Ask The Doctor Q4 2019

Questions submitted by readers and answered by the CLL Society Medical Advisory Board

Remember that we cannot give medical advice and any suggestions should be reviewed with your treating doctors.

By Richard Furman, MD

My last blood work indicated a return to normal levels. I have always been at 0 stage, does this happen often; can I be “considered ” cured?

Answer from Dr. Koffman: There have been many well documented cases of spontaneous remissions in CLL.  Also blood counts can often fluctuate up and down

And remember that a significant percentage of CLL patients never need any treatment, so hopefully you will be part of that group.

Generally, we like to wait 5 years with no evidence of disease before we feel comfortable saying that someone is cured.

If the CLL never causes any problems and you live a normal lifespan, whether it is “cured” or not is moot.

 

My Oncologist just prescribed me Hydroxyurea 500mg . I started Imbruvica and Allopurinol one month ago. She is concerned about my White count, (went from 120K to 240K in the last month). Is it normal to start Hydroxyurea because of this?

Here is the answer from Dr. Furman. There is no reason to believe the hydroxyurea will impact the lymphocytes.  Hydroxyurea is used to control a markedly elevated WBC when it is comprised of myeloid cells.  Most importantly, while myeloid cells can cause problems when the go too high, we do not see problems with CLL cells when they go too high.

Here is the answer from Dr. Koffman: CLL cells are a type of Iymphocyte or lymphoid in origin, not a myeloid cell. Hydroxyurea is not generally used in CLL.

I would urge you to get a second opinion from a CLL expert.  We have a list on our website (https://cllsociety.org/toolbox/cll-doctors/) and if insurance or geography is a problem we offer a free online consult through our expert access program: https://cllsociety.org/cll-society-expert-access/.

 

My husband was diagnosed 3.5 years ago and is still W&W. He seems to get dehydrated at a much faster rate and experiences cramps in his feet/calves often during the night. On a recent plane ride, his hands also cramped to the point he was in tears. Is there a connection between CLL and these symptoms? His labs are stable and show nothing out of the ordinary. He has had kidney tests and other tests to try and figure out he dehydration component. No luck. Has there been any studies that show a correlation between CLL and dehydration/cramping?

Here is the answer from Dr. Furman: I am not aware of any connection.

Here is the answer from Dr. Koffman: A couple of suggestions from me.

Try putting a bar of soap under the fitted sheet where his calves would be- don’t ask, but it often works and it’s safe.

Consider taking magnesium 5000 to 1000 mg at bedtime if his docs say it’s OK. That’s what I do.

Finally, there many meds that help this. A neurologist might help.

 

My husband was diagnosed in 2017 with CLL/SLL and in 2019 diagnosed with metastatic melanoma (a big surprise with no primary found). He has tried and failed treatment for his MM with Keytruda, then Opdivo/Yervoy (though tolerated them well) and we are now looking at a possible trial for the MM. How do the immunotherapy drugs affect his CLL/SLL?

Here is the answer from Dr. Richard Furman: The data thus far do not show any benefit of checkpoint inhibitors on CLL.  There are also no data demonstrating any downside.  There is a theoretical (and case reports) of CLL patients developing an autoimmune hemolytic anemia after receiving checkpoint inhibitors.

 

I have been on ibutunib for 2 months. I have started having sore feet. Will this get better in time?

Here is the answer from Dr. Koffman: While there are many causes for sore feet, if it is related to the muscle aches and cramps that are common early on with ibrutinib, it should get better with time. If not see your doctor.

 

I was reading up on the shingrix shot on the CLL Society website. So are you saying yes or no.? My personal care physician says yes. Hemotologist says yes. I am a stage 0 thankfully. I did have a very mild case of shingles once many years ago *long before cll diagnosis) and that dr said I was lucky cause I would never get it again.

Dr. Furman says yes to the new herpes zoster vaccine.

 

First diagnosed in 2009. After several clinical trials, finally settled on Imbruvica three years ago which seems to have stabilized my condition well. Currently dealing with the side effects of having a compromised immune system, specifically Fifths Disease. Curious to see if others are dealing with similar issues.

