A “Rose” by Any Name..
A significant sub-group of CLL patients are diagnosed with something called SLL (small lymphocytic lymphoma). If like many of us you feel that CLL does not get much respect when compared to more frequent blood cancers such as non-Hodgkin’s lymphoma, just think what SLL folks go through. They get either of two almost flippant viewpoints from many experts:
- (1) CLL and SLL are the same disease, the WHO says they are, so stop bothering us.
- (2) SLL is a lymphoma, the very name says it is a lymphoma, so treat it like a lymphoma and get done with it.
Neither of these slam dunk choices is quite satisfactory to patients diagnosed with the SLL variant of CLL. No wonder SLL patients are confused and frustrated. Well guys, here is your chance to learn more about it. And if you log in you can participate in the discussion that follows, perhaps ask questions of the expert.
Dr. Terry Hamblin needs no introduction in any CLL patient community. I and my husband PC had the pleasure of meeting him in Bournmouth, UK. There is a story behind that meeting that I would like to share with you.
After several cycles of Rituxan therapy PC became hypersensitive to the mouse component of Rituxan and was forbidden to use it ever again. Ofatumumab (“Arzerra”, “Humax-CD20”) was still in clinical trials and not FDA approved. But the company agreed to let PC have “compassionate use” access to the drug. We were delighted! But our happiness was short lived when each and every USA CLL expert that we contacted declined with regret to administer the drug. It seems there was too much paperwork and they just could not find a way of finessing the redtape. I wrote to Terry, pleading for his help. Within 24 hours he wrote back and said if we can come to the UK he is both willing and able to administer the drug. Terry and I spent big chunks of time discussing CLL and all things hematological while PC was getting his four infusions. I learnt more hematology during those sessions with Terry than at any other time. The ofatumumab infusions bought PC another year and half of precious life. I will never forget the debt I owe this brilliant and compassionate physician / researcher.
Without more preamble, here is Terry’s take on SLL. I took no editorial liberties with his text. But I could not resist adding a bit of highlighting and bolding here and there. I also added bits and pieces where I thought it might be useful information for our members. But my editorial comments are color coded in blue, so that you can tell where I have meddled.
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SLL as opposed to CLL
Dr. Terry Hamblin
The WHO refers to them as a single disease but patients worry whether they really are. Small lymphocytic lymphoma (SLL) has the same diagnostic markers as chronic lymphocytic leukemia (CLL) – CD5+, CD19+, CD23+, weak surface Ig, weak CD79b, and FMC7 negative – but it is a lymphoma and not a leukemia. Is SLL just CLL situated somewhere else or does it really need a different approach?
Obviously there is some difference. By definition, SLL does not appear in the blood. Presumably the cells have something different about them – they must have some increased tendency to go to lymph nodes than blood or bone marrow.
When CLL appears in the lymph nodes, the histological pattern is that of SLL, and when SLL eventually appears in the blood, as it does in 25% to 50% of cases, the picture is that of CLL. But SLL tends to end up in the hands of oncologists and CLL in the hands of hematologists.
The IWCLL definition of SLL requires enlarged lymph nodes with the same tissue morphology and immunophenotype as CLL with no cytopenias due to bone marrow infiltration and fewer than 5 x 109/L peripheral blood B cells. Some would also suggest that there should be less than 30% lymphocytic infiltration of the bone marrow, though this is disputed. Most CLL specialists have only seen rather few cases of SLL, and for this reason only small series of cases (around 30 cases) have been reported. It seems that SLL is only about one tenth as common as CLL.
Researchers have sought for differences between CLL cells and SLL cells. It has been reported that they express different chemokine receptors. Chemokines are chemicals that induce cells to migrate to different tissues. CLL cells strongly express CCR1, CCR3, CCR6 and CCR7; SLL cells only express CCR6 [1, 2]. The lymphocytotoxin- gene, which has an important function in the regulation of the immune response, is expressed at a much lower level in SLL cells compared to CLL cells [3]. At present these differences are of research interest only and have no practical implications for either diagnosis or treatment of SLL.
The usual prognostic markers – FISH, IgHV gene mutations, CD38 and ZAP-70 have the same implications for CLL and SLL, but a recent publication suggests that trisomy 12 and the use of the poor prognostic IGHV gene V3-21 are commoner in SLL than CLL [4].
Therapy Options
It is when it comes to treatment that differences occur. As it is a lymphoma, the Ann Arbor system of staging is used for SLL.
- Ann Arbor staging is the staging system for lymphomas. It was initially developed for Hodgkin’s disease, but is used for non-Hodgkin’s disease as well. Stages are determined by location of the tumor:
- Stage I : the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.
- Stage II : the cancer is located in two separate regions, two different lymph nodes or organs, and both affected areas are confined to one side of the diaphragm – that is, both are above the diaphragm, or both are below the diaphragm.
- Stage III: the cancer has spread to both sides of the diaphragm.
- Stage IV: indicates diffuse or disseminated involvement of more than just lymph nodes, including any involvement of the liver, bone marrow, or lungs.
While this is entirely inappropriate for CLL, in SLL it provides for a potentially curative treatment. In stage 1 or stage 2 disease – where the lymphoma is localized to single group of lymph nodes or at least lymph nodes on one side of the diaphragm, the disease is potentially curable by involved field or extended field radiotherapy with 80% freedom from relapse in stage 1 and 62% freedom from relapse in stage 2 [5].
J Clin Oncol. 1989 May;7(5):598-606.
Small lymphocytic lymphoma.
Morrison WH, Hoppe RT, Weiss LM, Picozzi VJ Jr, Horning SJ.
Department of Radiation Oncology, Stanford University, CA.
The clinical course of 54 patientswith small lymphocytic lymphoma (SL) was reviewed. The majority of patients had disseminated lymphoma at the time of diagnosis; 14 patients (26%) presented with Ann Arbor stage I and II disease. Five- and 10-year survival for all patients was 76% and 49%. The only clinicopathologic features identified that predicted a shortened survival were the presence or absence of systemic (B) symptoms (15% v 63% at 10 years, P = .01) and a diffuse rather than pseudofollicular nodal architecture (47% v 87% at 10 years, P = .04). Initial bone marrow involvement was not an adverse prognostic factor for patients who presented with stage III and IV disease. Ten patients developed a marked lymphocytosis consistent with progression to a leukemic phase (chronic lymphocytic leukemia [CLL]). These ten patients had a median initial lymphocyte count of 2,790, compared with 1,580 for those patients who did not progress to CLL (P = .0001). Developing CLL did not adversely affect survival (P = .48). Thirty-seven patients were treated with various combinations of radiation and chemotherapy; 17 patients received no initial therapy. Ten-year freedom from relapse (FFR) for stage I and II patients treated with irradiation was 80% and 62%; FFR for stage III and IV treated patients was 11%. Despite the marked differences in FFR, no statistically significant difference in survival could be demonstrated between the various stages. Selected patients with advanced SL received no initial therapy; these patients had a 10-year survival that was not statistically different from the immediately treated stage III and IV patients. Patients with stage I and II SL should be treated with irradiation; prolonged FFR and possibly cure of the disease can be achieved in these patients.
PMID: 2651577
J Clin Oncol. 1996 Apr;14(4):1282-90.
Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University.
Mac Manus MP, Hoppe RT.Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, USA.
PURPOSE: To evaluate retrospectively the results of radiotherapy for 177 patients with stage I (n = 73 [41%]) and II (n = 104 [59%]) follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkin’s lymphoma (NHL) treated in the Department of Radiation Oncology, Stanford University between 1961 and 1994. PATIENTS AND METHODS: Histology was follicular small cleaved-cell in 101 (57%) cases and follicular mixed small cleaved-cell and large-cell in 76 (43%). Forty-five patients (25%) had staging laparotomy; 34 (19%) had extranodal involvement. All patients had received radiotherapy, either to one side of the diaphragm (involved or extended field) or to both sides (total lymphoid irradiation [TLI] or subtotal lymphoid irradiation [STLI]. Radiotherapy doses ranged from 35 to 50 Gy. RESULTS: The median follow-up duration was 7.7 years. The longest follow-up duration was 31 years. Actuarial survival rates at 5, 10, 15, and 20 years were 82%, 64%, 44%, and 35%, respectively. The median survival time was 13.8 years. At 5, 10, 15, and 20 years, 55%, 44%, 40%, and 37% of patients, respectively, were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence. Survival and freedom from relapse (FFR) were significantly worse for older patients. Relapse rates were lower following treatment on both sides of the diaphragm or staging laparotomy. Univariate analysis showed that youth and staging laparotomy were associated with significantly better survival and that FFR was better following treatment on both sides of the diaphragm or laparotomy. CONCLUSION: Radiotherapy remains the treatment of choice for early-stage low-grade follicular lymphomas. Patients who have remained free of disease for 10 years are unlikely to relapse.
