Purine Antagonists for Chronic Lymphocytic Leukaemia

Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

“…A Cochrane Review based on published trial data was also not able to detect any overall survival benefit but a significant degree of heterogeneity was found. 2,3 To overcome the limitations of meta-analyzing data derived from published trials, a collaborative IPD analysis was conducted integrating individual patient data from all trials to examine whether, with larger patient numbers available, any clinically worthwhile survival differences could be detected, and whether apparently discrepant trial results might be, at least partially, explained by variations in analytical methods.…”

Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

“…A Cochrane Review based on published trial data was also not able to detect any overall survival benefit but a significant degree of heterogeneity was found. 2,3 To overcome the limitations of meta-analyzing data derived from published trials, a collaborative IPD analysis was conducted integrating individual patient data from all trials to examine whether, with larger patient numbers available, any clinically worthwhile survival differences could be detected, and whether apparently discrepant trial results might be, at least partially, explained by variations in analytical methods.…”

Immunohistochemistry for human concentrative nucleoside transporter 3 protein predicts fludarabine sensitivity in chronic lymphocytic leukemia

“…In the absence of significant patient symptoms, signs, or laboratory abnormalities, many patients are placed on a 'waitand-watch' policy given that standard chemotherapy has not yet been shown to confer a survival advantage. 4 Although several independent prognostic factors, 28 including CD-38, 29 ZAP-70, 30,31 b-2 microglobulin, 32 chromosomal abnormalities, 29 including deletions of 17p or 11q as detected by FISH, and immunoglobulin Vh genes 29 have been identified to discriminate CLL patient populations between favorable and less favorable prognostic groups, the majority of chemotherapeutic decisions are still based upon prognostic groups defined by the Binet et al 33 or Rai 23 staging systems, rather than a validated predictive assay. 34,35 A recent study found that patients with high-risk cytogenic features such as deletions of 17p or 11q were associated with reduced progression-free survival, and whom should be considered for non-F-ara-A-based therapies.…”

Treatment of primary CLL cells with bezafibrate and medroxyprogesterone acetate induces apoptosis and represses the pro-proliferative signal of CD40-ligand, in part through increased 15dΔ12,14,PGJ2

“…5,6 A recent meta-analysis involving five trials with 1838 randomized patients supports the argument that greater response rates are achievable by using purine antagonists such as fludarabine but highlights that this carries with it a greater risk of toxicity. 7 The study found no conclusive evidence that treatment with purine antagonists improves survival.…”

Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

“…A Cochrane Review based on published trial data was also not able to detect any overall survival benefit but a significant degree of heterogeneity was found. 2,3 To overcome the limitations of meta-analyzing data derived from published trials, a collaborative IPD analysis was conducted integrating individual patient data from all trials to examine whether, with larger patient numbers available, any clinically worthwhile survival differences could be detected, and whether apparently discrepant trial results might be, at least partially, explained by variations in analytical methods.…”

Immunohistochemistry for human concentrative nucleoside transporter 3 protein predicts fludarabine sensitivity in chronic lymphocytic leukemia

“…In the absence of significant patient symptoms, signs, or laboratory abnormalities, many patients are placed on a 'waitand-watch' policy given that standard chemotherapy has not yet been shown to confer a survival advantage. 4 Although several independent prognostic factors, 28 including CD-38, 29 ZAP-70, 30,31 b-2 microglobulin, 32 chromosomal abnormalities, 29 including deletions of 17p or 11q as detected by FISH, and immunoglobulin Vh genes 29 have been identified to discriminate CLL patient populations between favorable and less favorable prognostic groups, the majority of chemotherapeutic decisions are still based upon prognostic groups defined by the Binet et al 33 or Rai 23 staging systems, rather than a validated predictive assay. 34,35 A recent study found that patients with high-risk cytogenic features such as deletions of 17p or 11q were associated with reduced progression-free survival, and whom should be considered for non-F-ara-A-based therapies.…”

Treatment of primary CLL cells with bezafibrate and medroxyprogesterone acetate induces apoptosis and represses the pro-proliferative signal of CD40-ligand, in part through increased 15dΔ12,14,PGJ2

“…5,6 A recent meta-analysis involving five trials with 1838 randomized patients supports the argument that greater response rates are achievable by using purine antagonists such as fludarabine but highlights that this carries with it a greater risk of toxicity. 7 The study found no conclusive evidence that treatment with purine antagonists improves survival.…”

Systematic review of purine analog treatment for chronic lymphocytic leukemia: lessons for future trials

“…A Cochrane Review based on published trial data was also not able to detect any overall survival benefit but a significant degree of heterogeneity was found. 2,3 To overcome the limitations of meta-analyzing data derived from published trials, a collaborative IPD analysis was conducted integrating individual patient data from all trials to examine whether, with larger patient numbers available, any clinically worthwhile survival differences could be detected, and whether apparently discrepant trial results might be, at least partially, explained by variations in analytical methods.…”

Immunohistochemistry for human concentrative nucleoside transporter 3 protein predicts fludarabine sensitivity in chronic lymphocytic leukemia

“…In the absence of significant patient symptoms, signs, or laboratory abnormalities, many patients are placed on a 'waitand-watch' policy given that standard chemotherapy has not yet been shown to confer a survival advantage. 4 Although several independent prognostic factors, 28 including CD-38, 29 ZAP-70, 30,31 b-2 microglobulin, 32 chromosomal abnormalities, 29 including deletions of 17p or 11q as detected by FISH, and immunoglobulin Vh genes 29 have been identified to discriminate CLL patient populations between favorable and less favorable prognostic groups, the majority of chemotherapeutic decisions are still based upon prognostic groups defined by the Binet et al 33 or Rai 23 staging systems, rather than a validated predictive assay. 34,35 A recent study found that patients with high-risk cytogenic features such as deletions of 17p or 11q were associated with reduced progression-free survival, and whom should be considered for non-F-ara-A-based therapies.…”

Treatment of primary CLL cells with bezafibrate and medroxyprogesterone acetate induces apoptosis and represses the pro-proliferative signal of CD40-ligand, in part through increased 15dΔ12,14,PGJ2

“…5,6 A recent meta-analysis involving five trials with 1838 randomized patients supports the argument that greater response rates are achievable by using purine antagonists such as fludarabine but highlights that this carries with it a greater risk of toxicity. 7 The study found no conclusive evidence that treatment with purine antagonists improves survival.…”