It is all too easy to forget details when they are scattered over many articles and not consolidated in a review that is a handy reference that you can lay your hands on when you need it.
Below is the abstract (highlighting and emphasis is my contribution) of a recent article by Dr. Claire Dearden of the Royal Marsden Hospital (UK) that I think is an excellent “Best Practices” review of CLL and its many complications. You can download the full article by clicking on the link. For those of you who believe in keeping your own “CLL Library”, this is a must have addition. My thanks to our vigilant member April for bringing this article to my attention.
After you have read the abstract and / or the full length article, we can discuss any questions or comments you have.
Disease-Specific Complications of Chronic Lymphocytic Leukemia
Claire Dearden
Department of Haemato-Oncology, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, Sutton, Surrey, UK
The majority of disease-specific complications in chronic lymphocytic leukemia (CLL), notably infection and autoimmunity, relate to the underlying alterations in immune function. Both cellular and humoral immunity are impaired with qualitative and quantitative defects in B cells, T cells, NK cells, neutrophils and the monocyte / macrophage lineage. Virtually all patients have reduced immunoglobulin levels, even in early stages, and this is associated with an increased frequency and severity of infection. Although prophylactic intravenous immunoglobulin may be of clinical benefit in selected patients, it does not reduce mortality and is certainly not cost-effective. Autoimmune complications occur in up to a quarter of CLL patients and predominantly target blood cells. Autoimmune hemolytic anemia (AHA) is the most common manifestation; immune thrombocytopenia, pure red cell aplasia and autoimmune neutropenia are less common, while non-hematological autoimmunity is rare.
The UK CLL4 trial is the largest prospective trial in CLL to examine the significance of both a positive direct antiglobulin test (DAT) and AHA. The study confirmed the usefulness of the DAT in predicting the development of AHA or not, demonstrated that AHA occurred more frequently in patients receiving treatment with chlorambucil or fludarabine alone compared with the combination of fludarabine and cyclophosphamide, and showed that a positive DAT and the development of AHA were poor prognostic markers. Management of CLL-associated autoimmunity rests on good supportive care and the use of immunosuppressive therapies such as steroids and cyclosporine. Splenectomy remains useful, and monoclonal antibodies (rituximab and alemtuzumab) have given promising results.
23 comments on "CLL Complications – an expert overview"
This may be a selfish request but can you write an update on ITP, especially focusing on the two new platelet stimulating drugs (Nplate and Promacta/eltrombopag).
Thanks. I will add it to my list of to-do articles. You are right, it is time to do an Update on the subject.
I heard this lecture at ASH.
I walked away with two strong impressions:
The prevalence of both AHA and ITP from auto-immunity, and dangerous infections from immuno-deficiencies are both underplayed as sources of morbidity and mortality. You need to be thinking and planning for these complications in the course of your disease.
Auto-immune disease is a yet another marker of a bad prognosis.
Brian:
Since you were our eyes and ears at the conference and actually heard this lecture, how about giving us a longer review of it? Our members have access to the full text article (if they click and download from the link provided above) and it would be great if you walk them through it. We can discuss any questions that come up after that.
I guess I am delegating this one to you – I will be on the road tomorrow getting back to Sedona – so pinch hit for me please. Thanks!!
I’m pretty sure I saw a study of some kind a while back that indicated that people with cytopenias due to marrow damage did not have as good a prognosis as those due to autoimmune problems.
Having had two post chemo bouts with s. pneumonia, one of which resulted in two hospital stays, I agree with Brian’s comment about infections. In addition to having oncologists not up to date on tests and treatments, you can add to the lament the fact that doctors treating such things as pneumonia prescribe standard courses of drugs not realizing that our weakened immune systems need more. It was only after I saw an infectious disease specialist, who had an extensive background working with AIDS patients, that I was put on a prolonged treatment course more suitable to my weakened immune state. I should add that the currently called for med treatments in the ‘Red Book’ are not what we CLL patients need. One of those darn near killed me!