PMID: 8648385
For advanced stage disease treatment is the same as for CLL, except that local symptoms are more commonly controlled by radiotherapy (though hematologists often forget that this is an option for CLL also). The real problem is when to begin treatment. So many indications to begin treatment in CLL are related to the blood count that when to start with SLL may be confusing. Obviously the appearance of B symptoms or of cytopenias is an indication for both, but it is not clear what degree of enlarged lymph nodes or spleen should trigger treatment. Generally people talk about symptomatic enlargement as being the indication to start. My own feeling, now that FCR has been shown to be a better treatment than any other, is that very large lymph nodes with a largest diameter of 10 cm should be an indication to begin, but the only practical way of establishing this for abdominal glands is by CT scan. So perhaps here is a reason for using CT scans. Even so it should be possible to select those patients who need a CT by judicious use of ultrasound.
References
1. Wong S, Fulcher D. Chemokine receptor expression in B-cell lymphoproliferative disorders. Leuk Lymphoma 2004; 45:2491–2496.
2. Trentin L, Cabrelle A, Facco M, et al. Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas. Blood 2004; 104: 502–508.
3. Nagy B, Ferrer A, Larramendy M, et al. Lymphotoxin beta expression is high in chronic lymphocytic leukemia but low in small lymphocytic lymphoma: a quantitative real-time reverse transcriptase polymerase chain reaction analysis. Haematologica 2003; 88:654–658.
4. Daudignon A, Poulain S, Morel P et al. Increased trisomy 12 frequency and a biased IgVH 3–21 gene usage characterize small lymphocytic lymphoma . Leuk Res 2009 published on line doi:10.1016/j.leukres.2009.11.003 Accessed 30th January 2010.
5. Morrison W, Hoppe R, Weiss L, et al. Small lymphocytic lymphoma. J Clin Oncol 1989; 7:598–606.
Take-home points:
Terry, you can see from the lively discussion below how very much our members appreciated your article. With your permission I would like to summarize what we have learned. For those of our readers who are not members and therefore shut out of the discussions, I have decided to add this recap to the end of your article.
- SLL is less common than CLL – about 10% of patients are originally diagnosed with SLL.
- SLL has the same morphology as CLL, which is why the IWCLL calls them both the same disease. The same prognostic indicators are still relevant (IgVH gene mutation status, FISH, CD38, ZAP70), the same “risk bucket” definitions still apply.
- It makes more sense to use the Ann Arbor lymphoma staging system (see link above in main article) rather than the more familiar Rai or Binet staging systems since SLL is a lymphoma and not a leukemia – this is particularly true in early stage SLL. Late stage SLL looks a lot like CLL and the distinctions in staging systems become moot.
- Early stage SLL is defined as having enlarged lymph nodes; red blood cell, platelet and neutrophil counts all in the normal ranges, and peripheral blood ALC less than 5.0K. Bone marrow infiltration should be low, less than 30% according to some experts (but this is still a controversial cut-off point). In other words, except for a couple of pesky swollen lymph nodes everything else should look perfectly normal.
- When SLL progresses to later stages it gradually involves more and more of the lymph nodes, starts spilling over into the blood (you will see increased WBC, ALC) and infiltrates the bone marrow. At this point, distinctions between SLL and CLL disappear for all practical purposes. Late stage SLL and CLL are treated exactly the same way, same decision points of when to start therapy and what to use for frontline therapy etc. Late stage SLL and CLL are the same beast, no difference.
- Here is the most important take-home message as I understood it. Early stage SLL, while it is still restricted to just a few swollen lymph nodes, before it has spread to the rest of the lymph nodes, blood and bone marrow, presents patients with a chance of possible CURE – by judicious use of targeted radiation therapy.
- Think of it this way. Early stage SLL is localized to a few lymph nodes only, we can hit it hard with radiation just as we can any localized lymphoma or solid cancer. Radiation therapy has its own risks and toxicity but which of us would sneeze at the risks of radiation when weighed against the rewards of a possibly full CURE?
- Compared to early stage SLL, equally early stage CLL does not give us the option of targeted radiotherapy since CLL is not localized to just a couple of locations. CLL is a leukemia; its home is the blood. From day one, CLL is present everywhere blood is present, that means everywhere in your body.
- The problem with correct treatment of SLL seems to be one of (a) understanding the nature of early stage SLL, that in its infancy it marches to a different drum beat than early stage CLL (b) confirming the localized nature of the SLL while it is still in early stage (c) having the expertise to know that early stage SLL is treatable and perhaps curable with targeted radiation.
- As you can see, detection and monitoring of swollen lymph nodes is a whole lot more important in early stage SLL than CLL. This is especially so if you want to take advantage of the window of opportunity presented in early stage SLL: a chance to possibly get rid of the disease once and for all and hit a home run CURE. The single best method for detecting and accurately measuring the size of lymph nodes buried deep in your abdomen is CT scan with contrast. MRI leaves the picture a bit fuzzy. PET scans are not as definitive either.
- Bottom line, if you have just been diagnosed with SLL and you fit the profile described above for early stage SLL, you have some decisions to make. Will you take the conventional wisdom of Watch & Wait prescribed to all CLL patients, or will you make a push for detailed evaluation of your disease status (number, size and location of your lymph nodes, level of bone marrow involvement, ALC and other blood counts) and see if you are a good candidate for targeted radiation therapy that may be able to get this monkey off your back once and for all?
- This decision is time sensitive. If you wait too long and your SLL has gradually spilled over into more and more lymph nodes, the blood and bone marrow, at that point you are no different than any other late stage CLL patient. It is no longer possible to do targeted radiation with an intention to cure. Targeted radiation may still be possible to reduce a particular pesky node that is interfering with some essential body function, but that is a different kettle of fish.
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58 comments on "SLL Versus CLL: How Different Are They?"
Now I am truly confused. I was diagnosed with CLL/SLL and have understood it to be the expression of CLL in the lymph nodes that leads to the addition of SLL to the original diagnosis. I have understood that they are treated as once disease, i.e., expression of leukemia. What I am now not clear about is whether one can be treated for SLL and not “compromise” treatment for CLL and which is more important to treat or watch. By your simple schematic, I would be a stage 3-4 in SLL terms. If there is anybody on this site with this diagnosis and experience with the distinction or “companion” aspect of CLL/SLL – maybe I better think of it as CLL and SLL, I’d appreciate your insights. Chaya, any additional thoughts from you would help. I am feeling a tad dumbstruck and plain dumb.
My first small town Oncologist told me there was absolutely no difference between the two, they are the same disease. Simply one presents in the blood/marrow the other in the lymph system. Does not sound like that is the case especially when it comes to treatment. Thanks for continuing to educate us Chaya.
Having been diagnosed with sll/cll in summer 2009, my understanding from my haematologist is that these are one and the same and the treatments and outcomes are therfore the same. I had a ct scan privatley that showed a number of lymph glands involved above the diaphragm. A Bone marrow biopsy showed less than 30% cll cells. Now I am wondering should I have been offered treatment rather than watchful waiting as the study seemed to indicate. Is it too late to go down that road now? How do I broach this with my heamatologist? I too feel confused as to the future, do I actually have a chance to be cured?
