title: Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997.
abstract: Chemotherapy-related myeloid neoplasia (t-MN) is a significant late toxicity concern after cancer therapy. In the randomized intergroup phase 3 E2997 trial, initial therapy of chronic lymphocytic leukemia with fludarabine plus cyclophosphamide (FC) compared with fludarabine alone yielded higher complete and overall response rates and longer progression-free, but not overall, survival. Here, we report t-MN incidence in 278 patients enrolled in E2997 with a median 6.4-year follow-up. Thirteen cases (4.7%) of t-MN occurred at a median of 5 years from initial therapy for chronic lymphocytic leukemia, 9 after FC and 4 after fludarabine alone. By cumulative incidence methodology, rates of t-MN at 7 years were 8.2% after FC and 4.6% after fludarabine alone (P = .09). Seven of the 9 cases of t-MN after FC occurred without additional therapy. Abnormalities involving chromosomes 5 or 7 were found in 10 cases, which suggests alkylator involvement. These data suggest that FC may induce more t-MN than fludarabine alone.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA. m_smith@fccc.edu
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
authors.forename: Donna
authors.initials: D
authors.lastname: Neuberg
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Gordon
authors.initials: G
authors.lastname: Dewald
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Paietta
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Hussein
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D019046:Bone Marrow Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine