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Clinical Overview and DiscussionOf Laboratory Medicine inThe Oncology Practice

Cancer & Hematology Centers of 

Western Michigan

• 8 Cancer Centers located in Western Michigan -privately owned but working collaboratively with area hospitals

• 3 Centers include on-site, physician owned laboratories

• 19 Oncologists/16 are also Hematologists• Treatment of all types of solid tumor cancers, blood

related cancers along with coagulation disorders and hematological disease

• Dedicated to bringing state of the art cancer care treatment to the community

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Grand Rapids Furniture City

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Johnson Cancer Center

Lab Staff of Today

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Main Laboratory Instrumentation

Laboratory Equipment:

• Sysmex XN 1000• Roche Cobas 6000• Siemens PFA 100

In-House Test Menu = 75 tests on these 3 instruments

Sysmex XN‐1000

Roche Cobas 6000

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Clinic Laboratory Instrumentation 

and Test Menu

Laboratory Equipment:

• Roche C111• Sysmex KX-21N

In-House Test Menu on these 2 instruments = 20

Sysmex KX 21N Roche C111

Role of the Laboratory

• The lab plays a huge part in overall flow of the patient through the centero Lab results drive treatment options

• Speedy on-site testing allows for real time decision making by the provider

• Laboratory Information System interfaced to patient’s Electronic Medical Record for easy and fast access to laboratory results

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Help, Healing and Hope for our Patients

Role of the Laboratory

• Test menu developed to support both cancer care needs and general lab testing

• Annual in-house test volumes =150,000 panels (over 1,000,000 tests per year)

• Patients are drawn for all needed tests whether done on site or sent out to a reference laboratory

Capital Acquisitions

• Factors to consider when purchasing equipment• Space limitations• Extensive test menu • Reliability – relatively no down time• Back-up equipment not an option

for us• Increases overall cost of test• No room for extra equipment

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Important Features for Capital Acquisitions

• Quick turn around time - stat option essential

o Many chemotherapy treatments cannot be given until lab results are available and within range

o Several insurance companies require lab values to be submitted with the treatment billing invoices or coverage will be denied

• High level training program for testing personnel in order to be knowledgeable and efficient in the use of the new equipment and to be able to train others

Down Stream of Down Time

• Instrumentation down time halts care in a cancer care environment

o Phone Support - Need reliable and knowledgeable support to get instrument up and running as quickly as possible

o Field Service - Need engineers to respond in a timely fashion when issues are more severe

o Down Time - Results in sent out lost revenue and increase wait times for patients

When there is down timePatient satisfaction is greatly decreased !

Revenue Benefit of the Lab

• Test menu developed for practicality & revenue. • Tests to be brought in-house are determined by the

test cost and insurance allowable reimbursement.• Important to maximize equipment capabilities to

lower cost of individual test.• Decrease in turn around time of lab tests yields

increased number of patients that can be treated in a given time.

• This equates to increased revenue from chemotherapy treatment.

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Why have a P.O.L.?

• Provide physicians with consistent, in-house testing so they can compare apples to apples.

• Quick turn around times, with results populating the patient’s EMR, allow the physician to make changes in the patient’s treatment regimen.

• The physicians get spoiled with this level of service and it becomes their expectation.

• Be proactive in introducing new tests that would play a beneficial role in their practice of medicine.

Why Sysmex Works at CHC

• CHC has been a Sysmex customer for over 20 years• Equipment needs expanded as the physician practice grew

from 4 to 19 doctors o K 1000→ K 4500→ XT 2000i→ XN 1000

• The XN-1000 is a perfect fito Meets our space limitationso Very little down timeo Additional parameters that provide useful information to the physicians.o Quick turn around times.o Allows us to be a reference lab for our off site clinicso Interfaced with our LIS and EMR to provide real time results that populate in the

patient’s electronic chart• Account Managers - honest and knowledgeable with strong,

trusting, working relationships.• Customer Service Representatives - easy to work with, go

above and beyond to exceed our expectations.• Field Service Engineers - friendly and quick to respond.

XN‐1000

• Cancer and Hematology Center Laboratory at LHCP is enjoying the benefit of the new Sysmex XN-1000.