I was diagnosed with CLL in 2000. Stayed indolent and lymph counts never increased consistently. Then node swelling in Dec. 08 with some nodes in my neck approaching 10 cm by March 09 and CT scan showing all nodes affected. Plan was to put off treatment until really needed. Moved from Alberta to BC in July ’09. Went in to new doc in Sept to find my IgM level had skyrocketed (was normal in the Spring) with resulting very high risk of internal bleeding due to agglomeration of red cells (“rouleau”). Started chemo immediately with VCRP (vincristine, cyclophosphomide, Rituximab and oral prednisone). Lymphs responded immediately and shrank within 2 days! Now at the end of 6th and last cycle with all counts in a normal range (lymphs are low but expected to recover to normal range). Some residual node lumps (grape-sized) in my neck which my doc says is common. She has declared me in remission and expects it to last at least a year and hopefully several years.
So I am feeling very grateful for quick and effective treatment. When I asked my doc about CLL and SLL and high IgM – were these expressions one disease or three, she was emphatic that it was CLL. The lymph expression is a common complication, but in my case different because my blood WBC had not increased. IgM expression is related to CLL lymphs and is apparently an unusual but reported expression of the disease.
When I asked why she did not chose Fludarabine as part of the chemo, she said that she was following the protocol in BC Cancer Agency for initial CLL treatment. A plus of this approach is that F is still available as an option to use later.
Hope these comments help.
Wow… in Dec 2002 I was diagnosed with CLL/SLL with my Oncologist favoring the SLL term in my case. My diagnosis was done with a needle biopsy of lymph node. the lab came back with as I said the duel CLL/SLL label. I never really got much of an explanation of how to one disease could be called two different things Now I don’t think it matters at this point what it is because originally I had a stage 4 ranking of full involvement. After rounds of Fludaribine Rituxin, then CHOP a few times and then Chop minus one plus Rituxan again. Never did a get any better than a partial remission of the nodes. I now find myself needing monthly IVIG treatments trying to keep infections at bay. The nodes are still growing back and I just don’t have anymore good treatment options left. Transplant is not an option for me because I have and extremely rare blood matching and secondly no funding for a transplant if that were not the case. What to do? Kit
I you are diagnosed with SLL, you are eligible to receive Zevalin or Bexxar, since SLL is coded as a “lymphoma” and your insurance should pay for it. I’m looking into that right now, depending on my bone marrow involvement. Oncologists I trust have told me that’s the way to go if you need to treat and are SLL.
Considerations as to when to begin treatment for SLL include node size (some say individual node size, but must oncs I’ve talked to look at the size of the node clumps or clusters), how fast they are enlarging (the bigger they get the harder they are to bring down, and the harder the treatment is on your kidneys), and, although not a purely “clinical” indication: vanity. When people start to notice your neck swelling, and ask what those lumps are, and when the disease is “in your face” literally everyday, the psychological aspects of having SLL are in my opinion important factors to consider.
Regarding monitoring node growth: I suggest ultrasound. Wish I’d stumbled on that sooner instead of having 5 CT scans in 2 years. Ultrasound machines have come a long way and can detect and measure most nodes. I say this based on personal experience. No more CT or PET scans for me…
Doug.
Velly Interesting Chaya!
My original diagnosis after a neck biopsy in 2003 was SLL/CLL.
I went 8 months on wait and wait until my neck nodes made me look like a bullfrog.
Fludarabine was the treatment of choice in 2004 which lasted 11 months before the nodes started their march back to the bullfrog stage again.
Then it was FCR which I finished in June 2007 and I remain in remission with no sign of lymphadenopathy since.
I have never had any night sweat, fevers, weight loss ( other than during treatment) no swelling of the spleen normal liver etc etc.
I was told back in 2004 that I had Ann Arbor stage IV and Rai stage IV.
I have always felt that the Rai stage IV classification was not correct and at my last check up with my new Hematologist we both agreed that I had lymphoma and not leukemia.
There is no doubt that survival statistics for lymphoma are better than for leukemia and I have been living with the sword of damaclese hanginmg over my head believing that I had stage IV Rai. I might add that I have visited the Mayo Clinic and another clinic in Toronto in Canada, I liev in Halifax Nova Scotia and at no time has anyone every suggested to me that I did not have aggresive CLL ( I’m 11q, unmutated IGVH, 30% plus CD38 and negative ZAP 70)
So I remain confused, enjoying my remission and will probably work with my hematologist on the basis of lymphoma rather than leukemia.
jswift426, I feel better to know I am not alone in feeling dumb after going through this article twice. I feel I have yet to figure out where I fit with this disease(s) and haven’t had all the diagnostic results referenced (weak CD79b, and FMC7 negative).
john_namaste, I am being followed at BCCA as well but have no diagnosed lymphadenopathy. What struck me about your post is your IgM spike being described as “an unusual but reported expression of” CLL. My IgG
is twice normal and was present on diagnosis; I have had no explanation of what that has to due with my SLL (vs a precursor to multiple myeloma). Nor have I had any explanation of my 10 year life expectancy. Is it based on age, bone marrow infrastructure(rouleaux formation), percentage of SLL cells or just generic averages? I intend to ask them about ultrasound as an alternative to further CT scans. Was that option discussed with you?
Thank you to everyone for sharing your experiences.
Great article and much needed for us! I have to say, though, that I still find myself befuddled……Tom was dx through a lymph node biopsy with SLL. A following BMB put him at stage IV SLL with diffuse marrow involvement. MDAnderson has him listed as SLL/CLL. His past 5 BMB’s have stated that his disease is consistent with CLL. The radiation treatment is very interesting for those who present early with SLL, but do Drs. actually go this route? Tom sees an oncologist and a hematologist and both have been in agreement about treating this like CLL.
Tom is also unmutated using the VH3.21 gene. No Trisomy 12, but deleted at varying percentages for TP53, 17p and double deleted on 13q.
I do enjoy Dr. Hamblin’s input on this. He has been more than helpful to me numerous times. What a great Dr, researcher and man!
Jenny Lou
Chaya,
Iam very pleased ro see Dr. Hamblin in print again!
Must admit, I find it all extremely confusing as well; and weel; so scary.
Live well, and thanks for all your information
Mette
Trush1
Thanks so much, Chaya, for all you do for us! And thank you, Dr Hamblin, for this excellent information.
I was diagnosed with SLL, Stage IV, w/trisomy 12, in April, 2007 – tx at that time – “w and w”(my doctor continues to insist on calling what I have SLL, rather than CLL – even though, all the “new” information I had gotten at the LRF Educ. Conference in NYC, Oct., 2007, at SF in Oct., 2008, as well as online, has linked the 2 as the same disease – CLL/SLL). However, my recent treatment – from the same doctor (4/09 – 9/09) – has been FCR x6, which, I am still hearing, is a common treatment for CLL. Decision to treat was based on the concern that there may be a problem due to one/a few/some enlarging nodes very close to a tube/vessel that goes to one of my kidneys – otherwise, I was having little, or no typical B symptoms, and was feeling ok. As it turns out, I’ve had no problems w/the FCR treatment – am now in CR (but w/, I’m told, tiny am’t. of residual nodes here and there – reported to be “unmeasurable” by means of the PET/CT Scan w/ contrast which I had after treatment). So far, so good, one might say, right? I’ve been feeling good, and feeling that, according to all reports, that I’ve gotten the right treatment for my disease.
However, if I’m reading the above article by Dr. Hamblin, and accompanying comments by Chaya, correctly, (and, possibly Dr. Hamblin can hopefully comment on my question(s) here?) I may actually have had the wrong treatment for my specific disease. Should I possibly have had, e.g., radiation treatment (instead of FCR) just for the enlarged nodes near my kidney? and then continued w/”w and w”? Should I have been offered, or requested, Zevalin or Bexxar (as one of the commentors above suggests could be an option for SLL)? Should I switch to an oncologist, rather than a hematologist? And, are there currently doctors anywhere who specialize in treatment of SLL?
I would appreciate any comments, and/or suggestions, as to what, if anything, I should do at this point?
Several questions are yet to be clear after reading this article.
1.If SLL presents in the nodes, does this mean it is known that the origin of the cancer is primary at a node or can the origin be in the bone marrow at a hard to detect level and only accumulates in the nodes due to unknown favorable micro-environmental conditions?
2. More generally, is the “seeding” of eventually detected SLL/CLL a mask as to the origin of the clone(s)?
3. Does the origin of the clone determine any of the heterogeneous characteristics specifically having to do with immune dysfunction?
