Question about treatment course

Maybe the doctor thinks that if she can get him into the hospital, she could get him to have the splenectomy. I hope she doesn't push him into that by instilling fear.

If you honestly believe that nothing has changed, then nothing has.

I got more Information out of him when he got home. Apparently she had some sort of epiphany when he rejected any further non-emergent platelet transfusions and responded something along the lines of "Yeah. I think maybe we were treating us and not treating you." I was pretty unhappy when he told me that. He doesn't think she's trying to scare him into a splenectomy but I don't really know. I know she has asked him repeatedly why he is so resistant to the surgery and he has explained multiple times that he would prefer exhausting medicinal avenues before permanently losing an organ without any guarantee that will "fix" him.

On a positive note, we met with our family naturopathic doctor and it was a serious breath of fresh air. She gave us some ideas to support him while we put out this fire, so to speak, and then when he's stable we will be looking at long term options to support his immune system, etc. My husband seemed in much better spirits after that.

They are still waiting on insurance approval for his first dose of NPlate, but supposedly they got verbal approval and are just awaiting written, so it could possibly be today or tomorrow. I haven't really had much chance to research it, is there a link anywhere that discusses what to expect with it (mostly as far as duration? I was under the impression it was a longterm therapy, but his doctor is so stressed out by the bone marrow fibrosis possibility she has repeatedly said she doesn't want him on it for very long at all.)

Bee:

Your husband has an appointment with a second opinion in a few weeks, right? Consider using N-Plate for now until that appointment and see what the next doctor says. Has your husband asked this doctor how many patients have used N-Plate under her care? My guess is that she isn't familiar or up to date with it. N-Plate was specifically engineered for ITP and although long-term use can mean a few years, it hasn't seemed to cause much fibrosis and patients have been going into remission during its use.


An increase in bone marrow reticulin has been observed in several patients.75,77,78 However, current evidence does not indicate progressive bone marrow fibrosis with prolonged exposure. TPO-RAs have not been shown to induce malignancy or myelodysplasia in patients with ITP thus far,77 but they are not indicated in patients with myelodysplasia because of the potential risk of acute myeloid leukemia (romiplostim carries a warning). Although it seems these agents have acceptable short- and intermediate-term safety profiles, long-term safety data beyond 5 years are limited.

Although splenectomy is recommended after the failure of steroids, there is an argument to be made for waiting one year or more after diagnosis before proceeding. We generally follow the recommendations of the International Consensus8 and often lean toward either rituximab (lower response rate, modest likelihood of cure) or TPO-RA (higher response rate, less likelihood of cure) after considering the many factors aforementioned based on personal clinical experience and patient preference. This difficulty is exemplified by the responses of each of the authors to how they would advise the patient presented in the case report.

www.bloodjournal.org/content/120/5/960.full?sid=9e00c230-10f8-405a-964d-299484e271a0&sso-checked=true

I am hopeful since the second opinion is with a Mayo Clinic that they will be a bit more on top of their game re:ITP. I have gotten the same impression that she really isn't that familiar with the TPOs and if we don't switch doctors she will be very resistant to using it long(er) term due to her assessment of fibrosis risk. So I have everything crossed that the second opinion situation will be a good one and allow us to transfer his care to a doctor that has the most up to date info and won't be such an uphill battle for everything.

And thank you again for the info. It will be very helpful if for some reason the second opinion situation doesn't work to be able to point her to references that contradict her current assumptions.

I'm sure you're pretty frustrated about now.

I think there are many hemos who are impatient and don't get certain treatment courses time to work. I certainly got that from my first hemo. I also got tired of the way he made scared all the time - like he felt I was going to walk out of his office every meeting and just bleed to death on his sidewalk or something. I didn't need that extra pressure, I'm a grown up and was well aware of the risks involved with walking around with single digit counts at the time.

I know it can also be frustrating to not be there with your husband at the doctors meetings. I sense you might be feeling like you're maybe not getting getting the right gist of the conversation or your questions aren't being heard. A couple thoughts...
1) I started using an app on my smartphone to take notes about every meaningful conversation I had with any of my doctors ... the key being that I made the notes as soon as the meeting was over in order to have both the words and my emotions fresh.
2) I have a co-worker who's spouse has a medical condition that, amongst other things, affects her short-term memory. He will send pre-typed notes along with her if he can't be there with the doctor and he has her record (audio) the entire meeting on her smart phone.
...so just some thoughts that might help.

Remember it's very important to make sure you're not pushed down a road you don't want to go down with treatments. I think if you asked all the members of this forum, the majority would say the splenectomy is not high on their treatment list. I, myself, was within a matter of hours of having them do the operation during my second hospital stay. Instead, I decided I wanted to exhaust every and all drug treatments first. Ultimately my counts returned to normal and have stayed there for three months now. Looking back, I realize I didn't need either of my hospital stays nor the surgery. But I was scared and uneducated. By the time I got of my second hospital stay I knew exactly what I wanted and advocated loudly for it, including a second opinion which lead to switching hemos.

It will get better, I promise.