Happy to help.
Let me dig up my notes from ASH and I will post a longer comment that reviews my take on the most important points from the lecture.
On the personal side, by the end of this month, I should have a clearer picture if my disease is back post transplant. I will be gathering opinions on treatment options from my bicoastal sources. I have appointments with Rai, Furman, Castro, Kipps, Forman and Sharma (my local onc). If my nodes are grown or there’s CLL in my BM, I will almost certainly be heading for a redo transplant.
mickey1214
You have hit on a pet peeve of mine. Over the last several years I have heard from literally hundreds of patients who were put at risk because their local oncologists were either unfamiliar with “Best Practices” or just plain “forgot” to do the needful. Among the more frequent omissions that can put patients at risk:
1. Unawareness of the significantly increased danger of skin cancer in patients with CLL. This seems to be a “silos” issue, with dermatologists not knowing about CLL and regular oncologists dismissing skin cancer as a dermatological issue. I have lost too many friends to aggressive skin cancer because their local oncologists failed to warn them about the much higher risk faced by CLL patients.
2. Need for prophylactic anti-viral medication and/or monitoring for shingles reactivation in patients undergoing fludarabine containing therapies. There are several good anti-viral meds on the market now and there is absolutely no reason why patients have to suffer the excruciating pain associated with shingles (post-herpetic neuralgia)
3. Checking for potential AIHA (autoimmune hemolytic anemia) complications in patients presenting with low red blood cell counts prior to initiating single agent fludarabine as frontline therapy. Most experts would now tell you this is contra-indicated and can make incipient AIHA much worse.
4. Unawareness of the seriousness of pulmonary infections in CLL patients. Pneumonia is the single biggest cause of death in CLL patients. “Walking pneumonia” may be OK for the general public, but in CLL patients you might be walking yourself to the grave if you and your oncologist fail to take pneumonia seriously.
5. Last but not least, I am still surprised that oncologists do not give strong guidance about TLS (tumor lysis syndrome) in patients going into therapy with high tumor load. How many of you have had no guidance about allopurinol medication ahead of time, or even advised to stay well hydrated? How many of you have had the first Rituxan infusions done too fast to suit the schedule of the infusion nurse and paid for it with massive infusion related adverse effects?
I repeat, what you and your oncologist do not know can kill you. Who is going to watch out for you when your oncologist misses the mark? YOU ARE. This is your body, your life. Either you or your caregiver needs to keep an eye out for stuff like this. The single biggest reason why I continue pounding away on my laptop is that I hope Updates will become your “Owner’s Manual” for protecting yourself.
I feel lucky. My hemotologist/oncologist did start out the Rituxan slowly. 50 (mg?) on a Friday, then on the next week 100 (mg?) on M-W-F (all combined with saline) over hours of time with additional saline drips on Tues and Thurs. Then I started the Rituxan/Fludarabine the next week. I was told to drink more than 8 glasses of water – to drink lots and lots of water and stay hydrated.
I have been informed by my doctor that I may not die from CLL, directly, but from an infection caused by a compromised immune system due to CLL and treatments.
The higher risk for skin cancer and other cancers has not been discussed to any length, beyond the fact that I am at higher risk and need to have skin cancer checks every year now. And my doctor said I am at very high risk of developing a second cancer over the 30 year period of time.
I am also trying to stay up to date on drugs, side effects, infections of opportunity, etc. so I actively participate in my treatment and overall quality of life. I did have my first ever bout with pnemonia during treatment and was in hospital for 2 days.
I am sad I cannot attend the conference at Niagra in April. Hopefully, next year! Seems like a great opportunity to learn.
I have been told that I may have early stages of ITP, although my CLL has been slowly progressing for the past 7 years and I have not yet had any treatment. I have not had treatment for ITP either (just very low platelet count really). Are there any good articles about ITP that you have come across?
