Hi all. Well, 2nd line treatment day one came yesterday, and I dutifully scrubbed up and turned up at the hospital for 0830 to start my planned Venetoclax ramp up. I was somewhat apprehensive tbh, partly because of side effects, partly because of having to hang around haem/onc waiting room for 6 hrs between labs, and partly because... well... Ive had eight good years remission from my first line FCR and got very comfortable packaging CLL away somewhere in the dark recesses of my brain...and here was that glaring neon hospital light re-illuminating it all too brightly. Still, I had been feeling frankly awful for several weeks now, with the lowest energy levels I'd ever experienced, unable to do any little thing without getting exhausted, turning lemon-pale and hearing my heart pounding in my head from dawn to dusk. I began to feel as if Bruce Springsteen new something about CLL when he wrote the lyrics 'at night I wake up with bed soaking wet, and a freight train running through the middle of my head' 😜
I had my rasburicase infusion (sensitive to allopurinol) . We all chatted in our infusion chairs about the depressing state of nurses' pay and NHS conditions. Lots of support for the amazing nurses. Back to haem clinic, consented, took Venetoclax dose 1. Then came my blood results.
HB down to 6.0 from 10.1 4 weeks ago. There was my freight train right there. Cross matched and Blood transfusion booked. Further tests showed (unsurprisingly I guess) that I was haemolyzing. Blood transfusion cancelled. Venetoclax ramp up put on hold. High dose corticosteroid, folic acid anticoagulants prescribed. Back next week to assess blood changes. Of course, having got the Venetoclax on board before the great haemolytic anaemia reveal, I got to hang around the waiting room for 6 hours anyway for obs and evening bloods. Result!
So, that's my story. Recent bone marrow shows around 60% infiltration. Spleen is up. No notable external or internal lymph node bulk this time (had really bulky disease first time round). Wbc hovering mid twenties, so it's all lurking in marrow and spleen this time... Hence AIHA response I suppose?
I'm sharing, because it's new to me and there's a relative paucity of info around the CLL sites (couple of good previous threads on here). I've also found several good open access papers (willing to share links if peeps interested).
The question emerging from my story is does anyone have any more recent experience of developing auto immune hemolytic anaemia in progressive CLL disease states, and what (if any) impact did it have on planned or current treatment. Especially interested in any Venetoclax clax/Rituximab stories in this context.
But also just want to say hi to everyone again, and state the obvious but fundamental truth that this disease never seems to come back for the same dance with you. It really keeps you on your toes doesn't it?
Best wishes from my slightly yellow face and pounding head.
Julia
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I have no advice but I wanted to say that I enjoyed your writing style. Sorry to have you back from your fcr induced remission. Did you get O infusions before your V or is it a monotherapy?
Thanks LeoPa. I enjoy writing about my experiences, and I also know how useful it is to share this stuff... Not just to get answers, but to give us all the sense that we aren't alone in our (very varied) CLL journeys.
Venetoclax-wise, I'm scheduled for 2 years V plus 6 months ritixumab. I was in this week to start the 5 week Venetoclax ramp up required to mitigate against tumour lysis before the monthly Ritux infusions kick in. But AIHA trumped that.
I'm really hoping that it won't put my treatment back too much. I'm feeling that, once I'm out of this critical anaemia phase, hopefully aided by the steroids, the CLL treatment itself will clear out my bone marrow and, with it, the root cause of the anaemia. But I don't know the protocols around concurrent AIHA and progressive CLL, so I'll need to talk to my consultant re that next week.
I'll continue to share progress. At some point, someone else is going to come up against this scenario, so it will have value to record it in the long term.
Meanwhile, the skull drum and bass feels less percussive today, and mycomplexion is more chalk than lemon, so maybe things are moving in the right direction... 💓
Hopefully the high dose steroids will halt your hemolysis quickly. Are you sill in the hospital? Since rituximab is sometimes given to treat AIHA and often given prior to venetoclax ramp up, is your medical team considering starting that treatment for you? Best wishes to you.
Hi Classical Jazz. Thanks for your response. They sent me home with steroids and an appointment next week for repeat bloods. I'm in an information vacuum right now because I saw the Clinical nurse specialist as my Consultant was busy (although he had advised her to put me on steroids and discharge) , and she didn't know what would happen with my scheduled Venetoclax/Rituximab going forward ! I too thought Rituximab would be a player, and wondered if just getting me started on treating the CLL asap wouldn't just knock the AIHA back anyway. But I can't find definitive protocols. I'm going to email my consultant on Monday and ask for a call so I at least know what to expect. Not very good at passive patienting 😬
Messaging or calling your physician directly sounds like a good idea instead of waiting a week, since "HB down to 6.0 from 10.1 4 weeks ago" is so significant a drop. Between the low oxygen carrying capacity of your blood and the steroids, a week is a long time-- worries about dizziness, infection, etc. with those low lab numbers should be monitored frequently. Is your physician a CLL specialist or do they have consultation access to a CLL specialist?