• 5 new reportable parameters:• Immature Granulocytes (IG)

• Nucleated RBC (NRBC)

• Immature Retic Fraction (IRF)

• Reticulocyte Hemoglobin Equivalent (RET-He)

• Immature Platelet Fraction (IPF)

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Immature Granulocytes

• Automated IG counts (% and absolute) reported with every automated differential on the XN-1000.

• Measured by fluorescent flow cytometry.

• IG includes metamyelocytes, myelocytes and promyelocytes.

• Comparison studies showed 94% correlation with the manual differential.

Benefits of IG Parameter @ CHC

• IG provides a more accurate and precise automated count than a manual differential because over 32,000 cells are counted by the instrument versus 100 cells on the traditional manual differential.

• We have a substantial number of patients with CML (Chronic Myelogenous Leukemia)

• XN-1000 differential has reduced the number of manual differentials for this patient population by 75%

CML with Metas, Myelos and Pros

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XN 1000 Automatic Differential on 

CML patient 

IG = 28.9%

(Metas, Myelos and Pros)

Manual Differentialon CML patient. 

Metas, Myelocytesand Promyelocytes

IG = 27% 27 %

Benefits of IG Parameter @ CHC

• IG is particularly beneficial for patients receiving WBC production stimulation drugs (Neupogen and Neulasta).

• Purpose of chemotherapy drugs is to kill cancer cells -Side effects is destruction of other cells, including WBCs.

• Patients with WBC less than1000 are very susceptible toinfection.

• Drugs such as Neupogen and Neulasta stimulate WBCproduction in the bone marrow.

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Benefits of IG Parameter @ CHC

• Because the circulating WBC count is at such a low level, stimulated WBC’s are released from the marrow sooner – without the chance to fully mature.

• Immature forms are mainly Metas and Myelos with an occasional Pro or Blast.

• The IG parameter is useful when increased WBC is easily explained by the drug stimulation and the IG’s are expected.

Patient Receiving   Neulasta

IG = 11.9%

Neulastainjection

Metas in Patient Receiving Neulasta

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Canned Text Comments for IG

CML (Chronic Myelogenous Leukemia)

• IG parameter reflects the combination of Metas, Myelos and Promyelocytes

Neulasta / Neupogen injection

• Patient is receiving neupogen/neulasta which is the most likely cause of the increased IG’s

Benefits of NRBC Parameter

• Automated NRBC counts (% and #) are reported with every CBC.

• NRBC are measured by fluorescent flow cytometry on the XN-1000.

• Accurate detection of NRBC counts even at low numbers

• Eliminates the need to perform a time consuming manual differential and corrected WBC.

• Provides quick and accurate WBC count so chemotherapy eligibility based on WBC can be determined and chemo orders be processed or held.

NRBC’s in Peripheral Blood

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Benefits of Accurate WBC

• ANC (absolute neutrophil count) is followed and used to determine whether chemo will be given.

• When the ANC is 1000 or less it raises the question of whether chemo will be given:o Depends on where the patient is in the their cycleo Possible dose reduction verses holding

• ANC <500 – chemo not given

Patient with 

Normal WBC = 10.25 

High NRBC = 19.4

Normal WBC with High RBC

Patient with 

LowWBC = 1.14

High NRBC = 11.4

ANC = 530

ANC= 530

Low WBC High NRBC

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Patient with 

Low WBC = 0.68

High NRBC = 30.9

ANC = 280

ANC = 280

Low WBCHigh NRBC

Canned Text Comments for NRBC’s

Hold Ups and Holding Chemo

• Hold ups in the lab delay the entire flow of through the infusion center o Example: Performing a manual diff to get an accurate WBC.

• Chairs are scheduled for each patient for a particular block of time based on their treatment.

• Lab result delays cause pharmacy orders to be delayed…cause chair time to get off schedule.

• Nurses & support staff end up working O.T. – very costly. Average of one hour of nurse O.T. = $50/hour

• Increases cost of providing health care and impacts bottom line and profitability of the practice.

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Effects of Holding Chemotherapy

• Holding chemo is necessary for the health and safety of the patient but causes problems of its own.

• Chemo drugs need to be authorized for payment.• Included in the authorization day of treatment,

dose and time frame.• Any changes require a need for reauthorization.• Example:

o Patient authorized to get chemo for 6 months. o Chemo is held for a week due to low platelet count. o This extends patient’s treatment out to 6 months and 1 week. o Insurance stops paying at 6 months unless reauthorization

obtained.

