Characterization of treatment and outcomes in a population-based cohort of patients with chronic lymphocytic leukemia referred for cytogenetic testing in British Columbia, Canada.
This study evaluates outcomes in chronic lymphocytic leukemia (CLL) based on first-line therapy in a large consecutive population-based cohort of 669 patients with fluorescence in-situ hybridization (FISH) data in British Columbia, Canada during the period when chemoimmunotherapy was standard first-line treatment. When analyzed as a time-dependent variable, patients who required treatment (n=336) had a 4.7 times higher hazard of death than patients who did not (95% confidence interval 2.8-7.9, P<0.001). The majority of patients received fludarabine-rituximab (FR) in front-line. On multivariate Cox regression analysis, fludarabine-based first-line therapy predicted longer time-to-next-treatment (TTNT) (HR 0.53, 95% confidence interval 0.33-0.87, P=0.012) but no difference in overall survival (OS) compared to alkylator-based therapy. Deletion 17p was an independent predictor of worse TTNT and OS. The most common second-line treatments were cyclophosphamide-vincristine-prednisone-rituximab and FR. There was no difference in OS between patients retreated in second-line with the same first-line regimen (n=33) versus different regimen (n=113). In conclusion, front-line treatment with fludarabine leads to a longer time until need for next treatment than alkylator-based therapy; however, fludarabine or alkylator therapy produces no difference in OS. This study provides a historical baseline for the comparison of novel agents with standard treatments in CLL on a population-level.
Division of Hematology, Leukemia/BMT Program of BC, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada; Cytogenetics Laboratory, Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
Steven J
SJ
Huang
Division of Hematology, Leukemia/BMT Program of BC, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
Lauren J
LJ
Lee
Division of Hematology, Leukemia/BMT Program of BC, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.
Alina S
AS
Gerrie
Cytogenetics Laboratory, Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
Tanya L
TL
Gillan
Cytogenetics Laboratory, Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
Helene
H
Bruyere
Molecular Cytogenetic Laboratory, Royal Columbian Hospital, New Westminster, BC, Canada.
Monica
M
Hrynchak
Pathology and Laboratory Medicine and Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
Adam C
AC
Smith
Pathology and Laboratory Medicine and Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
Aly
A
Karsan
Division of Hematology, St. Paul's Hospital and University of British Columbia, Canada.
Khaled M
KM
Ramadan
GlaxoSmithKline, Mississauga, Ontario, Canada.
Kavisha S
KS
Jayasundara
Division of Hematology, Leukemia/BMT Program of BC, Vancouver General Hospital, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada. Electronic address: ctoze@bccancer.bc.ca.
Cynthia L
CL
Toze
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001955:British Columbia; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000627:therapeutic use; D015996:Survival Rate; D014750:Vincristine / Q000627:therapeutic use
D000069283:Rituximab; D014750:Vincristine; D003520:Cyclophosphamide
Chemoimmunotherapy; Chronic lymphocytic leukemia; FISH; Population-based; Survival; Treatment