Hello Jibs, I had a bad bout of AIHA prior to starting any treatment for Cll. The first attempt at controlling my AIHA included steroids, rituxin infustiins and cyclophosphamide pills. My AiHA came back in short order and that regimen was repeated.
A couple weeks later my AIHA came back with a hemoglobin level of 7. I had both the tinnitus and night sweats you describe. There was an ocean roar in my ears and my bedding felt as it had been dipped in the ocean, I was sweating through several tee shirts a night.
I became allergic to rituximab and was given ofatumumab instead. An ivig infusion was added and gradually my hemoglobin got back to ten or so. At that point I was started on ibrutinib to treat my Cll. I eventually switched to acalabrutinib and that’s where I am now. It’s been about 3 yrs and my labs and hemoglobin stay mostly normal. There are some data out there about how well ibrutinib can keep AIHA under control. Paradoxically, there are stories of ibrutinib triggering AIHA as well.
From what I have read, though, in most cases ibrutinib has been shown to be very effective in treating AIHA. It makes sense that ibrutinib treatment that helps our Cll would also help AIHA since AIHA can be triggered by active Cll ( I hope using sense and since in the same sentence is not confusing for our non native English health unlocked members , not trying to sound homophonic here).
So might venetoclax be a drug that can both trigger and treat AIHA too as ibrutinib might? I don’t know the answer to that.
I do know there are a lot of data showing how ibrutinib can control AIHA and that might be worth a discussion with your doctor. Good luck to you. AIHA sucks.
It is really good to hear from you, especially as I saw a reference to one of your previous posts on AIHA (healthunlocked.com/cllsuppo..., and you said something that really resonated with how I'm feeling right now. You said you could barely walk down the drive to pick up the newspaper, and that frustrations with a slowness in getting the AIHA under control left you with your first real feelings of despair since getting a CLL diagnosis.
I have gone from cycling 90 miles a week on a turbo trainer, lifting weights, doing yoga and walking daily, in addition to heavy diy projects and generally running a big house/family to being confined pretty much to a sofa with a TV remote/books/crafts and other sundry sedentary pursuits in less than 8 weeks. The pounding heart/palpitations/yellow-grey pallor/night sweat features are not adding to a sense of optimism. I'm only 4 days in to my steroid binge, and am feeling a marginal reduction in some of my symptoms, but it is marginal and I really don't know what to expect going forward.
It is in that lack of info that I think my main anxieties reside. How long will my CLL treatment be delayed? Why even delay it all if my heavily infiltrated bone marrow is likely the cause of the AIHA in the first place and knocking that back might resolve the autoimmune response? Will I have AIHA for ever now or is this a one-off? These are rhetorical questions here btw...I'm not expecting you to answer them. I have crafted then into an email and sent it to my consultant though. I am expecting him to answer them ... 🙂
I too have encountered conflicting views on venetoclax/ibrutinib trigger/resolution potential in AIHA contexts as you point out, but the general consensus seems to be that BCL2 and BTK plus Ritux are effective in knocking out AIHA along with the neoplasm:
management of AIHA if CLL-associated must consider the stage of the hematological malignancy: in patients with stage A CLL it is the same as AIHA, whereas in patients with active CLL, it is the treatment of the neoplastic disease (Autore et al, 2021)
New targeted drugs (BTK inhibitors and anti BCL2) are usually used in the second-line treatment of CLL...Even if there are no specific studies on their role in the setting of CLL with AIHA, it is real practice to use them after or together with steroids to manage AIHA because they exert a beneficial impact on CLL-related pre-existing AIHA with an effective control of the autoimmune phenomena. (ibid)
(from Autore et al. 'Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia: A Comprehensive Review (2021)' ncbi.nlm.nih.gov/pmc/articl... )
So. I'm not sure what happens next. I was due to start venetoclax last Wednesday...did start it in fact...before they decided I was haemolyzing and sent me off with steroids instead.
Was your CLL progressive to the point of already requiring treatment when you developed AIHA? Was your planned treatment delayed in order to fix AIHA? This is the bit I'm sgruggling to get my head around.
