Clinical protocols

[Hawaii Bill]

I am facing my second round of AA treatment with ATG. I have been trying to get into a clinical trial at NIH but my counts are not quite severe enough. There is also some question about whether I was treated with h-ATG or r-ATG the first time around, and that might affect which one to give this time.

When I was evaluated by Dr Paquette earlier this year, he mentioned in his letter that my original dosage of ATG was not the standard.

So I am researching protocols and dosages on the web so that I can review them with my hemo before I go in for the next round. I asked NIH, but they said they don't share their protocols.

So far, I found one article that indicates the standard dosages for ATG and Cyclosporin, dated 2005 from Dr Maciejewski:

http://asheducationbook.hematologyli...ull/2005/1/110

Does anyone else have any links or knowledge about this? Also, if one had h-ATG the first round, is r-ATG best the second time? What about vice-versa?

Thanks in advance!

[Lisa V]

Hi Bill,

Ken has had 2 ATGs, both of them horse. The reasoning was that it worked the first time for him (he relapsed during the cyclo taper) so why switch? Better to hold the rabbit in reserve in case the horse doesn't work.

Refresh my memory, did you have a response the first time? If not, then a switch may be in order. Most doctors don't seem to want to backtrack from rabbit to horse, though. From what I've read, rabbit is considered both stronger and easier to tolerate (although judging from some patient responses this may be debatable). Whatever the reasons, the usual order seems to be horse, then rabbit, and then there are others (skunk, goat) if those don't work out, but we rarely hear of them.

I'm not sure what the daily dosage was, but our doctor consulted with someone in the midwest (not sure who, it may even have been Maciejewski?) who recommended a longer series of infusions with each successive ATG. The first time around he got it for 5 days, so the second time they gave it to him for 10 days. Presumably if he had to do it again they'd want to give him 15 days. The good news is he had a quicker and stronger response the second time around, so that seems to have been the right call for him.

Cyclosporine dosage is another matter. It's usually calculated based on body weight, but may require quite a bit of tinkering based on cyclo and creatinine readings in the blood. Ken's has had to be decreased significantly from what he started out at (900 mg/day) due to kidney issues. He's now at a maintenance level of 175 mg/day, which seems to be working out for him. His situation is a bit different than most people's because his Trisomy 8 clone suggests he may never be able to taper without relapse, but really, everybody's situation is unique. There is no one-size-fits-all protocol. You start with the standard and then adapt it to fit your needs.

Hope this helps,

[Hawaii Bill]

Lisa, thanks for your reply. It is exactly the kind of thing I was looking for.

IF I had horse the first go-round (still waiting for a definitive answer from the hospital), then the idea of using horse again makes sense because I had a good response the first time, from a BM cellularity of 0 to better than 50% in three months, and counts that recovered for 6 months before they started declining again. It probably was the CsA taper that caused the relapse. I had 5 days of ATG, and as I mentioned, Dr Paquette mentioned the dosage I got was not standard.

I will definitely bring up the 10 day approach with my doctor. How long did Ken have to stay in the hospital after the 10 days??

The Cyclo dose is interesting. I don't know how much I was given via IV on the 5 days I received it along with the ATG. But afterward, I was taking 300mg twice a day for at least 3 months. According to Dr Maj's article, the dosage for me, at 109 kilos, would be between 1308-1635 mg daily, for six months. I may have been given less because back then I was taking Diltiazem for my chronic tachycardia, and diltiazem is known to increase CsA levels... This time around, that should not be an issue, as I had my atrial flutter problem fixed last August with a cardiac ablation. I remember I was very glad to get the CsA dose lowered, as I was tired of the upset stomach it caused at that level.

I've been on CsA at 200 mg bid for 3 months now to see if it could bring back my counts, but the best it might have done is extend time a little between transfusions, which is great, but not enough.