My case of CLL, diagnosed in Sept. ’06 was due to observed cervical nodes (approximately 1cm and smaller) and a blood test that revealed a peripheral blood tumor burden of ALC 23k. My progression in spite of “good” markers may be an example of Terry’s opinion on a condition for when to begin treatment when he said “Very large nodes with a largest diameter of 10cm should be an indication to begin ……” for the nodes at Dx became 10cm or more by Spring of 2009. Treatment of RF on the 2nd cycle resulted in a renal failure event NOT due to uric acid levels. I suspect the overload of so much cellular debris in combo with post treatment meds were the major factors.
4. If a CLL patient who has been treated but only achieves a partial remission defined by a normal Absolute Lymphocyte Count (ALC) while retaining observable disease in the nodes, is it correct, or in anyway meaningful, to characterize the disease as now being SLL?
5. If SLL/CLL cells are morphologically the same, is that also true of their respective micro-environments when compared with “pure” SLL patient nodes? Is this even known for I believe lymphnode micro-environment study is fairly extensive?
Thanks Terry, for being involved in this forum and for Chaya’s efforts to make this such a high quality informational site!
It is a NEW YEAR and we should all think about contributing $s toward CLL Updates.
Hold your horses everybody. It is night time in the UK, I am not sure Terry has seen the article up on our website let alone all your questions. Rather than muddying the waters some more with my comments I would like to wait and see what Terry has to say.
I am in the process of writing an article on radioimmunotherapy – as an update on our prior article on Bexxar / Zevalin in http://www.clltopics.org
Given the level of interest in targeted radiation as a therpy option in early stage SLL phenotype patients, it might be a good idea for me to move it up to the front of the queue.
A lot of questions.
First, jswift426: The disease was redesignated as CLL/SLL when it was realized that they had the same histology and cell markers. You don’t have to have enlarged lymph nodes to call it CLL/SLL. I think adding the SLL is confusing in most cases and unnecessary. If you have stage 3 or 4 SLL then effectively you have CLL, and there is no need to make the distinction. Radiotherapy is the treatment of choice for stages 1 and 2, but otherwise, treat as if it were CLL.
pennycam: Yes you might be a candidate for radiotherapy. Discuss it with your specialist.
john_namaste: The IgM (I take it to be a paraprotein) is probably a red herring. It does occur in CLL in about 1% of cases and is usually unrelated to the CLL. IgVH sequencing or even immunophenotyping can often sort this out. I don’t know where this fashion for using CVP-R for CLL came from. There are no studies that recommend it and the risk of an unwanted peripheral neuropathy from the vincristine is high. Chlorambucil plus rituximab is just as effective. This regimen is good for follicular lymphoma and some oncologists don’t bother with the distinction. The other possibility is that you really have lymphoplasmacytic lymphoma or marginal zone lymphoma, both of which have an IgM paraprotein secreted by the tumor. Without more information I can’t really comment.
kitjors: The diagnosis of lymph nodes should never be made with a needle biopsy. All authorities advise strongly against it. If CLL/SLL is the correct diagnosis then treatment should not be started just because it is stage 4 (this is a common error that oncologists make). Treatment should begin only when the indications in the CLL guidelines are fulfilled. You don’t mention if they were in your case. Treatment of choice for those able to sustain it is FCR.
doug: Bexxar or Zevalin are ways of delivering radiotherapy to all CD20 positive cells in teh body, but the bone marrow must be free of disease or else secondary aplastic anemia may result. This treatment is still experimental for CLL/SLL. If SLL is stage 1 or 2 treatment with radiotherapy should begin without waiting for the CLL-type indications.
I agree that ultrasound is a good way of assessing abdominal glands, but it is difficult to get accurate measurements of size and comparisons between one scan and the next are unreliable. To get an accurate sizing CT with contrast is necessary, PET is not. Bexxar or Zevalin do far more damage to normal tissue than a CT scan.
I hope my history doesn’t add more confusion to the situation but I think people should be aware that long survival is possible with treatment that is different from any of the options mentioned. I’m from the UK and was diagnosed with SSL in 1994 at the age of 39. At that time I was stage 4 with bone marrow involvement and experiencing night sweats. I under went 6 cycles of fludarabine and went into complete remission. Rather unusually I then has an immediate autologous stem cell transplant. At the time this was considered a possible cure but the treatment was new so there were no long term survivers to verify this. I was in remission until mid 2007 when I became anaemic, neutropenic and thromocytopenic. CT and BMB showed all lymph nodes were once again involved and my bone marrow to quote my haematologist was “stuffed”. Treatment followed immediately this time a short course of prednasone then 6 cycles of FC but no R. Again I had a very good response with near complete remission (slight residual traces in my bone marrow). I’m now 2 years into this remission and feeling fine.
I think this just proves what a difficult disease we are dealing with where there doesn’t seem to be any clear treatment which can be considered the best.
jswift426 – I was dx’d in 2008 with SLL stage IV (Zap 70+, Unmutated, Trisomy 12, CD38+) and am on W&W. Initially I too was thrown for a loop on what to read – do I have Leukemia or Lymphoma?
After a year of education here is what I have gleened out all I’ve read: 1) I’m comfortable having CT scans on a more frequent basis (I bucked this at first); my blood work is completely normal, yet my nodes are definitely enlarging and need to be closely monitored (The suggestion of ultrasound was interesting and new to me though…) 2) When it is time to treat I’ll be looking for a drug that largely targets the nodes/
In my personal opinion, I think SLL and CLL should be seen as two separate diseases. I’ve plead this case to my physician’s; stating that the symptoms that I ~do~ have are not CLL-based (no B-Symptoms). Yet, for example, I struggle constantly with the “Lymphoma Itch” whereas ~many~ (most?) other CLLers I talk to don’t have this problem.
Initially too, when I would read through the CLL clinical trials, often the criteria was based on blood counts – I felt I’d never qualify for a trial; again my blood counts are all normal. Lately I’ve noticed that more and more trials are also including criteria for lymph node progression/size.
Good luck sorting it all out for yourself! Can’t wait to hear more from Terry.
1lukigurl
I hope I am not beating a dead horse with this follow-up to Dr.Hamblin’s reply to john_namaste, but is a constant IgG spike equally a red herring in SLL? It was the reason for my 3 month monitoring instead of the expected 6 month watch and wait interval.
Derek Caine: Rai stage 4 means that your platelet count is less than 100 due to marrow infiltration.
qb: you need to know whether your IgG is a monoclonalo or polyclonal increase. If it is monoclonal then it is likely that you have an associated MGUS which is unrelated to CLL and probably insignificant. Around 5% of CLLs have an associated MGUS, just based on age.
trudyshafer: stage 4 SLL should be treated just like CLL
Waynewells:If SLL presents in the nodes, does this mean it is known that the origin of the cancer is primary at a node or can the origin be in the bone marrow at a hard to detect level and only accumulates in the nodes due to unknown favorable micro-environmental conditions? Either may be true.
More generally, is the “seeding” of eventually detected SLL/CLL a mask as to the origin of the clone(s)? Don’t understand the question.
Does the origin of the clone determine any of the heterogeneous characteristics specifically having to do with immune dysfunction? Unknown.
If a CLL patient who has been treated but only achieves a partial remission defined by a normal Absolute Lymphocyte Count (ALC) while retaining observable disease in the nodes, is it correct, or in anyway meaningful, to characterize the disease as now being SLL? Not meaningful.
If SLL/CLL cells are morphologically the same, is that also true of their respective micro-environments when compared with “pure” SLL patient nodes? Is this even known for I believe lymphnode micro-environment study is fairly extensive? Unknown.
Chayra – this is all so fascinating to me. I was diagnosed in 2004 w/ Stage 2 SLL almost 18 mos after a large lump popped out at my temple. (An unusual place, I am told). W&W until 2006 when I endured 10 weeks of hell with Rituxan. Like PC I was allergic to the stuff and it took me a solid year to recover from the side affects. Last summer a wrinkle in my eyelid proved to be SLL in one of my eye sockets! Dr. Hamblin – God Bless Him – was kind enough to respond promptly to my e-mail and assure me that radiation w/be a good treatment. When I saw the oncology radiologist at my comprehensive cancer center, he surprised me by saying well, let’s zap the big lump at your temple and the nodes in your neck while we are at it. I was stunned!!! ( My SLL specialist had never mentioned this as a possibilty…..???) I was terrified and warned him that I was verrrry drug sensitive. We agreed on two small doses on consecutive days. The lumps were gone within a week. I could not believe it. I have kept thinking – it can not be this simple – and I have actually been afraid to ask why it is not being used more often.