Anyway, I hope my Consultant gets back to me on Monday. I feel thoroughly unclear on where I'm going with this, and pretty bored with being a chronic low energy person. I often would read about people saying they literally couldn't do anything physical with various conditions, and I'd think "a..I bet you could if you really tried". Well, I take all that back that's for sure. The rapid demise in energy/function has been a real shock/lesson to me.
Meanwhile, I've now got Springsteen's 'I'm on Fire' in a loop in my head. Could be worse I guess... 😆
I'll update if I get any useful info in due course.
I am very interested in knowing what your consultant provides in response to your AIHA questions. Your CLL experience has been different than mine, of course. My profile provides a brief summary of my 8 years with CLL. Although my CLL has not been treated, I did develop AIHA out of the blue. Steroids did not help so my specialist put me on obinutuzumab for 6 cycles. I am 15 months post obinutuzumab and am still B cell deleted with normal hemoglobin.I totally can relate to your AIHA thoughts and wish you the best going forward.
Hi Tesoro5858. Thank you for your response. It is really interesting to talk to anyone who has been through the AIHA experience just to get a frame of reference for a condition I was blithely ignorant of this time last week (although it was busy doing its thing anyway). I'm hoping to get more answers this week, and I will definitely update here as AIHA has obviously touched a small sub-set of members here, and will undoubtedly do so in the future. Watch this space...
I saw your reply to @thb4747 and again noted your comment re being 60% bone marrow infiltrated with CLL. I assume that you had a recent bone marrow test to determine that. I am not a medical professional, but 60% does not sound like it would cause marrow to not produce healthy blood cells. Also, your elevated reticulocytes indicate that your marrow is functioning to ramp up production of red blood cells (RBC) to try and compensate for the hemolysis. This phenomenon was noted in the reference that you posted (thanks for that as there is scant AIHA information that has CLL specifics). The authors noted the difficulties in diagnosing AIHA in some CLL patients , one reason being the marrow's inability to produce RBCs (ie reticulocytes). The fact that my retics were elevated at greater than 6% (high normal is 1.5% at my cancer center), I figured that I did not need to treat my CLL then which my specialist confirmed. He outlined, in order, the lines of AIHA treatment (mine was 2nd line due to being refractory to steroids) and treating the CLL was far down the list in my case. Since the obinutuzumab treatment put my CLL in partial remission (MRD is still detected), I understand why. 😊
Hi Tesoro. Thanks for this. I had been interpreting the 60% BM infiltration (from pre venetoclax treatment work ups a couple of weeks back) as a potential root cause of the AIHA.
I guess it may well be in some way, but you're right to point out though that it would be reticulocytopaenia rather reticulocytosis that would indicate a more acute bone marrow failure. I'm still kicking out immature rbcs in response to the ongoing haemolysis, so there's still some useful BM action. That is a useful shift in my interpretation thanks to your input (don't think I'm getting enough O2 to my brain🤪)
The auto immune pathways themselves are so complex, I'm really struggling to get my head round them. I'll keep on trying though. Consultant wants to see me on Wednesday to discuss. I'm assuming he'll go 4 weeks steroids then revert to the planned venetoclax. I'll update after Wednesday.
Your statement that "I had been interpreting the 60% BM infiltration (from pre venetoclax treatment work ups a couple of weeks back) as a potential root cause of the AIHA." along with the helpful paper you later reference, which states in the discussion section, "Management of AIHA in CLL requires the evaluation and exclusion of the other possible causes of anemia, including bone marrow infiltration/failure, bleeding, vitamin or iron deficiencies, and renal disease." prompts me to give you the following information on bone marrow infiltration and CLL. I've read that typical BM infiltration levels at diagnosis with CLL are around 25%. Sorry, I can't provide a reference. However, at the other end, you'll find quite a few members of this forum reporting BM infiltrations of over 90% prior to commencing treatment and with not autoimmune complications.
The good news is that members of this community have shared that their autoimmune complications have been successfully resolved. Quarry reported his AIHA experiences which finally required a successful splenectomy to resolve it. He is still in watch and wait for his CLL 8 years on - which again puts your BM infiltration theory into doubt.
Hi AussieNeil. Thanks for this - really useful as I've been looking for figures on bone marrow filtration across the CLL spectrum, but have only found a very old paper so far (back from an Orwellian 1984).
