Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia.
Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated the relationship of 25(OH)D serum levels with time-to-treatment (TTT) and overall survival (OS) in newly diagnosed CLL patients participating in a prospective cohort study (discovery cohort) and a separate cohort of previously untreated patients participating in an observational study (confirmation cohort). Of 390 CLL patients in the discovery cohort, 119 (30.5%) were 25(OH)D insufficient. After a median follow-up of 3 years, TTT (hazard ratio[HR] = 1.66; P = .005) and OS (HR = 2.39; P = .01) were shorter for 25(OH)D-insufficient patients. In the validation cohort, 61 of 153 patients (39.9%) were 25(OH)D insufficient. After a median follow-up of 9.9 years, TTT (HR = 1.59; P = .05) and OS (HR 1.63; P = .06) were again shorter for 25(OH)D-insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, Rai stage, CD38 status, ZAP-70 status, immunoglobulin heavy chain variable (IGHV) gene mutation status, CD49d status, and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing, 25(OH)D insufficiency remained an independent predictor of TTT (HR = 1.47; P = .008), although the association with OS was not significant (HR = 1.47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing.
Division of Hematology, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Tait D
TD
Shanafelt
Matthew T
MT
Drake
Matthew J
MJ
Maurer
Cristine
C
Allmer
Kari G
KG
Rabe
Susan L
SL
Slager
George J
GJ
Weiner
Timothy G
TG
Call
Brian K
BK
Link
Clive S
CS
Zent
Neil E
NE
Kay
Curtis A
CA
Hanson
Thomas E
TE
Witzig
James R
JR
Cerhan
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D053719:Tandem Mass Spectrometry; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
D014408:Biomarkers, Tumor; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1