Many us have what is called Secondary Antibody Deficiency. It can be diagnosed via low Total IgG (ImmunoGlobulin G), and often low IgA and IgM, too, as well as repeated infections. Some of us also develop Immune Thrombocytopenia (ITP), which reduces platelet counts even before the bone marrow gets full.
Researchers at several universities in Ontario, Canada reviewed the effectiveness of IgG Replacement Therapy (IgRT) in preventing or reducing the severity of infections. Many of the patients on the therapy had CLL.
Clinical outcomes of immunoglobulin treatment for patients with secondary antibody deficiency: Data from the Ontario immunoglobulin treatment case registry
PLoS One. 2023; 18(11): e0294408. Published online 2023 Nov 16.
"Results
There were 140 patients (58 males; 82 females; median age 68) with SAD during the study period; 131 were on subcutaneous Ig (SCIG) and 9 were on intravenous Ig (IVIG). The most common indication was chronic lymphocytic leukemia (CLL) (N = 52). IgRT reduced the average annual number of infections by 82.6%, emergency room (ER) visits by 84.6%, and hospitalizations by 83.3%. Overall, 84.6% of patients reported their health as better compared to before IgRT. Among those patients who switched from IVIG to SCIG (N = 35), 33.3% reported their health as the same, and 62.9% reported their health as better.
Conclusions
This study demonstrates that IgRT significantly improved clinical outcomes and patient-reported general health state in patients with SAD. This study also further supports the use of SCIG in patients with SAD."
This study is somewhat subject to selection bias, in that the province has policies that determine who qualifies for therapy. Their web guide doesn't even mention CLL:
I don't know that it's any easier to qualify for this therapy in Ontario. Perhaps someone in Ontario can provide a link to the criteria for SCIG or IVIG there. CLL patients all over the world experience similar rationing of this therapy due to its very high cost. The question that often comes up is whether the Total IgG level alone suffices to qualify. In most cases I've seen, no. The study did document the the Total IgG level:
"The median level of IgG in all patients with SAD was 3.70 [2.35, 4.85]g/L before IgRT and 8.00 [6.45, 9.60] g/L after IgRT initiation (Table 2). "
But this study emphasizes the benefits of the therapy, and should be shared with hemo/oncos all over the world, in my opinion.
=seymour=
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SeymourB
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Among other things, the Response to Reviewers.docx said:
"3. Vaccination responses to specific vaccines (the pneumococcal polysaccharide vaccine, anti-Hib,..) should be checked to give an indication regarding immune function, even if the patient, especially with hematologic malignancy, has not suffered from infections, as they may be at risk of severe sepsis. Did the authors check the vaccine responses before the initiation of IgG therapy?
Response: We followed the guidelines by starting secondary antibody deficient patients on IgRT when IgG are low, especially <4g/L or when there is a history of recurrent sinopulmonary infections (European Medicines Agency. Guideline on core SmPC for human normal immunoglobulin. Committee for Medicinal Products for Human Use). The results of the pneumococcal and hemophilus serology tests are not widely available in Ontario, unfortunately. The current turnaround time for the pneumococcal serology test result is more than one year in our region. This is not useful in clinical setting.
4. What were the indications for IgRT in patients with normal IgG levels?
Response: Normal IgG levels at our sites are between 7.0 and 16.0 g/L. Only two patients had normal IgG levels prior to initiation of therapy. The indication for treatment of the first patient was low IgG2 and low IgG3 levels. The patient was on chronic immunosuppressive therapy for severe scleroderma affecting both lungs and having undergone double lung transplant within a few years after starting IgRT. The other patient had an abnormal protein electrophoresis showing abnormal band in IgG kappa, with total gamma globulins of 5.0 despite total IgG showing a level of 8.6 g/L before IgRT. "
I would note that in the U.S., the pneumococcal polysaccharide vaccine titer test refered to above is easily available through Quest Diagnostics or LabCorp. I've had it done several times by my allergist/immunologist, and did not respond well. That test, plus 2 long lasting sinus infections that antibiotics failed to easily clear were what got my insurance company to get me onto SCIG back in 2018. I went off of SCIG in April, 2020, because I heard about low plasma collection due to the pandemic, and felt others needed it more than I.
