Thursday, September 30, 2010

HCV Treatment and Neutropenia(low white count)

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White blood counts: What is to low ?
Combination therapy with interferon and ribavirin commonly drives down the white count and especially a certain type of white cell called neutrophils that are important in fighting bacterial infections. It is important for people to appreciate that it is the interferon part of the treatment that really drives down the white count. It is possible that the (ribavirin) part contributes, but studies show that when they use interferon alone, they see the same problem. As a result, if the white count or the neutrophil count gets to be very low, doctors might typically adjust down the interferon dose and not the Ribavarin dose.
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With time and experience, studies have showed that people treating hepatitis C can tolerate a lower white count on treatment than originally thought. If they are able to keep the neutrophil count (ANC) above 750, people do not typically develop infections.

Also, doctors sometimes use a second drug called GM-CSF or Neupogen to keep up the white count. Neupogen is a drug that is used primarily for cancer patients receiving chemotherapy. It is effective in getting the bone marrow to make more white cells. Like interferon, it has to be injected.

How To Figure Out If Your Neutrophil Count
Neutrophil% x White Blood Cell = Absolute Neutrophil Count
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For example, if a person's white blood cell count were 6,000 cells, and neutrophils made up 50% of those, that person's absolute neutrophil count would be 3,000.
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A normal range for neutrophil% is between 33% and 72%. This makes the normal range for the ANC between 1500 and 7200. Since every individual is unique, you should consult your physician or nurse if you have questions concerning your white blood cell count and ANC.
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If you’re total white count is 1.0 (1000) or below then your neutrophils would be around 500… to low to continue therapy. Although treatment is not always discontinued (in some cases) the dose is cut back until the white count increases.

Here Is The Latest Abstract
Hepatology. 2010 Oct;52(4):1225-31.
Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C. ,Roomer R, Hansen BE, Janssen HL, de Knegt RJ.
Departments of Gastroenterology and Hepatology, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract

Neutropenia During HCV Treatment
Neutropenia during treatment with peginterferon alfa and ribavirin for chronic hepatitis C virus (HCV) infection is a common cause of dose reductions of peginterferon alfa. These reductions are performed to prevent bacterial and fungal infections, which are common during HCV treatment and can be attributed to neutropenia. .

What Are The Aims Of This Study ?
The aims of this study were to investigate the occurrence of infections and their relation to neutropenia and to identify potential risk factors for infections during HCV treatment.

How Many People In The Study ?
In this single-center cohort study, 2,876 visits of 321 patients treated with peginterferon alfa and ribavirin were evaluated for neutropenia, infections, dose reductions, and potential risk factors for infection during HCV treatment.

The baseline mean absolute neutrophil count (ANC) was 3,420 cells/μL, and 16 patients had a baseline ANC of less then1,500> .

How Many People Had Infections ?
Ninety-six infections were observed in 70 patients (21.8%).

Thirteen infections (13.5%) were defined as severe.

Infections were not correlated with neutropenia during treatment.

Did Dose Reductions Decrease Rate Of Infection?
Dose reductions did not lead to a decrease in infection rate. Multivariate logistic regression analysis revealed that age >55 years (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.19-3.56, P = 0.01) and baseline hyperglycemia (OR 2.17, 95% CI 1.15-4.10, P = 0.016) were associated with an increased risk of infection during HCV treatment.

Did Cirrhosis and COPD Have Risk Factors ?
Cirrhosis and chronic obstructive pulmonary disease were not risk factors for infection.

Was Infection Associated With Treatment and Low White Count ?

Conclusion:
Bacterial infections during treatment with peginterferon alfa and ribavirin are not associated with neutropenia. Older patients and patients with poorly controlled diabetes mellitus have a greater risk of developing infections during HCV treatment. (HEPATOLOGY 2010).
PMID: 20830784 [PubMed - in process]
LinkOut - more resourcesk

Bacterial Infections and Low White Count During Treatment
White blood cell:
One of the cells the body makes to help fight infections. There are several types of white blood cells (leukocytes). The two most common types are the lymphocytes and neutrophils (also called polymorphonuclear leukocytes, PMNs, or "polys").

Lymphocytes are made in lymphoid tissue in the spleen, lymph nodes, and thymus gland. There are different kinds of lymphocytes. Lymphocytes identify foreign substances from germs (bacteria or viruses) in the body and produce antibodies and cells that specifically target them. It takes from several days to weeks for lymphocytes to recognize and attack a new foreign substance.