Here is the answer from Dr. Furman: Fifth’s disease is caused by parvovirus.  It is unusual to be a problem in adults as about half get exposed as children and are protected.  People who are immunocompromised can run into trouble with parvovirus infections as the immune system may not clear the virus and the patient will most commonly suffer from not making red blood cells (red cell aplasia).  IVIG (gammaglobulin) is usually very effective in controlling the infection.

 

When first diagnosed with CLL (asymptotic) should a FISH test be initiated.. ?

Answer from Dr. Koffman: There is some controversy about FISH testing at time of diagnosis, so that decision in my opinion, should be a shared medical decision made after discussion with your treatment team.

However, it is mandatory that you have testing done before starting any treatment. See: https://cllsociety.org/cll-101/test-before-treat/

That will explain the prognostic and predictive tests.

 

It appears we are advancing very well with treating CLL (elimination of cells, symptoms, and etc.) and getting great responses in the form of CR and R. My question is how are we coming in the realm of the immune system? For example; most of deal with chronic infections even while in remission and the longer we live with the disease our immune system continues to deplete. Most of us will die because of an infection. Are there any advances, studies, etc that are looking at improving the immuglobulin levels and immune system responses or is this just something well beyond our reach? It just seems like we are focused on the symptoms of CLL and not the overlying theme of depleted immune system….

Here is the answer from Dr. Furman: Currently, the only data that we have regarding improvement in immune system function is that we do see fewer infections with ibrutinib treatment for year 2 compared with year 1 and year 3 compared with year 2.  I suspect the majority of the benefit is just removing the CLL cells which are the likely cause of the immune system dysfunction.  Additionally, avoiding chemotherapy as therapy will prevent the damage that is the result of the chemotherapy itself, and result in a healthier immune system.

 

Should I be concerned about a monocyte percentage of 15.4%? The lab Kaiser uses indicates that it is within normal high range.

Answer from Dr. Koffman: It is always best to look at the absolute count, not the percentage. If it’s normal, no worries.

I have had a high absolute monocyte counts for many years with no adverse consequences.

 

I have CLL which has improved to a normal white cell count. Is it okay to get a shingles shot?

Answer from Dr. Koffman: There is some controversy about the new killed shingles vaccine, Shingrix as it has not been studied in CLL patients with some CLL doctors recommending it and some not.

There is a study being done at the NIH on the vaccine, so you might consider that. It would be a good way to get the shot for free (they cover most of your travel expenses too) and to help answer questions about how effective it is in CLL.

Here is link to a Q+A about it and a related trial: https://cllsociety.org/2019/04/two-new-free-vaccine-trials-at-the-nih/

That’s what I would personally do if I had any B cells.

The older “live” vaccine is contra-indicated, but that is rarely used now.

 

I saw a new cancer doctor yesterday but she’s not a CLL expert. She said CLL doesn’t usually cause insomnia but all you have to do is Google ‘insomnia leukemia’ and you can see it’s a common problem.

My insomnia has gotten worse as my WBC has gone up.

What are your thoughts?

Here is the answer from Dr. Furman: CLL is not typically a cause of insomnia.

I would add that anxiety that often accompanies CLL can cause sleep issues.

 

Is there any treatment for CLL-related anemia?

Here is the answer from Dr. Furman: There are many treatments for CLL related anemia. The most important issue is to determine the cause of the anemia.

 

How important is having an MRD test after having front line treatment followed by 2 years of maintenance therapy and back on watch and wait?

Here is the answer from Dr. Furman: Testing is only really helpful when it guides therapy. If the MRD test is not impacting any management decisions, that it is not very important.

 

My 87-year old mother has had stage 0 CLL for over 20 years. Recently she was diagnosed with terminal vulval cancer-state IV. Is there any information out there concerning the interaction of the 2 cancers? Since she is in hospice, no more bloodwork is being done, but when she was diagnosed with the vulvar cancer her hemoglobin had dropped to 8.3 and her white blood cell count had risen to around 30,000.

