About 4 months out from my mom's aplastic anemia diagnosis...

[mola-tecta]

I have spent a lot of time browsing the past threads on this forum and they have helped me understand a great deal more. I know they aren't very active but I see a few of you still floating around here, so I wanted to post.

I'll try to be short about it - my mom (69yo) had increasing weakness and bruising until ending up in the ER with Hgb of 4.6, platelets of 4, WBC 3.2, ANC 1, ALC 2; she spent a week in the hospital where they did a bone marrow biopsy and a million other tests to figure out the cause.

July 12th she was diagnosed with aplastic anemia, with bone marrow cellularity of 20%, reticulocytes between 0.02-0.03 (range 0.018 - 0.158 x10E+12/L), very tiny PNH clone (<1%) and started horse ATG on July 14th in combination with cyclosporine + Promacta. Had almost no issues with the ATG treatment but became refractory to platelets pretty quickly and thankfully HLA matched ones were found. She was released once they found the appropriate dosing for the cyclosporine to not be at toxic levels. Her doctor does not seem to specialize in AA but is at a premiere blood cancer center that I know sees a good number of AA patients.

Fast forward to today - my mom is still going twice a week for blood draws and is getting platelets about every 10-11 days (down from every 7 days) and blood transfusions about every 3-4 weeks. Her WBC have responded really well (ANC 2.4, ALC 2) but so far the lack of meaningful response for Hgb and platelets has concerned her doctor. I was under the impression that a response at this point would be considered fairly early but the doctor seems to be considering a very strict 6 month timeline to respond to the ATG or different measures will be taken.

Today's (Nov 22nd 2021) counts:

Hgb 9.4 (last received 1 unit blood 11/11), platelets 35 (last received 1 unit 11/18) ANC 2.4, ALC 2, Retics 0.54

She is currently taking 125mg x2 a day of Cyclosporine, 150mg Promacta, 20mg prednisone, along with acyclovir, levofloxacin, fluconazole, B12, Folic Acid, Vitamin D3/Calcium, Famotidine and metoprolol (for heart palpitations). She had been getting injections of Aranesp/darbepoetin alfa every other week but has asked to stop as they don't seem to be doing much but making her blood pressure spike incredibly high.

Right now my mom is having a lot of trouble with the side effects of her medications, specifically the cyclosporine and prednisone. I have not read anywhere that prednisone is valuable in the treatment of AA except for preventing serum sickness in the weeks during and after ATG but her doctor seems hell-bent on keeping her on it (and has tried to raise it) despite the side effects she is having, such as facial swelling, retaining water, muscle weakness, etc. She also is having trouble with tremors from the cyclosporine althought the first few months did not have this issue until her doctor tried to raise the prednisone.

I was hoping to know if anyone else was kept on prednisone for an extended time and how it impacting them, as well as if anyone has had any luck with treating cyclosporine-induced tremors beyond lowering the dosage. Both of these medications are making it very difficult for her to do things although she can mostly complete her ADLs with a great deal of effort.

Besides that, her doctor's adherence to a strict 6 month timeline for the response has me worried, as I've read it can take longer for some people to have meaningful response (especially if they are older) and have been told this disease is one of patience so it's making me feel like the clock is ticking away for something to happen and there is nothing I can do about it.

Thanks for reading if you are out there.

[Matthew42]

Dear OP,

My mother is exactly the same age as your mother. She was diagnosed with SAA in early March of this year.

She is 7 months past horse-ATG. Her neutrophils are averaging over 1.0 (which is good), but her hemoglobin and platelets are still quite low. She requires transfusions for blood every 2-3 weeks. She still needs platelet transfusions once a week (sometimes 2). In the past two months, she's had spikes in her hemoglobin a few times (once she went from 8.6 to 10.5 without a transfusion in a few days). Her platelets only ever rose one time without a transfusion (a few weeks ago).

The hematologist said that it looks like my mother is a slow-responder and says that we have to give it more time. Sometimes once you see spikes in a slow-responder, it can take almost a year or so for the stabilization to be reached in terms of hemoglobin. And platelets are usually last level to rise (not always). The hematologist said that neutrophils staying high is a good sign, too. If horse-atg were unsuccessful, neutrophils would not be staying up, nor would there be spontaneous rises in hemoglobin without a transfusion around the six-month mark.

Your mother shouldn't take all that medicine, maybe (just my opinion). She is doing better than my mother, actually. I think you just need to give it a lot more time, and her anemia will go away. If her neutrophils are 2.4 (excellent), something is surely working. I was under the impression that if a person's neutrophils reach 1.0 and stay up around there, that is evidence the horse-ATG is working. If you look at some people who did not have a successful horse-ATG treatment, their neutrophils never really went up at all, nor did they have any real rises in hemoglobin and platelets without a transfusion by six to nine months.

My mother also has iron overload. It's been a rough road since last February. Things have gotten a little better, but she is still very much transfusion-dependent.

The other week, my mother suddenly had a big drop in hemoglobin (went from 8 to 5 in less than a week). The hematologist didn't act concerned. It's just the nature of the disease. My mother's hemoglobin almost goes up close to 11 and then down to 7 or 6 real quickly two or three weeks or two later?...real strange. The important thing is that she does get big rises without a transfusion, but her blood doesn't hold above transfusion level for more than 2-3 weeks (used to be every week she needed a RBC transfusion).

PS: I don't know if you know this (probably not), but if your mother has a small PNH clone, it is very likely she will respond to horse-ATG treatment (or rabbit). It's the greatest predictor of a response to immuno-suppressant therapy. My mother has a small PNH clone, too.

Most of what I learned about this blood disease has been on this forum. Also, every aplastic anemia is different, no matter how much they all have in common.

Also, aplastic anemia is not cancer, or pre-cancer like MDS, so it's unique. It's more like PNH in that fact that it is autoimmune in nature (for most, especially if you have a PNH clone...that is what I was told).