Holding Chemotherapy

• Anemiao Chemo rarely held for anemia - easy to correct with PRBC

transfusion.

• Low ANCo Usually chemo dose is reduced and supported with Neulasta.

• Plateletso Many times chemo is held because of low platelets.o Transfused platelets are quickly killed off by the chemotherapy

drugs. o Best to wait for patient’s marrow to recover and begin platelet

production on its own rather than to transfuse platelets for very little benefit.

Immature Platelet Fraction (IPF)

• IPF is a measure of immature platelets in the circulating blood

• An increased IPF with thrombocytopenia may indicate:o Peripheral destruction or consumption of platelets such as:

• Idiopathic thrombocytopenia (ITP) • Thrombotic thrombocytopenic purpura (TTP) • Disseminated intravascular coagulation (DIC)

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Immature Platelet Fraction (IPF)

• Another important use of the IPF - monitor marrowrecovery post chemotherapy.

• Platelets are killed off by chemotherapy drugso Some drugs such as Gemzar can destroy most of the circulating

platelets and suppress production in the bone marrow.

• In bone marrow recovery, platelets are producedto resupply the peripheral blood.

• When platelets are needed in the blood, immatureplatelets are released early from the marrow.

• A high IPF post chemotherapy is a good indicationthat platelets are being produced.

Immature Platelet Fraction (IPF)

• Normally a platelet count of <20,000 warrants a platelet transfusion.

• With a platelet count <20,000 and high IPF, a transfusion may not be needed.o A high IPF means platelets are being produced. o Normal Range for IPF = 0.9 – 7.0 %.

• Eliminating a platelet transfusion saves time and money; increases profitability.

Normal and Immature Platelets

IPF

Normal

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Normal Platelet = 219

Normal IPF = 3.3 %

Normal 

Normal Platelets

Normal IPF

Low Platelet = 14 

Increased IPF = 15.4%

The increased IPF indicatesplatelets are being producedin the bone marrow and being released early into the peripheral blood. Immature platelets are functional plts.

Increased IPF

High IPFPlatelets being made

Canned Text Comments for Platelets and IPF

Fluorescent Platelets

• Platelet count obtained by Fluorescent Flow Cytometry methodology which is specific for Platelet Mitochondria, providing the most accurate enumeration

Immature Platelet Fraction• An elevated immature Platelet Fraction indicates

platelets are being produced• A low platelet and low IPF is consistent with a

platelet production disorder

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Example of report with canned text

1.Platelet count obtained by Fluorescent Flow Cytometry methodology which is specific for Platelet Mitochondria, providing the most accurate enumeration

2.An elevated immature Platelet Fraction indicates platelets are being produced

Example of Table View

Interesting Case and the Value of IPF

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Low Platelets with High IPF

The patient’s platelet count has dropped from 137,000 on day one ofthe 3rd cycle down to 17,000 on day eight. However, the IPF issignificantly high at 50%. This means the bone marrow is responding byproducing and releasing platelets from the bone marrow at a rapid ratein order to compensate for the shortage in the peripheral blood. Thepatient does not receive any blood products at this time because of herown body’s ability to respond to her platelet need.

Summary

Before having the ability to run and report the immature plateletfraction parameter, this patient would have been given a platelettransfusion on day eight of her third cycle. The IPF test gave a good lookat what was going on in the patient’s bone marrow and how her ownbody was responding. The IPF is a valuable tool in bone marrow plateletassessment and production rates. The IPF in this case saved the patienta platelet transfusion resulting in reduced medical costs and increasedpatient satisfaction

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Reticulocyte Profile

• Retic profile includes • Reticulocyte (% and #) • Immature Reticulocyte Fraction (IRF) • Reticulocyte Hemoglobin (RET-He)

• Reticulocyte counts on hematology analyzers have been around for some time.

• IRF and RET-He are new advances

Immature Reticulocyte Fraction

• IRF is a direct cellular measurement of erythropoiesis. • It is useful to the clinician in the management of anemia

and in the use of erythropoietic stimulating agents (ESA) such as Procrit.

• High IRF means the bone marrow is producing RBCs and sending them out of the marrow in response to anemia.

• Reticulocyte is an immature red cell; Immature Retic Fraction is even a younger stage.