Well, I did ask the Radiologist and he just said he didn’t know, but had been doing it for years with good results. ???
Hi,
Does anyone know what moves a patient with “SLL” to “CLL”? I am surprised to read only 25-50% of patients with “SLL” develop into “CLL”.
Thank you
Thanks, Dr. Hamblin. I didn’t want to add too much ‘medicalese’ to my MGUS query but I have a large(27.3g/L) monoclonal IgG Kappa band in the gamma region plus a weak monoclonal lambda light chain band in the gamma region. With all that, I am content to assume this is unrelated and insignificant to my SLL and I am very appreciative of your consideration.
I too was diagnosed in 2004 with stage 1 SLL/CLL because of an enlarged 6 cm. lymph node in my neck and an increased number of lymphocytes in my blood but my WBC count never got above normal. No BM was ever done. I was on w and w for 2 years by which time more neck nodes appeared as did several larger ones in my chest, which were picked up by C-T scan. In 2006 I was started on FR treatment but could only get 4 rounds because of neutropenia. Gradually i rebounded and have been in remission since with totally normal labs and no palpable nodes and only very small ones appearing on C-T – these have remained stable in size. My questions now are, is this still SLL? How do I know if I have converted to CLL? When/if the nodes become enlarged again, should I seek treatment for SLL or CLL? (originally my oncologist had told me that SLL and CLL were the flip side of the same coin and would eventually become the same).
Following my dx of SLL in Oct.2001 I was on W&W for 3 years. Nodes would swell & subside; eventual decision to treat was based on the node size. Blood counts normal. Treatment with Rituxan alone very effective in 2004. After another 3 years treated with R alone again. Blood counts still normal. Then 1&1/2 years later (in 2009) WBC rose dramatically (from normal in Jan. to 29 in July to 140 in Dec). Looking back at my old records, I see they did call it CLL in some reports although the main dx was SLL, and I hadn’t researched it in the first years & thought that CLL didn’t really apply to me although I knew it was related.
Got a FISH test and have Trisomy 12. Do not know other prognostic indicators.
Two weeks ago finished my first cycle of FR. Nodes way down & white blood counts too (WBC = 1.8). Other counts holding. No longer concerned with its name, just staying away from infection & trying to lead a “normal” life, whatever that may be.
tess: the same prognostic factors that work for CLL also work for SLL. So if you have mutated IgHV genes, del 13q, and are CD38 and ZAP-70 negative you are likely to have indolent disease. If it is confines to one lymph node then it is going to take a very long time to spread to the blood. Even if you never get radiotherapy you may die of old age before you develop CLL.
qb: I reported the 17th case of myeloma and CLL in the same person in Blood in 1981. It is hard to tell whether common things occurring together are due to related pathology or just chance. MGUS occurs in 6% of those over 60. So you would expect to see it in patients with CLL. Admittedly, the levels are not usually as high as yours, but they can be. As long as investiogations have been done to exclude myeloma, then that is what you have. When I had two patients with IgM levels over 90 who had CLL I thought that it must be being produced by the CLL cells. We did some careful experiments and found that the IgM was different from that that the CLL cells were making. We also showed that very little IgM is secreted by CLL cells although they do make free light chains. Recently it has been shown that the amount of free light chain produced is a prognostic factor.
b.le SLL becomes CLL when the peripheral blood B-ymphocytes exceed 5 x 10 to thepower of 9 per Liter. Treatment is indicated when the IWCLL guidelines are reached. I am sure that they are reproduced somewhere on this site.
I’m a 51 year old female who started out with diabetes and COPD. I now have inflammatory arthritis, osteoarthritis, brittle bones ect.. and CLL too. Diagnosed 2 years ago. I am atypical with FMC+ and Trisomy 12. As far as I know they’ve never tested me for mutation status ect..but say I have an indolent kind of CLL. What has concerned me is that when this all started I had one small enlarged node in my neck. I now have palpable multiple enlarged nodes on both sides of my neck, my throat and my shoulders, who knows whats happening internally.
My bloodwork remains quite stable. So I’m on watch and worry. I have a few questions I cant seem to get answered.
Should I have another fish test ect.. to see if I’ve developed SLL and new chromasone abnormalities as well?
Does the new lymph node enlargement indicate my CLL is progressing or I’ve developed SLL, regardless of my blood work?
And with all my other medical problems, does delaying treatment pose a risk to me? I’m concerned that by the time they treat this, I may not be strong enough to withstand it.
I was dx in 2008 at the age of 40 with CLL/SLL by accidental find on a mammogram. Felt a lump on my neck 4 years earlier but blood work came back fine so the Dr. told me it was nothing. Now my WBC is slowly increasing from 33,000 to 45,000 over the course of 1 1/2 years since diagnosis. I have normal genes with a small percentage of 13q deletions, CD-38 and ZAP-70 neg. and mutated. Still on W & W because I feel fine, have no B symptoms and nodes aren’t too big. Liver and spleen slightly enlarged. I am lucky enough to live near Sloan-Kettering and am being seen there regularly every 3 months. My question is which service should I be in, leukemia or lymphoma? I am presently in the lymphoma service but wonder if I should change.
Thank you Chaya for educating us.
Stay well,
Monique
It’s really great having specific SLL discussions.
I don’t feel quite so lonely any more !!!!!
Does the same’ bucket’ rating apply to SLL as CLL?
A recent article on this site spoke of good remission rates for mini allo’s as a follow up to early treatment on follicular lymphoma. As a relatively young and healthy SLL-er, happily on w & w, (no blood involvement but numerous medium nodes and nodular bone marrow infiltration). Are mini allo’s a potential treatment option?
Some people, including Dr Hamblin advocate 10cm node size as warranting intervention; others say 5cm, as larger nodes tend to be difficult to reduce. This is quite a difference; what factors (other than B symptoms) are liable to influence my treatment timing and options?
When the time for treatment eventually approaches, where in the UK would Terry Hamblin recommend for a referral?
Thank you Chaya for instigating this discussion and to Dr Hamblin for his considered and informative article and blog responces.
I was diagnosed with Cll, 1994. W&W for 8 years. During this time, I had lymph nodes in both breasts, 1996. My oncologist then diagnosed me with CLL/SLL.
I had several breast bx done and was watched closely by a radiologist and surgeon also. Lymph nodes bil. axillae. In 1999, dramatic changes when I was diagnosed with colon cancer and had a colon resection but needed no treatment.
2002, I had chemo, R/F for large abdominal nodes.
Since I did flunk Leukeran, 2009. I have been on R/B since Dec. 2009.
Rough at times, but I’m handling it. I have had three months of this.
I have had this disease for 15 years. At ten years I changed onc ologists. I believe my diagnoses is CLL/SLL.
What a whammy if I really had SLL at the beginning and no one knew about it. After almost 16 years of this merry go round, nothing surprises me.
As always, thank you for the updates.
Rita
St. Louis
Dear Dr. Hamblin,
Thank you for your reply. So kind of you to take the time to respond to us all. Thank you to Chaya as well for having you here.
I asked the question about SLL moving to the blood- I was recently diagnosed with CLL back in June 2009. My blood counts were low (lymph count was still under 4.4) but has since risen to above 6.5 I had swollen lymphs everwhere so at the time of diagnosis was a stage 3 on the lymphoma staging and stage 1 for CLL.
There were a series of events that lead up to me going to the doctor because of swollen nodes- failed pregnancy and drugs that were taken to initiate the miscarriage (that I found out suppress your immunity) and a strep throat and possible unknown virus- other than that I felt great- had a 18 month old and was under 40…I was just wondering if you know what has caused others to move from sll to cll- frustrating that I may have been able to get rid of this cancer before it got out of hand!
I found out I am unmutated, CD38+ and ZAP 70+ 39%. I haven’t had FISH done yet as they don’t offer it here. I havent been treated but feel good altho they tell me I will likely require a BMT after my first treatment is completed (whenever that may be done).