I'm in a trial that's gathering Total Ig tests regularly, and I think my diligent hand washing and household sanitary habits acquired during the pandemic, plus my own and my wife's masking when indoors outside the home have kept infections down considerably. We haven't eaten at an indoor restaurant in 3 almost years now. I've only needed an extended series of antibiotics after a secondary bacterial infection after a 3 week COVID infection in May, 2022.
Thank you for this. As an Ontario resident, I may need this in the future. Currently in Watch and Wait with SLL. No life threatening infections requiring hospitalization yet. But it’s nice to have academic evidence to plead my case (should the need arise) in the future. I think the current requirements for IgRT in Ontario are pretty tight.
Wow, thanks for this! "IgRT reduced the average annual number of infections by 82.6%, emergency room (ER) visits by 84.6%, and hospitalizations by 83.3%. Overall, 84.6% of patients reported their health as better compared to before IgRT. Among those patients who switched from IVIG to SCIG (N = 35), 33.3% reported their health as the same, and 62.9% reported their health as better." (My emphasis) I've also included Figure 1 from the paper you referenced, visually showing the very significant reductions in the annual number of infections, ER visits and hospital admissions for those on IgG replacement therapy.
Being able to reduce your risk of hospitalisation to this degree, goes a long way towards justifying the high cost for replacement IgG. With compromised immune systems, we are at greater risk of hospital acquired (nosocomial) infections.
As I've said before, if anyone, on learning that you have cancer, asks what they can do to help, ask them if they can donate blood or plasma.
Neil
Major reductions in infections, ER visits and hospitalisations on IgG Replacement Therapy
AussieNeil, I'm sure it has been said here on various occasions, but how low does your IgG have to get before a doctor would consider IgG replacement therapy? I don't think I am there, but in October when my specialist tested, my IgG was 529, my IgA was 58, and my IgM was 9. Of course, being on A & V, I expect them to be low.
If you don't have serious infections, there is no need for IgG replacement therapy. If you are subject to serious infections, then how low your IgG count needs to be to qualify for IgG depends on your country of residence. It's usually 400 or 500.Neil
I can add to this post because I started IVIG on October 1, with the order to repeat once a month ongoing. I'm W&W since March 2018; although, in my six month visit on September 11 and 12 in Boston I was told: :It's not too soon to start treatment". On that same visit my Specialist said I should also start IVIG, even before I start the Zanubrutinib, because I've been sick too frequently and the sicknesses have taken longer each time to recover. Due to the bad way that Medicare Part D covers Tier 5 medications like Zanubrutinib, I decided to wait until January 2024 to start the pill. I've had one more IVIG at the beginning of November, and my next one is the first week in December.
In 2023 I had an URI in January that lasted six weeks, then in May another URI that went ten weeks, and in early October when I had the first IVIG I had again been sick for over three weeks. Each of the URI went from sore throat to cold to cough to infected stuff coming up a lot. I'm very lucky no Pneumonia. When I had the IVIG that first time, overnight my productive cough went away totally. My Wife was amazed that Morning and said its a miracle. I asked what was, and she said: "you didn't cough once, and your breathing was better" Amazing, just fantastically amazing. I've had no sickness since that first IVIG, and I'm now over one month into my Medicare Season (My work). Every Medicare Season for the last five years I've gotten sick three to four weeks into it, and then couldn't beat it until close to January. Now not even a sniffle, and I'm working incredible hours seven days a week.
I've had no side effects at all with the IVIG. I was anxious at first because I read on Google of all the potential and somewhat usual side effects, like headaches, but I've had none of them.
The other thing that is amazing is that my energy and stamina has increased since IVIG dramatically. I used to need a nap around 4pm every day, and sometimes twice a day. Now since IVIG my energy is well up and I don't need to lie down a number of times a day. I guess its logical because the other people's Immunoglobins are fighting for me daily; whereas, before the infusions only my weak immune system was fighting a fight it couldn't win. So now my energy reserves are available for the rest of life, aside from being used to fight infection attacks. Unreal.
I had the same experience as you; was getting severe sinus infections 6-8 times a year prior to starting IVIG. I now have at most, 1 a year. And yes, my fatigue improved dramatically after starting IVIG. I can tell when the antibodies are waning, as I get tired more easily and when I do get sick, with some thing, this is when it happens. It has been a real Godsend for me.
Seymour, thanks for that positive info. I am blessed to live in Ontario (for a whole host of reasons) and to have qualified for IVIG, converted a few months later to SCIG.