Here is the answer to your question from Dr. Furman: There is no known relationship between vulvar carcinoma and CLL beyond the fact that CLL patients do seem to have diminished anti-tumor immune surveillance and are at an increased risk for secondary cancers.  This is most commonly seen as squamous cell and basal cell carcinomas of the skin.  I always emphasize the importance of routine cancer screening to help diminish the risk (colonoscopy, annual skin exam, annual GYN exam, mammogram).

 

My white blood county was varied around 150,000 for several years. Eight days ago it was 109,000 and two days ago it was only 50,000. What does this mean? Other numbers didn’t change much and I am just on wait and watch with some swollen lymph nodes. I have been running a fever off and on for the last six days.

Here is the answer from Dr. Furman: The WBC represents a relatively small amount of the total tumor burden.  Whether the cells are circulating or residing in a lymph node depends upon cytokines and immune activation.  Many things can impact this, including fevers, infections, etc.  I suspect that things will return to where they were once the fevers clear.

 

It appears we are advancing very well with treating CLL (elimination of cells, symptoms, and etc.) and getting great responses in the form of CR and R. My question is how are we coming in the realm of the immune system? For example; most of deal with chronic infections even while in remission and the longer we live with the disease our immune system continues to deplete. Most of us will die because of an infection. Are there any advances, studies, etc that are looking at improving the immuglobulin levels and immune system responses or is this just something well beyond our reach? It just seems like we are focused on the symptoms of CLL and not the overlying theme of depleted immune system….

Here is the answer from Dr. Furman: Currently, the only data that we have regarding improvement in immune system function is that we do see fewer infections with ibrutinib treatment for year 2 compared with year 1 and year 3 compared with year 2.  I suspect the majority of the benefit is just removing the CLL cells which are the likely cause of the immune system dysfunction.  Additionally, avoiding chemotherapy as therapy will prevent the damage that is the result of the chemotherapy itself, and result in a healthier immune system.

I would add that ibrutinib can slightly raise the IGA, but not the IGG or IGM.

 

My dad has undergone Hemagioma spine surgery.
And with recent blood report we got to know that as below. Please suggest to me if this is considered as very serious and what should be done next, as I don’t have any idea on this.

Reports
Wbc – 22000
Lymphocytes – 80%
Plate late count- 1.38 lakhs
Hemoglobin- 11

Answer from Dr. Koffman:  There are many possible causes for father’s lab results, some not at all serious, others that could mean he needs more close management and work-up Please have the blood count repeated and based on that result, discuss with his doctor about an appropriate referral including to a  hematologist to get a diagnosis.

 

Was in remission 4 years after FCR. Now it has come back. My question is since I’m feeling so bad why don’t they go ahead and start next treatment which is going to be some type of pills. Instead they are watching the numbers! Thank you for your response.

Answer from Dr. Koffman: The indication for treatment are the same for frontline therapy and subsequent lines of therapy.

You can look at the indications here:

https://cllsociety.org/2016/03/cll-watch-wait-start-treatment/

Feeling “so bad” may be an indication for treatment if it’s due to the CLL and not due the lingering effects of FCR or due to other causes..

Hopefully your local doctor can help sort this out. If you are feeling uncomfortable, consider asking for a second opinion or  using our free online  consultation through our Expert Access Program at: https://cllsociety.org/cll-society-expert-access/

 

How many CLL patients have been successful using Copiktra to reduce enlarged lymph nodes before more chemo? Is it new or just in the USA since September 2018?

Answer from Dr. Koffman: Copitra is only approved in the USA at this time. Trials have been done in other countries. 

Reducing nodes with Copiktra before chemo is not a usual approach to CLL management, so there would be no data on this as I have never heard of it being done.

I urge you to consider asking for a second opinion or using our free online consultation through our Expert Access Program at: https://cllsociety.org/cll-society-expert-access/

 

My daughter is 45 and has been diagnosed with CLL. It is currently being watched and she is not receiving active treatment. My questions, she seems to get every bug that is going around, colds etc. Are there any holistic supplements that can help with this? Vitamins etc.

