UPDATE to https://healthunlocked.com/cllsupport/posts/151558926/start-treatment-just-based-on-fatigue

[TLSAtlanta]

Hi everyone. Back in December I posted looking for feedback on whether or not to start treatment based on persistent fatigue that was out of sync with the blood work and size of nodes. As usual everyone who commented were so helpful and gave me lots to think about. I intended to report back after the CT and BM tests came back. But then, the day before the tests, my adult child had a serious medical event and was 3 plus weeks in ICU. All turned out well thanks to world class medical treatment, but it was an intense stretch where the outcome was not certain at all. The fatigue I had been dealing with abated quite a bit during that time - the magic of adrenaline I suppose- and I thought I would definitely push treatment off for another year or so. Once everything settled down however, family encouraged me to get the CT and BM tests that had been postponed just to see where I was in terms of tumor load. I updated my bio with the details, but basically the cancer is concentrated in the bone marrow (as NewDawn I think suggested could happen) with quite high infiltration in BM and increasing abdominal nodes also indicating progression. The fatigue came back too of course once I wasn't in a constant state of fight or flight. So I start V&O in March. I am in Boston now where kid lives and will have treatment at Dana Farber. I am sure there is some anxiety that I successfully repress, but I feel very optimistic and excited to get started. Here are some thoughts on all of this.

The whole W&W thing needs to be seriously revamped. It's a holdover from before they knew so much about the genetics of this cancer and did not have all the targeted therapies. This of course is hardly a novel observation and I know that there are studies ongoing intended to move towards treatment based on risk stratification (ashpublications.org/thehema.... I came across (maybe posted here..?) a study that was proposing to more precisely identify very low and low risk CLL/SLL and just have them routine monitored by their GP with the idea that the majority of those truly have an "indolent" and "chronic" cancer, whereas the intermediate and high risk profiles get channeled into specialist care to determine best treatment approach based on individual symptoms and labs. This would substantially modify or replace the blanket W&W approach.

Asymptomatic vs below guideline symptoms. I think that this, or the messaging about it, gets easily confused, especially in combo with W&W. The first 2 hematologists I saw definitely conveyed the message that I had more of a 'technical' cancer than a real one and that the odds were I would either never need treatment or at least would not need it for many years. The message was go away and don't worry about it until bloods are completely messed up. That made no sense to me because I only got diagnosed after a year of bouts of serious fatigue and enlarged nodes. (My symptoms were dismissed as a combo of menopausal and neurotic.) I think there is a scenario where you get Dx inadvertently and have no symptoms in which case that approach I would like to think would have worked for me. But after a year of symptoms leading to a diagnosis I was confused and angry with this messaging.

The 2018 treatment guidelines, while informed by experts, are still pretty arbitrary and based primarily on pre genetics and pre targeted therapy experiences of those experts. These will change I think (or hope) in the next few years to better fit the risk stratification approach. The classic B symptoms are an interesting example of the arbitrariness of cut offs and definitions. I had some hot flashes with perimenopause pre my SLL Dx, but the nature, persistence and intensity of the mini day and night (usually more severe at night) sweats was different and tracked the other symptoms of bothersome lymph nodes and fatigue. (Also they were not like the much briefer and short lived menopausal hot flashes of my mother and sisters). The fatigue waxed and waned but I had fewer and fewer good days over time. It was really last summer when the fatigue set in so much that I wasn't able to work full time or do anything fun, but I still questioned whether it was a B symptom justifying treatment.

So let me wrap this up with advice and gratitude. Advice- if you get Dx because of symptoms push hard to get a genetic profile so you can try to assess risk and if you have intermediate or high risk features go to a specialist in CLL. Work on having confidence that you are the expert on you- yes fatigue can be caused by stress, depression, anxiety and lymph nodes can wax and wane for non cancer reasons- but be the expert on yourself and try to sort out what makes sense. But also being an expert on yourself requires educating yourself as much as possible, including engaging with but also listening to the disease experts. (not all of them of course- some 'experts' are bad or bad fits, and you have to acknowledge that and switch to the extent you are able to). Gratitude- this site, its crazy good moderators and contributors have been amazing. I learned so much, was directed to so many high quality resources, and was reassured by others shared experiences (the posts by men who reported bothersome and increasing hot flashes was a real "i know i am not crazy' moment, as were all the posts of the various permutations of fatigue and unwellness). Thank you all so much.

[lankisterguy Volunteer]

Hi TLSAtlanta,

We have had many discussions about this in the past, and I have engaged Dr. Furman about it often, since fatigue usually drives me to ask for treatment. There is a Pinned Post that has input from several CLL experts here.

healthunlocked.com/cllsuppo...

