Questions submitted by readers and answered by the CLL Society Medical Advisory Board
By Richard Furman, MD
Is it likely that CLL in remission but MRD+ can contribute to a later diagnosis of CMML based on bone marrow pathology and FC? Does the co-existence of both have any greater prognostic impact on either or both? Thank you!
CMML is a disease of myeloid cells, whereas CLL is a disease of lymphoid cells. One is not linked to the other, although chemotherapy (fludarabine, FC, bendamustine, chlorambucil) can increase your risk of myeloid cancers (AML, CMML).
May a 68 year old CLL patient receive the vaccine Shingrix?
Shingrix is a recombinant vaccine. That means that it is made in the laboratory and not from a live virus. As such, it is safe for patients with immunosuppression, including CLL. Additionally, while Shingrix is reported to be 90% effective in patients with normal immune systems, it is reported to be 60% effective in immunosuppressed (bone marrow transplant) patients.
I’m 41 and in otherwise reasonable health despite Stage 1 CLL. I was just wondering in what time frame I can expect before I reach a stage in which I would need chemotherapy, statistically speaking. I understand CLL is a rare condition and therefore not much is known about it, but how old are MOST CLL patients who receive chemotherapy?
CLL is not a rare cancer. There are almost 20,000 new cases diagnosed each year and over 200,000 patients alive with the diagnosis. The rate of progression for a newly diagnosed patient to requiring therapy is extremely variable. Some patients will not need treatment for more than 20 years, while some will progress within 1 year. The important thing is that we have many better (in my opinion) and safer options than chemotherapy now available. There are quite a few prognostic markers that are helpful in predicting time to treatment, but the most important indicator is the rate of progression. Prognostic markers are only really helpful for predicting how a population of patients will do, not one individual. Clinical behavior is the most important.
Do lymph nodes go back to normal size after cancer treatment?
Lymph nodes often go back to being close to normal size after treatment.
Two docs. One says to start treatment, the other says “it’s not needed”. The debate is the effects of the elevated lymphocytes. At what “number” is medication necessary? My last count was 196.6. My hemoglobin is 10.9 and platelets 205, both, I think within normal range. Whose advice do I follow? I prefer not to start treatment, but am I jeopardizing my health? I am 84 and was diagnosed with CLL about 5 years ago.
There is no absolute lymphocyte count that indicates treatment is required. Treatment might be required based upon the rate of change of the lymphocyte count, but more commonly it will be a hemoglobin less than 11 gram/dl or platelets less than 100,000 / microliter. There are of course many subtleties. It is worth trying to understand why each physician is making their recommendation or alternatively, obtaining a third opinion from a CLL expert may also be helpful.
How do you know how long you have had CLL? I found out I had CLL in September 2017. My doctor said I have had it for a while and I had all the symptoms when they found it.
There really is no way to know how long one has had CLL. There are some equations used to calculate backwards to when the clone was only one cell, but this requires sophisticated testing to determine how quickly the clone is proliferating.
My husband has CLL and recently had a bone marrow biopsy to help figure out what to treat him with. My question is what does 23% of CLL in the bone marrow mean? Is that high?
23% of marrow being CLL can mean one of two things. Normally, one’s bone marrow consists of bone marrow cells and fat. The proportion of cells to fat changes as we age. The general rule is that the cellularity (proportion that is cells) should be 100 – the age of the patient, with 80% being the most cellular (anyone younger than 20 years of age) and 20% being the least cellullar (age over 80 years). The question is whether the 23% is of the whole marrow or of the cells? Regardless, 23% is quite low and suggests there is still plenty of space for the normal marrow to function.
I have been diagnosed with indolent CLL (13q deleted & IGVH mutated) and placed on watch and wait. Currently, my only significant CLL related medical difficulty is low gammaglobulin levels. If the CLL progresses and I undergo successful treatment with a drug like Ibrutinib what is the likelihood that my gammaglobulin levels will return to normal?
