Interferon-based Neutropenia § Infection - for willing § info gurus

[BeatHepC]

Do you know of any studies showing a correlation (or lack there of) between interferon-induced neutropenia and bacterial infection? My latest ANC came back at 0.6 (WBC at 1.8) and I have just taken my first shot of Neupogen. The last thing on earth I want is for an INF dose-reduction to occur. So, I'm hoping to find any good information to arm myself with in case my mext ANC (tomorrow) comes back on the low-side again. Thanks.

[willing]

As far as I know, the most direct challenge to the prevailing "ANC <.75 => remediate or reduce dose" rule is the following item from the April, 03 Hepatology which comments on a study by <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12395340">Soza, et al</a>. Hopefully Raheem will see your post : he's been surfing way below .75 for a while now. Mine went down to .6 while on tx and no infections resulted. Staying at dose seems like the right move.
---
Threshold for Neutropenia in the Adjustment of Interferon Treatment in HCV Infection
To the Editor:
We read with great interest the article by Soza et al.1 in the November
2002 issue ofHEPATOLOGY in which no association was reported to
exist between the onset of bacterial infection and neutropenia in
chronic hepatitis C patients undergoing combination therapy with
interferon alfa and ribavirin. Due to the reversible suppression of bone
marrow induced by interferon, along with the inhibition of myelopoiesis
and the potential risk for decreased neutrophil counts, patients
with pre-existing neutropenia (1,500/mm3) have been excluded from
previous large-scale, randomized, therapeutic trials with interferon and
ribavirin.2 In addition, to avoid increasing the risk for infection during
the period of antiviral therapy, dose adjustment and the complete
discontinuation of interferon generally are recommended when the
neutrophil count decreases below 750/mm3 and 500/mm3, respectively.
3,4 The exact risk for serious infection is therefore not yet known in
patients whose neutrophil counts have decreased below these levels
when no change in the interferon doses has been made.
The results of the present study fill this gap. This is the first time to
our knowledge that a large cohort of chronic hepatitis C patients has
been treated by combination therapy without applying criteria as to
the neutrophil count before and during the treatment.1 The baseline
neutrophil count was one of the variables studied here, associated with
at least one neutrophil count below 1,000/mm3 during treatment. We
reported previously that in a small group of 14 post–hepatitis C cirrhosis
patients, the onset of severe neutropenia (_750/mm3) during
the first 2 months of combination therapy with interferon and ribavirin
was caused only by the baseline neutrophil count.5 This finding
suggested that post–hepatitis C cirrhosis patients with pre-existing
neutropenia and an elevated rate of hepatocellular carcinoma have a
high risk for increased neutropenia, which leads to reducing their
interferon doses. In this case, these patients may seem unlikely to
achieve a sustained virologic response because the response to interferon6
and to combination therapy7 is known to depend on the dose as
well as on the duration of the antiviral treatment. However, similar
sustained response rates were obtained whether or not chronic hepatitis
C patients developed a significant level of neutropenia when the
dose of interferon prescribed remained unchanged.1
Although no immediate changes were made in the interferon doses
prescribed to our cirrhosis population, none of the 4 patients with
severe neutropenia showed any signs of infection during the treatment.
Moreover, the intensity of the flu-like symptoms, especially fever, did
