Houston, This doesn't make sense...

[gauf]

What the hell?!!  Labs look great.  This is unexpected because I felt sure things would go south this week.  Because a 12 week PCR with an ultrasensitive test was getting drawn this week; I did a DD of Peg last Thursday to give myself one last powerful push before settling down for the long haul.... Still on 1600 Riba. I had a miserable week. Nausea for the first time, fatigue, insomnia, headache... all the usual suspects. My Nuepogen was reduced from 3 shots to 2 just prior to the DD. So what would one expect to see on this weeks labs? Certainly no change at best and  probably a drop. NO! Everything improved?!  The biggest jump was to my platelets? WBC is up. HGB is up. Just too weird.

I had such a rough week that I figured it was time to reduce the RIBA to 1400. After reading the post on RIBA concentrations and in lieu of these labs, I just may increase it. But no more DD of peg, I have to keep working.

I again have to assume something in my supplement regimen is working.  

I posted here the lab results of today followed by last weeks contrast for any interested.

8/7/09
WBC 6.71 4.0-11.0 k/uL  
  Repeated and verified
RBC 3.39 4.5-6.0 M/uL                 L
Hemoglobin 11.2 13.5-17.5 g/dL    L
Hematocrit 37.7 40-52 %              L
MCV 111.2 80-100 fL                   H
MCH 33.0 27-34 pG  
MCHC 29.7 32-36 g/dL                 L
RDW-CV 16.9 11.7-15.0 %           H
-------------------------------------


8/1/08
WBC 6.43 4.0-11.0 k/uL  
RBC 3.27 4.5-6.0 M/uL                      L
Hemoglobin 10.9 13.5-17.5 g/dL         L
Hematocrit 36.8 40-52 %                   L
MCV 112.5 80-100 fL                        H
MCH 33.3 27-34 pG  
MCHC 29.6 32-36 g/dL                      L
  Repeated and verified
RDW-CV 17.1 11.7-15.0 %                H
Platelet Count 48 150-400 k/uL          L


"Houston, All systems functioning normally... how about those reentry procedures?"

"Negative 13, you need to stay in orbit for another 36 weeks to successfully complete this mission..."

" Copy that Houston.... as long as life support systems continue to hold..."

[gauf]

Platelets this week at 57.

[jmjm530]

The possibility exists that you may not be metabolizing ribavirin very well, as studies suggest that serum concentrations and hemoglobin response are more important than a patient's weight.

Bottom line I would think is what's happening with your viral response? Are you UND yet and at what week?

If you're already UND by a very sensitive test, then you might think twice about upping the riba. On the other hand, if you're not showing a fast enough viral response, then you might try and get hold of the Swedish High Dose Riba study (full text) and see what doses some of the patients were on.

Of course, this assumes you are willing to take the inherent risks in a more agressive strategy. Forgot if you're on Procrit, but all members of that study eventually went on epo and two (out of ten) required multiple transfusions. It's a shame HPLC testing is not available here, but you could get tested in Europe if so motivated.

-- Jim

[gauf]

I was UND <50 between wk 3 and 7. Had the <2 test drawn yesterday and get results 10 days or so. I have taken the riba with food and try to take it with something high fat. I have been on 1 shot of procrit a wk since week 4 or 5. Should I increase the riba some if I can tolerate it?

[jmjm530]

What do you mean "between wk 3 and 7" ? Is your memory that bad :) Since you're on Procrit, that may be the reason your hgb is advancing up, as it can take up to six weeks to fully kick in. If you show up UND at <2 maybe best to leave well enough alone but I would go back to single Peg shots once UND, at least that's the plan my docs had with me.  Beyond that -- after getting your 12 week results --  you might want to shoot K. Lindahl an email with all your stats/history and see what she suggests. Her email is out there on the web somewhere.