I don't think your doctor is an expert in any way in aplastic anemia, even if he or she is experienced treating aplastic anemics.

Things will get better.

Wishing your mother great health and happiness,

Matthew

[Ruth Cuadra]

Dear mola-tecta,

I'm glad to hear that you have found the threads in this forum useful for understanding the complexities around aplastic anemia, PNH, and treatment with ATG. When I was diagnosed with aplastic anemia in 1996, Internet resources were scarce and it was hard to find information. Now we have numerous resources to help.

As Matthew42 said in his reply, it does sound like your mother is doing well. Her doctor's insistence on repeating ATG at the 6-month mark is curious to me as it is well known that it can take upwards of a year and sometimes longer to gauge a person's response. Hemoglobin and platelets typically take longer to respond but her ANC count indicates that she is responding. It doesn't sound like she is in any immediate danger so you might ask to review her case with an AA specialist at your center for more guidance.

Her medications seem reasonable to me. Cyclosporine, while the cause of annoying side effects, should be considered your friend. When she is ready to be begin tapering off (usually around 12 months post-ATG), the taper must be VERY slow to avoid relapse. Her prednisone dose is not very high and must also be tapered very slowly. I remember the swelling, water retention, weakness, and tremors from these drugs, but in hindsight those troubles were soon forgotten once I recovered. Stopping Aranesp at this point also seems reasonable. Promacta didn't exist when I was treated, so I have no experience there. As with needing to be patient after ATG, you should encourage your mother to be patient until the medications can be removed.

Please post your questions here and we will all try to answer.

Regards,
Ruth Cuadra

[Marlene]

My husband did not have ATG to treat his SAA so I can't speak to the cyclo and prednisone. When John's ANC hit .5, they started pulling him off all the anti-biotics and ant-fungals one at a time. They would stop one and then watch to see if he spiked a fever over the next two days. If not, then they pulled another and so on. If he spiked a fever, then they would put him back on the one they just pulled. With your mother's ANC at 2.4, it's puzzling that they still have her on those. The anti-fungals and antibiotics are either being used prophylactically or to treat an active infection. If she does not have an infection, then an ANC of 2.4 is more than adequate to warrant her being taken off of them. That class of anti-biotic (which includes Cipro)is probably one of that last ones that I would have thought to use prophylactically. Levofloxacin should be used only for infections that cannot be treated with a safer antibiotic. Many docs use this class of drugs as first line treatment for infections and we always push back for a safer option. Especially if you have any central nervous system issues. One of the rarer side effects is tendon ruptures.

They left him on the acyclovir for six months after treatment.

It's difficult to challenge the doctor but if he has little to no experience with treating SAA, then I would seek a second opinion. Your doctor can also consult with the NIH, Dr. Young.

[Matthew42]

I agree with Marlene: my mother was taken off antibiotics once (except acylovir) where where neutrophils averaged over 500. Now, my mother's neutrophils are always between 900-1500 (for the past 6 weeks). Acyclovir is not not essential, although the doctor told her she should take it.

We were told by mother's hematologist that neutrophils rising to over 1000 (1.0) and staying up is a true sign of recovery. Neutrophils will rise first and then hemoglobin and platelets for most. In slow-responders, it can take almost a year for the hemoglobin and platelets to really stay up and hold. You can still have big spikes without transfusions and then sudden big drops on your way to recovery. It is normal. My mother, for example, recently went from 8.6 to 10.5 without a transfusion in a few days. We were amazed. However, 3 weeks later she dropped to 5.4 and needed 3 units of blood. The doctor was not alarmed: this is just classic aplastic anemia.

Yes, platelets are usually the last thing to rise for fast and slow-responders (not always, though, as every aplastic anemic is different)

One more thing: look at your mother's CBC results to see if her neutrophil % is higher than her lymphocytes % at times. If it is, it's another sign that her autoimmune condition is calming down a little, all pointing to bone marrow recovery.

You will hear this over and over again on this forum: aplastic anemia is a disease of elimination that requires a lot of patience to make a full recovery from ATG + cyclosporine. I've read of an older woman with aplastic anemia who took over 2 years for her ATG treatment to kick in. She was transfused every week with blood and platelets for the entire time (2 years). She went on to make a full recovery and was doing well 5 years later (can't remember).

Please take care of yourself and your mother.

We are here to talk when you need us.

Health and happiness,
Matthew

[mola-tecta]

Thank you both for your replies. I was surprised to see responses so quickly


Matthew42,

Your thread about your mother is one I have been following in the past months. I am sorry that we are in the same boat together like this. It has definitely been a rough road and it's only just getting started I suppose. Hopefully your mother will continue to make improvements and see more stability in her numbers soon.

I believe my mother has only had a spike in Hgb without transfusion once (something like 8.6 to 9.5) but I have yet to see any spike in platelets, although she is needing them slightly less than she was. It sounds good that your mother is seeing more and more of them.

I have been combing through a lot of information and research on aplastic anemia and this is one of the only places online that I found which talks about what the recovery process is actually like, how blood results change and fluctuate and what kinds of things to look for. It's good to know that your mother's doctor thinks the ANC count staying up is a very good sign that there is response happening. My mother's hematologist did at least agree that the white cells have responded very well but it's still not what he wants to see, which is I assume transfusion independence.

As it has only been 4 months for my mother I agree that she needs more time to respond. Her hematologist makes me feel like the clock is ticking to respond better by 6 months. The time to meet with him seems very limited and I can understand why as the whole blood cancer center is incredibly busy (how sad to think of that). I agree he is not necessarily an expert on AA but so far has done everything correctly, including getting her into the hospital to prepare for ATG the same day he made the final diagnosis. The part I am questioning now is why the lack of patience with a disease that seems to require almost nothing BUT patience.

My mother has iron overload too and despite still having unstable blood counts, the hematologist wants to start Exjade immediately. My mother is really worried about this seeing as there are warnings about it dropping blood counts, among other side effects.

I appreciate your response and I wish the best for your mother as well, I hope to see more updates from you with good news.