The comment from Dr. Furman is especially appropriate for your query.

+++++++++++++++++++++++++++++++++++++++

Rick Furman Jul 4 2020

Wendy,

It does sound like treatment is indicated at this time. One thing to keep in mind, is that watch and wait is meant to differentiate those who are not going to need treatment for a long time from those who will need it shortly. Once CLL is active, there is no benefit to delaying therapy. Along those lines, watch and wait was a strategy developed when we only had chlorambucil and prednisone. Ineffective therapy with an impact upon bone marrow function. Now that we have all of these new agents, the downsides to starting therapy, in terms of marrow damage, are not there.

Rick Furman

+

Re: Significant Fatigue Triggering Treatment

From: Rick Furman

Date: Sun, 05 Jul 2020 16:42:28 EDT

Active is defined by the traditional measures:

1.Hemoglobin < 11

2.Platelets < 100,000

3.Symptomatic LAD or splenomegaly

4.B symptoms

5.ALC doubling in less than six months

There seems to sometimes be an interest in deferring therapy for as long as possible. In truth, once the disease is active, there is no benefit for delaying. This translate to meaning, there is no advantage not starting treatment with a hemoglobin of 10 g/dl, even if you are feeling fine.

There won't be any refinements in iwCLL or NCI guidelines for sometime given the need to generate data to impact those guidelines. There are several protocols testing early initiation of treatment (including on at Cornell with acalabrutinib) for various populations.

My approach is that with ibrutinib, we know 80% of the population will do exceeding well with single agent ibrutinib. Some high risk features (deletion 17p) predicts for patients doing less well with ibrutinib. Our belief is that earlier treatment might help prevent the development of the aggressive cells that lead to the aggressive behavior.

Rick Furman

+++++++++++++++++++

An opinion from Dr. Richard Furman Wed, 05 Sep 2018

"Nothing has changed as of yet for watch and wait patients. My belief is that for 75% of patients, watching and waiting, and then starting BTK inhibitor therapy will be sufficient to provide extremely long-term disease control of their CLL. For the other 25%, we have issues with transformation and BTK inhibitor resistance. These patients do need something different. One theory of mine is that earlier initiation of treatment might be beneficial. We are currently writing a trial to test this, but for now, we are still doing it the way we always have."

<

Len

[TLSAtlanta in reply to lankisterguy]

Thanks Len. I found your info to my original post really helpful and did some research on Dr Furman as a result of your post. I even looked into a current study they are doing there where they do fixed duration BCL2 then BTKi and only if necessary the CD20 antibody. But it was too much to commit to travel to NYC, if I lived there I think it would be great. In my case my symptoms were out of sync with my labs and node size, but consistent with the Bone Marrow, which wasn't tested until I decided to do treatment.

[lankisterguy Volunteer in reply to TLSAtlanta]

Hi again TLSAtlanta,

Most of the CLL experts I have met, acknowledge that every CLL patient and their disease presentation is different / heterogeneous. So they use the guidelines as only guidelines, and adapt to the reality of what the patient really needs.

>

Since you are seeing docs at Dana Farber, there should be no reason to travel to NYC. You should be able to get "fixed duration BCL2 then BTKi and only if necessary the CD20 antibody" without being on a trial. The trial would only be to generate statistical data.

I know that Dr. Furman thinks very highly of Dr. Jennifer Brown and Dr. Matthew Davids.

DF seems to have quite a list of younger CLL experts in addition to the 2 seniors mentioned above cllsociety.org/newly-diagno...

Inhye Ahn, MD, Dana Farber Cancer Institute, Boston

Philippe Armand, MD, PhD Dana Farber Cancer Institute, Boston

Jennifer R. Brown, MD, Dana-Farber Cancer Institute, Boston

Matthew S. Davids, MD, Dana-Farber Cancer Institute, Boston

David C. Fisher, MD, Dana-Farber Cancer Institute, Boston

Arnold S. Freedman, MD, Dana-Farber Cancer Center, Boston

Josie Montegaard, NP Dana-Farber Cancer Institute, Boston

Christine Ryan, MD Dana-Farber Cancer Institute, Boston

Aswin Sekar, MD, PhD Dana-Farber Cancer Institute, Boston

>

Len

[PoisonDwarf]

I totally agree with you. Thanks for succinctly summarizing many of my thoughts & experiences.

I also believe guidelines need revising & updating. Not just due to advances in testing & the treatment landscape. Smarter treatments also require smarter guidelines. One size does not fit all but a truly individualized treatment plan is cost prohibitive & a long way off.

