
authors.initials: AO
authors.lastname: Abdallah
authors.forename: Jameel
authors.initials: J
authors.lastname: Muzaffar
authors.forename: Nathan
authors.initials: N
authors.lastname: Petty
authors.forename: Clyde
authors.initials: C
authors.lastname: Bailey
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002869:Chromosome Aberrations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D000077269:Lenalidomide; D007938:Leukemia / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000139:chemically induced / Q000453:epidemiology* / Q000235:genetics; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide