Talk:Chronic lymphocytic leukemia

No longer T-cell?

What's the authority for saying that "so-called" T-cell CLLs are a separate disease group (and not a subset of CLL)? Who recognizes it?

eMedicine still considers T-cell CLL as CLL as of October 2008. eMedicine Chronic Lymphocytic Leukemia Approximately 2-5% of patients with chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL) exhibit a T-cell phenotype.

Is this a consensus or is this still under debate? Is it something that the broad oncology community agrees on, or is there a different perspective among sub-specialties or disciplines? How do you reconcile this with the eMedicine authors? Nbauman (talk) 18:43, 3 February 2009 (UTC)

It is the consensus of the National Institutes of Health and the World Health Organization's ICD-O. Please note the difference between Leukemia,+T+Cell,+Chronic at the U.S. National Library of Medicine Medical Subject Headings (MeSH) (the 2007 version) and Leukemia,+T+Cell,+Chronic at the U.S. National Library of Medicine Medical Subject Headings (MeSH) (the 2009 version). Per the latter link, T-cell prolymphocytic leukemia is "A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia." --Arcadian (talk) 18:27, 4 February 2009 (UTC)

I noticed the fact tag you added, so I've added a ref: "In 1989, the French-American-British (FAB) Cooperative Group distinguished five subgroups of T cell leukemia, namely, T cell CLL, T cell PLL, human T lymphotropic virus type I-positive (HTLV-I+), adult T cell leukemia/lymphoma, and Sézary syndrome. 640 When a new entity called large granular lymphocytic leukemia was defined (see Chap. 94), the existence of T cell CLL as a distinct entity became a topic of debate. 641,642,643,644 Because of this finding, the World Health Organization commissioned a panel of experts to draft a new classification of the hematologic neoplasms. 645 At a meeting in November 1997, the panel proposed a categorization of peripheral T cell neoplasms that largely was based on the Revised European-American Lymphoma (REAL) classification (see Chap. 90). 646 However, because of its aggressive clinical behavior, T cell CLL was reclassified under the heading of T cell PLL, without regard to subtle differences in morphology. 647 Even together they account for less than 5 percent of all chronic lymphoid leukemias." --Arcadian (talk) 18:40, 4 February 2009 (UTC)

I think that part of the confusion arises from the historical division of all leukemias into four groups. Once upon a time, if you had a leukemia that was chronic and involved lymphocytes, then you had "Chronic Lymphocytic Leukemia" -- considered a specific disease entity instead of a description of its characteristics. It's like people saying that they're tired all the time, so they have Chronic Fatigue Syndrome, when they might have any one of dozens of other diseases that just happen to present with fatigue. WhatamIdoing (talk) 19:06, 5 February 2009 (UTC)

Causes?

I just noticed that this article doesn't address the causes of CLL. It seems a little odd. Anyone have a favorite source? WhatamIdoing (talk) 03:11, 26 June 2009 (UTC)

There is no specific cause for CLL. Genetic abberations such as translocations lie at the root of all forms of cancer, and CLL is no exception. I'm sure there are theories... JFW | T@lk 19:39, 24 September 2009 (UTC)

There are a few chemicals like Agent Orange and some poorly described (but obviously present) genetic predispositions, but the fact that the cause isn't known should probably be addressed. I think that readers will want to "know what's not known" for the most common form of leukemia. Also, it would be a good place to identify what's been ruled out (e.g., radiation). WhatamIdoing (talk) 20:01, 24 September 2009 (UTC)

We could have a Causes and Risk factors subsection maybe in the epidemiology section. Rod57 (talk) 18:09, 28 June 2010 (UTC)

one word: Oncogene — Preceding unsigned comment added by 41.34.31.194 (talk) 07:05, 13 August 2011 (UTC)

There are no translocations in CLL, its an exception with that respect. However, there are some genetic aberrations that are very common, i.e. loss of a critical region in chromosomal band 13q14 that occurs in more than 50% of patients . If you remove that region in mice, they get a CLL-like disease, speaking in favor of that region to be important in developing the disease. — Preceding unsigned comment added by Aimee Anouk (talk • contribs) 15:05, 16 May 2013 (UTC)

HSCT

doi:10.1182/blood-2009-05-206821 Blood - review of indications for allogeneic stem cell transplantation. JFW | T@lk 19:39, 24 September 2009 (UTC)