• 3 stages of Retic maturation shown by low , medium and high fluorescence. o The IRF is made up of the Medium (MFR) and High (HFR) fluorescing

Retics.

Erythrocyte Maturation

Red line shows where the IRF ‘s are in the maturation cycle

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Male with mild AnemiaHGB = 11.5

Slightly increased IRF = 16.2(Normal IRF = 1.5‐13.7)

Bone marrow compensating

Slightly increased IRF

Male with severe AnemiaHGB = 8.0

Very high IRF = 30.0%

Bone marrow compensating

Male with anemia 

Bone Marrow compensating

Normal Range for IRF 1.5‐13.7

Female with AnemiaHGB = 9.5

High IRF 34.6%( nl = 1.1‐15.9)

Bone marrow compensating

Female with Anemia 

HGB=9.5

Very High IRF

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Erythropoiesis

Male with AnemiaHGB = 9.4

IRF= 0.0 %

Bone marrow not compensating

Patient will most likely need  transfusion in the near future

Male with anemia but bone marrow not compensating

IRF = 0.0 %

RBC Breakdown

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HGB Molecule: 2 alpha, 2 beta, 4 heme and 4 iron 

Reticulocyte Hemoglobin (RET‐He)

• RET-He - direct measurement of the incorporation of iron into the reticulocyte hemoglobin.

• Lack of iron availability in the bone marrow is the primary cause of decreased RET-He.

• Retics have a limited life span of 1-2 days o If they are released from the marrow low in iron, they will have a

decreased quantity of hemoglobin.

• RBCs normally circulate for 120 days o If they are deficient in iron and hemoglobin they will remain so for

their entire lifetime.

Reticulocyte Hemoglobin (RET‐He)

• RET-He Normal Range: = 28.2 – 36.6 pg

• Low RET-He results trigger the provider to begin iron therapy much earlier.

• Patient’s experience with iron deficiency can be better managed and anemic period decreased.

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Female withIron Deficiency Anemia 

Low HGB = 11.8

Low RET‐He = 27.1

(nl = 28.2‐36.6)

Male withIron Deficiency Anemia 

Low HGB = 12.8

Low RET‐He = 25.2

(nl=28.2‐36.6)

Male with Anemia 

Not due to Iron Deficiency

Low HGB = 11.5

Nl RET‐He = 35.1

(nl=28.2‐36.6)

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Female with Anemia Not due to Iron Deficiency

Low HGB = 9.6

Nl RET‐He = 33.7(nl = 28.2‐36.6)

Below is a typical pattern of blood count response to chemotherapy treatment. With each treatment, counts drop a little lower and for a little longer. The counts come back up but not as high as at the beginning of the previous treatment.

Things to remember about chemotherapy. 

• Chemotherapy is designed to attack fast growing cells  

• Cancer cells are fast growing cells• Blood cells, skin cells and mucus 

lining cells are all fast growing and all vulnerable to the effects of the chemotherapy drugs.

• WBC, RBC and Platelet (Hematopoietic) precursors are fast growing cells and are prime targets for chemotherapy drugs to weaken and destroy.

Getting in the Ring

Think of Cycles of Chemotherapy like a boxer in a ten round fight.

• In the first round the boxer is at his strongest, but each sequential round he is in a weaker and weaker condition.

• A patient undergoing chemotherapy treatments begins each cycle in a more weakened condition than the previous and thus takes longer to recover from each treatment going forward.

• In addition, if the person entering the boxing / chemo ring isn’t in top shape to begin with the fight is even tougher.

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Summing It Up

Sysmex XN – 1000 – Our Healthcare Partner

• Easy to use

• Ready state – no wait to start

• Fast processing of results

• Customized “rules” to fit our needs

• Reflex testing

XN 1000 Maintenance

• Sysmex XN 1000

• No routine maintenance

• No start up maintenance Run controls and ready to go

• Simple step by step reagent replacement

• Walk away shut down – load cell clean and go

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Overall Results

• Accurate and rapid laboratory results greatly improve efficiency throughout the entire cancer center.

• Improves patient satisfaction by decreasing wait time and providing valuable information for treatment plan.

• New parameters on the Sysmex XN-1000 expand the patient’s hematology picture.

• Allows physicians to make quick and important changes in the care and treatment of their patients to improve outcomes.

Lab Staff of Tomorrow