We have a full length review of ITP issues on our flagship CLL Topics website. I believe I published the ITP article sometime in December 2007. You can find it by searching for the keyword ITP in the search box at the top of the website home page. As always, it gives citations to important literature articles on the subject.
I am so grateful for this site. The next doctor’s visit, I am going to bring up the above issues. I agree, my doctor never checks or asks about skin cancer, and he needs to know our immune system many times needs something stronger to help us.
Do the other people on this site have a special doctor for skin cancer.
Brown Eyes.
To Brown Eyes,
Yes. I go to an expert dermatologist (in Berkeley CA)every six months. They can be hard to find. I’ve had two squamous cell and one basal cell carcinomas removed since 2004. It’s great because you can stop worrying about any skin abnormalities you might have.
My husband is stage IV for 5 years and has had two courses of chemo (FCR and PCR). Post-splenectomy he had a terrible break out including a lot of skin thickening on his face. His oncologist sent him to a dermatologist who thought it might be pre-cancerous lesions, but biopsies showed that the condition was caused by warts. His immune system couldn’t handle it and the virus went nuts. After diagnosis and treatment the condition cleared up and has not returned.
I have had skin cancer on my face about as long as I have had CLL. 8 or 9 years. My dermotologist has been prescribing ALDARA – 5% cream (IMIQUIMOD)three times a week at $25.00 per treatment. I also use it for flu shots in the fall.
I still have outbreaks but they seem to me managable. My CLL has progressed slowly with the WBC see-sawing from the 40s up to 88.7 now, and platelets holding in the lower 100 (112 on Feb 23)
I have had Pneumonia once last year, but found the Hospital was too dangerous to get treatment, even a private room was not enough help! (Untrained attendants, lack of hand washing and little consideration for basic hygeine) After three days, I talked the doctor into getting me out of there!
I find you CLL TOPICS to be very helpful, and comforting!
CLL02
I am 55 yr old female and I have had CLL since Jan 2002, watch & wait , no treatment, but have had many infections, strep, pneumonia,etc. However last Nov was diagnosised with Mono, was treated, but same symptoms returned in Dec, and end of Jan. again, was treated and recovered, but was told once treated for Mono you can’t get it again. Do you have any info on recurrent infections in CLL patients?
Mononucleosis is caused by Epstein-Barr virus. And yes, EBV traces remain in the body for the rest of the life of the patient once he/she has been infected. And yes, it can reactivate if the patient is sufficiently immune suppressed and that gives the virus a window of opportunity. I do not know who told you that once treated you cannot get EBV infection again. That is not correct information.
We have full length articles on our CLL Topics website on infectious complications in CLL patients. You can search for the articles by using the key words “infectious complications” in the search box at the top right hand side of the home page of the website.
Dear Chaya, Thank you very much for the info. Very grateful, Ellieoak
Chaya
My first posting since joining this site today.
Quoting a previous reply..
“I have been informed by my doctor that I may not die from CLL, directly, but from an infection caused by a compromised immune system due to CLL and treatments”.
My doctor is open & honest in the fact he thinks ive had CLL for at least a year, maybe longer.
My history.
49 year old male who has suffered from Crohn’s disease since the early 80’s, it was finally diagnosed when i suffered peritonitus in 1987 & survived it luckily!!
Im immunosupressed having Crohns & take Azathioprine as a maintenance drug since last resection in 2002.
Do i need to worry more with having Crohn’s & CLL or do i stand they same chances of progression as any other sufferers?
I was only diagnosed recently from a routine bloodtest to check my liver etc due to being on the Azathioprine, abnormal blood results meant i was retested.
Retest of bloods with the Phenotyping did indeed diagnose B cell CLL (i am not anaemic at present).
I have been referred to a local Haemo who has sent me for a CT scan which i had last Monday & wait results to see how my lymph nodes look.
The Consultants view is its watch & wait till things progress, which is the hardest thing to accept, but then having lived with Crohn’s for many years i can accept this idea.