-- Jim

[gauf]

LOL, no my memory is fine. I started treatment a wk later than the doc thought, so my 4 wk PCR was actually taken at 3 weeks which was between 50 and 600. The 8 wk PCR (which was actually at 7 wks showed me UND <50. So I went UND between wk 3 and 7. And very well might have been UND at 4 wks, which would make me an RVR. My HGB started improving 2 wks post procrit. Who is K.Lindahl.

[jmjm530]

http://www.ncbi.nlm.nih.gov/pubmed/15660393

[gauf]

Interesting study.

"After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24."

Yikes, that is a lot of riba!

[jmjm530]

Don't even think about it unless you are prepared to buy a plane ticket to Stockholm :)

[gauf]

....maybe just 2000 then.....

[mikesimon]

I really wouldn't interpret those labs as showing improvement. They are basically unchanged. I had labs drawn at Quest for 2 different doctors on the same day at the same time. There were differences on the two sets of lab results that were very similar to yours. Hemoglobin was different by .3 and RBCs by .4. Platelets -  3,100 difference. You can see differences like yours in labs drawn at the same time-  different vials of blood will have slightly different values and there can be minor testing discrepancies. I wouldn't get too excited about the impact of supplements but it's nice to see that your values haven't gotten worse.

[mikesimon]

Platelets differed by 3,000.

[gauf]

Figured that too, but they continue to swing up only. Seems they would also swing down. Anyway, it sure looks good on my cbc tracker!

[jmjm530]

If you titer up -- and I'm not suggesting that -- do it in 200 mg intervals spaced 2-3 weeks apart -- and test hgb weekly or more if you develop symptons.

[mikesimon]

Even if you call it "unchanged" it's good. Mike

[gauf]

Yah, exactly what I'll do. Thanks guys.

[jmjm530]

Why don't you wait to see if you're UND with the sensitive test first? Remember, you can't win if you don't cross the finish line no matter how much riba you take :)

[gauf]

Am I missing something Jim? Is the Riba only really effective while the VL is detectable? It has bearing on the "mop up" phase, right?

[FlGuy]

Don't see any results in there (like absolute neutrophil count or percentage) that would drive a decision about Neupogen. Unless doc is looking at wbc only, which (from my expereince) 6.43 is a high number for someone on tx.

[jmjm530]

That's why I suggested you email LIndahl. Many here seem to think riba's most potent effect is early, however I did hear that Lindahl thought it might have some effects later as well. That was the theory I was under when I wanted to max out riba even after UND but other than my early burst, I was never able to tolerate more than 1200/day with 40-60,000 units of Procrit per week. Going beyond your current riba dose really should be between you and the doctors, so I'm bowing out :)

[HCA]

My doc emailed Lindhahl eighteen months ago for info on HDLC test and never got a reply.I think she has moved on.Those trials were many years ago.
I could not find a lab that could meaure Riba serum levels.Tried QuestLabs who tried to help but couldn't.
All the studies I have read suggest Riba is most critical in the early weeks of treatment to supress the design of a wild type mutant.This theory endorsed by HR..
Studiies indicate Riba reduction post sixteen weeks into treatment does not compromise SVR.
Personally I don't think increasing Riba dose mid treatment is likely to be beneficial-it is the saturation of the liver cells at the point when the T Cells are given the attack order by the interferon that counts.I think pre-dosing Riba makes a lot of sense.
In any event I am just an informed lay man -I don't claim to be an expert.

[nygirl7]

Maybe I'm stupid and missing the whole thing but if you are UND and did so as it seems as an RVR - why are you even thinking of changing anything?  Perhaps you are just lucky this time being on the procrit - not having a steady decline and you'll be ok and not experience the death sides that some of us get?

If you weren't UND and were trying to get there it would seem maybe it would be in order however you ARE UND..............so what's the deal...........be happy, keep going and get that SVR without experiencing hell at the same time!

WOO HOO that's GREAT news - who wants CHANGES in your labs!!!!!!! no WAY!