Do you have any patients with CLL that are unmutated but have not required treatment for a very long time? Any thoughts you may have would be appreciated.
Thank you for your time.
Regards,
Theresa
CANADA
Dr Hamlin:
Thank you for taking the time to share information and answer our questions.
I was diagnosed with SLL in 2004. At that time the biopsy showed my markers were CD5,CD20 and CD23.I had a lump in my neck that I first noticed it in the late 1970’s.In Sept 2009 I ask my doctor what he thought it might be and he said most likely a cyst.Because of my previous diagnosis I requested a biopsy. When it was removed it turned out to be 2 nodes that were setting on top of one another.It also came back with markers CD5,CD20,CD23 same as 5 years ago. In every paper that I have ever read written on CLL/SLL it mentions the CD 19 marker which I do not have. How common is it to have SLL without a CD19 marker? Is there any significance in the fact that I dont have that marker and instead have CD20? My doctor has me on watch and wait.
Another thank you to Dr. Hamblin, Chaya and all the wonderful CLL community responders.
Dr. Hamblin – I’m not clear on something. Does early stage SLL have enlarged lymph nodes with blood counts in the “normal” range for WBC, lymphocytes & neutrophils? Whereas with early stage CLL there are probably no enlarged lymph nodes but the WBC and lymphocytes are increasing above the “normal” range?
Thank you,
Patti Kruse
Linda77
Should I have another fish test ect.. to see if I’ve developed SLL and new chromasone abnormalities as well?
Once CLL has been diagnosed you don’t go back to having SLL. Think of it this way: SLL is a type of precursor to CLL when the disease starts in a lymph node. When it spreads to the bone marrow and blood it becomes CLL. Thereafter it is always CLL, but while it is just in the lymph nodes, it is potentially curable with radiotherapy. Another FISH test is only justified if treatment becomes necessary, to determine whether FCR will work or not. You can have a better idea of when and whether you will require treatment by getting the IGHV mutations done.
Does the new lymph node enlargement indicate my CLL is progressing or I’ve developed SLL, regardless of my blood work?
No. It is CLL. New lymph node enlargement might move you from stage 0 to stage 1, but SLL means lymph node enlargement and no blood involvement.
And with all my other medical problems, does delaying treatment pose a risk to me? I’m concerned that by the time they treat this, I may not be strong enough to withstand it.
No. Watch and wait is the correct program.
atk92: The important thing is that you are under the care of a Dr who knows about CLL. Some are in lymphoma service and some in leukemia service. At MSK I would guess that they know what they are doing.
doreensll
Does the same’ bucket’ rating apply to SLL as CLL? Yes.
A recent article on this site spoke of good remission rates for mini allo’s as a follow up to early treatment on follicular lymphoma. As a relatively young and healthy SLL-er, happily on w & w, (no blood involvement but numerous medium nodes and nodular bone marrow infiltration). Are mini allo’s a potential treatment option?
Yes
Some people, including Dr Hamblin advocate 10cm node size as warranting intervention; others say 5cm, as larger nodes tend to be difficult to reduce. This is quite a difference; what factors (other than B symptoms) are liable to influence my treatment timing and options?
The CLL guidelines are widely available. I don’t have space to reproduce them here. Perhaps Chaya can give a link.
When the time for treatment eventually approaches, where in the UK would Terry Hamblin recommend for a referral?
That all depends where you live. Write to me privately at terjoha@aol.com
tess Sorry to say, but it looks like you will need treatment in the next 18 months. You must get a FISH test before treatment, at least for del 11q and del 17p as this will determine what treatment you will need.
never_saydie
Probably they never tested for CD19. It is always present when looked for. Your markers are CLL/SLL and if your blood is clear it is SLL and you should be considered for radiotherapy.
pkruse
Dr. Hamblin – I’m not clear on something. Does early stage SLL have enlarged lymph nodes with blood counts in the “normal” range for WBC, lymphocytes & neutrophils? Whereas with early stage CLL there are probably no enlarged lymph nodes but the WBC and lymphocytes are increasing above the “normal” range?
That’s quite right, Patti.
I was dx in 1991 and, due to a thick neck, tx in 1993 with Chlorambucil for 8 months. (White count was about 30K when treatment began.) Lymph nodes and WBC both were reduced to normal after the first treatment. Had an apparent remission from 1993 to 2005 when lymphadenopathy reappeared. WBCs were normal till 2007. Since then half of the readings are “normal” and half of them are only very slightly above normal range. Lymphadenopathy increased until now with the largest being a left pelvic sidewall lymph node of 8.1 cm. and the next largest being a left common iliac node at 4.7 cm. I have no symptoms from the enlarged nodes and no “B” symptoms except for slight anemia.
I guess I have transformed from CLL to SLL, while most people go the opposite way.
Right kidney has shown some perinephretic stranding, induration of fat, and aberrant soft tissue in CAT scans over the past 2 ½ years. BUN is in the low 40’s and Creatinine is in the 1.4’s. Left kidney is slightly reduced in size on recent CAT scan.
When treatment is indicated, I am interested in trying Chlorambucil + Rituxan even though Chlorambucil is not in favor nowadays. I have 10 reasons for preferring Chlorambucil over Fludarabine in my case.
Comments on my case, especially from Dr. Hamblin, would be welcomed.
Mal
After reading never_saydie’s post, I re-read materials on CD markers as mine have never seemed quite right either but I remain confused. In addition to CD 5/19, I have “dim/partial” 11c and 23, and 38neg. My bone marrow biopsy was definitive for SLL but I have no lymphadenopathy and normal blood work(except for the pesky MGUS).
How does this make me Rai stage 4a? Have I glossed over some other relevant indicators? Obviously,I would love the opportunity to knock this out with radiotherapy but does my staging preclude this?
qb: I’m not sure this is the answer, but perhaps Dr.H can comment–
I had roughly 60% bone marrow involvement when originally diagnosed with SLL in 2001. This made it stage 4 which does preclude direct therapy to the nodes.
Thank you, Chaya, for sharing your earlier experience with PC and Dr. Hamblin.
Dr. Hamblin, you are a very special doctor who is obviously committed to the needs of others as evidenced again in your willingness to spend your valuable time answering so many questions. Thank you for that!
Dr. Hamblin,
I am re-reading some of these comments. I believe I had it wrong.
I was diagnosed with bit of a high wbc and on w&w 8 years. In between lymph nodes appeared.
So, no matter if I was treated from then on for nodes or blood work, since the high wbc came first, I truly have the CLL.
Thank you so much for your help.
Rita
St. Louis
Thanks Chaya for your fantastic service to the CLL community and particularly for raising the CLL/SLL question and to Dr Hamblin for his most informative input and responses.
Chaya’s original article has prompted a very instructive discussion, and it looks as if the SLL/CLL continuity/overlap extends the individuality of expression of this type of leukaemia. Several years ago, my doctor dismissed a lump under the skin on my upper thigh as benign. In January 2009 a regular blood test showed I had neutropenia and further tests through to March confirmed I had CLL/SLL with 54% bone marrow involvement CD19+, CD20+, CD23+, CD38-, FMC7-, sLambda+, no FISH abnormalities, swollen spleen and multiple sub cm swollen lymph nodes. By then my blood cell counts and IG counts had dived to below the lower healthy limits except for the leukocytes, but they only averaged around 4. I was classified Rai IV and CMV got me (took me two months to get over the worst of it – I got puffed walking around the house). Recently I mentioned the thigh lump to my haematologist as it had been itchy and was surprised to hear it was a swollen lymph node. I also found the neutrophenia showed in a regular blood test several years ago and was ignored. I’m now on watch and wait until I can no longer fight off infections or doubling time becomes an issue. (My lymphocyte counts oscillate and last month’s jumped 50% to 5.8, the highest yet.) Recommended treatment is FC and if no improvement FCR as Rituximab isn’t on the Government PBS scheme in Australia. I’ve often wondered why I was getting all the B symptoms (night sweats/hot flushes, frequent infections, tiredness, trouble concentrating, etc) with such low WBC numbers and put it down to exercise historically keeping them low in the blood, while bone marrow involvement was increasing (I used to cycle over 100km a week). I suspect I’ve had SLL for many years which changed to CLL recently – it could have been picked up much earlier.
