BACKGROUND: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has 
demonstrated superior efficacy over interferon β-1a for relapsing-remitting 
multiple sclerosis (MS), and is currently under investigation in phase 3 trials. 
One unresolved issue is the duration and significance of the lymphopenia 
induced. The long term effects on lymphocyte reconstitution of a single course, 
and the consequences that this has on disability, morbidity, mortality and 
autoimmunity, were examined.
METHODS: The lymphocyte reconstitution (n=36; 384 person years) and crude safety 
data (n=37; 447 person years) are reported for the first patients with 
progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was 
expressed as a geometric mean or, when a non-negligible number of individuals 
failed to recover, as a median using survival analysis.
RESULTS: Geometric mean recovery time (GMRT) of total lymphocyte counts to the 
lower limit of the normal range (LLN; ≥1.0×10(9) cells/l) was 12.7 months (95% 
CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10(9)/l) was 7.1 months 
(95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10(9) cells/l) and 
CD4 lymphocytes (LLN ≥0.4×10(9) cells/l) were 20 months and 35 months, 
respectively. However, CD8 and CD4 counts recovered to baseline levels in only 
30% and 21% of patients, respectively. No infective safety concerns arose during 
447 person years of follow-up.
CONCLUSIONS: Lymphocyte counts recovered to LLN after a single course of 
alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), 
but usually did not recover to baseline values. However, this long lasting 
lymphopenia in patients with a previously normal immune system was not 
associated with an increased risk of serious opportunistic infection.