Greetings from your UN-mutated colleague! The blood work from last week's visit to oncology revealed (besides the other troubling CLL indicators) that my Ig levels (which were already low), have dropped since first being diagnosed in February 2020. I've dealt with early-winter, chronic bronchitis on an almost annual basis in recent years and the oncologist/hematologist has just decreased the time between visits to every three months.
Feb 4 2020 Jul 13 2021
IgA 27.0 17.0
IgG 451.0 383.0
IgM 25.0 15.0
Q1: Should I be concerned about these results, which appear to be significantly below acceptable thresholds?
Q2: On-line sources suggest I'm a prime candidate for IGIV therapy, but I can't find anything that clarifies what will trigger the therapy. Since I won't see the Doc until mid-October, I'd be grateful if someone could shed some light on what criteria is used to determine whether or not IVIG will be administered.
Q3: One site stated that oncology will test for low IgA before prescribing IVIG. Does this mean they won't administer IGIV when the IgA is low/deficient?
Thanks very much!
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Jungle-Jim
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I believe the trigger to start IVIG is below 300 IgG AND recurring infections. I think these are guidelines. If you have recurring infections your oncologist may be able to start IVIG. Others will chime in with the specifics.
I’d be surprised if eligibility was as low as 3 for IgG in the US Mark given that hypogammaglobulinemia is classed as IgG levels less than 600 mg/dL.I’ve heard of patients from the US being given IVIG once their level drops below this but of course there may be funding/insurance arrangements I’m not familiar with.
I know of patients who continue to function very well on exceptionally low immunoglobulin levels and much depends on recurring and resistant infections not impacted by antibiotic therapy. I’d required hospitalisation and had sepsis leading up to my IVIG.
I have a question about IgD. I can’t remember reading anything on Health Unlocked. My Ig’s are tested every 4 weeks when I receive my IVIG and because it is a separate test and has to be sent out they were testing once a year but since I had zero for so many times the have stopped even testing. My IgG runs in the 800 but the IgA is 5 and IgM is <10. This is with IVIG. Before IVIG the IgG was below 200, IgA was 3 and IgM was <6 and the IgD was a trace.
They told me the IVIG only addresses the IgG…that has held true for me. I have had IVIG going on 5 years. They are not at all concerned about the IgD being zero.
Immunoglobulin D (IgD) deficiency is a defect of humoral immunity that is characterized by abnormally low serum levels of IgD immunoglobulins. Little is known about the normal function of IgD, and few clinical signs or symptoms are associated with its absence. Individuals with low or absent levels of IgD do not appear unusually predisposed to infections."
...
"Epidemiology
Frequency
One report indicates that approximately 11% of 371 American Red Cross blood donors and 6% of 1529 study subjects had low or undetectable IgD levels (< 0.002 mg/mL). In the study group, a number of the individuals with low IgD had rheumatologic disease (eg, juvenile rheumatoid arthritis, lupus, psoriatic arthritis, vasculitis), but the frequency of low IgD within groups of patients with each disease did not differ from the normal controls using chi-square analysis. [10] In another study, using a cutoff of 2.15 IU/mL, assays of 245 healthy adults and 301 healthy children revealed that approximately 13% of each group had low levels of IgD. [9]
Mortality/Morbidity
Low or undetectable levels of IgD, in the absence of other concurrent disease or immune defects (eg, common variable immunodeficiency, complement deficiency), are not associated with morbidity or increased mortality. Specifically, patients with low or undetectable IgD levels do not demonstrate an increased incidence of infections of any type. [14]"
I am sorry if I misled you as my doctors are not the least bit concerned that I have zero IgD….so unconcerned that they no longer test for it. They really aren’t concerned about my IgA or IgM levels either as they are what they are concerned about to keep my IgG level in the normal range and monthly IVIG is doing just that.
Last week:
IgG 993 (716-1594)
IgA 5 (71-377)
IgM <10 (46-208)
So as you see I am doing great!
You and the articles were right a lot of doctors don’t bother to test or simple don't full understand that it even exists.
My low IgA and IgM do t bother me at all.
Thanks for all the info you provided on IgD it was very good stuff!
Seymour, all the very very best to you as you continue your journey!