Thanks for the ref to Quarry's story. I'll take a look at their posts. In relation to that distinction between progressive and w & w CLL, another paper I found usefully subdivided Patients with CLL/AIHA into having either:
“simple”, “complex”, or treatment related autoimmune cytopenia. Those patients with autoimmune cytopenia complicating non progressive CLL that does not require treatment, can be considered to have “simple” autoimmune cytopenia and can usually be managed with therapies similar to those used to treat with primary autoimmune cytopenias. In contrast, patients with autoimmune cytopenia complicating progressive CLL meeting standard criteria for treatment of their CLL have more “complex” treatment requirements . Treatment decisions for these patients with “complex” autoimmune cytopenia can be especially difficult when cytopenias are caused by both autoimmune mechanisms and BM failure. (Zent and Kay, 2010)
I think you and tesoro are right in that my 60% infiltration (as of 4 weeks ago) now is clearly not high enough to have knocked out reticulocyte production though, so I'm probs more firmly in the autoimmune mechanism camp. Happy to ditch my BM theory as it seems preferable to manage/treat the autoimmune mechanisms - although my BM has an imminent Venetoclax deep clean booked anyway.
I will say this has been a pretty unpleasant interlude physically, but I'm learning a lot and it's great to speak to so many community members about their own autoimmune experiences. The good news is that (where caught and managed in time) it doesn't seem to have an adverse affect on prognosis and, as you say, the stories here are all of eventual resolution.
Don't throw away the BM infiltration theory; you can get cytopenia for just one blood cell with way lower than 90%. Strangely, production drops not across the board, but for different blood cell types per patient, continuing with the heterogeneous nature of CLL. My CLL/SLL was diagnosed after I developed severe neutropenia (stage 4 - under 0.5) and my BM infiltration was subsequently found to be 54%. But that's different from an auto-immune condition, where you have B cells that destroy the blood cells after they've been produced. It's possible to do tests to detect any antibodies that are doing the attacking. For AIHA it's the Coombs/DAT (Direct Antiglobulin Test).
Thanks for the 2nd reference article! I noted that my CLL specialist co-authored three of the cited references and the specialist that I saw prior (now retired) was also co-author of another few references cited. This article stated that obinutuzumab could be used to treat AIHA, the first I had seen it in print. My specialist said rituximab was the text book next treatment line but he thought that obinutuzumab, as a 2nd generation of the monoclonal antibody rituximab, was more effective, so that is what he ordered.
Amazing...It's so exciting to see the clinical research networks feeding into practice in real-life isn't it? In ways that actively involve the delivery of our own care. Just how it should be... 🙂
Jibs, I was in discussions to start treatment when my AIHA happened. Indeed I shall always wonder if I might have been spared a bout with AIHA had I started cll treatment earlier. I think my AIHA was probably triggered by rising lymphocytes which went from 100k to 200 k over a few months.
My hemoglobin now sits around the 14 range which is fine for me. I don't do anything high aerobic these days, and was not before my AIHA, so I have found my energy level is okay so long as my hemoglobin stays over 10. I walk about 4 miles a day now, lift light weights, play golf, do a little yoga and wander the casino floor if I'm feeling lucky.
Now and then I worry my AIHA will return and that my cll has shortened my earth time somehow. Most days I just try to enjoy life and not think about it. What would be a really bad outcome for me would be to live until I'm 90 and have spent 20 years of that time worrying about how long I'll live. Lol.
It sounds like you have a good perspective on things. My lay prediction is that your AIHA will resolve and whether you need cll treatment or not right now, you will get off your sofa soon and return to doing whatever it was you were before your AIHA episode.
I’m not sure if my story will help you or not but I’ve had AIHA 3 times — 2006, 2013 and 2017 — and each time my HGB dipped lower than the time before. On the last occasion I was in hospital in Alaska and my HGB dropped to 34 before they got me responding. I argued on arrival at the hospital that they should just get straight on to giving me O negative blood as they would find me almost impossible to match (I am O negative myself). Being very litigation conscious, of course, they wouldn’t do that and it took about 3 days to sort out with blood that didn’t quite match (as I told them). Blood also had to be flown up from Seattle which was an additional complication
I was initially diagnosed with CLL in 2001 and the first AIHA episode occurred while I was in W&W. I responded successfully to Prednisone (Rituximab wasn’t a thing in 2006). I had FCR to treat CLL starting at the end of 2008 but only managed to complete 5 cycles.
The second AIHA episode was treated initially with Prednisone followed up with 3 cycles of FCR (my CLL numbers were up also) and then 3 cycles of Rituximab alone.
Episode 3 was similar — Prednisone plus blood transfusions in Alaska, followed by 4 cycles of Rituximab when I got back to NZ (I wasn’t allowed to fly until my HGB got back over 80). My Wellington-based haematologist and the Anchorage doctors were communicating with each other throughout
Over all 3 AIHA episodes I had a total of 18 blood transfusions.
