title: Safety and tolerability of subcutaneous cladribine therapy in progressive multiple sclerosis.
abstract: OBJECTIVE
  To evaluate the safety and tolerability of subcutaneous (s.c.) cladribine therapy in patients with chronic progressive multiple sclerosis (CPMS), and to evaluate the effects on lymphocyte subsets.
  
  
  BACKGROUND
  Cladribine, a synthetic antineoplastic agent with immunosuppressive effects, may favourably affect the course of CPMS. However results of a previous reported clinical trial showed significant myelosuppression in some patients.
  
  
  METHODS
  19 patients with severe (mean extended disability status score [EDSS] = 6.7) CPMS were treated on a compassionate basis with cladribine 0.07 mg/kg/day s.c. for 5 days per cycle, repeated every 4 weeks for a total of 6 cycles. Patients underwent clinical evaluation, EDSS, and hematologic analysis before, during, and following therapy.
  
  
  RESULTS
  The treatment was very well tolerated with no clinically significant side effects observed. Between baseline and the end of cycle 6, mean decreases were noted in absolute lymphocyte count from 1697 to 463 (p = 0.000012), CD4 count from 865 to 187 (p = 0.0000008), CD8 from 418 to 165 (p = 0.005) and CD19 from 197 to 26 (p = 0.000002). Platelet, granulocyte and RBC counts were unaffected. Approximately one year after completion of therapy, some recovery of CD4 and CD8 counts had occurred although both counts remained suppressed compared to baseline (302 and 227 respectively); the CD19 count had recovered essentially to normal by one year. EDSS scores post-therapy revealed some deterioration in 8 patients and stable scores in the remaining 11. Global patient evaluations of the treatment were mixed.
  
  
  CONCLUSIONS
  Cladribine therapy, at lower doses than previously reported, was remarkably well tolerated in CPMS, with no significant myelosuppression. Profound effects occurred in total lymphocyte count and CD4, CD8 and CD19 subsets.
authors.affiliation: Division of Hematology, Toronto Hospital, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Selby
authors.forename: J
authors.initials: J
authors.lastname: Brandwein
authors.forename: P
authors.initials: P
authors.lastname: O'Connor
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002908:Chronic Disease; D017338:Cladribine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012449:Safety; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D017338:Cladribine