Ruth Cuadra,

I cannot understate how valuable this forum has been to learn about aplastic anemia as well as hear much more detailed stories about what recovery and response mean. I already feel like the current internet does not have nearly enough information, I can't imagine how little there was in 1996!

It makes me feel a little better to hear that her ANC response seems to be a good thing and gives me a little hope. Both Hgb and platelets definitely need more time to respond.

I have been trying to find other clinicians in the area that state specific expertise in aplastic anemia but it's been a real challenge. There is a large medical school with a large heme/onc division including programs for rare blood disorders as well as benign hematology but none of them list aplastic anemia as an expertise except the children's hospital. Wondering if it would be worth trying to contact some of the programs anyway. I would love to have more guidance and a better understanding.


Cyclosporine is a beast of a drug but at least we know it's doing it's job. I just wish there was something that could help my mom's tremors? Of course she doesn't want to lower the dose because it has a job to do. I think my mother has been very patient with this disease but both her and I are feeling very stressed over the hematologist's disappointment with the response so far.

Again I am very thankful for both of your responses and it helps so much. Part of the reason I am so rabid for information is that my father had leukemia but I was much younger and never understood why they did the things they did to him, or why they didn't do other things, etc.

Sorry for writing a novel! Best of wishes to you both.

[mola-tecta]

I wasn't expecting more replies while writing my last post! Thank you very much!

Marlene, I am also questioning why she is still on the antimicrobials despite her ANC improving a great deal (almost to normal levels). I know she has been on them for prophylactic reasons (I forgot to mention the monthly infusions of pentamidine too, ugh) and I understand wanting an abundance of caution as it seems infection is one of the biggest causes of mortality among AA patients.

Interesting to note her hematologist did his fellowship at NIH. I have no idea how to even begin to ask about having him to consult someone else without sounding like I am trying to play doctor myself. My mother has been very steadfast in following everything the hematologist wants but I am very proud of her for standing up and saying she wants to quit the Aranesp and also try to come down on the prednisone more.

Matthew42,

Looking at the past several months of blood results, her neutrophil % has very often been higher than the lymphocyte %. Every time she has been able to negotiate a reduction in the prednisone, it gets a little worse for about a week before leveling out again. Her ANC has been consistently above 1.5 for at least two months now.

I fully agree that patience is absolutely key and I have definitely heard of stories from people who took 9, 12, 24 or more months to show meaningful response. Both me and my mother are pretty on board with this and I am certainly willing to be patient and support my mother as best I can for as long as it's needed. In an effort to feel less useless in all this I've even been donating platelets as often as I can although I haven't been able to in a little while due to dumb circumstances.


Thanks again, and take care all.

[Marlene]

Yeah those can be difficult conversations to have with a doctor. I usually start by asking the purpose and goal of a drug and if still makes sense. Or, just ask since the ANC is good, what's the purpose of the anti-biotic and anti-fungal. There should be a good reason to keep it on board. Especially since anti-biotic use can lead to intestinal infections like C-Diff.

There's no harm is discussing that you've been talking to other SAA patients in recovery for support and asking him to explain why your mom's post ATG treatment is different from others regarding the prednisone and other drugs. Quality of life is important and it's also important for you to feel you have a voice in the treatment. If he is offended, then maybe it's an indication to find another doctor for a second opinion.

We were lucky in that our local hematologist was open to hearing our concerns and did not dismiss us.

When John was hospitalized and counts were not improving I researched all the drugs he was on and found that one of the "special' antibiotics can cause AA. They blew me off during rounds but the nurse researched it and the next day they took him off it. We were already going on 80 days without a white count and getting very frustrated. They then said that pretty much all anti-biotics can suppress the bone marrow. A comforting thought.


Here's a paper by Neil Young on how he treats SAA.

https://ashpublications.org/blood/ar...plastic-anemia

Last two thoughts: 1) Not knowing her platelet transfusions threshold but if her platelets are holding 10K or 15K without any bleeding you may want to consider stopping platelet transfusion. John lowered his threshold to 8K. Some go as low as 5K.

2) I think you have time on the iron overload. Unless there was an issue of high iron before she got sick, you most likely have leeway on when to address this.

Hope this helps. It's not easy to navigate all of this stuff. You mom is lucky to have you help her.

[Matthew42]

Every one thinks that needing blood and platelets is why aplastic anemia is so dangerous. But from the research I've done, the biggest danger is getting infections from low neutrophils (my mother's hematologist pretty much told her this in so many words). That's why she was happy that her neutrophils shot up over 500 quite early, and then very happy when they averaged around 1000.

While people can get antibodies to blood, which causes real problems, it is usually the case that people can get hundreds and hundreds blood transfusions for years now because of the safety of blood without too many serious issues. Sure, you're going to get severe iron overload, but that is not the what makes AA most dangerous, either, unless you have already have a serious heart or liver problem. High iron has to fester in the body for quite some time to really wreak havoc (unless you already have a heart or liver condition). It takes years to really develop a heart condition from high iron, even if the iron overload is severe. Liver problems can happen earlier but still takes a while before iron deposits accumulate. That said, it is still a serious issue that has to be addressed. My mother has her liver enzymes checked every few weeks. The hematologist said that enzymes will get high if iron starts to build up in the liver.

Thirdly, you can live with super low platelets indefinitely, as long as you don't have internal blooding from whatever reason (fall, medicine, etc.). There is a man online whose platelets have been under 10 for years from autoimmune ITP disease. He's fine (just don't fall or get hit).

I also want to mention that having a cardiac issue with AA is dangerous because weak hearts need higher hemoglobin.

So, you see that people with VSAA (very severe) are at greatest risk for real danger because their neutrophils average under 200. That said, I am not making light of the seriousness of needing RBC and platelet transfusions.