It would be nice to think that better education would increase SLL cures through early radiation treatment intervention, but is this realistic given the transient nature of swollen lymph nodes and the difficulty of identifying them if internal?
Neil
Chaya and Dr. Hamblin, This has been one of the most informative (for me) discussions I have ever read. It is now rather clear to me that I must have had SLL for a number of years before my CLL diagnosis three and a half years ago. At about this same time, my dermatologist kept removing more and more skin cancers. Periodically my neck lymph nodes would swell up as well as nodes in my arm pits. Since I did not feel badly, I did not check with any physician about the problem. I thought the lymph glands were simply doing their job and that the swellings would go away. It certainly never occurred to me that I should see an oncologist and ask questions. Cancers were something that happened to other people: NOT ME. A recent CT scan shows enlarged lymph nodes in my abdomen as well. (Thanks for the caution about CT and MRI scans also.)
Meanwhile, back at the ranch, with a WBC count which was 17,000 at the time of diagnosis and is now 88,000, I am still considered to be in wait and worry stage. With the additional problem of having idiopathic pulmonary hypertension, my future doesn’t look too rosy.
Decisions,decisions! I thank you so much for giving me food for thought. Ignorance has not been bliss.
Betty
Take-home points:
Terry, you can see from the lively discussion how very much our members appreciated your article. With your permission I would like to summarize what we have learned.
1. SLL is less common than CLL – about 10% of patients are originally diagnosed with SLL.
2. SLL has the same morphology as CLL, which is why the IWCLL calls them both the same disease. The same prognostic indicators are still relevant (IgVH gene mutation status, FISH, CD38, ZAP70), the same “risk bucket” definitions still apply.
3. It makes more sense to use the Ann Arbor lymphoma staging system (see link above in main article) rather than the more familiar Rai or Binet staging systems since SLL is a lymphoma and not a leukemia – this is particularly true in early stage SLL. Late stage SLL looks a lot like CLL and the distinctions in staging systems become moot.
4. Early stage SLL is defined as having enlarged lymph nodes; red blood cell, platelet and neutrophil counts all in the normal ranges, and peripheral blood ALC less than 5.0K. Bone marrow infiltration should be low, less than 30% according to some experts (but this is still a controversial cut-off point). In other words, except for a couple of pesky swollen lymph nodes everything else should look perfectly normal.
5. When SLL progresses to later stages it gradually involves more and more of the lymph nodes, starts spilling over into the blood (you will see increased WBC, ALC) and infiltrates the bone marrow. At this point, distinctions between SLL and CLL disappear for all practical purposes. Late stage SLL and CLL are treated exactly the same way, same decision points of when to start therapy and what to use for frontline therapy etc. Late stage SLL and CLL are the same beast, no difference.
6. Here is the most important take-home message as I understood it. Early stage SLL, while it is still restricted to just a few swollen lymph nodes, before it has spread to the rest of the lymph nodes, blood and bone marrow, presents patients with a chance of possible CURE – by judicious use of targeted radiation therapy.
7. Think of it this way. Early stage SLL is localized to a few lymph nodes only, we can hit it hard with radiation just as we can any localized lymphoma or solid cancer. Radiation therapy has its own risks and toxicity but which of us would sneeze at the risks of radiation when weighed against the rewards of a possibly full CURE?
8. Compared to early stage SLL, equally early stage CLL does not give us the option of targeted radiotherapy since CLL is not localized to just a couple of locations. CLL is a leukemia; its home is the blood. From day one, CLL is present everywhere blood is present, that means everywhere in your body.
9. The problem with correct treatment of SLL seems to be one of (a) understanding the nature of early stage SLL, that in its infancy it marches to a different drum beat than early stage CLL (b) confirming the localized nature of the SLL while it is still in early stage (c) having the expertise to know that early stage SLL is treatable and perhaps curable with targeted radiation.
10. As you can see, detection and monitoring of swollen lymph nodes is a whole lot more important in early stage SLL than CLL. This is especially so if you want to take advantage of the window of opportunity presented in early stage SLL: a chance to possibly get rid of the disease once and for all and hit a home run CURE. The single best method for detecting and accurately measuring the size of lymph nodes buried deep in your abdomen is CT scan with contrast. MRI leaves the picture a bit fuzzy. PET scans are not as definitive either.
11. Bottom line, if you have just been diagnosed with SLL and you fit the profile described above for early stage SLL, you have some decisions to make. Will you take the conventional wisdom of Watch & Wait prescribed to all CLL patients, or will you make a push for detailed evaluation of your disease status (number, size and location of your lymph nodes, level of bone marrow involvement, ALC and other blood counts) and see if you are a good candidate for targeted radiation therapy that may be able to get this monkey off your back once and for all?
12. This decision is time sensitive. If you wait too long and your SLL has gradually spilled over into more and more lymph nodes, the blood and bone marrow, at that point you are no different than any other late stage CLL patient. It is no longer possible to do targeted radiation with an intention to cure. Targeted radiation may still be possible to reduce a particular pesky node that is interfering with some essential body function, but that is a different kettle of fish.
Chaya,
Thank you for your efforts to provide a forum for this type of stimulating discussion. I would also like to thank Dr. Hamblin for sharing his valuable insight. For the last week or so I have been pondering the classic chicken or egg question of SLL/CLL.
Although there is a growing pool of research regarding this question, the answer still is not clear with regards to where/when the B cell transforms from normal to malignant. Once transformed, the malignant cell turns on genes and makes proteins (cell surface markers and receptors, signaling proteins, cytokines, etc.) that are not found in normal cells. While these proteins help us to identify the malignant cells and make some prognostic predictions, it also confuses the picture as to where/when the cell first transformed.
Is SLL different from CLL due to the site of original malignant transformation (lymph node vs. bone marrow), or do they both start in the bone marrow but the attraction to accumulate in the lymph nodes is greater in the SLL cells than the CLL cells? Another possibility is that they both start in the lymph node but the CLL cells are programmed to leave the node earlier than the SLL cells.
While the success of radiation treatment in early SLL seems to favor a lymph node origin, mild bone marrow involvement and generalized prominence of multiple lymph nodes would suggest a bone marrow origin. Perhaps there is a difference in CD38 and ZAP70 positive SLL vs. CD38 and ZAP70 negative SLL with the positive cases acting more like classic CLL and the negative cases more responsive to early radiation treatment.
As already noted in the previous posts, it can be a challenge to identify patients with early SLL that might benefit from early radiation therapy. However, retrospective cases may be of value to get researchers pointed in the right direction. Patient databases/registries that allow researchers to query the data have been useful in other diseases to provide answers, identify trends, and design research projects to gain a better understanding of a particular disease.
Having participated in trying to establish a database/registry for another relatively rare disease, I am somewhat familiar with the amount of time, effort, legal issue, and expenses that are involved such an undertaking. It is no easy task and I am currently not in a position in the near term to try to start such an effort. However, I can also see how this type of resource might benefit the SLL/CLL community. Are you aware of any activity or interest in this area? Is that what the NIH natural history protocol is trying to achieve or does that protocol have a more limited scope?
Steven:
I hope this is the kind of information that will be generated by the NIH “Natural history of CLL” clinical trial. How far their research will go, how much detail we can glean from it – that remains to be seen.
A younger and fiestier version of me would have jumped at the idea of developing a patient community driven database / registry to explore this and other equally relevant questions. As you mentioned, the task is hugely complex, very important and not easy to do. I hope someday you or someone like you with the right skill set will rise to the challenge.
Dear Chaya and Dr. Hamblin,
I am adding my appreciation for the formidable discussion and enlightenment in the foregoing. I would like to take the discussion to the next generation. I am 57 and was diagnosed with SLL in 2008 first with fine needle biopsy and then later confirmed with BM biopsy. I therefore have stage 4 disease with too numerous to count small nodes both superficially and viscerally. My prognostic indicators are good and I am on watch and wait.