Neutrophils are also major players in the body's defense against bacterial infections. Neutrophils are made in the bone marrow and circulate in the bloodstream. Neutrophils move out of the blood vessels into the infected tissue to attack the bacteria. The pus in a boil (an abscess) is made up largely of neutrophils. Normally a serious bacterial infection causes the body to produce an increased number of neutrophils, resulting in a higher than normal white blood cell count (WBC). When the WBC is low, there may not be enough neutrophils to defend against bacterial infections.

The white blood cell count is done by counting the number of white blood cells in a sample of blood. A normal WBC is in the range of 4,000 to 11,000 cells per microliter. A low WBC is called leukopenia. A high WBC is termed leukocytosis.

A normal absolute neutrophil count (ANC) is in the range of 1,500 to 8,000 cells per microliter. If the ANC is below 500 for an extended period of time, the risk of serious bacterial infection may increase significantly. A low neutrophil count is called neutropenia.

Sep 17, 2009 —
SOURCE: Digestive Diseases and SciencesReduction in Neutrophil Count During Hepatitis C Treatment:

Drug Toxicity or Predictor of Good Response?

BACKGROUND:
Bone marrow suppression is a well-recognized toxicity of the treatment of hepatitis C virus (HCV). Reduction of the peginterferon dose because of neutropenia is common in clinical practice. However, reduction of peginterferon dose during the first weeks of HCV treatment is associated with failure to achieve sustained virological response. AIMS: The objective of this study is to investigate whether the fall of neutrophil count during hepatitis C treatment is associated with achieving sustained virological response.

METHODS:
We performed an observational study of patients who completed peginterferon and ribavirin treatment in an Infectious Diseases Department in Manchester, UK.

RESULTS:Of the 74 patients included in the analysis, 78% had genotype 2 or 3 hepatitis C and 15% had liver cirrhosis. Sustained virological response was achieved in 78% of patients. On univariate analysis, factors related to achieving sustained virological response were younger age, genotype 2 or 3, baseline neutrophil count, and fall of neutrophil count during treatment. Multivariate analysis showed baseline neutrophil count>3.5 x 10(3) cells/mm(3) [odds ratio (OR) 5.7; 95% confidence interval (CI) 1.24-26.3] and a reduction of neutrophil count>60% (OR 4.5; 95% CI 1.03-19.9) to be independently associated with achieving sustained virological response. Neutropenia was not associated with an increased risk of infections.

CONCLUSIONS:In this observational study, higher baseline neutrophil count and fall of neutrophil count during the treatment of was associated with achieving sustained virological response. These findings could have important implications for the monitoring and management of HCV treatment with peginterferon if they are confirmed in other studies.

NAMENEUTS (Neutrophils)NORMAL RANGE2.2-8.6 K/µl
DEFINITIONThese are WBC that play a key role in inflammation, allergic reactions, pus formation, and in destroying bacteria and parasites.

EXPLANATION OF TESTRESULT
Low neutrophil can mean infection or inflammation. Interferon treatment is associated with low neutrophil levels. Therefore, you must have normal levels of neutrophils to start interferon.

Low weight predicts neutropenia and peginterferon alfa-2a dose reductions during treatment for chronic hepatitis C

Y. Rotman1,2,4, L. Katz3, M. Cohen1,2,4, O. Cohen-Ezra1, V. Manhaim1, M. Braun1,4, Z. Ben-Ari1,4, R. Tur-Kaspa1,3,4
Article first published online: 11 FEB 2009DOI: 10.1111/j.1365-2893.2009.01079.x

Keywords:bone marrow depression;chronic hepatitis C;neutropenia;pegylated interferon alfa-2a;side-effects;weightSummary.

Treatment-induced neutropenia frequently complicates the treatment course of patients treated with pegylated interferon alfa and ribavirin for chronic hepatitis C.

We investigated the effect of weight on the risk for dose reductions caused by neutropenia in patients treated with a weight-independent dose of peginterferon alfa-2a.

We retrospectively analysed single centre data for 172 patients enrolled in a multi-centre, open-label trial of peginterferon alfa-2a and ribavirin for chronic hepatitis C.

Low body weight was significantly associated with dose reductions due to neutropenia.