Cell size

Does anyone know offhand whether this change is correct? It 'feels right' to me, but my brief search didn't produce a source that addresses this issue, and I don't know. WhatamIdoing (talk) 17:50, 28 September 2009 (UTC)

It's not a full answer, but PMID 1430257 is a good start. --Arcadian (talk) 23:27, 28 September 2009 (UTC)

So B-CLL cells are smaller than any other leukemic cell... but I didn't see any clear comparison to normal lymphocytes in my (very) quick scan. It's a start, though: at least it's not likely to be wildly inaccurate. WhatamIdoing (talk) 06:25, 29 September 2009 (UTC)

Research and Clinical trials

Could we have a section in/near Treatment mentioning any treatments undergoing late stage clinical trials that may be recruiting patients or nearing marketing approval ? Rod57 (talk) 00:25, 25 March 2010 (UTC)

Kind of yes, and kind of no.

A section titled something like "Research directions", that provides readers with a balanced summary of all B-CLL research would be an excellent thing. A section on "Investigational New Drug trials patients should sign up for" would be extremely unencyclopedic and unbalanced.

We don't want to promote clinical trials or to provide information that is really only interesting to patients (see WP:MEDMOS#Audience), but we do want to let people know how much work is done on this disease. I think that a section that shows the whole scope of research efforts (e.g., causes, epidemiology, prognosis, generic drugs, and non-drug treatments, as well as new drugs) would be very appropriate.

Do you have any good sources for such a section? WhatamIdoing (talk) 00:47, 25 March 2010 (UTC)

No, I was hoping others would. I agree we shouldn't be promoting clinical trials. I mention late stage clinical trials as that is roughly when most possible treatments become notable, and when people are more likely to be interested in them. I'll start a section when I find a good source. Rod57 (talk) 13:34, 23 June 2010 (UTC)

Possibly including Green Tea Extract Appears to Keep Cancer in Check in Majority of CLL Patients which suggests EGCG could be useful one day.

More phase II trials - some results : Thalidomide lenalidomide Bafetinib Theophylline flavopiridol forodesine

CLL trials in Dec 2009 in Europe Rod57 (talk) 13:52, 23 June 2010 (UTC)

Recent phase III trials cladribine vs fludarabine alemtuzumab Rod57 (talk) 14:14, 23 June 2010 (UTC)

We'd be better off with a paper that talks about the state of research -- you know, a "Whither Research for CLL?" opinion in a journal, or perhaps a good summary page at a relevant charity website. Relying on reports about individual clinical trials means that we will attract spam, and might mislead the reader (e.g., by presenting a wildly, although unintentionally, unbalanced summary). WhatamIdoing (talk) 20:06, 23 June 2010 (UTC)

Charity website pages will (hopefully) change so are not a good source. It shouldn't be too hard to mention a trial cautiously without misleading. Anyway; I see we now have a rather jumbled section 'Research directions' - I plan to rebalance and update it a bit and use  : Novel BTK, PI3K Inhibitors on Horizon for Relapsed CLL. March 2016 ? - Rod57 (talk) 20:45, 22 March 2016 (UTC)

Science News resource, News in Brief: Body & Brain

Gene therapy for leukemia Web edition: Thursday, August 18th, 2011 "Tweaking immune cells to attack cancer cells in leukemia patients can bring about remission, a small study shows. Scientists at the University of Pennsylvania genetically altered immune T cells to target malignant cells in chronic lymphocytic leukemia patients and mass produced the T cells before injecting them into three patients. The modified cells gravitated to bone marrow, where they killed malignant cells. In two of three patients tested the cancer went into remission, and a portion of the genetically modified T cells persisted, possibly as a cadre of defenders on standby. The researchers report the findings in the Aug. 10 Science Translational Medicine." by Nathan Seppa

99.181.140.213 (talk) 04:33, 26 November 2011 (UTC)

Gene Mutations

The IGHV mutation status section is imho mistitled with "Gene Mutations". I would expect genetic aberrations to follow under that heading. However, the mutational status of the IGHV genes is a normal process to develop the B-cell immunglobulin genes and also occurs in non-malignant B-cells. In CLL, IGHV mutational status is only used to stratify patients into prognostic subgroups. Therefore, a better title would be "Patient Stratification according to Genetic Markers" or something similar. Gene mutations would e.g. be mutations of the TP53 gene or the ATM gene that both in CLL lead to resistance against chemotherapy and could be adressed under the "Gene Mutations" heading. — Preceding unsigned comment added by Aimee Anouk (talk • contribs) 15:11, 16 May 2013 (UTC)

Chronic Lymphoid Leukaemia? Really?