Standard guidelines will always be needed, but I believe it is possible to make them more sophisticated, with built in safety parameters that better meet the needs of patients & healthcare professionals

Without diving into the weeds, here's two examples, that come to mind.

The guidelines should acknowledge that healthcare systems in different countries are not funded in the same way & they are struggling. Public healthcare systems do not provide equal access to genetic testing. eg: In Ontario, FISH & bone marrow testing is only done prior to starting treatment. How can I make informed decisions about early treatment without access to a FISH test?

CLL/SLL are classed as the same disease for good reasons I understand. I've also dealt with doctors from different specialties, all have heard of CLL, but none of them SLL outside hematology.

Why does it matter? My understanding is that disease progression and transformation is tissue based, either bone marrow or lymphoid tissue. That still applies if your diagnosis was CLL. If this is true, understanding the tumor microenvironment becomes key to the cure. Using the right language can help keep research focused.

Superficially, it can appear that maintaining any delineation between CLL & SLL is illogical and my argument runs counter intuitively to the very reasons I argue for making changes to the guidelines. Please judge for yourself. I welcome any input that highlights where & how my reasoning is flawed. I want to expand my understanding & improve my argument.

I was diagnosed 5 years ago with SLL. It was discovered only due to an incidental finding on a lung CT. I am now in the ridiculous position that my fatigue means I can no longer support myself financially, but my Hematologist will not consider genetic testing or even an IV iron infusion because none of my bloods or B symptoms meet the guidelines. The infusion was rejected because I am iron deficient not anemic, I have no history of repeated infection. I have no palpable nodes. My ALC is no where near 30 so doubling time isn't a consideration.

My Hematologist thinks I have no qualifying B symptoms but I haven't lost my mind!!

Gastroscopy/colonoscopy biopsy showed I have severe chronic, active H. Pylori gastritis. It was also positive for focal metaplasia. Does anyone here know if that is completely separate to any malignant B cell infiltration of the intestinal lining? I am scheduled to have a CT Enterograpgy with dye to rule out small intestine disease or any other cause for internal bleeding.

I have completed the quadruple treatment for H. Pylori. A urea breath test in 4 weeks will confirm if it's cleared. In the meantime, I've gone all winter with no heat in my bedroom until now & I'm cold. No more temperature spikes either. My internal thermostat has regulated & my night sweats that that were never drenching & post menopausal have stopped.

I spent 6 hours in the ED with colitis in my hand, the concern was to ensure the infection didn't become systemic. I took 1000mg of Penicillin for 10 days. First time in my adult life.

I have no palpable nodes, but CT scans show my insides are like a pebble beach. A recent doppler ultrasonography to rule out thoracic outlet syndrome showed a hilar lymph node was partially blocking the vein & had the technologist asking has no one looked at your lymph nodes? If these were inguinal nodes you wouldn't be able to walk!!

Lastly, I have another appointment with Neurology for nerve & EMG testing. Other specialities now accept that because I am under 5ft my skeleton is equivalent in size to the average 12 year old. Size is a risk factor for Carpal tunnel syndrome, it's not simply a repetitive strain injury. Size does matter. 🤣

It was a rheumatologist that first pointed out standard hemoglobin levels & the guidelines based on population studies are now recognized as not being an appropriate measure of anemia for some cases.

I believe in evidence based medicine, that is the reason I believe the treatment guidelines need a thorough review.

Does anyone know if a Canadian doctor can fire a patient, if the patient asks nicely? Current rules mean I cannot change my Hematologist, I think they also mean she can't get rid of me. Maybe I haven't framed the question in the right way!

Sorry for the essay. I wish you every success with your treatment. Please update us when you are able.

Thanks again for focusing my mind.

Lynn

[AussieNeil Partner Administrator in reply to PoisonDwarf]

I'd say the issue isn't that the iwCLL 2018 guidelines need updating, but that you and your haematologist disagree with their interpretation! I'm surprised that it's so difficult to get a second opinion in Canada

From Table 1 2018 International Workshop on CLL (iwCLL) guidelines on indications for treatment

nature.com/articles/s41408-...

The following extracts (with my emphasis) support your thoughts that you need treatment now;

Lymph nodes

Massive (i.e.,≥ 10 cm), progressive, or symptomatic

Constitutional symptoms

Disease-related symptoms (b)

(b) Unintentional weight loss ≥ 10% within the previous 6 months; significant fatigue (ECOG performance scale ≥ 2), fevers (38.0 °C) for ≥ 2 weeks without evidence of infection; night sweats for ≥ 1 month without evidence of infection.