By the way, my mother has had about 55 RBC transfusions and about 85 or so platelets transfusions. I am worried about platelet refractory, by my mother's hematologist insists on platelets once there under 20. I don't agree with this. My mother's platelets always seem to hold at 10. Another thing: she got edema from too much fluid from platelets. She was put on water pills that really hurt her kidney function. Her creatinine is 1.7 (it used to be 0.7). She has stopped all water pills, but the doctor says it takes time for the creatinine levels to go back to normal once you're on diuretics for a few months. They aren't concerned about her kidneys because it was medication-induced (I am, though!).

@Marlene: I agree with your last post very much. You can tell you and your husband lived this disease. Your advice and information is priceless.

[mola-tecta]

Marlene,

I appreciate your suggestions for ways to bring up these difficult discussions. The pushback he has given has made me and my mother apprehensive about asking questions to the hematologist. Prednisone seems to be very important to him, and though it is a somewhat small dose, my mother has been on it for four months straight and it seems to still be causing trouble, or at least making it worse.

Thank you for the link to Dr. Young's paper. It has been one of the most important I've referred to in the past months to see what the treatment guidelines are like.

This paper about supportive care has also been really useful:
https://www.nature.com/articles/bmt2...df?origin=ppub
And it even specifically says:

The risk of severe infections decreases rapidly with increasing neutrophil counts, and in patients with ANC > 0.5 10^9/L, antibacterial prophylaxis is not recommended.

Now to just figure out how to bring up something like this without sounding like I know better.

Her platelet transfusion threshold is 20. I honestly don't know what her platelet count would hold at if platelet transfusions were briefly stopped. The lowest I have seem them be at in the past 2 months is 9, 2 weeks after a transfusion. I can only hope that there are a few starting to hang in there as my mother was getting transfusions every 7 days average but I have noticed this increasing to 10-11 days average. Platelets don't really live very long and 10 days is about their lifespan. She has been lucky to have several HLA-matched donors available. (This is another reason I have been trying to give platelets when I can! I am so grateful to these people who continue to donate)

Matthew42,

No disagreement from me, everything I have read indicates that infection is the top mortality risk for AA patients. Looking back at past blood results her neutrophils recovered very quickly, within a few weeks after starting treatment they were over 0.5 and within another week or two were consistently 1+. I wish the hematologist was a little more excited about this Not sure if he has ever even talked about this beyond when I brought it up at the last appointment.

The information about iron overload is appreciated. So far my mother's liver counts have been perfect and her heart is doing very well as far as I know - she had a transthoracic echo and several EKGs done while in the hospital during ATG as her heart rate was hovering around 50, but nothing of note was found. In the past months it seems to have recovered fine and pulse is back to normal 60s/70s. Before all of this AA stuff happened my mother was only taking the small dose of metoprolol for palpitations/PVCs, and has been for years.

Unfortunately I don't know exactly how many RBC transfusions my mother has had but I can't imagine it has been much more than 20. However her ferritin is still >3000 so I suppose I can understand the concern. The concern my mom has about taking Exjade is that it says it is contraindicated for people with platelets <50 and can actually cause blood cell lines to drop, among other unpleasant side effects. It seems to me it would make more sense to wait until her counts are a little more stable.

I hope your mom remains non-refractory to platelets. My mom was very quickly refractory which made keeping up her platelet counts was very difficult for several weeks before they found matches. They had even dropped to 0 at one point

Thank you both for your valuable time and information, as well as just hearing me and reflecting my concerns. We are at different stages in the journey but just hearing more about the ins and outs of response and progression are beyond valuable to me.

I hope you both have a good Thanksgiving, assuming you are Americans of course

[Hopeful]

Originally Posted by mola-tecta

I have spent a lot of time browsing the past threads on this forum and they have helped me understand a great deal more. I know they aren't very active but I see a few of you still floating around here, so I wanted to post.

I'll try to be short about it - my mom (69yo) had increasing weakness and bruising until ending up in the ER with Hgb of 4.6, platelets of 4, WBC 3.2, ANC 1, ALC 2; she spent a week in the hospital where they did a bone marrow biopsy and a million other tests to figure out the cause.

July 12th she was diagnosed with aplastic anemia, with bone marrow cellularity of 20%, reticulocytes between 0.02-0.03 (range 0.018 - 0.158 x10E+12/L), very tiny PNH clone (<1%) and started horse ATG on July 14th in combination with cyclosporine + Promacta. Had almost no issues with the ATG treatment but became refractory to platelets pretty quickly and thankfully HLA matched ones were found. She was released once they found the appropriate dosing for the cyclosporine to not be at toxic levels. Her doctor does not seem to specialize in AA but is at a premiere blood cancer center that I know sees a good number of AA patients.

Fast forward to today - my mom is still going twice a week for blood draws and is getting platelets about every 10-11 days (down from every 7 days) and blood transfusions about every 3-4 weeks. Her WBC have responded really well (ANC 2.4, ALC 2) but so far the lack of meaningful response for Hgb and platelets has concerned her doctor. I was under the impression that a response at this point would be considered fairly early but the doctor seems to be considering a very strict 6 month timeline to respond to the ATG or different measures will be taken.

Today's (Nov 22nd 2021) counts:

Hgb 9.4 (last received 1 unit blood 11/11), platelets 35 (last received 1 unit 11/18) ANC 2.4, ALC 2, Retics 0.54

She is currently taking 125mg x2 a day of Cyclosporine, 150mg Promacta, 20mg prednisone, along with acyclovir, levofloxacin, fluconazole, B12, Folic Acid, Vitamin D3/Calcium, Famotidine and metoprolol (for heart palpitations). She had been getting injections of Aranesp/darbepoetin alfa every other week but has asked to stop as they don't seem to be doing much but making her blood pressure spike incredibly high.

Right now my mom is having a lot of trouble with the side effects of her medications, specifically the cyclosporine and prednisone. I have not read anywhere that prednisone is valuable in the treatment of AA except for preventing serum sickness in the weeks during and after ATG but her doctor seems hell-bent on keeping her on it (and has tried to raise it) despite the side effects she is having, such as facial swelling, retaining water, muscle weakness, etc. She also is having trouble with tremors from the cyclosporine althought the first few months did not have this issue until her doctor tried to raise the prednisone.

