PREFERENTIAL REDUCTIONS IN LYMPHOCYTE SUBPOPULATIONS INDUCED BY MONTHLY PULSES OF CHLORAMBUCIL - STUDIES IN PATIENTS WITH CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS

Thirty-three patients with chronic progressive multiple sclerosis (MS) were assigned to intervention groups receiving monthly pulses of chlorambucil (CB) for about one year. The monthly doses ranged from 0.4 to 1.5 mg/kg. Administration of CB resulted in preferential reduction in different lymphocyte subsets which was dose- and time-dependent. The number of B-cells (CD20) decreased more rapidly than NK-cells (CD16, CD56, CD16+CD56+) or T-cell (CD3) and T-cells subsets (CD4 and CD8). At 1.2 mg/kg, CB administration resulted in a preferential drop of T-suppressor/cytotoxic cells (CD8) compared with T-helper cells (CD4), and of the less mature "virgin" CD4 cells (CD4+CD45RA+) compared with "memory" CD4 cells (CD4 + CD45RA-). The expression of activation markers (transferrin receptor, CALLa, HLA-Dr and CD38[OKT10]) within CD4, CD8 or CD20 lymphocytes was not altered by CB administration. Our data, which show that CB administration results in a preferential fall in B-cell numbers, contrast with the effects of long-term administration of the related immunosuppressive drugs, azathioprine and cyclophosphamide.