Answer from Dr. Koffman: No supplements have been proven to lower infection risk in CLL or any disease state. ZICAM, a homeopathic med, might lower the risk of a cold if taken at the first sign of any symptoms.

It is important that your daughter be up to date with all her vaccines and get those for immune compromised patients including the 2 pneumonia vaccines. We will publishing on this very soon, but the CDC had a table for immune-compromised vaccination schedule. The flu jab is a important. No live vaccines.

If she is getting multiple respiratory infections, she should ask he doctor about IVIG.

Wish there was a supplement that would help

 

I have CLL. I’m in the wait and watch stage. I got the ZOSTAVAX vaccine before I got CLL. Do you recommend getting the new 2 shot SHINGRIX vaccine now that I have CLL?

Answer from Dr. Koffman: Though not all doctors agree, I think the SHINGRIX is a good idea. It is recommended for the general population that they get the new vaccine even if they had already received the old one as you did because the new vaccine is so much better. Consider the trial at the NIH where you can get the shot for free and at the same time help advance our understanding about how well it works. To learn more, see: https://cllsociety.org/2019/04/two-new-free-vaccine-trials-at-the-nih/

 

I was diagnosed with chronic lymphocytic leukemia with extremely high count of the natural killer white cells. The oncologist I went to said he had never seen this before. Is there any information on the NK cells? I am not finding much.

Here is the answer from Dr. Furman: Nothing that I am aware of.

I would add that I guess that’s good news.

 

I have CLL 13q deletion unsure if mutated or unmutated but wondering which is the better one to be? What does FISH tell?

Answer from Dr. Koffman: Deletion 13q is the most common FISH abnormality in CLL and is generally thought to confer a more favorable prognosis. The answer is more nuanced and for greater details, you can review this deeper dive: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866061/

FISH probes the nuclei of CLL cells for specific well-known chromosomes’ long (q) or short (p) arms such as 11q or 17p to see if the counts are correct, namely 2 copies. If one or more copy is missing, it is called a deletion.

FISH results can be prognostic and predictive. For more on this see: https://cllsociety.org/2019/09/more-details-on-prognostic-and-predictive-tests-and-when-should-i-do-them-for-my-cll/

If by mutation, you are referring to IgVH mutation, then it is preferable to be mutated.

 

Years ago, there was a “line in the sand” with platelet count to begin chemotherapy. My earliest recollection was 100,000. Obviously that no longer is valid. Is there a similar level of immunoglobulin that is the standard today?

Here is the answer from Dr. Rick Furman: First, there is certainly no line in the sand with regard to platelet counts and initiating treatment. The decision should always be patient specific. 

Regarding IVIG, the classic indication is for patients who are hypogammaglobulinemic and are symptomatic from recurrent infections or have had a life threatening infection. The Ig criteria only specifies being below normal. 

Given the shortage of IVIG, many who meet these criteria are not receiving IVIG. 

 I would add that the old limit of platelets below 100,000 was a soft indicator for treatment and was more important when chemotherapy was the only treatment option and was known to decrease platelet counts. As to IVIG, as Dr. Furman points out, the most important indication is recurrent and/or serious infections, not a specific blood level, especially true with the shortages we are facing these days.

 

 I am 72 years old. I was diagnosed with CLL with 17p deletion in January 2018. My hematologist started me on Imbruvica in January 2019. I was originally taking 420 mg, but my hematologist lowered the dose to 280 mg in July 2019 to reduce side effects. My white blood cell count continues to drop, currently at 13 units. (13,000 per microliter) I am scheduled for surgery to repair an umbilical hernia on November 13, 2019. Is it typical practice to stop Imbruvica for a period of time before and after surgery?

Here is the answer from Dr. Furman: Because ibrutinib impacts platelet function, it is necessary to hold it prior to surgery.

I would add it some cases it needs to be held after surgery too. Your local hematologist and the surgeon can advise you.