[gauf]

ANC on 7/3 was just .26 and nuepogen increased to 3 from 1 shot a wk. In a week ANC went to 2.3, and have steadily climbed to a current 5.14 Went down to 2 shots nuepogen a week ago.
-----------------

Well, I am very glad I titered up the riba and increased dose from 1200 to 1600. I believe I could have tolerated more and still do, but it may be a mute point by now after 12 weeks. I just do not want to leave any stone unturned as long I am tolerating it. Guess I will hold at 1600 unless opinions change my mind. You guys rock!

[Marcia2202]

Wow, I really admire your tenacity!! I'm sooo rooting for you!!

Marcia

[geterdone]

Hope this helps

jasper


http://www.natap.org/2003/june/060903_3.htm

In the seminal article on viral kinetics in hepatitis C, Neumann et al. used 3 differential equations to resolve the decrease in HCV-RNA levels during daily interferon therapy into 2 distinct phases. The first phase was the initial sharp decay in HCV-RNA levels that occurred within the first 24 hours of therapy. The researchers related this first phase decline to the antiviral "efficacy" (e) of interferon in blocking viral production and secretion. The value of e was calculated to vary from 0 (no blocking) to 1 (100% blocking). The second phase decline described the subsequent, more gradual decrease in HCV-RNA levels, which the researchers attributed to the rate of killing or clearance of virally infected cells (f), superimposed on . The differential equations also provided estimates of the spontaneous clearance of HCV RNA from serum (viral half-life) and the rate of virus production. These mathematic formulae accurately predicted both group and individual data during therapy and revealed that HCV has a high rate of replication (1012 virions/d) and short half-life in serum (1.5 to 4.6 hours), particularly in comparison with hepatitis B virus (1011/d and 24 hours) and human immunodeficiency virus (1010/d and 5.8 hours) analyzed in a similar manner.

Serum HCV RNA was measured frequently before, during, and at the end-of-treatment and the follow-up period. By using an appropriate model for viral dynamics, kinetic parameters were derived from nonlinear, least square fitting of serum HCV RNA quantifications. “…The first phase of viral decay (day 1) and the second phase of viral decay (days 2 to 21) were similar for all treatment groups. After about 7 to 28 days, a third phase of viral decay was seen in several patients, and this phase of decay was significantly faster in patients treated with peginterferon alfa-2a plus ribavirin”… compared with those treated with peginterferon alfa-2a alone. “…The decay of this third phase was associated with the virologic end-of-treatment response and sustained virologic response. In conclusion, the third-phase decay of initial viral kinetics, which may represent a treatment-enhanced degradation of infected cells, was more pronounced in patients treated with peginterferon alfa-2a plus ribavirin. This finding suggests that combination treatment leads to a better restoration of the patient's immune response”.



Gauf,

CRS but I think it was willing who discussed Lindahl with me about this subject and had led me in an unnatural direction towards the end of treatment. If I can remember which file it is in I’ll repost it but this may be suffice for the time being. The meds have done there job for you so far and you may want to back off and coast for a while and then towards the eot, say week 40 put the hammer down and man the torpedoes. Remember, CRS but patched this together and the above was part of my formulation for peace of mind after all said and done. I also had a very erratic time line of dosing since the beginning of TX. The only red flag is see is all the artificial supps you have been taking and how is your body going to react when they stop as it seems to me that the roller coaster ride will go on for some time after the treatment ends.  Good Luck!

Jasper

UND since week 8

180-peg INF  x44 weeks
1200mg Riba x20 weeks, reduction because of sx.
1000mg Riba x24 remaining weeks until stoppage.
Abrupt stoppage INF after week 44 shot
Continuation 1000mg Riba, 2xam/3xpm, 15 days
Time laps of INF from last shot, 15 days
Time laps of Procrit from last shot 19 days

Continued weekly Riba 1000mg of monotherapy through week 45,
No Procrit or INF during this week.

So, to me in my particular situation, it would seem logical in the last 4 weeks of SOC treatment to create a window of opportunity (mine was by default) to allow any undetected virions to surface, and in that last 4 weeks of Treatment, to repeat the “first stage” of treatment (or reverse spin) for a short duration of time because in this stage is when the initial and strongest eradication of the virus is eliminated and by having low or very little natural INF production at this point and time and through the chemical signaling process of the cascading induced INF in the serum the virus signaling process picks up on the lessening effects of the INF.

