title: Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes.
abstract: Patients with chronic lymphocytic leukemia (CLL) are known to have an increased incidence of second cancers, but the contribution of commonly used frontline therapies to the incidence of second cancers is unclear. We report on the characteristics, incidence, outcomes and factors associated with second cancers in 234 patients receiving fludarabine, cyclophosphamide and rituximab (FCR) based regimens in the frontline setting. The risk of second cancers was 2.38 times higher than the expected risk in the general population. Ninety-three patients (40%) had other cancers before and 66 patients (28%) after FCR. Rates of therapy related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) (5.1%) and Richter transformation (RT) (9%) were high, while solid tumors were not increased. Overall survival of patients with second cancers after frontline FCR was shorter (median of 4.5 years) compared to patients with and without prior cancers. Second cancer risk after frontline FCR is mainly due to high rates of t-AML/MDS and RT, and as speculated the survival of affected patients is shorter.
authors.affiliation: Department of Leukemia.
authors.forename: Ohad
authors.initials: O
authors.lastname: Benjamini
authors.forename: Preetesh
authors.initials: P
authors.lastname: Jain
authors.forename: Long
authors.initials: L
authors.lastname: Trinh
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: William
authors.initials: W
authors.lastname: Wierda
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000453:epidemiology; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D000069283:Rituximab / Q000008:administration & dosage; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine
keywords: Lymphoid leukemia; chemotherapeutic approaches; pharmacotherapeutics