Saturday, 24 May 2014

Blood counts don't predict disease activity

Kousin-Ezewu O, Azzopardi L, Parker RA, Tuohy O, Compston A, Coles A, Jones J.Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity.
Neurology. 2014 May. pii: 10.1212/WNL.0000000000000520. [Epub ahead of print]

OBJECTIVE: To test the hypothesis that accelerated peripheral blood mononuclear cell recovery after alemtuzumab treatment of multiple sclerosis is associated with recurrent disease activity and to investigate the claim that CD4 counts greater than 388.5 × 106 cells/mL at 12 months can be used to identify patients who may benefit from further treatment.


METHODS: A total of 108 patients were followed for a median of 99 months (4 years) post alemtuzumab. Patients were classified as active or non-active after each cycle of treatment based on clinical relapse, increasing disability, or new T2/enhancing MRI lesions. These outcomes were correlated with CD4, CD8, CD19, CD56+ NK, and monocyte counts.

RESULTS: Of 108 patients, 56 (52%) relapsed at some point during follow-up. Mean annualized relapse rate after alemtuzumab was 0.17 vs 1.67 prior to treatment (equating to a 90% reduction). Of 108 patients, 28 (26%) met the criteria for sustained accumulation of disability. Median time to the lower limit of normal for CD19, CD8, and CD4 was 3, 19.5, and 32 months, respectively. There was no significant difference in the recovery of any cell population between patients with and without disease activity or accumulation of disability after treatment.

CONCLUSION: This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab.



How does Alemtuzumab work..many immunologists will claim because it inhibits T cell activity. Others argue that it could be because of B cell activity. After alemtuzumab treatment, T cells are depleted for over 1 year and closer to 2 years whereas B cells are only reduced for about 3 months after which time more B cells than normal are produced and is one reason a reason why Alemtuzumab may cause B-cell mediated autoimmune conditions because they return before T cell regulation recovers. But what is clear is that overall repopulation of white blood cells do not link to the return of disease activity. Does this mean white blood cells are not the problem. 

One could argue that it is cells in the brain that is important, however I suspect that a small subset of cells are causing the problem but the trees are lost because people concentrate on looking at the woods. 

In animals we know that if we deplete the white blood cell pool then this is necessary for activity and when they recover in numbers then disease returns. However these cells do not need to return to normal levels and rarely ever do recover. However, return of disease does not depend on absolute numbers of cells and disease can return when there are very few cells present.

Maybe we have to find ways to refine this further.

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