Wednesday, September 29, 2010

The end point of treatment in CLL

There has been an interesting exchange of letters in the correspondence columns of Blood (Blood 2010; 116:1187-8) between Ken Foon and Michael Hallek concerning the end-point of treatment. Confusion arises because what was published in the Guidelines in Blood in June 2008 was not agreed by all the authors and it had to be revised in the electronic records in December 2008.

The problem arose because the 1996 Guidelines were widely used for both clinical practice and for clinical trials, and these suggested that a complete response should mean that there were fewer than 30% lymphocytes in a bone marrow trephine following treatment. If the trephine showed lymphoid nodules then the type of remission should be categorized nodular PR. Since 1996 there has been evidence that a deeper remission than just <30% lymphoid cells in the bone marrow, might be more advantageous to the patient, and also that it is possible to distinguish whether a nodular PR comprises tumor tissue of just reactive lymphocytes.

In order to retain a comparison with older trials, the new Guidelines now suggest that the old (1996) criteria are retained, but that in trials aimed at maximizing CR rate, assessment should be made of minimal residual disease by 4-color flow and that lymphoid nodules should be assessed by immmunohistochemistry. Why should this not be done for all patients? I guess it is because the experts are not sufficiently convinced that attempts to wipe out all trace of discernible CLL is beneficial to the patient - witness the recent CALGB trial of post-treatment Campath.

The second point concerns the use of CT scans. The Guidelines suggest that CT scans are not required for either the initial valuation of follow-up in clinical practice. However, they recommended that they be used in clinical trials - one at the start of therapy and the other at first restaging after therapy if it had been previously abnormal. A second CT is not necessary if residual disease can be detected some other way - such as blood tests or clinical examination.

I think this is now clear.

9 comments:

Anonymous said...

Would you as a treating physician try to obtain MRD negativity?

Anonymous said...

Would you as a trasting physician now try to obtain MRD negativity for your firstline therapy?

Terry Hamblin said...

Yes, but only in certain circumstances if I thought potential cure was an option.

Anonymous said...

By potential cure are you speaking only of SCT, or are you thinking of driving a younger patient into a long MRD negative remission in hopes of better treatments several years down the road

Terry Hamblin said...

Both.

Anonymous said...

This is a bit off topic, but I will ask since I canot find an answer elsewhere. I am ZAP-70 and CD38 negative, 13q as sole deletion and have had CLL for 4 1/2 years with little progression. However, my IGVH is only 1.7% mutated. Should I consider myself high risk or is the 2% cutoff somewhat arbitrary. I know you have written on this before (I think you should publish that data) but any insight would be appreciated.

George said...

Still I'm not sure Terry if it is the biologically less aggressive CLL that gets to MRD negativity and hence long remissions rather than the MRD negativity itself....

Terry Hamblin said...

No, that is not known.

Terry Hamblin said...

Anon

I have published on the 2% cut off at http://www.ncbi.nlm.nih.gov/pubmed/18053068

This may well be the reason for your anomolous result.