My only symptoms at present appear to be the fact im absolutely fatigued & have been the last 12-18 months.
Awkwardly fatigue is also a symptom of Crohn’s so i guess i wasnt particularly worried & accepted it.
I am presently signed off sick & struggling to manage daily tasks without resting throughout the day.
My present thoughts are to give up work, either through medical retirement if thats an option or worse case is i just leave work.
My work is office based only & have allowances for the fact i have Crohn’s ie working day pattern (early start/early finish)& only having to travel 10 minutes to the office.
There doesnt appear much more i can do to help manage either the Crohn’s or CLL.
Your thoughts please.
Dave
PS
This is a wonderful site!!
Depending upon the course of these two illnesses you have a potentially complicated problem. There is no need, however, to presume the worst.
Crohn’s Disease follows a variable course and it’s therapy can be tricky, utilizing some potentially risky drugs to gain and maintain control. Both infliximab and azathioprine, for example, have the potential to predispose to various indolent infections and both (as well as other drugs used for Crohn’s Disease) may underlie the development of some lymphoproliferative diseases. Still, many patients do exceedingly well.
Having said that I suggest that you seek expert opinions about your CLL and also about the Crohn’s Disease (unless your illness is currently well controlled and your current gastroenterologist seems to have a good handle on things). Coordination of therapy is of paramount importance.
Your principle issues will be good surveillance and protection from infection while maintaining good nutrition and the best overall health consistent with maximal “down-regulation” of the Crohn’s Disease and good maintenance overall. You will also need to continue surveillance for secondary cancers (even more so than usual of the gastrointestinal tract, though the incidence in Crohn’s Disease is still reasonably low).
Good luck,
Rick
Results of my CT scan (i have a copy of them) read as below.. my GP doesnt think theres much to worry about?? & i have to wait till end of October for next Consultants appointment where i hope to discuss these further.
CT NECK, CHEST, ABDOMEN & PELVIS.
There are two large right submandibular nodes measuring up to 11mm in short axis & several nodes in the left axilla measuring up to 14mm in short axis. None of the right axillary nodes are significantly enlarged but they are numerous. Numerous small nodes are also seen in the superior mediastinum, anterior to the trachea &anterior to the aortic arch, measuring up to 8mm in short axis. No indication of axillary or retroperitoneal lymphadenpathy. In the pelvis i note moderately enlarged obturating nodes bilaterally measuring up to 10mm in short axis on the left. There is no indication of orgenomegaly.
teakbank12
Your GP is right (but a little insensitive in not explaining things in more detail) about not worrying about the results of the CT scan.
Yes, the CT scan shows enlarged nodes. It confirms, once again, that you have CLL. So what else is new? Except in very early stage or with very indolent cases or people in deep remission after therapy, chances are excellent that a CT scan will show enlarge nodes for most if not all CLL patients. Yours is no different.
The devil is in the details. The important information is not that you have enlarged nodes, but just how enlarged they are. None of your nodes are bigger than an inch. That is good news. When they get bigger than 4-5 inches across, then it is time to worry because some very important drugs (such as Campath) become contra-indicated in casees with such bulky lymph nodes.
The other good news your GP should have stressed is the lack of organ involvement in your case. Splenomegaly (enlarged spleen) and hepatomegaly (enlarged liver) are both common in advanced CLL. In fact both of these indications are considered in defining the Rai Stage of the patient.
Count your blessings. A time may come when you may feel nostalgic for CT scans that looked as good as this. I hope that time never comes for you.
Chaya
Many thanks for a basic understanding which is what i needed!!
I am waiting to see my consultant again, but thats not till late October & couldnt wait that long to hear roughly what the CT would show.
I guess it will just be regular bloodtests & visits to the Consultant then.
I may not have need of treatment yet which is good, but i’m totally fatigued at present (which is not helped by my Crohn’s).
Dave
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