Could the medics here confirm that CLL is commonly called "Chronic Lymphoid Leukaemia" as is stated in the lede, and only in the lede? I have only seen this term used here, and never come across it anywhere else. I'd like to remove it altogether, but there are editors here who I would defer to. Thanks -Roxy the dog (resonate) 23:10, 24 March 2014 (UTC)

Firstly, I apologise for paging you, but I am slightly conflicted here, and really would like to ask you to spare a moment to give me an opinion before I boldly remove what I want to remove. WhatamIdoing - Doc James - MastCell

Secondly - There is no secondly. Thanks -Roxy the dog (resonate) 23:51, 8 April 2014 (UTC)

Yes, it's a valid but less popular name. It appears to parallel "myeloid": you use "lymphoid" and "myeloid", or you use "lymphocytic" and "myelogenous". WhatamIdoing (talk) 02:14, 9 April 2014 (UTC)

Reviews

Blood has a series of reviews on CLL here. JFW | T@lk 09:03, 29 July 2015 (UTC)

IGHV mutations/FISH systematic review

doi:10.1182/blood-2015-10-620864 JFW | T@lk 08:05, 8 April 2016 (UTC)

Review

doi:10.1111/bjh.14184 JFW | T@lk 13:07, 20 June 2016 (UTC)

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Survival for +/- IgVH

I thought that the survival for CLL that was IgVH positive was about 24 years, while the survival for IgVH negative was 6-8 years. The article cites SEER for a 5-year survival of 83.2%, but they don't distinguish between IgVH +/- or ZAP-70 +/-.

N Engl J Med. 2005 Feb 24;352(8):804-15. Chronic lymphocytic leukemia. Chiorazzi N1, Rai KR, Ferrarini M. PMID 15728813 DOI: 10.1056/NEJMra041720 "Patients with clones having few or no V-gene mutations or with many CD38+ or ZAP-70+ B cells had an aggressive, usually fatal course, whereas patients with mutated clones or few CD38+ or ZAP-70+ B cells had an indolent course."

N Engl J Med. 2003 May 1;348(18):1764-75. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. Crespo M1, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M, Marcé S, López-Guillermo A, Campo E, Montserrat E.

Look at Figure 4 here.

There was a later article in the NEJM which stated this more explicitly, but I can't find it right now. --Nbauman (talk) 00:18, 3 April 2018 (UTC)

Lancet

doi:10.1016/S0140-6736(18)30422-7 JFW | T@lk 08:38, 15 April 2018 (UTC)

UK guideline doi:10.1111/bjh.15460 JFW | T@lk 12:34, 17 July 2018 (UTC)

Sweats / Night sweats

... are not mentioned at all in this article. Why not? -Roxy, the dog. wooF 17:25, 4 October 2019 (UTC)

Well, they were, but User:Doc James removed that on the grounds that it isn't mentioned in the (not exactly stellar) source that happens to already be cited at the end of that particular sentence (i.e., not because it's wrong, but because Wikipedia editors these days seem to prefer removing accurate content to adding a second ref). Of course, hematological malignancies top the list at Night sweats#Associated conditions; it's real. It just wasn't already cited in that particular sentence.

I think that this particular symptom might be more typical of advanced cases, rather than a typical or early symptom. WhatamIdoing (talk) 01:12, 5 October 2019 (UTC)

Per this ref night sweats is not that common.[1]

Will add that. Doc James (talk · contribs · email) 01:28, 5 October 2019 (UTC)

Queen's University Student Editing Initiative

Hello, we are a group of medical student’s from Queen’s University. We are working to improve this article over the next month and will be posting our planned changes on this talk page. We look forward to working with the existing Wikipedia medical editing community to improve this article and share evidence. We welcome feedback and suggestions as we learn to edit. Thank you. Orsini.M1 (talk) 20:16, 23 November 2020 (UTC) (Medandchill (talk) 16:48, 1 December 2020 (UTC))

Hello people from Queen's.

Do me a favour when using Talk pages, add new entries at the bottom not in the middle or at the top.