I was hoping to know if anyone else was kept on prednisone for an extended time and how it impacting them, as well as if anyone has had any luck with treating cyclosporine-induced tremors beyond lowering the dosage. Both of these medications are making it very difficult for her to do things although she can mostly complete her ADLs with a great deal of effort.

Besides that, her doctor's adherence to a strict 6 month timeline for the response has me worried, as I've read it can take longer for some people to have meaningful response (especially if they are older) and have been told this disease is one of patience so it's making me feel like the clock is ticking away for something to happen and there is nothing I can do about it.

Thanks for reading if you are out there.

Hi mola-tecta,
I am sorry to read of your mother's diagnosis. You are correct that prednisone is only used for serum sickness during ATG in the standard treatment of Aplastic Anemia. It MUST be tapered gradually.

Prednisone causes a false rise in WBC/ANC. So, do not be surprised to see those numbers fall once she is off the drug.

I think you should search out a specialist in AA in your area and set up an urgent consult with that person. There are many nuances to treating the disease so you want a doctor that has successfully treated many patients.

Your mother has a small PNH clone, which is a good sign that her aplastic anemia is immune mediated, but more medication isn't always the answer with this disease.

Here is an article from Dr. Young, an expert in the treatment of AA in the US.
https://ashpublications.org/blood/ar...plastic-anemia
Note the paragraph titled "What not to do" where it mentions that corticosteroids (prednisone) should not be used in the treatment of the disease.

Don't delay in seeking out an expert for a second opinion so that you can sort out her medications and dosages. Good luck!

[Hopeful]

Sorry - I didn't see all the other replies before I responded! It looks like you have received much good advice

[Matthew42]

Latest news:

My mother went to the hematologist today. She told her that her neutrophils are a good indication of ATG success, but it doesn't tell the whole story. My mother has to have her blood rise one more time for the hematologist to declare the horse-atg treatment a total success. She had a big rise in hemoglobin a month ago, but since then, there have been no real big rises. We just need one more rise for the doctor to say it worked. Even if she needs transfusions for a few more months after another big rise, the hematologist said it would not be a big concern, apart from iron overload. We're crossing our fingers.

Note: she reiterated that platelets would be the last line to rise, most likely, and that's okay. Also, she reduced her cyclosporine to a much lower dosage as she believes Promacta + ATG is what is really moving things along. I'm just saying what she said. But cyclosporine is still needed.

Health and happiness to everyone.

[mola-tecta]

Hopeful,

Thank you so much for your response! I have definitely noticed the trends with prednisone and ANC, but they usually balance themselves out.

I have started reaching out a little to the hematology division of the med school/center in hopes someone from the benign hematology or rare blood disease section will have an interest in a second opinion, but so far no response. It has been the holidays though so I'm not surprised. I'm not really sure if this is something I can call the office about or not?

Matthew42,

I am hoping for the best for your mother. A big rise would be really fantastic to see and I hope that lowering the cyclosporine will be good if your mom is also having side effects with it. I am also really glad your mother's hematologist is so forthcoming with information! I feel like I have to squeeze the information drop by drop out of my mom's hematologist.

As far as it goes for my mom, she had a small rise in Hgb without any transfusion again! It's very small of course (8.2 on monday --> 8.6 on Thursday) but it's enough to stave off another transfusion for now, since she was expecting the number to drop below the usual transfusion threshold (8). Hopefully she can make it a full month before needing another bag of blood. (last bag given 11/11)

She also last got platelets on 11/26 and they are still holding in the 50s, so I am still hoping that going longer between needing transfusions is a good thing.

Also, her appointments are usually early in the morning and they run a cyclosporine trough level then, before she takes her morning dose. This time her appointment was much later and they ran a non-trough level cyclosporine and found it was actually much higher than they wanted to see. (700? or so?) so she might see a small reduction in the cyclosporine dosage. She also was able to negotiate another small prednisone drop (20mg --> 15mg) so hopefully both of these things will help a little with some of the side effects.

My mother is about to start the Exjade but interestingly her ferritin has gone down to 2400 (from >3000), probably from all the weekly tubes of blood (at least 12 vials a week + 2 of the blood culture bottles that look like hot sauce bottles) so hopefully the combo will get the iron overload in check.

Take care everyone.

[Matthew42]

Hello mola-tecta,

Thank you for your kind wishes.

My mother's blood held over 9 for a week. Her blood still dropped (no rise), but she's never held above 9.0 seven days after a transfusion. I guess that's a good thing.

I'm wondering why your mother's hematologist is so adamant on starting Exjade? 2400 is really not that high in iron overload terms. Sure, if you google, they act like anything over 1000 is really high on the surface, but from the research I've done, it's not alarming. My mother's hematologist says my mom has iron overload, but it's not that concerning right now, even though she was over 3000 two months ago. She just talked about addressing it later on. Every hematologist is different.

I've read about people who have had super high iron overload for several years, and they ended up perfectly fine. Again, already having a heart or liver problem makes the issue more pressing.

Have you tried natural means to lower iron overload? I've read about wheatgrass/turmeric/quercetin/resveratrol doing wonders for some people.

Health and happiness to you and to your mother.

[mola-tecta]

Matthew42,

I don't know why he is so adamant about the Exjade, the same as I am not sure why he is so adamant about the prednisone, about the Aranesp, about the antimicrobial prophylaxis, about his strict 6 month timeline.

All of these things together make me feel that he is following most all of the right treatments but isn't familiar with the particular nuances of aplastic anemia vs other blood disorders.

I don't know how to phrase this sort of thing of course. If you ask why the Exjade, then obviously the answer is because of iron overload. There isn't much nuance in it. Trying to get the kind of information out of him that your mother gets from her hematologist is like trying to get blood from a stone, sort of. He doesn't offer up much unless you really know how to ask. He never even mentioned the ANC improvements ever until I asked about it.


