BLOOD COUNTS TO TRACK FOR CML PATIENTS
By Kelly Harless of the Asian CML Support Group



What blood counts should we track?

An individual who has been diagnosed with CML should have routine blood tests, including a Complete Blood Count
(CBC), blood differential and liver function tests (LFTs), done on a regular basis to help monitor treatment response.  
The following counts are important to determine one’s clinical status:

COMPLETE BLOOD COUNT AND DIFFERENTIAL:
A Complete Blood Count (CBC) that measures the number of white blood cells (WBCs), red blood cells and platelets in
the patient's sample of blood should be routinely monitored in CML patients.  There are actually five kinds of white
blood cells, each with a different function.  The five types of white blood cells are monocytes, lymphocytes, basophils,
eosinophils and neutrophils.  A blood differential that measures the relative numbers of these different kinds of WBCs in
the blood and includes information about abnormal cell structure and the presence of blasts or myeloblasts (immature
white blood cells) should be done in tandem with the CBC.

The overall White Blood Cell (WBC) count is important to monitor as a significant elevation in WBC may indicate
infection, lack of response to treatment, or worsening of leukemia.  Conversely, some treatments for leukemia suppress
the WBC and it is important to make sure the WBC does not dip below a critical range.  The normal range for WBC is
generally from 4.0 to 11.0 k/ul.  

Neutrophils are a type of white blood cell involved in fighting infection.  It is important they remain at adequate levels.  
As with platelets, neutrophil levels may become depressed in patients on myelosuppressive therapy such as imatinib
mesylate (also called IM, Gleevec or Glivec).  The normal range of the percentage of neutrophils is between 45% and
70%.  

More important than the percentage of neutrophils is the absolute neutrophil count (
ANC), which should fall between 1.0
to 8.0 k/ul.  The reason the ANC represents the true clinical picture better than the percentage of neutrophils is that, in
cases where blood counts are suppressed by therapy, the percentage of neutrophils will be higher when the overall
counts are low.  One may calculate the ANC by multiplying the percentage of neutrophils (in decimal form) plus the
percentage of bands (in decimal form) by the total number of white blood cells.  The number of bands is usually quite
low or even zero, so one may also obtain a fairly accurate ANC by leaving the percent of bands out of the equation

The
basophils should remain within the normal range, generally between 0% and 2%.  Some clinicians believe that, as
in the case of neutrophils, the absolute basophil count is more important than the percentage of basophils and should
fall between 0 to 0.3 k/ul.  The absolute basophil count is calculated by multiplying the percentage of basophils (in
decimal form) by the total number of white blood cells.

One should monitor
blasts in the peripheral blood.  Blasts are immature white blood cells and individuals with leukemia
have an excessive number of blasts in their peripheral blood and bone marrow.  With appropriate treatment, there
should not be any blasts in the peripheral blood and fewer than 5% in a bone marrow aspirate.

Platelets also constitute an important component in the hematological picture for a CML patient.  An escalated and
uncontrolled platelet count may indicate disease progression and is cause for concern.  In general, with appropriate
treatment, platelet levels should fall within the normal range (150 to 450 k/ul) without platelet-lowering medication.  
Platelet levels may be depressed in patients on myelosuppressive therapy such as IM and it is important they remain at
adequate levels.   

Finally, one should keep an eye on
hemoglobin and hematocrit counts.   If one’s treatment suppresses the counts, it is
important not to become too anemic.  Normal hemoglobin levels range from 14.0 to 17.0 gm/dL and the hematocrit
value should fall between 40.0% and 52.0%.

When are low counts cause for concern?  The answer to that question depends somewhat on the individual patient, the
larger clinical picture and the therapy received.  In general, for patients on imatinib mesylate therapy (Gleevec or
Glivec), the following levels may warrant a decrease in dose, an interruption of therapy or the use of growth factors:
WBC less than 1.0 k/ul; platelets less than 50 k/ul; hemoglobin less than 10.0 gm/dL; and ANC less than 1.0 k/ul.

It is important to note that the normal or reference range for blood counts will vary slightly between laboratories, but the
following table provides a summary of the normal ranges for the counts discussed above.