So, this is where I had restarted as with the beginning of Treatment, but in a shorter duration with the a max dose of 180 plus ¼ more of INF and upped the Riba to 1200mg for the next four weeks. The Procrit was split up to 2x a week, Tue and Thur. for the gradual increase in the serum and as to not to triple shock the system of all full dose meds as in the beginning of treatment and not to have the major/minor side effects. The saving grace in my particular situation (I think and am not totally sure) is at the stoppage of the Procrit my hemoglobin was at 13.8 or there about and had been steady for several months.


Defcon 5, Restart Treatment at week 46 // shot 45

Done - Week – 45, Mono Ribavirin 1000mg Friday – Saturday
     Insurance gap, No INF-peg or Procrit

Done - Shot 46
180 INF Plus 1/4
Riba 1200mg 3x am 3x pm Friday - Thursday
Procrit .50ml 2x weekly

Done - Shot 47
180 INF Plus 1/4
Riba 1200mg 3x am 3x pm Friday - Thursday
Procrit .50ml 2x weekly

Done - Shot 48
180 INF
Riba 1000mg 2x am 3x pm Friday through Friday / Saturday Dropped to 800mg
Procrit .50ml 2x weekly

Done - Shot 49
180 INF
Riba 800mg Saturday through Monday / Tuesday Dropped to 600mg through Thursday.
Procrit .50ml 2x weekly

It would be advised to discuss this with your doctor and not act upon this yourself. I am NOT advocating this to anyone except for myself because it is a best course of action for me given my past 49 weeks, (week 45 in mono Ribavirin) of treatment and the tracking of my blood work (excel spreadsheet) through out treatment and the side effects of the medications through the different up dose stages at the beginning and through out treatment and the inter related and the cumulative side effects of each and the effects placed on my body during the duration of that time. It, to me is a better alternative than just stopping abruptly and suffering the possibility of shock syndrome to the immune system and the consequence of post TX symptoms. No body knows your body better than you not even your doctor and at some point in time during treatment (around week 35) you have to start thinking about the end of the journey and what will be the aftermath of it.

Defcon 5, Restart Treatment at week 46 // shot 45

Done - Week – 45, Mono Ribavirin 1000mg Friday – Saturday
     Insurance gap, No INF-peg or Procrit

Done - Shot 46
180 INF Plus 1/4
Riba 1200mg 3x am 3x pm Friday - Thursday
Procrit .50ml 2x weekly

Done - Shot 47
180 INF Plus 1/4
Riba 1200mg 3x am 3x pm Friday - Thursday
Procrit .50ml 2x weekly

Done - Shot 48
180 INF
Riba 1000mg 2x am 3x pm Friday through Friday / Saturday Dropped to 800mg
Procrit .50ml 2x weekly

Done - Shot 49
180 INF
Riba 800mg Saturday through Monday / Tuesday Dropped to 600mg through Thursday.
Procrit .50ml 2x weekly

Done - Shot 50
135 INF
Riba 800 mg 2 am 2 pm Saturday through Monday / Tuesday Dropped to 600mg through        Thursday.
Procrit .50ml 2x week Tuesday and Thursday

Done - Shot 51
90ml INF
Riba 400 daily 1 am 1 pm, Friday through Thursday
Procrit .25 2x week Tuesday and Thursday

Done - Shot 52
35ml INF
Riba 200 daily 1pm Friday through Thursday
Procrit .25 once a week, Tuesday

Done - Shot 53
1/8 INF
No Riba
No Procrit

Was UND at week 48 SOC and waiting 6 month PCR in Sept. Lab Corp. 140639

[rita863]

Ground control to major Tom!!!  

Sounds good to me!!!!

i really have nothing to add to the above post, i just wanted to say to you Houston!!!


Peace
rita