 

I seemed to have blown out both my calf muscles I week apart doing relatively easy chores. Is there any correlation to my cll. haven’t needed a treatment in 2 years, in remission, blood levels fine , and am in otherwise good health and reasonably good shape. I am 66 yrs old.

Here is the answer from Dr. Furman: I am unaware of any connection.

 

Question re: pneumococcal vaccine for CLL patients. The NCCN’s recommendation is very general: “Get a pneumococcal vaccine every 5 years”—no mention of which one: PCV13 (Prevnar-13) or PPSV23 (Pneumovax-23). The CDC’s Advisory Committee on Immunization Practices now recommends, for the non-CLL population ≥ 65, PCV13 followed a year later by PPSV23. My question: What about the CLL patient? Specifically, should a CLL patient, age ~60, who received PCV13 four years ago at diagnosis, receive another pneumococcal vaccine? If so, which one and when?

Answer from Dr. Koffman: Please take a look at the vaccine information we have: https://cllsociety.org/2019/10/vaccines-for-cll-patients/

Here is the CDC’s specific wording for CLL patients for Pneumonia vaccines which are different from adults with normal immune function: “Age 19 years or older with immunocompromising conditions (congenital or acquired immunodeficiency [including B- and T-lymphocyte deficiency], ….. leukemia, lymphoma, Hodgkin disease, ….): 1 dose PCV13 followed by 1 dose PPSV23 at least 8 weeks later, then another dose PPSV23 at least 5 years after previous PPSV23; at age 65 years or older, administer 1 dose PPSV23 at least 5 years after most recent PPSV23 (note: only 1 dose PPSV23 recommended at age 65 years or older).Since you have already had PCV13 first, and its way more than 8 weeks, you could get a PPSV23 now and another 5 years later when you are 65 or older.

 

Is there any online proof that this has ever been successfully done, and if so, can you give me a URL to read about it? “Currently, the only known cure for CLL is a successful allogeneic stem cell transplant (getting a whole new blood system from someone else to replace your cancerous cells). Transplant is a high-risk treatment, but IF it succeeds, it is possible for the CLL to be eliminated.”

Answer from. Dr. Koffman: There are several articles published in peer reviewed medical journals that show that some CLL patients that had received an allogeneic hematopoietic stem cell transplant, have not had their disease recur for many years, suggesting that they may be indeed cured. Here is the URL of an abstract of one of many such articles:https://www.tandfonline.com/doi/abs/10.1517/14712598.7.12.1789

In recent years, a small subset of patients who received FCR (mostly mutated IGVH with no adverse markers) have also had very prolonged remissions that look a lot like a cure.

There is hope that some new combinations of drugs may also be curative, but it will take years to see if these hopes are realized.

 

Hi, I did blood work and all the readings are good except Lymph Absolute, it’s at 3.5 .. should I worry?

Answer from Dr. Koffman: I assume you were told you had CLL at some point.

An absolute lymphocyte count (ALC) of 3,500 is of no concern. In fact, in order to diagnose CLL, the ALC must be > 5,000 as you need 5,000 or more monoclonal B cells for the diagnosis and that can only be confirmed by flow cytometry.

The trend is your friend. Follow the trend and you will be aware of how you are doing.

If you were never told that you had CLL, it is possible you have monoclonal B cell lymphocytosis (see https://cllsociety.org/2019/10/e-r-i-c-barcelona-2018-professor-john-seymour-on-mbl-or-monoclonal-b-cell-lymphocytosis-a-cll-chronic-lymphocytic-leukemia/) but there are many other possible causes. Again, the trend is your friend.

 

Is CLL and Non-Hodgkin Lymphoma the same?

Answer from Dr. Koffman: CLL is one of many subtypes of the much broader category of Non-Hodgkin Lymphoma. Specifically, CLL is a type of B cell lymphoma.

 

What blood tests pick up leukemia?

Answer from Dr. Koffman: A CBC or Complete Blood Count could show too many blood cells, sometimes much much higher than seen with infections and other reasons for the counts to be high. Most often, but not always, the white blood cells (WBC) are the ones that are too high. Occasionally the opposite is true and too few of one or more type of blood cells is seen on the CBC, and finally abnormal cells that are not supposed to be in the peripheral blood can be seen on the blood smear that is part of the CBC.

