Hematological effects of intermittent 2-hour infusions of cladribine in multiple sclerosis patients: a comparison of 2 dosage patterns.
Cladribine is a lymphocytotoxic purine nucleoside with potential for treatment of autoimmune diseases. However, optimal administration regimens remain to be established. Twenty multiple sclerosis patients enrolled into this study were given 30 intermittent 2-hour cladribine infusions (0.07 mg/kg per infusion) each. Ten patients received cycles of 5 consecutive daily infusions at 5-week intervals (clustered dosage) on an inpatient basis; the other 10 patients received 1 infusion weekly (nonclustered dosage) on an outpatient basis. Red blood cell (RBC), platelet, and total white blood cell (WBC) counts were assessed at 5-week intervals during the treatment and at 13-week intervals during a 26-week follow-up period. Major WBC and lymphocyte subsets were assessed cytometrically at 15-week intervals during the treatment and at 13-week intervals thereafter. The clustered dosage produced a lasting decline in granulocyte count, a delayed decrease in monocyte count, and a transient decrease in RBC count. The nonclustered dosage caused a larger and persistent decline in RBC count, a smaller (P = .051. compared over the study period) decrease in monocyte count, and no change in granulocyte count. Both regimens transiently reduced natural killer and B-cell subsets (by 40%-60% and >80%, respectively) and caused lasting declines in CD4+ T-cell subsets (by >50%). No significant change was found in CD8+ T-cell subsets. These results show similar potency of these regimens with respect to major lymphocyte subsets, while suggesting that the nonclustered dosage is less toxic to myeloid precursors and more toxic to erythroid lineage precursors.
Grieb
P
P
Laboratory of Experimental Pharmacology, Polish Academy of Sciences Medical Research Centre, Warsaw.
Kamienowski
J
J
Janisz
M
M
Kuśnierczyk
P
P
Kawiak
J
J
Hoser
G
G
Chrapusta
S J
SJ
D000328:Adult; D001772:Blood Cell Count; D017338:Cladribine / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy*
D017338:Cladribine