Different subjects need different sections so that we can follow conversations logically.

I have edited this page to make things clearer. Thx. -Roxy the inedible dog . wooF 07:35, 2 December 2020 (UTC)

Prognosis

We noticed that the first sentence in the Prognosis section does not match up to the information mentioned in the rest of the article. The sentence we propose to remove is: "Prognosis depends on the subtype". We propose to insert the following sentences into the beginning of the Prognosis section instead: “Prognosis can be affected by the type of genetic mutation that the person with CLL has. Some examples of genetic mutations and their prognoses are: mutations in the IGHV region are associated with a median overall survival (OS) of more than 20-25 years, while no mutations in this region is associated with a median OS of 8-10 years; deletion of chromosome 13q is associated with a median OS of 17 years; and trisomy of chromosome 12, as well as deletion of chromosome 11q, is associated with a median OS of 9-11 years." Thank you for your time. (Medandchill (talk) 04:00, 2 December 2020 (UTC))

We notice that the survival statistics cited in the Prognosis section has no citation, and incorrectly refers to subtypes of CLL which do not exist. We propose removing this sentence, and replace it with a 5-year relative survival statistic from the National Cancer Institute. I wish to replace the sentence “Some subtypes have a median survival of 6-8 years, while others have a median survival of 22 years (which is normal lifespan for older patients). [Citation Needed]” with the following revision: “While prognosis is highly variable and dependent on various factors including these mutations, the average 5-year relative survival is 86.1%” LB1212 (talk) 00:02, 5 December 2020 (UTC)

Thanks for sharing this. Please not that the citation goes immediately after the punctuation like this (no space after period). Thanks for noting a missing citation as well! JenOttawa (talk) 02:53, 5 December 2020 (UTC)

I noticed that your reference # 1 did not fully auto populate with the citation tool. This is not your fault- it some times happens. I looked up the PMID 31278397 and it works better. When you are editing the actual article, please try pasting the PMID into the tool (versus DOI or website) to share the correct citation information. Thanks again for all these great suggestions!JenOttawa (talk) 02:58, 5 December 2020 (UTC)

@LB1212 and @Medandchill, if you look at lay-oriented sources such as https://www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/introduction or https://hillman.upmc.com/cancer-care/blood/types/leukemia, they do refer to "subtypes of CLL". Maybe this is not the professional jargon, but the phrase does seem to be used. It also appears in this patent application – perhaps it's just outdated? WhatamIdoing (talk) 04:27, 5 December 2020 (UTC)

References

@WhatamIdoing thank you so much for your feedback and providing those references. I looked at them and I believe that we are discussing the same things, just with different words. Because genetic mutations of CLL are mentioned a few times throughout the page, I believe that replacing "subtypes" with "genetic mutations" will provide a more streamlined reading experience. Genetic mutations is also more precise and accurate compared to just mentioning subtypes. Thank you for your time. (Medandchill (talk) 19:14, 7 December 2020 (UTC))

That sounds good, Medandchill.

I wonder whether there are any other prognostic factors that would be useful to mention up front? In general, for any type of cancer affecting primarily older people, age and health status is a significant factor for long-term survival. If you're 99 years old at the time of diagnosis, then you still might not reach the five-year survival point, even if the treatment produces perfect results. But I don't know if the sources you're looking at bother with that kind of obvious information. WhatamIdoing (talk) 21:28, 7 December 2020 (UTC)

Causes section

In order to include more detail and a relevant source, we propose to replace the first sentence of the Causes section, “CLL is caused by multiple genetic mutations and epigenetic changes,” with the following sentences: “CLL can be caused by many different genetic mutations, the most common being deletions in the 13q14.3 region, (seen in 50% of CLL cases), as well as trisomy in chromosome 12 (seen in 20% of cases), other deletions (i.e., in 11q22-23, 17p13, or 16q21 regions), and less commonly, translocations (for example, involving the 13q14 region). CLL can also be caused by a number of epigenetic changes, which can be classified into 3 different methylation subgroups (naïve B-cell-like, memory B-cell-like, and intermediate)." --Step1 jan (talk) 06:22, 2 December 2020 (UTC)