‘Recurrent or severe bacterial infection despite continuous oral antibiotic therapy for 6 months
• IgG <4 g/L (excluding paraprotein)’
I was given IVIG for 15 months because of recurring respiratory infections and an IgG just over 4. They’ve now reduced eligibility and I’m no longer offered the monthly infusions. My IgA & IgM are severely depleted below yours but this is not factored in. My IgG is around the 4.5 mark now but hasn’t been checked for some time during the pandemic. I’m on prophylactic antibiotics as part of my treatment (Venetoclax on a trial). The critical factor is recurring, serious infections that don’t respond to antibiotics and especially requiring hospitalisation.
It’s such an expensive, scarce treatment that the NHS are only offering it in very serious circumstances and at the moment, most units don’t want regular day patients. You can request it to be self administered at home by sub cut if your local unit provide this after instruction.
I’d push for it if the bronchitis is becoming an issue.
You need to have had some serious recent infections (e.g. requiring hospital admission or at least antibiotics) and have low IgG to qualify for IgG infusions. The IgG threshold depends on where you live, which in the USA is generally under 500. It's under 400 in some other countries.
If you do qualify for IgG infusions, see if you can arrange for subQ infusions. You can avoid the risk of COVID or other infections by doing these in your own home weekly, compared to the usual monthly or more when infused via IV. The subcutaneous delivery results in a much more even blood serum level of IgG over time, both because of the slow diffusion from under the skin and because of the more frequent top-ups.
I have IVIG every 4 weeks and that was started 4 years ago when my IgG dropped to 250 and I was having one infection after another. The IVIG raises the IgG but does nothing much for the IgA, IgM and IgD. They no longer test me for the IgD as it is a separate test and must be sent out and tested 0 so many times they just quit taking it. IgG is now 800 to 1000
IgA is 5
IgM is <10
IgD is 0
The IVIG keeps me in a very good place. I don’t mind going to the Chemo lab for the IVIG every 4 weeks and Covid has not been an issue…..they are super cautious as we are in a hot spot.
All the very best to you as you deal with your numbers as you are dropping with rather low numbers. Infections will most likely determine your coarse of action.
I will be very honest….I resisted the IVIG for the longest time as my doctor wanted me on it when I hit 300 but I held at 300 for a very long time and had no infection issues but then they dropped again and things changed.
We are all in this together and you will be fine…..there is so very much out there now. I have had CLL for 32+ years and I am back on Watch, Wait and Worry. I have been off and on treatment for 17 years.
You hang in there and please keep us posted on how you are doing….we learn from each other.
Yes, you should be concerned, and your oncologist has demonstrated her concern by changing your visit schedule to quarterly. Your current IgA, IgG and IgM numbers are low by any standard and the rapid downward trend is bad.
“Q2: On-line sources suggest I'm a prime candidate for IGIV therapy, but I can't find anything that clarifies what will trigger the therapy?”
Of course, you are a good candidate for IGIV therapy; you have CLL, you have really low Ig numbers and a rapid downward trend in three measurable antibodies, you are in your seventies, you have a history of “early-winter, chronic bronchitis on an almost annual basis in recent years”, people with chronic bronchitis are at higher risk for serious problems from normal seasonal flu and pneumonia. You have already checked most of the boxes necessary to convince your health insurance provider to cover the costs of hospital administered IVIG. If you develop a history of actual antibiotic resistant infections (the last box to check) Medicare should certainly cover the cost hospital administered IVIGs, not SubQ home infusions. Private insurance may provide coverage with you being at higher risk because of CLL, your low Ig numbers, your age and chronic bronchitis, it is worth a try.
What it takes to trigger IVIG therapy is the appropriate prescription from a doctor.
If I were in your shoes, I would not wait for an October appointment with your Oncologist or another visit with your General Practitioner, I would ask for a prompt referral to an Immunologist who works with CLL patients. This type of Immunologist would be able to answer all of your questions regarding your antibodies and is probably better equipped to address any remaining requirements of your insurance provider.
“Q3 One site stated that oncology will test for low IgA before prescribing “IVIG. Does this mean they won't administer IGIV when the IgA is low/deficient?"
Don’t know. You already have low IgA (and everything else) IVIGs has little to do with IgA. I been down this road a couple of times and this issue has never come up.
