title: Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study.
abstract: Monocyte-derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell-cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) reflects the monocyte-derived cells in the microenvironment, and that higher AMC is associated with increased CLL cell survival in vivo and thus inferior CLL patient outcomes. We assessed the extent to which AMC at diagnosis of CLL is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated AMC, clinically used prognostic markers, and time to event data from 1,168 CLL patients followed at the Mayo Clinic, the Duke University Medical Center, and the Durham VA Medical Center. Elevated AMC was significantly associated with inferior clinical outcomes, including time to first therapy (TTT) and overall survival (OS). AMC combined with established clinical and molecular prognostic markers significantly improved risk-stratification of CLL patients for TTT. As an elevated AMC at diagnosis is associated with accelerated disease progression, and monocyte-derived cells in the CLL microenvironment promote CLL cell survival and proliferation, these findings suggest that monocytes and monocyte-derived cells are rational therapeutic targets in CLL. Am. J. Hematol. 91:687-691, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.|Durham VA Medical Center, Durham, North Carolina.
authors.forename: Daphne R
authors.initials: DR
authors.lastname: Friedman
authors.affiliation: Duke Cancer Institute, Durham, North Carolina.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Sibley
authors.affiliation: Duke Cancer Institute, Durham, North Carolina.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kari G
authors.identifier: 0000-0002-7313-1875
authors.initials: KG
authors.lastname: Chaffee
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Susan
authors.initials: S
authors.lastname: Slager
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.affiliation: Division of Hematopathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.|Durham VA Medical Center, Durham, North Carolina.
authors.forename: J Brice
authors.initials: JB
authors.lastname: Weinberg
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Wilcox
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D011379:Prognosis; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D061665:Time-to-Treatment