“Must Have” Information: Couple of CLL Experts Speak Out

CMEOne of our members brought to my attention a very nicely done overview of the CLL scene today. (Thanks “grifj”!)  The paper is authored by Dr. Tom Kipps of UCSD and Dr. Kanti Rai of LIJH – you cannot find two better qualified or more highly regarded CLL experts in this country. Here is the link to the article; all you have to do is click on it to read it.  Trust me, it is a lot less painful to learn about this disease and your options when you are not facing urgent situations requiring your immediate decisions. 

The paper is meant for the continuing education of medical professionals (“CME”). But it is surprisingly easy to read and well written. What I liked most was the brief case histories presented, followed by interesting multiple choice questions. If you are a type A personality like me, taking this pop quiz about CLL is almost irresistible. (Not to brag, but I aced the quiz – smirk.)

Even if you do not know all the answers, the good thing is that the paper gives the “correct” answers and then goes on to explain why the authors felt that was the correct answer. Here is a quotation of the sort of things discussed

An Older Patient With High-Risk Features

MR is a 70-year-old man with CLL diagnosed 3 years ago. He had been doing well until about 4 months ago when he began experiencing progressive fatigue, night sweats, and abdominal fullness with early satiety after eating. He otherwise maintains an excellent performance status of 0/5 by the ECOG criteria and lacks significant medical co-morbidities. On exam he is noted to have significant palpable cervical lymphadenopathy and a spleen palpable 7 cm below the left costal margin. His white blood cell count (WBC) was noted to be 125,000 with 97% well differentiated lymphocytes, which was significantly increased from that of his WBC of 13,000 noted at diagnosis. His hemoglobin was 10.1 gm% and his platelet count 98,000. His leukemia cells were noted to express high levels of ZAP-70 and to use unmutated IgHV. Cytogenetic analyses demonstrated the cells to have deletions at 11q22.3.

1. This patient is:

a. high risk

b. low risk

Correct Answer (a) The patient is at high risk (Stage IV), as the patient’s platelet count is below 100,000. He also has anemia, most likely reflecting disease-related marrow suppression. In addition, his prognosticmarkers are unfavorable—unmutated IgV(H) gene, and ZAP-70 positive—and he is symptomatic.

2. This patient should:

a. be placed on wait-and-watch status

b. have treatment started immediately

Correct Answer: (b) This patient is in need of therapy. He has symptomatic disease and evidence for compromised marrow function. Left untreated he probably would develop worsening cytopenia and increasingly symptomatic disease. Studies have shown that patients with high-risk stage disease benefit from therapy.

3. High risk patients without significant symptoms should:

a. be placed under observation

b. given a therapeutic regimen that will stop progression

c. treated with the goal of achieving a complete response

Correct Answer: (c) Even if prognostic markers are favorable, symptomatic high-risk patients should be placed on a therapeutic regimen with the goal of a complete, or maximally achievable response.

4. A preferred therapy for this patient would be:

a. Fludarabine + cyclophosphamide + rituximab (FCR)

b. Fludarabine + rituximab (FR)

c. Bendamustine-rituximab

Correct Answer: (a) In view of his adverse leukemia-cell cytogenetics, namely the deletion at 11q, he should be considered for combination chemoimmunotherapy. Clinical studies comparing the outcome of treatment with fludarabine versus fludarabine and cyclophosphosphamide have demonstrated the combination of the purine analog with an alkylating agent to yield higher complete response rates and longer progression free survival times after therapy than treatment with fludarabine alone. The difference in outcome is particularly apparent for patients with CLL cells that have the 11q deletion.

A worthwhile discussion

Let’s talk about this and the other questions raised and answered in this interesting article. Not all the answers are obvious and you may not agree with the authors’ justifications for their choices. Some of the information in the article is downright scary, such as the survival statistics quoted in their Table 4. I am not sure I agree with these statistics, there are lot more details to be considered before I will buy these bleak statistics. So, read the article carefully, take the quiz, then post your thoughtful comments here. I will do my best to moderate the discussion.

In a way this article came to my attention at just the right time. I am getting ready for our second workshop on August 14th. We will be discussing FCR therapy protocol in great detail and this article helped me formulate my thoughts. I am looking forward to seeing some of you at our workshop. Radha (our webmaster) will be sending out the venue and driving directions over this weekend. For those that are not able to attend the workshop, I will post the PowerPoint slides and my talk on this website.