Jungle-Jim—-I have been on IVIG Therapy about every 4 weeks for over two years. Mine was started when I kept having back to back infections such as sinusitis and bronchitis, almost constantly! My IGg was below 400 mostly, but treatment was only started when I was no longer able to overcome infections! According to my Dr, IGg is only value that matters, and is treated by IVIG. Being a Snowbird, the Rule-of Thumb in Florida is that it must be tested below 600 for treatment. I don’t know if that is a Medicare requirement or what, down there, but I must be tested before getting the Infusion? I hope that helps a little, but the Infusions have been a real life changer for me! God Bless! 🙏🙏🙏
Thank you Okeefish - your comments (and those from the other members) are very informative. The numbers are trending downward relentlessly, and I do have annual bouts of chronic bronchitis, but otherwise haven't (yet) had to deal with non-stop infections. When I see the oncologist in October, I'll have a lot to talk about - Jim
In Canada, the numbers seem less important than the risk of severe infections. My IGG was in the low 5’s for years and my cll specialist was concerned about the risk of infections while on w&w. But it wasn’t until I landed in the hospital with a life-threatening infection that I was immediately prescribed IVIG (and then it seems to be for an indefinite period of time). So, at least in Ontario, the patient needs to prove he/she needs the IVIG (by landing in the hospital)
As Aussie Neil pointed out, after several months of going to the hospital for monthly IVIG, I was offered the opportunity of switching to weekly self- administered SCIG at home. This seems to work very well - easy and painless, about 90 minutes/week, no infection for the last 18 months (but then COVID isolation no doubt helped) and my IGG is at a constant 8.
Thanks Vizilo - your comments are also helpful. I don't know yet what the mindset is here (South Carolina), but will find out in October. Again, I plummeted from a low 451 mg/dl to an even lower 383 mg/dl in just 14 months. The decline has been steady, with no positive spikes in between. I think its telling that the Doc cut my visits from every 6 months to every 3 months. In the meanwhile, I'll do more research on IGIV and SCIG. - Jim
I was about to write almost this same post! I’ve been on W&W for 11 years with no symptoms and have been relatively healthy. Last blood test my WBC had actually dropped from about 100k to 80k, but something make my oncologist decide to see me in 6 mos instead of 12 and to test my IGg numbers. The report coincided with a very bad bout of bronchitis, unusual for me in the summer, and showed my levels at 404. He said 400 is his level for treatment, or 500 with infection. I am scheduled for IVIG on Friday morning. Was wondering what to expect - from what I read I could feel rotten or I could feel great?? He wants a blood test two weeks after to see if the level goes up sufficiently and will decide what to do from there. In the meantime my primary did an antibody test for Covid which showed I have no antibodies and she wants to do a second vaccine. My oncologist agrees- but says wait several weeks after IVIG. Thoughts appreciated!!Kathy
Thank you KBC - I find it interesting seeing how different doctors in different locations manage Ig anomolies. While all of my CLL benchmarks are consistently trending in an adverse direction, I'm currently focused on the Ig numbers. From what the other members have said, you shouldn't have any problem with the infusions, and SCIG is an alternative you should discuss with your doctor. Wishing you the best... Jim
How you feel after an IVIG depends on what they put into the infusion to prevent reactions. Two big metro hospitals I used for IVIGs added Benadryl, lots of Benadryl. I was usually asleep during the infusion and needed someone else to drive me home. The next day I felt great, more energy. If you are on monthly IVIGs you can feel a bit of an energy let down at the start of the last week before the next infusion. The best part is no more infections.
Following a CAR-T infusion in March 2016, my wife's bone marrow does not produce immunoglobulins. Per NIH trial protocol, she gets an IVIG infusion (Gamunex-C) when her IgG drops below 400 (about every 3 months). A few months ago, her oncologist changes the IVIG infusion frequency to every other month. After 6 years of IVIG, she still has not had any IGIG side effects.
Thanks wmay. It's becoming increasingly clear that I'm not the "Lone Ranger" with regards to low/plunging IgG. Again, thanks to both of you for your input!
Bear in mind, replacement Ig is only IgG; there are only traces of IgA and IgM in the serum. It doesn't matter whether you have it IV or sub-cutaneously. I do it SubQ every week and now have an IgG level that is in the low end of the "normal" range.
The IGG is the one that determines getting the ivig. My Former Saint of a Dr retired just before Covid. He was amazing. Here in the US the insurance companies will not reimburse the hospital pharmacy for the cost of the liquid gold unless the IGG is under 400. Unless you have 2 active infections snd you are close to the 400 level. My new Dr has decided that once every 3 months is sufficient. I was on the LOXO 305 research drug which caused my liver count to go crazy. I have chronic bladder infections and still have to fight for the one thing that helps me… the IVIG treatment. And still changed my monthly appointments to every 3 months.