At current time, we do not see immunoglobulin levels return to normal with ibrutinib treatment. We do however, and more importantly, see fewer infections in patients the longer they are on ibrutinib, suggesting the immune system does heal.
What can you tell me about NOTCH1 mutation and its effect on CLL?
The classic NOTCH1 mutation does indicate that the CLL follows a more aggressive course.
I receive IVIG every 4 weeks and have since 2013. My immunoglobulin levels drop to almost nothing after 7 weeks. I was diagnosed with Small Cell CLL in 2012. I had chemo with Treanda, Rituxan and Neulasta from July 2015 to January 2016 after my spleen became extremely enlarged. My WBC’s went from 85,000 to a current norm of 2,000. I have also developed COPD. Is there any other treatment to help my immune system that either replaces the use of monthly infusions of IVIG or to use with the infusions to strengthen and assist this therapy thereby improving my immune system? I saw the small article by Ben Kennedy, MB ChB, FRCP, FRCPath but I am looking for more information.
IVIG is one of the more helpful measures for improving the immune system in patients with CLL. IVIG is typically administered on an every 4 week basis regardless of the Ig levels. With that schedule, I am not sure I understand how you have week 7 levels. We do often not see the antibody levels rise very high. The most important thing is whether you are having your infections prevented.
What is it that indicates progression of CLL, such as, which chromosomal changes? Blood counts?
Progression of CLL is based upon changes in the CBC, physical exam, symptoms, and CT scans if applicable. These changes are not dependent upon any genetic changes in the CLL clone. We do see “clonal evolution” where a CLL clone will acquire new genetic abnormalities and behave more aggressively. This does often result in clinical progression.
Has anybody completed treatment for CLL using Bendamustine and Rituxan with the markers Trisomy 12 and unmutated and if so were they able to achieve remission and for how long?
The data for bendamustine plus rituximab from the original study demonstrates a median progression free survival that has not been yet met for patients with trisomy 12. The follow up for the study is short (27 months) and even though first published in 2012, has not been updated.
I achieved a complete response to SLL after having 5 treatments with bendamustine/rituximab in 2012. My disease presented with many large internal lymph tumors. Will it progress in the same way? I have had lung cancer, which was treated with a lobectomy and have other co-morbidities. I am 82 and I’m concerned about progression at this point and how will it progress?
After treatment, CLL can relapse differently than how it first presented. Patients with large lymph nodes can have a lymphocytosis and vice-versa.
Does having CLL make you more vulnerable to complications from surgeries, such as cataract surgery? Since having CLL, I find that even small wounds take a lot longer to heal; thus I am concerned about a procedure such as cataract removal.
CLL usually does not make you more vulnerable to complications of procedures, especially a cataract, although the treatment for CLL or long-term immune impairment, might.
My white cell count is around 47,000. A lymph node in my neck, next to my Adam’s apple, suddenly appeared and was soft and rubbery with no pain. I feel great on watch and wait. Thoughts?
CLL lymph nodes often are rubbery and painless. The development of one node certainly will not change any treatment plan.
I was treated with ibrutinib plus venetoclax for 14 months and achieved MRD negative in the bone marrow. During that time my IGE went down from 1300 to as low as 88. After 1 month my IGE jumped to 322. All my other numbers like WBC and ALC are good and I don’t have any palpable nodes. Before treatment I had a lot of itching in my groin and on my feet. After treatment started with I plus V the itching went down. So, my question is: Since my IGE is going back up does that mean my CLL may be coming back? I had itching in my groin for over 10 years before I was diagnosed. Can the B-Cell give off high amounts IGE but not be CLL cells.
The IgE level is likely being impacted upon by the ibrutinib as ibrutinib inhibits IL-6, which leads to increases in all immunoglobulins. But the IgE is not related to the CLL clone and therefore does not mean the CLL is returning.
Richard Furman, MD is Director of the CLL Research Center at Weill Cornell Medical College and a member of the Lymphoma/Myeloma Service in the Division of Hematology/Oncology. He is a member of the Medical Advisory Board for the CLL Society.
Originally published in The CLL Tribune Q2 2018.