[Lisa V]

Bill,

Yes, find out which animal you got the first time and stick with it. No point in exhausting all of your options too soon. Are you doing the ATG here in HI or in CA? If it's local, you could suggest your doctor call Dr. Miller at Kaiser and find out where he got the info about the 10 day course of treatment.

They let Ken go home the day after his last infusion, which was not a moment too soon for him, let me tell you! He had his clothes back on and was sitting on the bed waiting as soon as they unhooked the IV, LOL. He was back working on the farm the next day too, which was certainly NOT how it went the first time around. The lower doses of both cyclo and prednisone the second time made it so much easier on him! We learned a lot from his first treatment. If you can get your doctor's records from your first course, your current doc should be able to gauge your responses to that and adjust the dosage appropriately if need be.

[Hawaii Bill]

I am just amazed that Ken was allowed home the day after the last ATG! That's what someone else said about Dr Paquette's approach, after a 4-day (second) dose of ATG.

Definitely something to ask my doctor about. I really hope to map out the treatment plan with him this time around; I think we are getting along well enough for that. Last time I was in the hospital I was like a deer stuck in the headlights.

[Lisa V]

Bill, there seem to be differing opinions about how long to be kept in the hospital for ATG. I didn't think anything of it since they let him out the next day after his first treatment as well, but I've heard from others that their doctors held them for observation for a couple of weeks!

He didn't have any issues with his first round, so maybe that's why. In fact his doctor was so confident he'd sail through the second round without issue that he even suggested the possibility of doing it on an outpatient basis! That struck me as a really bad idea. As much as he would have liked to have been able to sleep in his own bed, I didn't want to be responsible if anything went wrong or he had a delayed reaction that I couldn't handle. He spent so much of the time hooked up to the IV, including during the night, that I can't see how it would have worked anyhow.

As it was, he developed a nasty C. dificile infection that had him puking and spewing out both ends for a couple of days, so I was kind of glad he was in the hospital for that, even though it was their own fault for giving him a broad spectrum antibiotic when he didn't need one. Arguably this wouldn't have happened under my care, but it's still not something you want to do outpatient. If you're not showing any signs of serum sickness, however, I don't see why they'd have to keep you more than a day or so once the infusions are finished. Again, how you did on your first one should influence that decision.

[Hawaii Bill]

Thanks Lisa!

Yes, my doctor has seemed adamant about my staying in the hospital for some time after the ATG is done. My understanding is that ATG stays in the system up to 12 days after the last dose.

The first treatment, he said a month was probably what it would take. I was severe back then, but in 26 days, I had a fever of 101 on ONE measurement, and it turned out to be an mild E-coli infection rapidly treated with antibiotics. The rest of the time I was just bored. I guess I should really have been happy about that! When I started pressing to get out, the guideline was less than 2 transfusions a week. I finally got there, and got out.

If we can agree on getting out 5 days after the last ATG, assuming everything looks good, I think I'd be pretty happy with that. I think that even if I was neutropenic, it might be safer to be at home than in the hospital.

[Lisa V]

Bill, you bring up a good point about being neutropenic. Ken's ANC never dropped below 0.7 so that wasn't a big issue, but I imagine it could be. But a month in the hospital for a 4 day infusion????

Now that you've brought up the topic, is there a "standard" protocol on how long to stay in for observation afterwards? You've got me thinking that maybe their letting him out early did not reflect good judgement, that maybe they needed the bed or were trying to save us some money or something. It worked out fine, but I'm just wondering what the conventional wisdom is on this. Does anyone know?

[Hawaii Bill]

I don't know what my ANC count got down to the first time round, but I never was neutropenic in the sense that they would take special precautions, alter my diet, etc... I remember specifically asking one of the covering hemos if not going neutropenic meant the treatment was not going to be effective. He said it wasn't necessary. I was free to move around, but looking back, walking all around Queens may not be one of the best things to do when you are compromised! (That's not a hit against Queens, it would apply to any large hospital).