Matthew: you hit a great many nails directly on the head. I do give him notes but even then he sometimes has trouble following through. I appreciated your outlook on alarmist hemos. I definitely am getting that vibe from his doctor, and whether it is genuine concern on her part or not, it is NOT helping him. I think as time passes and he is still okay and his symptoms are still manageable with single digit counts he is getting a little more comfortable with it. Not too comfortable, but not as stressed out about it as he was a month ago.

Sandi: frustration is a good way to describe it.

He got his first NPlate shot last Thursday. Today's office visit was more of the usual. Count was 3 but we weren't expecting immediate results, so no big deal. The hemo told him she was planning on four rounds of Rituxan, although she was willing to consider six "but if it isn't working after four, it's not going to work." Next week will be his fourth. Thankfully we have the second opinion appointment next week and my husband is getting more comfortable sticking to his guns and not being pushed to splenectomy if we don't see a response on her timetables. So all in all, I'm feeling a lot better about things and I think he is too.

Good, it seems as though you are on the right track.

Rituxan can work 4 to 12 weeks after the first infusion, so you got incorrect information there. Also, it's unlikely that six treatments will do any more than four will. Studies are showing that even four treatments for ITP may be overkill.

I'll be happy once you get that second opinion!

That is good to know about the 4 vs. 6 treatments. I passed it on to hubby. I really don't understand the doctor's impatience with giving things time to work, but we are motivated by different things, I guess.

The median time between rituximab therapy and response was 14 weeks (range, 4 to 32).

This article is from 2007, but this info has not changed.

www.ncbi.nlm.nih.gov/pmc/articles/PMC2040174/


In all, 152 patients (61%) showed an overall initial response at a median time to response of 2 months.

Rituximab is an emerging new agent for the treatment of several autoimmune disorders and, in particular, many reports highlighted the effect of rituximab in idiopathic thrombocytopenic purpura (ITP). To date, rituximab has been administered with the same schedule proposed for Bcell lymphomas, i.e. 375 mg/m2 every seven days for four weeks. Very few dose-finding and pharmacokinetic studies have been performed in autoimmune diseases. In this context, the B-cell total mass is much less than in patients with lymphoma and, therefore, a reduced dosage of rituximab might still be sufficient for its therapeutic purpose. Based on this assumption, we performed a prospective clinical trial using lower dose rituximab in patients with ITP. We explored response rates of lower dose rituximab and correlated results with biological findings.

This study shows that with lower dose rituximab (approximately one seventh of the approved standard dose in lymphoma) the level of B-cell depletion and the response rates appear similar to those previously observed with standard dosages in a population of ITP patients with the same characteristics.

In conclusion, this study confirms the safety and the high potential activity of rituximab in patients with ITP. Furthermore, it highlights the importance for a more disease-specific therapeutic schedule and the need for randomized studies. Lower dose rituximab led to response rates similar to standard dose but with a slower timing of response.

www.haematologica.org/content/93/6/930.full

Bee
How is your husband doing? Any new info from the Mayo?
Emily

We are in a holding pattern and still with single digit counts. Wednesday is his last Rituxan dose. We don't see the Mayo doc until tomorrow but I can post an update on how that goes.

Question for those of you in the know: I was looking for something in his records online the other day and noticed from the beginning of the first hospital stay they noted giant platelets. I found a bunch of other references to it in his lab results over the past few months. Is this something meaningful at all? His hemo has never mentioned it.

Brand new platelets are larger than average, and shrink as they become older. The MPV or mean platelet volume is a measure of the average size, and thus indicates the average age of the platelets. When platelets are being destroyed, their average age becomes younger, and their average size becomes larger. This to me would be a clear indication that your husband's problem is with platelet destruction.
This may be what they were talking about.

If they are referring to MPV from a machine counted test, there can also be erroneous readings that the large platelets are actually platelets clumped together, which will also yield an erroneously low count. That is one reason why a visual inspection of a blood smear is important.

Bee:

That is completely normal for ITP. Do they do any manual counts on him or are they all automated?

It says manual review in some of his results so I think they do, periodically.


Just got back from our second opinion appointment. The hemo we saw was definitely an ITP guy and has coauthored some papers and was involved in the clinical trials for NPlate, so that was comforting to feel we were with someone who has seen tons of ITP patients and is current on the research. He is very pro-splenectomy and was up front about that, and quoted a 90% success rate, which is higher than I've read anywhere. So I knew we were coming at this from different goals, but he was very open to our questions. But he kept saying "I'm the splenectomy guy and even I agree with you on the timetable."

He is apparently friends with our current hematologist and offered to share my husband's care with her and will be sending her a note with his assessments, which included that since we have already gone down the NPlate/Rituxan path that we should give it adequate time to respond (I.e. 8 weeks from the last dose, not the 4 she is currently set on). He also said he would let her know that her concerns with the TPOs and bone marrow fibrosis were unfounded, so hopefully if she has an ITP patients in future she won't harp on that so much. All in all, it wasn't earth shattering or anything but was positive and if we end up at splenectomy we will feel like we exhausted all the other treatment options first.

Good news, Bee. It sounds like you got some validation for your ideas.

90% success rate though? I've never seen that in print.