My daughter is 19 and was afflicted with tubular interstitial nephritis, renal failure, and uveitis (TINU) about 6 months after I was diagnosed. She is being treated with 2gms of Cellcept per day. Recently she has developed significant cervical lymphadenopathy. Her blood counts are normal and her rheumatologists think the nodes are just “shoddy”. My question is when should our children with lymphadenopathy be biopsied or otherwise analyzed for early signs of SLL/CLL? I am aware of the the other articles posted on this site supporting the notion that our children are at higher risk for this disease.
Sam
Sam has raised a very interesting point which I never though of before. If I can put it another way using two quotes:
1. “The single biggest risk factor of getting CLL is a family history of CLL or other lymphoid cancers. CLL is a familial cancer. Remember that the next time you are reading about long term research. Your kids and grandkids may benefit from our dedication today.” (From “How I treat CLL Upfront – Nov 2009)
2. “Early stage SLL, while it is still restricted to just a few swollen lymph nodes, before it has spread to the rest of the lymph nodes, blood and bone marrow, presents patients with a chance of possible CURE – by judicious use of targeted radiation therapy.” (Point 6 by Chaya above).
Maybe I’m missing something but putting the two of these together, should not every child of an SLL/CLL patient have some sort of test to see if they have early stage SLL while it can still be cured.
Clum
Clum- If only life were logical, a nurse who is potentially a 3rd generation SLL/CLLer wouldn’t refuse testing for fear she will be refused life insurance that would protect her children if illness strikes. She participates in lymphoma research projects but,of course, gets no personal feedback. I think this conundrum is common in diseases with a bad prognosis but we who must watch and wait may better understand others’ choice to do so.
Getting kids tested for potential CLL / SLL is a very tough call to make. We outlined some of the problems associated with this in our article “Not the worst day of your life”.
http://www.clltopics.org/DC/WorstDay.htm
The technology is now avaialable for detecting CLL at extremely early stage, even before it has become full fledged disease. MBL (monoclonal B-cell lymphcytosis) can be detected and monitored via blood tests. It is thought to be the precursor of CLL. But not everyone who has MBL will progress to have CLL down the road. An earlier article on MBL on this site describes the details.
http://updates.clltopics.org/526-mbl-detection-does-not-mean-cll-down-the-road
Would you want a young kid officially tagged with MBL diagnosis – when it may prove to be nothing more than a transient worry – given the status of our health insurance system and patient confidentiality? Would it create legal, social, psychological and financial problems for the youngster in question?
Chaya,
You mentioned the Natural History study here. Has everyone who applied had an appointment? I applied in March, have had several e-mails back and forth but still no appointment. Has anyone else had this problem?
I hate to be pest.
Thanks
birdsfan:
You are not a pest.
I believe quite a few of our members have had appointments at the NIH with regard to this trial. You might get more responses to your question if you post on the discussion that follows “A perfect clinical trial for our times”. Therese has also posted there with new contact informatin etc.
Good luck!
Dear Chaya and Dr. Hamblin,
Wow!! I only wish this information had been available to us many years ago.
Starting in 1993,mammograms showed 2 2cm right axilla nodes. No amount of prodding to my doctors could budge them into doing something, and I have letters in writing saying that no cancer is present. Blood work was normal with the exception of a modest rise in lymphocytes. No further tests were done. (All at a major, top ten in the country hospital.)
In 2003, I developed minor B symptoms such as fatigue, but blood work was still within normal range with the exception of the high lymphocyte counts. The axilla lymph nodes remained. In 2004, started to have infections, night sweats, weight loss, but blood work remained in normal range. Not until I developed fevers and several 1 cm. neck lymph nodes, did I realize that I had lymphoma and insisted that my doctor do something. Within a month, I was diagnosed with Stage 4 SLL/CLL. Normal karyotype, less than 3% CD 38, no Zap 70 test or Immunoglobulin mutation tests.
Treated with 6 courses CVP +R successfully, with no peripheral neuropathy, now five years into remission, have developed strange stomach aches but have no obvious lymph nodes on exam, normal blood tests, although platelets barely in normal range, no B symptoms other than some fatigue. Treated at a major cancer center
Questions: I think I had Stage I SLL initially based on your excellent information on that topic. Is it possible that I am now presenting with SLL again and would radiation be a possiblity if nodes are found only in abdomen?
Sammy:
Our understanding of CLL & SLL has improved greatly over the last ten years. I am not very surprised that back in 2003 your doctors ignored swollen nodes because they did not see anything in the blood. Today most experts would follow up with other tests.
Are you a good candidate for radiation today? I do not know. I venture to guess it depends on your accurate (Ann Arbor) staging. Also important is the level of your bone marrow infiltration.
Have you considered a more focused form of radiation, as in radioimmunotherapy with monoclonal drugs such as Zevalin and Bexxar? (You can read about radioimmunotherapy by searching for these two drugs on our website http://www.clltopics.org )
Radioimmunotherapy has just been approved by the FDA to treat NHL patients. Using either of these drugs in leukemia patients is tricky business because it can cause serious damage to the bone marrow and the stem cell populations there if the patient has substantial bone marrow infiltration.
Bottom line, whether or not you can use radiation depends on your Ann Arbor Staging. Whether or not you can use radioimmunotherapy depends on your level of bone marrow involvement – in other words, are you still a SLL type or have you now become CLL variety.
Hope this helps, but in any case please be sure to talk it over with your own healthcare team before you get your heart set on radiation protocols.
Dear Chaya,
Thank you so much for your help. You have honed right into the dilemma. I am concerned over the slow but steady drop in my platelets over the past year which are at 155,000. So, I hear your concern about my bone marrow. Will be discussing this with my terrific doc next week.
Your help has me so much more informed and prepared to ask more incisive questions. I’m wondering if the CVP + R would be repeated given that I’ve had such a durable remission. Also take green tea supplements.
Thank you so much. Sammy
Dear Sam
I think that the description of the nodes is “shotty” not “shoddy” (though they do sound similar with an American accent). It refers to lead shot as it is used by a shotgun. 5-10% of CLL/SLL is familial. At this stage it is potentially curable with radiotherapy, so there is a case for excluding the diagnosis by biopsy, though the dilemmas referred to above obviously apply.
Thanks Dr. Hamblin and Chaya! I have just finished 6 rounds of FCR and have minimal residual disease. Bone marrow said diag was CLL/SLL and I haven’t had a visit with dr. about it yet. So glad to get informed so I can ask relevant questions. Thanks again for caring!
I’ve been diagnosed with CLL for about 4 years. Now I have a swollen tonsil and apparently SLL. I see the oncologist Friday.
It seems to me that CLL puts me at risk of all other sorts of cancer, not to mention that my diabetes puts me at risk of Alzheimer’s and practically every other chronic disease known to woman.
I am 66. Is it worth getting my throat burned for a few more years of what could be more terrible diseases?
I wonder if SLL is diagnosed less frequently because it is not as easy to find as CLL. I was diagnosed with CLL about 7 years, with blood counts that were completely within the normal range when repeated. The only way we confirmed the dx was with Flow and Fish testing which I requested. (Morale: be careful what you ask for!) Just this year, they found a tumor behind the orbit of my eye causing my one eye to droop I will shortly start radiation for this. One post-mortem study found SLL/CLL present in orbits of 75% of CLL patients, so while reports of this are sparse, other data suggests it may be common.
In my case, it is interesting to note that photographs confirm my eye has been drooping for many year — certainly back to a time when CLL could not be identified from a normal blood test. Does that suggest that SLL progressed undetected to the more easily detectable CLL? Is the later diagnosis of CLL causing us to miss treatment/cure opportunities?
This is a very interesting read and I believe CLL=SLL. I am having difficulty breathing and thought maybe it is RA causing this but on another thought I might be the CLL progressing further then I originally thought. It is time to see the oncologist again soon and these forums are helping me understand more of what to ask and expect from CLL. CANCER is so nasty. My Nuetrophils have recently gone high and this is sometimes and indicator that cancer is spreading in the body. It also says drugs like prednisone (on 45mg of this presently) can bring Nuetrophils up so it is hard to say if the CLL is spreading or the drug is causing this. I am scheduled for a catscan this coming week and hopefully that will give a better indicator of what is going on under the skin. All I know is living with CLL for almost two decades has been extremely mind numbing and stressful.
I’ve been diagnosed with SLL with a primary site in the breast, Stage 1. Has anyone any experience with that diagnosis?
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