not increase during the period of severe neutropenia. These data con-
firm the findings made in the study by Soza et al.,1 in which none of the
patients who developed infection had pre-existing neutropenia or levels
of less than 750/mm3 during the treatment. It is worth noting that
in the latter study the decrease in the lymphocyte counts was less
marked in the group with no infection than in the group with infection.
1 In our study, we established that the onset of severe neutropenia
was associated simultaneously with a relative lymphocytosis, which
might help to explain the absence of infection observed in patients with
severe neutropenia during the period of antiviral therapy.5 In addition,
the absence of infection observed here during the severe neutropenia
induced by interferon therapy suggested that the neutrophil function
was preserved in these patients: to our knowledge this point has not
been studied to date.
Based on these preliminary data, it can be concluded that the onset
of neutropenia during combination therapy with interferon and ribavirin
is not associated with subsequent infection, even in patients with
post-hepatitis C cirrhosis. However, changing the dose of interferon
affects the likelihood of achieving a sustained virologic response. Careful
clinical trials in which a lower neutrophil threshold is adopted in
the event of neutropenia are now required with a view to revising the
criteria on which dose adjustment and the discontinuation of interferon
should be based.
CHRISTOPHE RENOU, M.D.
ABDELOUAHID HARAFA, M.D.
Hepato-Gastroenterology Unit
Hyers Hospital
Hyers, France
CATHERINE CUMMINS, M.D.
Department of Family Practice
University of California
Irvine, CA
PIERRE MULLER, M.D.
Radiology Department
Hyers Hospital
Hyers, France
CHRITOPHE DEMATTEI¨, PH.D
ELISABETH JOUVE, M.SC.
CPCET
La Timone Hospital
Marseille, France
JEAN-JACQUES BERTRAND, M.D.
Virology Unit
Hyers Hospital
Hyers, France
PHILIPPE HALFON, M.D., PH.D.
Virology Department
Alphabio
Marseille, France
References
1. Soza A, Everhart JE, Ghany MG, Doo E, Heller T, Promrat K, Park Y, et al.
Neutropenia during combination therapy of interferon alpha and ribavirin
for chronic hepatitis C. HEPATOLOGY 2002;36:1273-1279.
2. Maddrey WC. Safety of combination interferon alpha-2b/ribavirin therapy
in chronic hepatitis C-relapsed and treatment-naive patients. Semin Liver
Dis 1999;19(Suppl 1):67-75.
HEPATOLOGY, Vol. 37, No. 4, 2003 CORRESPONDENCE 949
3. McHutchison JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi
VK, Goodman ZD, et al. Interferon alpha-2b alone or in combination with
ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998;
339:1485-1492.
4. Poynard T, Marcellin P, Lee SS, Niederau C, Minuk GS, Ideo G, Bain V, et
al. Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for
24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment
of chronic infection with hepatitis C virus. Lancet 1998;352:1426-1432.
5. Renou C, Harafa A, Bouabdallah R, Dematte&#305;¨ C, Cummins C, Rifflet H,
Muller P, et al. Severe neutropenia and post-hepatitis C cirrhosis treatment:
is interferon dose adaptation at once necessary? Am J Gastroenterol 2002;
97:1260-1263.
6. Chemello L, Bonetti P, Cavalolletto L, Talato F, Donadon V, Casarin P,
Belussi F, et al. Randomized trial comparing three different regimens of
alpha-2a-interferon in chronic hepatitis C.HEPATOLOGY 1995;22:700-706.
7. McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C,
Dienstag J, et al. Adherence to combination therapy enhances sustained
response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology
2002;123:1061-1069.
Copyright © 2003 by the American Association for the Study of Liver Diseases.
doi:10.1053/jhep.2003.50122
950 CORRESPONDENCE HEPATOLOGY, April 2003