Yeah, in hindsight I wish I had picked his brain on that number a little more. Maybe he is counting those with a short term post splenectomy remission as a success. Most of the ones I've read quote somewhere in the 70% range but they are talking over like five years. So maybe his definition of "success" is a little broader than mine. :laugh:

Bee
Thanks for the information from mayo. Since there are only a few treatment options, it seems like the hemo choice is about personality and finding one with more patience to see if treatment works more than anything else. Given my own lack of patience having my hemo bounce around with treatments has been hard. Did the mayo doctor give any indication how long he would stick with nplate? It seems like that can take some an immense amount of time to see results.

Again, thanks for reporting back.

The doctors sometimes actually create the problem that patients have with patience. When they jerk the treatments from the patient too fast and move on to the next and the next, it's just a set up for failure over and over again. The patient then believes that they are not responding to anything when in fact, they responded to some of them but didn't give it enough time. I've seen that with both Bee's husband and Emily. Both of you could have been possibly stable by now and I want to bite someone. I'm frustrated too (for you both)! :blink:

Emily:

N-Plate does not necessarily take a lot of time to see results. It can take a while to get stable but it's worth it if you just hang in there with the ups and downs and have a doctor who knows what he is doing with the drug.

I totally agree. I now know that i have to keep the doctor on track and not to panic. Had i realized that sooner, i would have stuck with NPlate. Oh well. For me, as far as I can tell, if I crash I just have to put up with more steroids. I also understand that I won't die if the number gets low. I am neither a calm nor patient person so ITP treatment is a huge challenge for me emotionally.

It's not all on you though, Emily. My husband is ordinarily my rock, the calm port in a storm. The combination of the dire warnings from his hemo, the steroid side effects, and the lack of response to anything threw him into an emotional state where I barely recognized him as the man I married. It's a lot to juggle and deal with emotionally, and when you are taking your cues from someone who acts like you might die at any moment, it's scary. It was only after we started arming ourselves with knowledge and hearing the stories of other, more "experienced" ITP patients that we were able to get a little more perspective and feel less reactionary. The past few weeks I am seeing him return to his old self despite the fact that nothing has changed in his platelet counts.

Is there any reason (besides not knowing which fix worked) you can't restart the N-Plate?

Husband just texted me that he's now scheduled for six Rituxan doses instead of four because she wants to see if it will start to work. I give up. :huh:

Grrrr. :S

Bee i am usually the rock in my family and i can't begin to imagine how hard this has been on my husband. I literally started a draft of my eulogy. I told him people to not forget to invite to my funeral! I told him what to do with my jewelry when i die. If i was on dex, i am pretty sure they would have to lock me up. On top of that i have been the breadwinner. Watching our income decrease by more than half has been just one more horrid side effect of a lovely trip with ITP. Having the doctor be in panic mode just adds the gas to the fire.

Enough complaining i suppose.

Sandi wrote: In all, 152 patients (61%) showed an overall initial response at a median time to response of 2 months.

This first line of a section you quoted actually came from a different article:
www.bloodjournal.org/content/124/22/3228

Sorry to nitpick!
You also wrote "OCD here, no ADD!"
OCD and ADD on this end. Wicked combination!!

Bee, There is NO protocol for 6 treatments with Rituxan. I have read a lot on the subject of Rituxan and have never seen more that 4 treatments used.

Perhaps the second opinion doc can talk some sense into your doc. The fact that they are friends could help or hurt, though. Hard to say.

At minimum, your husband should delay, delay, delay after the fourth treatment to give it time to work, but I would be prepared to possibly refuse further treatments.

I think it is time to think seriously about changing doctors.

Rob:

I knew about that when I did it. I clicked off of the website that I quoted from before I copied the actual link. It wasn't intended to be included with the article above or below it, but I guess no one had any way of knowing that. Too many open tabs and one Admin with no patience.....

Rob: I assumed as much since I couldn't find anything, anywhere talking about more than four. I'm just frustrated because it seems like she just wants to do *something* and wherever the dart hits the board is how he gets treated, so to speak. It feels so very random. If it were me, I'd already be seeing a different doctor, but I'm much more aggressive about "doctor-shopping" to get the right fit and much more insistent about evidence-based care than my husband is. He is mostly a go with the flow kind of guy, up to a point. I think I made my point to him about refusing further Rituxan, but it's just so mentally taxing to feel like I have to do that sort of thing all the time and I dislike feeling like the nagging wife.

You are correct in the friendship between the doctors being a bit of a good and bad thing. I don't think the 2nd doc wants to step on any toes, but am hopeful he can talk the primary doc off the ledge. I guess we will see how the next few weeks play out.

Is it time yet for a recheck on the h pylori? There are lots of antibiotic resistant strains, and it is normal to retest after 4-6 weeks.

His hemo ordered a recheck but blood only, and if my understanding is correct that can only say he has been positive recently and shouldn't be used to confirm eradication after treatment. The next time we see our primary care doc I am going to ask her to test for one of the other methods. I brought it up to the Mayo hematologist and he basically pooh poohed the entire thing and said they only found h pylori status relevant in Italy and haven't replicated the results here so he thinks it is fine to just throw the typical abx at it and not worry about confirmation.