There are quite few references to the ongoing efforts by CLL specialists to update the 7 year old iwCLL guidelines in this pinned post;

healthunlocked.com/cllsuppo...

Of note, it took I think around 6 years for the 2018 iCLL guidelines update and there was a general expectation that more changes would have been made to that version. The US NCCN CLL Guidelines, which were initiated by Dr Bruce Cheson and which subsequently led to the creation of the iwCLL guidelines, are updated at least annually, though that's mostly been to change treatment recommendations in line with FDA drug approvals for CLL and closely related lymphomas.

Neil

[PoisonDwarf in reply to AussieNeil]

Hi Neil,

I really appreciate & needed to read your response. Thank you.

It was a timely reminder to check my frustrations and focus on the real issues. That's when I can devise a solution based strategy. I am grateful that you & the admins have created a space where I feel able to rant about my frustrations, but most importantly to me, to hear cool your jets girl and maybe consider this? At times I will be barking up the wrong tree, but the knack you & other admins have of responding in ways that don't make me feel dismissed or disrespected enables me to take a step back & basically get over myself!!

Before I respond, a totally off topic question! A colleague has just returned from visiting family & grandkids in Queensland. He was talking about the devastating flooding & believed if they hadn't left when they did, they may have not been able to get out. I don't know where you're located, Australia's a big place, but there's been some crazy weather there. I just wanted to check that you & yours, in fact any HU member in Aus is OK & safe?

I agree with your conclusion. I appreciate all the links and will read carefully.

For any thing I say, I want to make it clear, I don't need to prove I'm right. Early treatment is not a hill I choose to die on, finding solutions is a different matter. This is already killing me financially.

There's a cost/benefit analysis to be done on early treatment. Without basic genetic testing I can't do that analysis. I have two complaints, debilitating fatigue and peripheral neuropathy deforming my hands & limiting the function/feeling of my upper limbs. Treatment may not cure my fatigue, it can also open a completely different can of worms. I only ask that my hematologist engage with me as an intelligent, educated, well informed patient.

Honestly, If gastroenterology can resolve absorption issues or other causes for my fatigue, great. If neurology can also establish the cause & treat/manage my increasing physical disability, even better.

It appears my CLL/SLL is the elephant in the room that no one will address. If lymph nodes alone are not the problem, then immune system involvement has to be considered. I've always had a wacky immune system. No specialist will do that until my hematologist engages. This she steadfastly refuses to do, which means no other heme/onc is able to either.

The guidelines rightly allow for doctor discretion, because they are exactly that, guidelines not rules set in stone. My Hematologist insists on a strict interpretation. This makes it highly debatable I meet the guidelines, if there is no consideration of extraneous factors.

My hematologist is the immoveable object here. Please tell me if I've missed something. I can't work round her or over her.

It's not a lack of clinical skills, she heads up a major regional cancer centre. She won't even countenance the idea this is a personality clash. We're adults, it happens, it's not personal, move on is my view. There are other Hematologists she can transfer me to.

I did get a 2nd opinion. The CLL specialist I spoke to was exactly what I was looking for. My GP has twice requested that the CLL specialist clinic take the lead on my care, with or without a local hematologist having oversight. They declined. My own doc is willing to try again, we will revisit once all upcoming test results are available. My doc is great, she is highly skilled & she cares. The health centre is the family & community medicine practice of a major teaching hospital. Her knowledge is up to date on latest practice, she is however a generalist & specialists have the final say.

I am not sure how much it's the 'accepted professional etiquette' here at fault, (one specialist won't step on another specialist's toes). It appears that each specialty works in it's own siloe, without any attempt at joined up doctoring. My symptoms are multifactorial, but viewing in isolation hasn't provided answers. The individual doctors are good & responsive, they acknowledge what they see & from the test results have ordered further tests or referrals to other specialities.

A classic example. When the first line iron deficiency protocol failed, at my GP's suggestion I requested an IV iron transfusion. Heme followed protocol with gastroscopy/colonoscopy to rule out occult bleeding, and 3-6 months iron supplementation. She'd reassess in 6 months maybe do a full iron panel. The scopes ruled out internal bleeding in the GI tract, & the gastroenterologist arranged a CT scan of the stomach to rule out any small intestine disease. What the gastroenterologist told me was he had 4 pages of notes & no one thought to mention I had a blood cancer. He also commented on the push back over my request for IV iron infusion. His hope is to help prevent me becoming anemic. His report was detailed & specifically used the words, "this is a contentious area and I am happy to discuss with you further." He's a kiwi with a sense of humour & a lovely bedside manner. There are great doctors here, this is still only the 2nd time I've experienced this level in 20 years in Canada. I have a plan for that though, it will involve the dean of anatomy at UofT 🤣

I'm prattling at this point, I know! I am reminding myself of all the positive experiences to halt the focus on the one negative.