Patients weighing less than 62 kg had a 35% risk for significant neutropenia as opposed to a 12% risk for heavier patients (P = 0.001), and this side-effect occurred earlier during treatment. Low weight was an independent risk factor by multivariate analysis (hazard ratio 0.956/kg).

The risk for treatment-induced neutropenia was associated with body surface area more than with the body mass index. In conclusion, a low pre-treatment weight strongly predicts the need for peginterferon alfa-2a dose reductions. This apparently reflects overall body size more than body fat content. It is prudent to frequently monitor blood counts for smaller-sized patients, especially during the first weeks of treatment.
Source

Diagnosing Neutropenia During Chemo (Not HCV Treatment)
Neutropenia can be a serious side effect of treatment, so your doctor will carefully monitor your blood cell counts during treatment. A complete blood count (CBC) is a blood test that measures the levels of these cells in your blood. To diagnose neutropenia, your doctor will evaluate the absolute neutrophil count (ANC) portion of the CBC. The result of the ANC dictates your risk of infection and what treatment may be necessary to prevent or treat existing infection.
When discussing your CBC results, your doctor may talk about specific numbers in relation to your results. Of course, he or she will explain them in detail, but the summary below will help you get see the "bigger picture" in relation to ANC values:

Normal ANC Values: Normal ANC values range from 2,500 to 6,000 neutrophils per cubic millimeter. Ranges vary on a number of factors, from someone just getting over being sick; the presence of infection, diseases and other conditions that may influence count; and even race.

Mild Neutropenia:
Once ANC counts drop to 1,000-1,500, this is considered to be mild neutropenia. If you have mild neutropenia, you aren't at a great risk of developing an infection, but your doctor will probably instruct you to look for any signs of infections and report back any changes.

Moderate Neutropenia:
Moderate Neutropenia occurs when ANC levels are between 500-1,000. If you have moderate neutropenia, then your risk of developing infection is moderate. If you develop symptoms of infection, like fever, you may still be able to monitor them at home, but some people may require hospitalization depending on other factors and test results.

Severe Neutropenia:
If you have a "neutropenic fever" (a fever as well as an ANC count below 500), hospitalization is usually required. People with severely low ANC counts often do not show any signs of infection when it is present. This is due to the lack of neutrophils to elicit a biological response.

Treating Neutropenia
kIf your ANC reveals a low neutrophil count, treatment may be necessary to prevent infection. Mild cases of neutropenia may only require monitoring at home for signs of infection while more severe cases may need hospitalization.
In some cases, your doctor may recommend a course of antibiotics to prevent infection before it develops. This is called prophylactic antibiotic therapy.

Other medications, called growth factors or granulocyte-colony stimulating factors (G-CSF), are often used to increase white blood cell production in the bone marrow. Commonly used growth factors include:
Leukine (sargramostim)Neulasta (pegfilgrastim)Neupogen (filgrastim)

Your doctor may also want to halt or delay treatment until your neutrophil count is stable. A lowered dosage of chemotherapy may also be necessary.

Neutropenia and HCV Treatment

Neutropenia - Interferon Therapy of Hepatitis C - HCV Advocate -
In conclusion, neutropenia is frequent during treatment of hepatitis C with .... The changes in neutrophil and lymphocyte counts during treatment are shown in Fig. 1. .... Among the exclusion criteria for therapy, low white blood cell and ... Bacterial infections did not occur in neutropenic patients, and the only ...
Maintaining the maximum dose of interferon and ribavirin
is important for achieving a sustained virological response
(SVR) so some medical providers will prescribe an injectable
growth factor, granulocyte colony-stimulating factor (G-CSFfilgrastim),
brand name Neupogen
Hepatitis C Support Project •
www.hcvadvocate.org ...

What About Neutropenia and Telaprevir ?

EDITORIAL
Decreases in hemoglobin, total white blood cell count, neutrophils, and platelets occurred during the study drug dosing period; median changes from baseline to day 28 were _2.8g/dL for hemoglobin (range: _6.2 to _0.8), _3.75_109/L for white blood cell count (range: _6.45 to _1.26), _2.39_109/L for absolute neutrophil count (range: _3.94 to _0.17), and _86_109/L for platelet count (range: _125 to 21). The only clinically significant hematology abnormalities were anemia in four patients and mild neutropenia in one patient.

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