Research: White blood cell depletion and Alemtuzumab

Hill-Cawthorne et al. Long-term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2011 [Epub]

Alemtuzumab depletes the immune system for a long time, how long for? and was this associated with enhanced infection?

Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has marked efficacy for relapsing-remitting multiple sclerosis (MS). 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.

Fig: A lymphocyte; the blood cell that is thought to trigger MS.

Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1 billion cells/litre) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥hundred million cells/litre) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (Virus killing cell)(LLN ≥ 2hundred million cells/litre) and T helper CD4 lymphocytes (LLN ≥4 hundred million cells/litre) 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.

Although removal of the immune system could be associated with the development of infections and tumours...This has not so far been a marked problem. This may be because treatment with drug occurs for only a few days each year that would allow the remaining immune cells to respond, should infection occur. In contrast constant immunosuppression from daily treatment would be anticipated to carry a greater risk of infection.

CoI MouseDoctor: None

CoI Prof G: Multiple