My first Oncologist in W&W for breast cancer was exceptional. Clinical/surgical skills are a given. His consulting room was set up to open the door to any questions, but left it to patients to direct the level of knowledge they needed. He explained I had a breast cyst, he could excise & perform a biopsy. It was enough for me to ask if that would that add anything concrete at this point? His answer was no, we'll continue with W&W. My brain didn't need to know at that point & breast lymphoma is exceedingly rare.

I saw him for 5-10 mins max once a year. Before the 3 year appointment, he saw me in the hallway & asked "how's your granddaughter?" After the mammogram, he confirmed results, I commented that's one hell of a memory, she wasn't born when I last saw you! His response was: "Nope, it's good note taking. You were obviously excited because it was the first girl in the family. I simply read my notes"!

I've come to understand that humour is culturally situated & there are differences between british & north american sensibilities. I have a gallows sense of humour and I'm not a delicate little flower. I now have a plan that employs a different tack to connect & engage with my Hematologist. I will now go away quietly.

Thanks for reading, or not!

Lynn

[AussieNeil Partner Administrator in reply to PoisonDwarf]

Lynn, I'd say you're on the right track.

As you say, Australia is a big place and while my co-admin and I have avoided the latest natural disasters, some haven't been so fortunate.

Neil

[BigfootT in reply to PoisonDwarf]

PoisonDwarf, There is a lot in your post, but to AussieNeil 's point you appear to at least meet the progressive lymphadenopathy criteria which I met 2 weeks ago at the Mayo clinic. I am now on my front line treatment. As your technologist alluded to....not all nodes are seen or felt, but that doesn't mean they aren't concerning and your cancer isn't progressing. In my case it was a mesenteric node near my kidney that was the largest, highest SUV and most concerning at 6x6cm. I had no idea it was there until a CT/PET, but it was one of many unseen nodes that drove the need to start treatment. As an SLL presentation, my ALC was only 1.7 and my bone marrow is only 10% infiltrated. No where near treatment criteria. My spleen is normal, but I have "innumerable" growing nodes from neck to pelvis. It's SLL.

I recently read that CLL is a Lymphoma that wants to be a Leukemia. The oddest of the Non-Hodgkins Lymphoma (from a presentation perspective) it carries both presentations......and unfortunately both names. That your doctor doesn't acknowledge this is concerning and likely one of the reasons there are so many hematology webinars trying to educate the non-CLL specialists about this very unique disease.

I wish you good luck and hope you can get a second opinion.

Bigfoot

[PoisonDwarf in reply to BigfootT]

Hi BigfootT,

Thank you for your reply.

I am so glad you have responsive doctors & hope your treatment is a successful. Please keep us updated when you can.

Onwards & upwards!

Lynn

[lankisterguy Volunteer]

Hi TLSAtlanta,

Dr Furman just posted an answer on [e-mail] (and I have his blanket permission to repost his comments on HU and have added it to the Pinned Post)

+++++++++++++++++++++++++++++++++++++

Re: Time to start treatment?

From: Rick Furman

Date: Mon, 17 Feb 2025 10:45:01 EST

In actuality, the Rai staging uses a hemoglobin of less than 11 g/dl. The Binet staging uses a hemoglobin of less than 10 g/dl. The idea is that the change in hemoglobin or platelets (to less than 100,000) if they are due to CLL cells infiltrating the bone marrow (not immune destruction - AIHA, ITP) indicate that the disease has progressed to the point where there is no advantage to deferring treatment any further.

If the anemia or thrombocytopenia are due to immune destruction, those often have to be treated, and such treatments often treat the CLL as well. We typically do not treat ITP unless the platelets fall below 50,000. It is always important to make sure another cause of anemia is not being missed, as you always want to make sure you are treating the correct issue.

The reticulocyte count is a very helpful means for distinguishing between the two circumstances. Reticulocytes are the youngest red blood cells. They are they red blood cells that have just emerged from the bone marrow within the past day and serve as an excellent means for looking at the bone marrow output. If the reticulocyte count is low, the bone marrow is not producing new red blood cells. If it is elevated, than it is making red blood cells and they are being destroyed in the periphery.

Rick Furman, MD

++++++++++++

Len