MBL: what does it mean for you?

The quite different criterion for diagnosing CLL - namely a B lymphocyte count of 5000/mictrolitre will make a big impact on how we see CLL. For a start, 10 years ago I suggested that the average survival for stage A CLL with mutated IgVH genes was 25 years. It is quite clear that some, perhaps many, of these patients would now be reclassified as MBL, so that those that weren't would have a corresponding worse prognosis.

I have just done a rough and ready analysis on 52 patients (34 mutated, 18 unmutated) who had stage 0 disease with an absolute lymphocyte count greater than 15,000/microlitre (who therefore pretty certainly did not have MBL), and the median survival for the mutated cases was 191 months (16 years) and for the unmutated cases 124 months (10 years). The numbers are not sufficient for this to be statistically significant, but I have no doubt that when I do accumulate enough numbers there will be enough. If I censor the deaths unrelated to CLL, then the difference is highly significant with no CLL deaths in the mutated group, while the average survival for the unmutated group stays at 10 years.

Looking at it the other way using stage 0 patients with a lymphocyte count of less than 15,000 per microlitre which will include most of the MBLs, there were 88 mutated and 41 unmutated. The average survival for the mutated group is 254 months (26 years) and for the unmutated group, 115 months (10 years) - again this is highly significant. Censoring deaths unrelated to CLL we have median survivals of 135 months (13 years) for the unmutated group and just 2 late CLL-related deaths in the mutated group.

Another way of examining the dataset is to look at the likelihood of needing treatment for CLL. Here again using my rough and ready calculation, if you have MBL it is far better to be mutated with only 25% needing treatment by 15 years, whereas in the unmutated group the median time to needing treatment is just under 7 years.

One caveat on this analysis: this does not apply to all MBLs. This is a very difficulty analysis to do because it requires MBLs to be picked up off the street and followed prospectively for many years. What I am talking about here are patients who would have been diagnosed as stage 0 CLL under the old criteria, but are now recategorized as MBL under the new criteria.