Reference Ranges for Peripheral Blood Counts and Differential

Reference Range        Units        Absolute Count
White Cell Count        4.0 – 11.0        k/ul        -
Platelet        150 - 450        k/ul        -
Basophil        0 – 2        %        0 – 0.3 k/ul
Blast        0        %        -
Hemoglobin        14.0 – 17.0        gm/dL        -
Hematocrit        40.0 – 52.0        %        -
Neutrophil        45.0 – 70.0        %        1.0 – 8.0 k/ul

How often should CBCs and blood differentials be performed?
 All patients taking IM should have their blood
counts monitored closely.  Complete blood counts (CBCs) should be monitored weekly in chronic phase patients during
the first month of IM treatment.  If platelet counts remain over 100,000/mm3 and absolute neutrophil count (ANC)
remains over 1,500/mm3, CBC monitoring can be reduced to every two weeks until 12 weeks of IM therapy has been
reached.  Thereafter, if counts are stable, monitoring may occur monthly or even longer if appropriate.  Patients in
accelerated or blast crisis should have CBCs performed more often.

LIVER FUNCTION TESTS:
In addition to monitoring CBCs and blood differentials, it is critical to monitor liver counts through Liver Function Tests
(LFTs), a group of blood tests that can help to show how well a person's liver is working. LFTs include measurements of
total protein, albumin, various liver enzymes such as ALT and AST, alkaline phosphatase (ALP) and bilirubin.  

Total Protein measures the amount of proteins in the bloodstream.  Normal total protein levels in the bloodstream range
from 6.5 to 8.2 gm/dL (grams per deciliter).  Two of the main proteins found in the bloodstream are albumin and globulin.

Albumin is a protein made in the liver. If the liver is badly damaged, it can no longer produce albumin. Albumin maintains
the amount of blood in the veins and arteries. When albumin levels become very low, fluid can leak out from the blood
vessels into nearby tissues, causing swelling in the feet and ankles. Very low levels of albumin may indicate liver
damage. The normal albumin range is from 3.9 gm/dL to 5.0 gm/dL.

ALT and AST are enzymes made in the liver.  They are also called transaminases.  ALT is sometimes called SGPT and
AST is sometimes called SGOT.  The normal range of ALT levels is between 5 IU/L (International Units per Liter) and 60
IU/L.  The normal range of AST levels is between 5 IU/L and 43 IU/L.  Elevated liver enzymes may be a sign of
hepatotoxicity (liver toxicity).  

Alkaline phosphatase (ALP) is another enzyme found in the liver.  Abnormally high ALP levels may indicate liver
problems.  The normal range of ALP is between 30 IU/L and 115 IU/L.

Bilirubin is a yellow fluid produced in the liver.  When bilirubin levels are too high, it can cause a condition called
jaundice in which the eyes and skin appear yellow, urine becomes very dark and feces are light.  There are two
measures of bilirubin:  Total Bilirubin, which measures the amount of bilirubin in the bloodstream and Direct Bilirubin,
which measures the amount of bilirubin made in the liver.  Normal total bilirubin levels range from .20 mg/dL (milligrams
per decileter) to 1.50 mg/dL.  Normal direct bilirubin levels range from .00 mg/dL to .03 mg/dL.

When are abnormal liver function tests (LFTs) cause for concern?  Any abnormalities in LFTs should be addressed and
monitored closely.  Current guidelines suggest stopping IM treatment when transaminases (liver enzymes) are more
than five times the upper limit of normal.  If liver function begins to return to normal, IM may be resumed at a lower dose,
then increased to the prior dose in appropriate cases.  

The consumption of alcohol may affect liver function, so it is important to eliminate or moderate one’s alcohol intake
while taking IM.  Also, acetaminophen (brand name Tylenol) may not be safe to take during treatment with IM since it,
also, is metabolized through the liver.  One should not take Tylenol or take it only under the guidance of a physician
while taking IM.

Reference Ranges for Liver Function Tests

Reference Range        Units
Total Protein        6.5 – 8.2        gm/dL
Albumin        3.9 – 5.0        gm/dL
ALT        5– 60        IU/L
AST        5 - 43        IU/
Alkaline Phosphase (ALP)        30 – 115        IU/L
Total Bilirubin        .20 – 1.50        mgdL
Direct Bilirubin        .00 – .03        mg/dL


How often should liver function tests (LFTs) be performed?  Because of concerns regarding hepatotoxity with IM
treatment, LFTs should be obtained before IM treatment is started, every other week during the first month of IM
treatment, and at least monthly thereafter.  Of course, if any indications of liver problems arise, closer monitoring of
LFTs is critical.







References and further reading:
http://www.labreference.com/differential.html
http://www.healthwise.org/kbase_hosp/kbase/topic/medtest/hw4260/results.htm
http://www.atdn.org/simple/liverfun.html
Deininger MW, O’Brien SG, Ford JM, Druker BJ:  Practical Management of Patients with Chronic Myeloid Leukemia
Receiving Imatinib.  Journal of Clinical Oncology, Vol 21 (8):1-11, 2003.