I propose to change the sentence "Some relevant genetic mutations may be inherited; in around 9% of CLL cases a parent had CLL." in the Causes section for the following three sentences: Some relevant genetic mutations may be inherited. Since there is no one single mutation that causes CLL in all cases, an individual’s susceptibility may be impacted when multiple mutations that increase the risk of CLL are co-inherited. Up until 2014, very few of these mutations or significant “risk alleles” had been identified. --Maferhuicom

Thanks for sharing both of these improvements. Good placement of your citations and use of wikilinks. JenOttawa (talk) 03:00, 5 December 2020 (UTC)

I have a small note regarding using your same reference more than once in one article. When you add your references while editing the actual article, you can see the options "automatic Manual Re-use". The first time you add the citation (if it is not already used in an article, click "automatic" and add your PMID, DOI, or website, then click "generate" to fill the template. The second time you want to use the same citation in an article, click "reusue" and search for your citation in the list. This adds in the a,b,c versus duplicating the citation in the list. If possible, practice this in your sandbox before editing live on Monday. Thanks again!JenOttawa (talk) 03:04, 5 December 2020 (UTC)

References

Introduction section

We propose to replace these two sentences in the introductory section: “Management of early disease is generally with watchful waiting. Infections should more readily be treated with antibiotics.” We propose to replace them with the following: “Early-stage CLL in asymptomatic cases responds better to careful observation, as there is no evidence that early intervention treatment can alter the course of the disease. Immune defects occur early in the course of CLL and these increase the risk of developing serious infection, which should be treated appropriately with antibiotics.” Thank you for your time.Shea46 (talk) 17:19, 2 December 2020 (UTC)

We noticed that a sentence in the last paragraph of the introduction could be expanded upon to include more specific detail. The sentence we propose to adjust is: “Males are affected more often than females.” We propose to add to the sentence by including a ratio between men and women. Our proposed sentence is as follows: “Men are diagnosed around twice as often as women (6.8 to 3.5 ratio).” Thank you for your time.(Bob Dargin (talk) 21:50, 2 December 2020 (UTC))

Thanks for sharing this here! Good use of lay language in your first two sentence replacement suggestion. The Lead (Wikipedia's name for an introduction) has it's own style and lay language is strongly suggested here for Wikipedia's non-medical background readers. Please note the placement of your citations, after the punctuation, not before! I know this is a little picky, we are definitely not marking these types of things, but when you edit on Monday please keep this in mind in order that the final Wikipedia article is formatted correctly.JenOttawa (talk) 03:09, 5 December 2020 (UTC)

Please note the information that I gave the suggestion above yours regarding the multiple use of the same reference. We try really hard not to have duplicate refererences in the reference list. Thanks again!JenOttawa (talk) 03:10, 5 December 2020 (UTC)

References

Signs and Symptoms Section

To provide context for the term SLL and explain its relation to CLL, we propose to add two sentences to the beginning of the Signs and Symptoms Section: "CLL can be grouped with Small lymphocytic lymphoma (SLL) as one disease with two clinical presentations. Wherein, with CLL, diseased cells propagate from within the bone marrow, in SLL they propagate from within the lymphatic tissue." Thank you for your time. Orsini.M1 (talk) 03:41, 5 December 2020 (UTC)

To provide fluidity between the newly proposed changes above and the existing sentences, we propose to edit the first portion of the first sentence in the signs and symptoms section from: "CLL is, in virtually all cases, preceded..." to "CLL and SLL are, in virtually all cases, preceded..." Thank you for your time. Orsini.M1 (talk) 03:49, 5 December 2020 (UTC)

References

Covid and CLL

In the UK, Boris and co have announced the end of locking down by july 19th. There have been measures and special consideration for those who are extremely clinically vulnerable, which includes CLL sufferers.

A BBC report today here has a section in it, the last account on the page, about a double jabbed CLL victim having no covid antibodies hence remaining in a very vulnerable state.

I dont think this goes to the level of having to report this in the article, as I dont believe this ref to be reliable in our sense. But I am concerned that this may pan out into something much more concerning.

Any thoughts? -Roxy the grumpy dog. wooF 14:29, 6 July 2021 (UTC)

Queen's Medicine Class of 2025 - MEDS 112 CARL Wikipedia Initiative

Hello Wikipedia Community!

We are a group of 21 medical students from Queen's University and we will be working to make relevant edits and improvements to this article. We will be making edits such as adding good quality references, updating information that is out of date, and fixing spelling or grammar.

We will be making our edits within the next coming weeks.

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