Soon after I was diagnosed with cll, my cll specialist continually expressed concern about my susceptibility to nasty infections, not because of my low IGG ( in the high 4’s) but because of my non existent neutrophils (0.2-0.4). He worried about this for 5+ years through my watch and wait period. He always thought I was a prime candidate for IVIG but in Ontario, you must be able to prove that you need the IVIG by almost dying (my words, not his).
Four years ago, his fears came true. I caught an innocent infection which turned into full blown septicaemia. I was treated at a regional hospital in a small Ontario city. I was lucky to have had a tough and very motivated internist on call. Not knowing whether it was a bacterial or viral infection and not having the time to figure it out (I was a matter of hours from leaving this earth), she threw everything at it and saved my life. In the process, I started receiving IVIG during my one week hospital stay. I had therefore met the IVIG threshold.
My monthly IVIG continued for several months before my cll specialist persuaded me to switch to SCIG - because the IGG levels stay more constant (around 8.0 for the last 3 years) and it’s easier to administer weekly at home.
In the 4 years since, I’ve had one minor bacterial infection early this year, after my dermatologist extracted a suspicious spot from my arm. Not wanting a repeat of the life threatening event, I visited an urgent care centre (for minor issues) at a small town hospital. I got antibiotics which cleared the infection within days. Unfortunately, even with all precautions, I picked up COVID somehow there.
Luckily, I had had 5 COVID shots, and my COVID infection was relatively mild and over in several days. Interestingly, my wife, who has never been sick a day in her life, suffered with COVID for a month. Anecdotally only, my cll specialist believes that my mild COVID had a lot to do with acquired immunity from the SCIG immunoglobulin ( produced from thousands of blood donors who had COVID vaccines and/or COVID infections)
So, other than that combined minor skin and COVID infection, I have had not so much as a cold in the last 4 years.
Thanks for posting! There is some data regarding prior infections in the paper that I shared, but the previous IgG level isn't tied directly to CLL diagnosis to try to see if Ontario is being more generous now.
Very happy to see this posting as I am scheduled to start IVIG on 8 Dec and have been trying to weigh the 'cost/benefits' (or pros/cons).
I'm 64 yo white male who has been on W&W since being diagnosed in Feb. 2020 and my hematologist/oncologist made this recommendation after my recent (9 Nov) appointment due to my IgG level being so low (317 mg/dL). He didn't say why he didn't make the same recommendation at previous visits (I subsequently checked my previous lab results and saw my levels have ranged from 328 (July 2 2021) to 253 (July 17 2023) ....the response from his office being, 'He wants to see your number above 500'.....ok, but 'why now'?
I've searched this site and saw some were given Benadryl and Tylenol prior to the IVIG (sub cutaneous is not an option here) to mitigate headache, allergic reactions and was told I could take myself 30-60 min. before the procedure, which I plan on doing.
Now my biggest question (besides how will it affect me...i.e. headaches, tiredness) is 'once I start on this, will I need to continue forever? At least now (with the studies you sited) I have strong entries in the 'pros' column....thanks again for posting!
No side effects for me other than a mild headache and boredom. Headaches disappeared after a couple of IVIG’s. I converted to weekly at home SCIG after a few months. Same immunoglobulin administered at home with a quarter of the dosage weekly. Weekly SCIG immunoglobulin infusion eliminates the IGG peaks and valleys of monthly IVIG. Easy and painless to self administer in about 60 minutes per week. the drug company provides all of the disposables required and I pick up the immunoglobulin every 3 months at the local hospital. More importantly, the infusion is made in your belly right under your skin rather than into a vein - reduces pain, risk of infection and side-effects.
For people, like myself, whose IGG does not improve with targeted cll therapy (I’ve been on Acalabrutinib for almost 3 years), the infusion needs to continue forever. You can take 1-2 week breaks when you’re travelling but for the most part, it’s endless weekly infusions - but the time and place is your choice. I usually read a book, watch tv, get on the phone or nap for the hour a week I need.
Thanks Vizilo....I've heard mine will start 'weekly' and may change to 'monthly' (or 'as needed') once my IgG level reaches the desired level (>500). Do you happen to know what your level was when you started and where it is now? I've heard infusions don't improve our ability to produce IgG on our own, except perhaps in rare instances....so, I can see how this would lead to continue indefinitely. I'll post my experiences as they occur. Thanks again!
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