I am no doctor of course but from what I have been able to read it would be far better to wait to address the iron overload until my mother's blood counts are more stable. Especially since some of the side effects of Exjade are lowering of blood counts - so wouldn't that mean giving it might cause the need for even more transfusions? Which might exacerbate the iron overload?

Of course, it's not so easy to get a second opinion, hence why I was asking if it makes sense to contact the hematology division of the med school/center.

Hoping for health and happiness to you and your mother as well!

[Marlene]

Matthew....Great news about your mom. She may plateau for a while before you see another jump. That's pretty normal. John would get a big jump and even drop back a little for while before having another big jump. It's about trends over time.

Mola-tecta,

How very frustrating for you guys. You can refuse to do the Exjade right now. Or,if you're not comfortable with that, you can do what we had to do. John would stop/start it depending on he felt. He never got to a full dose because it made him nauseated. You also have to monitor liver/kidney function closely. When he first started Desferral (because Exjade was not available then), they recommend to have your eyes checked before starting. I can't remember if it's the same for Exjade. John had to finally come off it because it was affecting his kidneys. Hopefully he will not start her at a full dose. IMO, it's best to start at a lower dose and work up. If she has side effects, stopping Exjade for a while and restarting will resolve them. They may come back though. John could take it for about three weeks, then have to stop for a week before restarting.

Ferritin is an acute phase reactant meaning it's a marker of chronic inflammation which means that many things can cause an elevation. Even how blood is drawn can impact the FE result. Once it hits 1000, then pretty much anything can elevate it and it's not accurate indication of the level in iron in the body. Johns would fluctuate pretty dramatically, sometimes by 1500. He started chelation 12 months out from treatment. FE was 4469. He was still transfusion dependent. He had daily red cell for about three months, then finally down to 2X a week before getting to weekly, then every two weeks. We estimate he had over 200 red cell transfusions so iron overload was a big issue for him.

As far as efficacy, phlebotomies are the most effective way to reduce iron. John started phlebotomies once his HGB reached 10. He went every other month starting with them only taking 1/2 a unit to ensure his bone marrow could keep up. It still took forever.

It's very difficult to keep ahead of the iron on Exjade while still getting red cells. The best you can hope for is to keep it from getting worse. Another option you can ask about is to infuse desferral while getting red cells.

Wishing you both the best....M

[Matthew42]

Thank you, Marlene. You are so informative about the disease.

My mother's age is another reason for the slow response, the hematologist said. It could be close to another 8-9 months or more or so before her bone marrow really heals (if it does). That's hard to believe. So, 1-2 years for the bone marrow to really heal from aplastic anemia is very true for slow responders. I couldn't believe this. In fact, some older woman took 2 years for her horse-atg to work. She was transfusion-dependent every week for two years for blood and platelets!! All of sudden, the atg worked. She went on to make a full recovery from aplastic anemia.

The hematologist also said that when neutrophils never come up at 6-9 months or so with no blood or platelet improvement, that's a sign that the horse-atg is probably not going to work, even in "very slow responders." There are exceptions, however, where slow responders have had no lines improve (blood, platelets and neutrophils) until after a year -- but it's rare. Knowing when to do a second treatment is tricky, however. How long do you wait? Who knows? With older people, it's best to ride it out, she implied. She went on to say that higher neutrophil stability is indicating that atg is working, but it doesn't prove it. She told us last week it looks like it is going to be a long waiting game for my mother, even if she gets another big rise in blood, or has her blood stabilize somewhat. So, she won't guarantee us anything, other than saying her higher neutrophils stability "points to" - but doesn't prove - a success.

By the way, she was really impressed with my mother's big jump in blood a month ago, 11 days after a transfusion (8.6 to 10.5), but she stole the joy away from us by saying she needed a second one for the first one to have any real meaning. LOL. Can't win.

As far as iron levels are concerned, they can be all over the place when people are getting regular blood transfusions. That is correct. There can be big fluctuations, which can make it difficult to know who needs iron overload treatment and for how long.


Health and happiness to all.

[mola-tecta]

Marlene,

Thank you for the kind message and for all your experienced information about how ferritin reacts and your husband's iron chelation treatment. I had no idea about how blood ferritin can be a sign of inflammation.

My mom did decide to start taking the Exjade, so we will see how she feels and what happens with her blood lines.

Also, I found an article that mentions improved hematopoiesis with relief of iron burden, so maybe it will even out? Fingers crossed?

On Monday my mother's Hgb was 7.6 and platelets 17. She got both blood and platelets, so... slightly less than 4 weeks between blood transfusions, and still holding about 10/11 days between platelet transfusions. If it was my body, I might have asked to hold off on platelets for another day or two to see how much it would continue to dip to get a better idea if there is any "baseline" or if it would just return to zero. I can absolutely understand not wanting to play around with that though, as my mother starts getting more frequent nosebleeds/bruises/broken blood vessels when the platelets dip below 20.

One thing I had wondered is if there has been improvement in hematopoiesis, but that it's hard to notice due to still being under the transfusion threshold they set. If my mother's bone marrow was only able to keep up production enough to make a Hgb of 4.6 before any treatment, maybe it has improved to produce enough for a Hgb of, say, 6.8, but you wouldn't be able to see it yet because they will transfuse blood below 8.

I'm hoping also that the markers of Polychromasia, nucleated red blood cells, ovalocytes, etc, are a sign that the marrow is trying it's hardest to pump out as much as it can right now, even if the "factory" is releasing products early, so to speak.

Matthew,

I am thinking of you and your mother often as we seem to be in the same boat on a lot of things. I'm really glad that your mother's hematologist offers up so much information to you and explains so many things thoroughly without giving false hopes or false doom. I'm also really happy you share that information here since my mother's hematologist is a lot harder to squeeze this kind of information out of.

Needing more time to respond definitely makes sense for anyone who is older. There is already less marrow cellularity due to age anyway.