I’ve been taking Venetoclax since April 2018 (half dose since November 2018) and (touch wood) all is going well. I’m aware of what to look out for if I feel AIHA is recurring and it was on my initiative that I approached the medics for episodes 2 & 3 as I was sure it was happening again.
The nurses in Alaska kept telling me they were surprised I’d pulled through so I’m particularly conscious of looking at my numbers very carefully and knowing the signs of when my HGB is on the wane — grey pallor, difficulty climbing stairs, loss of appetite, drum beat in my ears. The fact that my HGB went lower each time makes me very wary of having a 4th episode!
Hello thb. Thanks so much for sharing this. It is so helpful .
I'm particularly reassured to hear that, for you, Venetoclax doesn't seem to have triggered a further episode thus far. Your experience of having to wait 3 days for blood with an HGB of 34 sounds pretty terrifying too, although I assume you were being heavily monitored for cardiac function in hospital in Anchorage?
One of the things that I've found surprising is just being sent home for a week with an HGB of 6 with no monitoring apart from being told to 'give us a ring if you're worried'. I've been dizzy, had palpitations and felt generally more physically dysfunctional than I could imagine. It's not clear what I should be especially worried about in these contexts, given that having such a low HGB is clearly a cause to be worried in itself ...
Your second experience seems most aligned with my current situation as you were obviously in a progressive cll status when your AIHA kicked in. Can I ask how long you were treated with Prednisone prior to starting the FCR for the CLL?
My reticulocytes are high, my bone marrow 60% infiltrated and my spleen is getting bigger by the day. It seems likely to me that my AIHA is triggered by bone marrow failure, so treating the CLL would be the way to manage the AIHA. I simply can't find any protocols anywhere that lay out whether you can do that at the same time as suppressing the immune response with prednisone, or whether you need to get on top of the immune issues first. Hopefully my consultant will enlighten me sooner rather than later ...
Hi, my records aren’t that great I’m sorry. Suffice it to say that on each of the 3 occasions, frontline treatment was Prednisone and blood transfusions once HGB was below 80. The gap between starting Prednisone narrowed, so in 2017 it was 2 months, although this was because I had to get home first. My reticulocytes peaked at 437 in July 2017 but my bilirubin didn’t go quite as high as previously. My highest bilirubin reading was 341 in January 2013.
Hi to everyone who took part in/read this thread. Just a quick update as promised.
I returned to see my consultant after the first week on 50mg Prednisolone, having a diagnosis of wAIHA (IgG 4+; C3d 4+) to complicate my relapsing CLL. The time I spent researching and chatting with you on here in that week was well spent as I really did feel I was in an information void re where we were going (in addition to feeling really very unwell with my ridiculously low oxygen blood). I shared some of those research papers I found with my consultant by e-mail, and he spent time consulting with colleagues around the medical CLL networks too. The exclusion of autoimmune patients from novel treatment trials means literature is relatively scarce on how to manage progressive/relapsing patients developing AIHA, so there literally is an information void.
Anyway, drawing on the research papers and his discussions, he decided to start the Venetoclax up again, running it alongside the prednisolone which he will taper by 10mg per week as long as Hb remains stable/improved. Over the past two weeks, my Hb has climbed back up to 81 (from 62). I am feeling much more energetic this week (although that might me Pred energy ... a whole other story 😱) and my colour is gradually returning from the yellow spoke of the colour wheel to something a little more beige. I'm on week three of venetoclax ramp up tomorrow and, all being well, he'll pull the pred down to 30mg (which I'm happy about because it turns out I'm like a crazed cat on a hot tin roof on high dose pred).
His theory was that it was triggered by the CLL progression/bone marrow infiltration cascading into an autoimmune B cell response and, had we started treatment a few weeks earlier, I probably could have avoided the whole AIHA adventure. However, there was nothing to indicate it would happen. I'm female, IGHV mutated and don't have any of the genetic markers that seem to trigger a heightened susceptibility to AIHA. My white cell count was not particularly high at 21, and my Hb dropping to 10.1 in October was seen as part of the overall CLL progression indicating it was time to run the CT scan and BMB ahead of starting 2nd line treatment. No major red flags for an autoimmune crisis as far as I can see. I just bucked the trend (again).
Ah well ... only dead fish swim with the stream I guess...🦈
Thanks again for all the input on this one. The support and information was truly invaluable as ever.
Brilliant. I did miss this post so thanks for your response. This is one of the papers I sent to my consultant actually. Really good to have this info posted for all current and Autoimmune patients to be... 😊
I'm glad you found it elsewhere in time for it to be useful to you. It was published earlier this year but has only just come to my notice. It's an excellent reference for people dealing with one of these conditions on top of their CLL.
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