Your IGG is below 400 they should give you IVIG treatment. It should last at least a month. I, like you get respiratory infections frequently. They don’t really count the IGA or IGM. The Dr I currently have is the administrator of blood cancers. I emailed my former Dr who told me I Need to be seen every month. He said I-we should be getting the care we deserve. I hope you do
I have just had a letter from my suppliers who have a contract with the NHS to supply the IgG and all the accessories direct; syringes, syringe driver, infusion sets, vented spikes, sticking plasters, swabs etc. Instead of sending 12 weeks' supply of IgG per delivery, they will only send 4 weeks' supply at a time because there is a world shortage of the stuff. I have Hizentra from CSL Behring AG and they draw the plasma from dozens of countries (but not the UK because of Variant CJD) and I think they manufacture in a plant in Zurich. I don't believe it has anything to do with Brexit - just demand outstripping supply.
Wow - this is a little ominous, especially in view of the fact that the Delta variant is reaping havoc on the entire world. Something else to think about.
I was able to get SCIG through my immunologist based on failed pneumococcal pneumonia titers and several long sinus infections requiring antibiotics back in 2018, despite my IgG being in the 500's. Insurance paid for it. So it's all in the selection of diagnosis codes, and may differ at various insurance companies. I think the IgG at <400mg/dL plus a CLL diagnosis is generally accepted, though. I wonder if some insurance companies may not accept some diagnosis codes from a hematologist/oncologist that they accept from an immunologist.
I stopped SCIG early in the pandemic, because there was low plasma donations. I was no longer mixing with people (still!), and my wife and I were masking in public when we did go out (still!). I know that many of the people on SCIG/IVIG have inherited immuno-deficiency. I know a kid who has CVID (Common Variable Immunodeficiency).
The cutoff of 400mg/dL for IgG is the result of selecting that arbitrary level in multiple studies starting in the 1980s. I haven't seen anything that shows levels of infecton at 420 are noticeably less than at 380, for example.
When I got COVID back in May, I got a secondary staph infection. I now have some additional hearing loss which may resolve with time (unusual pressure on my eardrum persists). I see the audiologist to review the tympanometry nect Monday. My IgG is most recently at 413mg/dL.
IVIG/SCIG is insanely expensive - over US $13,000/month the last time I checked, and surely higher than that now. The plasma serum companies usually provide co-pay assistance. I'm not sure how various US Medicare plans cover it. If we lose our insurance, my plan has been to try to get it through the VA (Veterans Administration), where several products are on their formulary.
Thank you SeymourB - my latest IgG was 352 (then 375). The oncologist says she doesn't treat by numbers alone. She cites chronic illnesses and the failure to respond to antibiotics as some of the key triggers for prescribing IVIG/SCIG. This is consistent with almost everything I've read on this site. For now, I seem healthy enough, and I DO NOT want to rush to treatment (for CLL or low IgG). Even so, I feel as though the proverbial 'sword of Damocles' is dangling over my head. But then again, that's true for all of us who are in a W&W status. Jim
I think you have a good oncologist. I haven't seen any guideline that indicates treatment based on Ig numbers alone. SCIG/IVIG justification does seem to have a numerical aspect, but a few infections tips the balance.
We all know the sword!
I also see myself aging, and wonder how great an effect CLL treatment might have now vs. later. I'm seeing a gradual trend toward earlier treatment, because side effects are often not as bad now as they were with BR and FCR. I sure wish there was a genetic assay to determine likelihood of specific side effects.
I find that I'm driven by fears, and saying them out loud to someone else defuses them somewhat. Managing anxiety is a key part of my disease. I fear the sinus infection that becomes pneumonia, because I had that long before CLL. I also fear hospitalization and standards of care based on immuno-normal people. My recent COVID experience was not at all reassuring, except that I survived.
SeymorB, like so many others, I'm right there with you! My oldest son died of cancer (synovial sarcoma). Though he suffered with it big time, he taught me to celebrate every day of life and living. He rejoiced every day when he managed to climb out of bed, or even set up... because it was another day. I hope that if/when my CLL progresses to the latter stage(s), I will see it all through his eyes and focus on the day at hand. When I was in Egypt, I was astonished with the Great Pyramids and asked a local how the ancients managed to build them. His heartfelt response was, "one stone at a time."
BTW, many TX for your "Semper Paratus" comment... were you once part of the "brotherhood?"
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