My mother's neutrophils are still holding really well, even with the reductions in prednisone. They've fluctuated between 1.9 to 2.4. That's nearly normal levels, according to this lab's range! The hematologist did also reduce the cyclosporine down to 100mg x2 a day and the prednisone will be further dropped to 10mg. I think he finally saw the side effects my mother was having. I am hoping this will help my mother feel a little better in terms of side effects.



Thank you both again for responding and continuing to respond. This has been an incredibly lonely journey so having anyone to just bounce a thought off of has been a blessing.

Take care everyone.

[Matthew42]

Dear mola-tecta,

Again, your mother's neutrophils are absolutely excellent. My mother's are about 1000, which is a decent level for protection.

You can expect your mother's hemoglobin to be everywhere. Big drops are normal, too, even when there are big rises. Some people never have big rises while recovering - they just get little rises with stabilizing levels. The good thing about that is the need for less transfusions. Big rises and big drops, on the other hand, mean more transfusions, but it shows that the bone marrow is coming back to life in a big way; in other words, there is a lot or potential for the person to eventually reach a very high hemoglobin level at some point. That's how I read it.

Yes, we were told that age will lead to a much a slower recovery. But I was also told you can recover too fast. LOL. Again, you hear a lot of different things.

My mother did have a 5% increase in bone marrow cellularity a few months ago. The hematologist said that while this is low, it is still an improvement, showing a response to immunosuppressant therapy. But here's the kicker: greater cellularity in bone marrow doesn't always correspond with higher levels of red blood cells, ultimately. There is truth to that from my research.

My mom's hematologist is not that great, by the way...I just pull the info out of her. I force her to give me info. She's nice, but she's not very encouraging; in fact, she never was. For your information, she's experienced in treating aplastic anemia, but she's no expert (she said she wasn't). She also contradicts herself: she says, on one hand, that the treatment may not be working, but then says she thinks the Promacta is really helping things along with the neutrophils. LOL!!! She's goes on to say that she's excited about the one big rise in blood 11 days after a transfusion, but it could just be a one-off. But what would cause her neutrophils to go up and stay up, plus have 1 big rise in blood a month ago? The weather? LOL. I understand, though, why she wants another a big rise to really say for certain that everything is working 100%, but still...

My mother had her cyclosporine reduced to 200 mg a day, saying that it's not doing that much, other than anchoring the ATG. She said at 200 mg or lower, there shouldn't be too many side effects.

If my mother makes a full recovery, it won't be for a while because of her age. I already accept this fact. She already lost 6 weeks of her recovery time because she was on a very strong antibiotic which suppressed her bone marrow. We were warned by her hematologist about this.

I've read too many accounts of people in their 60's and 70's with aplastic anemia who went 1-2 years before getting off transfusions for good. With younger people, though, response time is to be much, much sooner. Like I said, even with older people, there still needs to be some improvement in one of the lines by a year or so (blood, platelets, or neutrophils). That's my understanding. If not, horse-atg has failed. Again, who knows? I repeat myself a lot because I just get very frustrated with everything, It's like no one really understands aplastic anemia very well. They understand blood cancer way better, even sickle cell anemia, or so it seems.

By the way, my mother's hematologist said she was never concerned about white blood morphology or red blood cell morphology in general. Aplastic anemics can have many abnormalities without concern in their CBC, except dysplastic cells like myeloblasts or Pelger-Huet anomaly, which can signify MDS. My mother, actually, had Pelger-Huet anomaly while on a strong antibiotic for six weeks. I got super scared, but it resolved itself after stopping the antibiotic. Dysplasia can be caused by medications, too, so just be warned. Aplastic anemics should not have dysplastic cells without reason, however; if they do, it can signify a transformation into hypocellular MDS, I think. Don't quote me on this, as I am far from sure.

This disease is tough to understand, tough to predict. Again, you just put your seatbelt on and close your eyes. LOL.

Take care and talk soon.

[Hopeful]

Hi Matthew42 and mola-tecta,

I'm going to share my personal experience and experiments with cyclosporine in case it is helpful. I am not a medical professional. So this is all anecdotal. I did a lot of research early on because I was having ill effects from my initial high cyclosporine dosage.

Cyclosporine dosing will vary based on the brand (Gengraf, Neoral, SandImmune, etc) and on the weight of the person. The metabolism of cyclosporine will also vary based on the person. I metabolize cyclosporine extremely quickly. So, in the early days, my local doctor was constantly trying to raise my dosage to get my trough rating "in range" (200+). It never happened despite being on an incredibly high dosage and feeling like I was poisoning myself.

Luckily, I consulted with an AA expert who said to forget the trough and dosed me based on my body weight. Papers that I read at the time supported this approach.

I read a paper that showed that cyclosporine levels in the system follow somewhat of a bell curve with the peak 1-2 hours after taking the drug. So, I tried an experiment and got my trough reading 2 hours after taking the drug. My level was over 1500, which freaked out my local doctor. Needless to say, I had a strong case for lowering the dosage to the recommended level for someone of my weight.

So, I would recommend reading the pamphlet for the cyclosporine brand that you are using to learn the recommended dosage, just for a gut check that you are in range. You don't want to be too low, and you don't want to be too high. Of course, always discuss any concerns with your mothers' doctor!

One other thing that I do is take a magnesium supplement with my evening dose. This was a recommendation from the late, great Hawaii Bill. Cyclosporine will deplete your magnesium, which can cause all kinds of issues, including heart arrhythmia. Taking a supplement will help keep your magnesium level in range. It also aids with sleep when taken at night. Have your mothers' magnesium and potassium levels checked every now and then just to make sure that this is not an issue for them.

With regards to bone marrow cellularity, I was told that the marrow is patchy, meaning that it could be 40% in one location and 50% in another on the same day. It takes a long time for the marrow to come back, especially as you age.

With regards to platelets, you should get your mothers' clotting factor checked to make sure that she is not susceptible to a spontaneous brain bleed. Internal bleeds are the biggest risk of allowing platelets to drop below 10-15k.