[newb]

Can't cite no studies, but to ease your mind- my WBCs got down to 1.1 and Abs Neuts were in the .4 to .7 range for many months, and I didn't have any major problems. I decided to stop the big dose 2x/weekly Neupogen shots 2 months before tx end since they didn't seem to make any difference in my counts, and still stayed infection free.

Good luck.

[CARUU]

My doc reduced my INF dose at about 14 weeks and then increased it as my ANC increased.  I can't seem to get it above 650/700 so I remain at 75% dosage.  I believe the 80% rule applies to the first 12 weeks of tx.  Full dose of riba is very important to maintain throughout.  I'm now 22/24 and was undetectable at 12 weeks. (I have to admit I sneak a couple of extra drops of INF into the syringe before injecting).

[raheem]

I just happen to have my blood work at my finger tips.  I'm currently on 42/48 Pegasys/ribavirin, 1b, 50yr. old male. I started tx on 6-1-03.  Within a month, my WBC was 1.5 and ANC was 900.  Within 2 months, my WBC was 1.5 and ANC was 660. Within 3 months, WBC was 1.2 and ANC was 516. The WBC and ANC drifted up and down a little until the end of December when WBC was 1.2 and ANC was 444.  I had 30 weeks of full dosage at this point.  However, my doc thought it was prudent to reduce the interferon dosage 25%.  He said "there is little evidence that dropping the interferon dose at this point in my tx reduces response rates (in contrast to dropping the ribavirin dose which clearly reduces the response rates)". He also said that "the data really don't show that infections are more common with an ANC just below 500 than just above it".  Some of the studies used have been with cancer patients NOT Hep C tx.  Anyway, the next blood test in January was even worse; WBC at 1.1 and ANC at 451. February; WBC at 1.4 and ANC at 658. March; WBC at 1.2 and ANC at 432. Despite the continuous low numbers, I have been absolutely infection free for 42 weeks!  Because of the profound neutropenia I have indeed been very careful about handwashing, eating right, not sticking my fingers in my eyes, limited social contacts, etc.  My doc is not a Neupogen advocate so his preference was to reduce the interferon dosage 25% after 30 weeks.  Hopefully, it will turn out to be the right decision. I stayed on the full ribavirin dose but did take Procrit about 4 months into tx for the anemia. It is an excellent question and the main side effect that I have struggled with all during tx.  I've read the Pegasys product literature but I get the sense that we are all (doctors and patients) kind of stumbling along through the combo tx process and there are no exhaustive HCV studies yet available that can really say to a reasonable degree of medical certainty that folks with HCV on tx with an ANC below 500 are at a severe risk for infection.  For me, taking proper precautions seems to have worked.....so far.

[Honey15637]

Best of Luck to you and please let us know tomorrow what you find out!!  You will be in my prayers!

[Galen]

My ANC dropped to 900 at the end of week 2 and stayed that way, so my doc reduced my inf by 25% from weeks 6 through 8.  At that point I insisted that my dosage be upped and that I get Neupogen.  I did Meupogen and Procrit from week 9 to the end at 48 weeks and not once did I get any other infections.  Even with the Neupogen, my neutrophils never got above 1,200.  I always sorta felt like hell from tx, but had no other infection, cold, or anything else throughout tx.

[Ballermarc]

HI Folks.. This is both a comment and a question, everytime I go to post a question, the forum tells be they are closed for questions..a bit frustrating, but I guess I gotta start earlier in the day. In reading about this topic, Interferon-based Neutropspenia, it brings to mind a frustration I have. I hear lots of references to different blood chemistry counts.My Dr. sent me a follow up letter noting that my white count was 6 hematocrit was 48,platelets 249,000 INR normal, viral load,500,000 and TSH 1.49. I attempted to track down on the internet what these numbers mean, and how much they vary, and what is normal and what happens and what does it mean if the counts are high, low, etc... I could not get any good information. Now you all are talking about neutropspenia,and all kinds of other lab#'s and their meanings. Is there any difinitive listing of what lab tests are done on us with hep C, and what they are testing for, and what it all means? Thanks, M

[cuteus]

I am in the east coast and I have better luck at posting a new question after 9 am.  we only get 6 a day, though I have seen more and less on different ocassions, so if you count about 6 for the day, just post your question within the existing thread.    Good luck

[Ballermarc]

Thanks, great reference. M

[Honey15637]

Does anyone know what RDW-CV means?  I can't find what that is on lab reports.

[Honey15637]

Thanks so much!! :))

[mll]

ok, I am soooo confused. What is neutropenia???????? My docs nurse called today and said my neutrophils have dropped and that I needed to have immediate blood work done tomorrow and that if they drop below 1000 he will either tell me I can't take my shot # 4 on Sat. night or he might reduce the dosage. I was lurking wondering what neutrophils were when I started reading this thread about neutropenia. Can someone fill me in?
Thanks
Michelle

[willing]

Hi Michelle - the import of this thread is that (1) tx wreaks havoc with your ANC (2) that's not necessarily a problem. Interrupting/lowering your IFN at week 4 on the other hand could have an impact. Getting excited because you're below 1.0 seems overly cautious : if you read the fine print on the insert that came with the meds you'll see it specifies a .75 threshold and, as evident above, many go pretty far below that. A fairly common theme on this forum is the need to "actively participate" in dosage reduction decisions.