Leukemia then is usually confirmed by a secondary blood test called flow cytometry that looks at markers on the surface of the blood cells that can give an “immune fingerprint” of the particular cancer and lead to the exact diagnosis. Sometimes a bone marrow biopsy is necessary to define the type of blood cancer, but not in the case of CLL.

 

Hi my husband has stage 4 CLL. He has had unexplained fevers for the past 4-5 days with no other symptoms. His oncologist and urgent care were not able to figure out what is going on. Do you have any idea what this could be?

Answer from Dr. Koffman: There are many causes of fever that can take some time and extensive testing to make a diagnosis.

Some possible causes include among others, infections, including atypical infections seen in immune suppressed patients, active CLL itself, and transformation of the CLL to a more aggressive cancer called Richter’s Syndrome. 

Your husband needs to push his doctors to be persistent in looking for the cause of his fever if the fever lingers.

 

Can a bad reaction (swollen lymph nodes, sore bones/muscles, significant pain) to the influenza vaccine give a false positive result in a PET CT scan conducted a few days later?

Here is the answer from Dr. Furman: It is possible for PET scans to be falsely positive a few days after a vaccine due to activation of the immune system by the vaccine.  One important consideration is the degree of the activity.  It would not be very widespread and massive with just a vaccine.

 

What can I do proactively to reduce the swelling and fluid retention from Imbruvica – I have CLL with enlarged spleen and lymph nodes. thank you.

Here is the answer from Dr. Furman: The swelling is an infrequent complication of ibrutinib and doing something proactively is absolutely unnecessary.  The ibrutinib would control the lymphadenopathy and may therefore help with reduce swelling.

 

My recent lymphocyte count is approx 136,000 and a recent CT scan of my abdomen showed multiple enlarged lymph nodes in the abdominal cavity.. Is this an indication of needing treatment?

Answer from Dr. Koffman: The high lymphocyte count is not a concern. If the nodes are symptomatic or massive then treatment might be indicated. Please see:https://cllsociety.org/2016/03/cll-watch-wait-start-treatment/

 

I was diagnosed by a local oncologist with CLL. Can you let me know if you think the diagnosis is correct? His CLL determination was based upon my lymphocyte count of 5500. However, IGHV results showed no clonal population and as a result couldn’t determine IGHV mutation status (the results state that clonal cells <50% of total b-cells mean the test can’t detect mutation). FISH testing was negative for 11q22.3, 12cen, 13q14.3, 13q34 and the tp53 gener region of 17p13.` Thank you for your perspective.

Here is the answer from Dr. Furman: The diagnosis of CLL or MBL (monoclonal B cell lymphocytosis) is a flow cytometric diagnosis and is not dependent upon IGHV or FISH testing.  Both can be negative for technical reasons or the number of circulating cells being too low.

I would add to diagnosis CLL you need a clonal population on > 5,000 typical CLL cells by flow cytometry. If that same clonal population is <5,000, then the diagnosis is MBL.

 

What is the implication and prognosis when someone has both the 13q deletion and the TP53 deletion? Thank you for your help.

Answer from Dr. Koffman: Sadly generally, the predictive power of the FISH testing is determined by the worst of the findings, in your case TP53. TP53 mutation would mean chemo was off the table and you might consider a clinical trial or a combination of novel agents when treatment is needed. The good news is that TP53 does respond well to many different new drugs and that you may go a long time before needing your first treatment.

 

I have a patient with a WBC of 142,000. His hematologist says its ok. I think that level is dangerous. any opinions?

Answer from Dr. Koffman: I assume you have CLL, and if you do the good news is that unlike with some other blood cancers, in CLL there is no danger in a high level of WBC or an indication for treatment as any WBC level. Please see: https://cllsociety.org/2016/03/cll-watch-wait-start-treatment/ on when to treat CLL. Your hematologist is correct.

 

---

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.