I hope this was helpful. Again, it is just my own opinion/experience.

Wishing everyone the best!

[mola-tecta]

Matthew42,

When you say,

I repeat myself a lot because I just get very frustrated with everything, It's like no one really understands aplastic anemia very well. They understand blood cancer way better, even sickle cell anemia, or so it seems.

I really feel you here. This echoes a lot of how I am feeling with the whole situation as well. Even when I tried looking at the benign hematology division, nobody has interest in aplastic anemia. Most of them specialize in hemophilia or sickle cell anemia. They even have people with interest and expertise in PNH, TTP, porphyria, and cold agglutinin disease... but not aplastic anemia?

So I understand the frustration involved. For example last week my mother had a small jump in Hgb (8.2 --> 8.6) and the hematologist said it was likely due to the Aranesp... when my mother hasn't had the Aranesp shot in over 4 weeks?

I did eventually email Leigh Clark at the AAMDSIF if they knew any other hematologists in the area that might have AA experience, and surprisingly they mentioned a doctor who is in the same group as my mother's current hematologist. I told my mother so she can think on it, if it gets to the point where she feels she wants a second opinion. We are coming up on 5 months post-ATG now.

Of course, my other concern with the hematologist wanting to repeat the ATG right after 6 months is the state of hospitals right now. I don't know how this hospital in particular is doing, but many across the USA are experiencing massive staff shortages as well as re-surging COVID cases. During ATG treatment they were checking my mother's vitals every 30 minutes, and over 8+ hours that is a lot of time to be investing in a non-ICU patient.

Looks like we just have to keep riding it out and hope for the best. It's SO hard to not try and invest so much into every little number change. It's driving me really crazy.


Marlene,

I deeply appreciate your response and telling your experience with this disease and with cyclosporine especially. It's incredible how much more I learn here, just from talking to other patients who have been through it.

I know that my mother was initially started on (I think) 750mg of cyclosporine total a day when it was first introduced but was lowered pretty quickly until she left the hospital on 350mg. From what I can tell she is on a generic version of Neoral (modified cyclosporine) . During every blood draw (2x a week) they test the cyclosporine trough levels, so they usually try to have my mother come in early in the morning before taking the morning dose.

Over time they have knocked down the dose to about 250mg, leaving her with trough levels usually between 250 and 300. This equates to about 3mg/kg dose.

Now my mother's dose has been lowered to 200mg. The reason is that she had a later appointment, about 2-3 hours after taking the morning dose, and the cyclosporine levels were 700+. The hematologist didn't like that and had her skip both her evening dose and the following morning's dose to re-measure the cyclosporine and it was still at 200. While I am familiar with the trough level monitoring (C0) I am not really familiar with the C2 level's significance. 200mg is about 2mg/kg now. I don't know why she is suffering so much from the side effects.

With every single blood draw they do a comprehensive metabolic panel (includes liver enzymes, sodium, potassium, calcium, glucose, bili, creatinine, BUN, eGFR, etc) as well as magnesium and phosphorus, LDH and cyclosporine levels. So far the magnesium levels have always been well within range (between 1.9 to 2.1) and so has potassium. I don't know if supplementing the magnesium will help at all right now.

As for clotting factors, the only tests I can see are for INR, Activated PTT and Prothrombin time which have been normal. Are there others they should be testing too?

I appreciate all the advice and the willingness to let me infodump everything here, it all just kind of sits in my head anyway so writing it down helps.

Thank you all again, it really helps me feel so much less lonely and isolated in this

[Matthew42]

Dear mola-tecta,

I am in the same situation as you. It's downright maddening.

They understand aplastic anemia a bit better in the Far East because the disease is more prevalent in that part of the world. I have read a few stories of people with severe aplastic anemia being treated by Chinese medicine with great success (more or less cured without ATG or bone marrow transplant). Eastern medicine may be an option at some point if things don't improve in 4 months or so. We shall see. I am hesitant for my mother to the rabbit because it so potent, leading to chromosomal changes in her bone marrow.

It's as if aplastic anemia is still a great mystery to modern medicine.

If my mother were much younger, I would have already declared the horse-atg a failure from the research I read. But because I've read too many accounts of older people taking well over a year for a real response, I am going to hold off and let time go by (another 4 months or so). That's all we can do. I thank god my mother's neutrophils improved a lot, as that gives me some hope that the ATG is doing something. The hematologist said that neutrophils going up and staying makes it seem the ATG is working, but it doesn't prove it. LOL. I'm not really sure what that all means.

The waiting game continues...

[Hopeful]

Hi mola-tecta,

I feel like your mother's metabolism of cyclosporine is completely the opposite of mine. I never saw trough levels of 200, but I guess everyone is different and this is why aplastic anemia is so hard to treat! It's also why you want to see a doctor that treats lots of patients! In her case, cyclosporine measurements are absolutely critical to avoid toxicity. For me, not so much.

I would check all the medications that your mother is taking and make sure that none are interacting with cyclosporine, making it hard for har body to clear it. If there is a drug interaction, then the mg/kg dosage for cyclosporine is irrelevant

Mola-tecta, have you considered having a free consultation at NIH?

Try to stay positive mola-tecta and Matthew. There are signs that things are going in the right direction.

[Matthew42]

My mother's neutrophils are holding steady at around 1100 for about 5 weeks now. Her neutrophil % is now sometimes higher than her lymphocyte %, which is a good thing because it appears that her autoimmune condition is calming down. That's what I read.

She is soon to go into her 8th month since ATG. Her blood continues to drop steadily after a transfusion. Who knows if we'll ever get a big second rise in blood like we did 6 weeks ago? It's hard to be hopeful sometimes. I know that her neutrophils staying up over 1000 is really good, considering she used to average 500 before October. I don't know what would be making her neutrophils stay up for so long if it's not the ATG.

The waiting game continues...

Health and happiness to everyone.