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1 REVIEW OF ANATOMY AND PHYSIOLOGY OF 2-4

BLOOD

2 INTRODUCTION 5
3 DEFINITION 5
4 INCIDENCE 5
5 TYPES OF LEUKEMIA 5-7
6 ETIOLOGY 7
7 RISK FACTORS 7
8 PATHOPHYSIOLOGY 8
9 CLINICAL MANIFESTATIONS 8
10 DIAGNOSTIC EVALUATION 9
11 MANAGEMENT 9-10
12 NURSING MANAGEMENT 11-12
13 COMPLICATIONS 12
14 PROGNOSIS 13
15 CONCLUSION 13
16 JOURNAL REFERENCE 13
17 BIBLIOGRAPHY 14

REVIEW OF ANATOMY AND PHYSIOLOGY OF BLOOD

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 Blood is a fluid of connective tissue .It circulate continuously around the body , allowing
constant communication between tissues distant from each other .Its transport

 Oxygen from the lungs to the tissues , and carbon dioxide from the tissues to the
lungs for excretion
 Nutrients from the alimentary tract to the tissues , and cell wastes to the excretory
organs , principally the kidneys
 Hormones secreted by endocrine glands to their target glands and tissues
 Clotting factors that coagulate blood ,minimising bleeding from ruptured blood
vessels

Blood is composed of clear , straw –coloured , watery fluid called plasma in

which several different types of blood cells are suspended .Plasma normally
constitutes 55% of the volume of blood .The remaining 45% is counted for by
the cellular fraction . Bloods makes up about 7% of body weight (about 5,6%
litres in a 70kg man )

COMPOSITION OF BLOOD CELL

a)PLASMA : plasma is a clear ,slightly yellow liquid , containing a large number of organic
and inorganic substances dissolved in water .Plasma contains approximately 91% of water
and 9% of solid .Of the solid ,about 7% are the plasma protein which consist of serum

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albumin ,serum globulin ,and fibrogen .Normal plasma volume is about 5% of total body
weight (3500ml)

b) Erythrocytes : Red blood cells are biconcave discs ,they have no nucleus and their
diameter is about 7 micrometers .The main function is in gas transport , mainly of oxygen but
they also carry some carbondioxide .Their characteristics shape is suited to their purpose ,the
biconcavity increases their surface area for gas exchange , and the thinness of the central
portion allows fast entry and the exist of gases. The cells are flexible so they can squeeze
through narrow capillaries , and contain no intracellular organelles , leaving more room for
haemoglobin , the large pigmented protein responsible for gas transport .Erythrocytes are
produced in red bone marrow ,which is present in the ends of long bones and in flat and
irregular bones .Their lifespan in the circulation is about 120 days .The process of
development of stem cells takes about 7days and is called erythropoiesis.The normal 4.5 to
5.5millions in males and 4 to 5 in females

c)Leukocytes (White blood cells): These cells have an important function in defence and
immunity .Leukocytes are the largest blood cells but they count for only about 1% of the
blood volume .They contain nuclei and some have granules in their cytoplasm .The two main
types

 Granulocytes (polymorphonuclear leukocytes)- Neutrophils ,

Eosinophils and basophils
 Agranulocytes – monocytes and lymphocytes

Rising of white cell numbers in the blood stream usually indicate a physiological problem ,
e.g infection ,trauma,or malignancy

 Granulocytes ( polymorphonuclear leukocytes)-During their formation

,granulopoiesis ,they follow a common line of development through myeloblast to
myelocyte before differentiating into three types
 Neutrophils – these small , fast , and active scavengers protect the body against
bacterial invasion and remove dead cell and debris from damaged tissues.
Neutrophils live on average 6-9 hours in the blood stream
 Eosinophils – Eosinophils , although capable of phagocytosis, are less active in
this than neutrophils , their specialised role appears in the elimination of parasite ,
such as worms which are too big to be phagocytosed .They are equipped with
certain toxic chemicals ,stored in their granules which they release when the
eosinophil binds to an infecting organism .
 Basophils – Basophils which are closely associated with allergic reactions ,contain
cytoplasmic granules packed with heparin (an anticoagulant) , histamine (an
inflammatory agent) and others substances that promote inflammation .Usually
the stimulus that causes basophils to release the content of their granules is an
allergen .
 Agranulocytes - The monocytes and lymphocytes make up 25 to 50% 0f the total
leukocyte count .They have a large nucleus and no cytoplasmic granules.

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  Monocytes – These are the largest number of white blood cells .Some circulate
in the blood and are actively motile and phagocytic while others migrate into
tissue s where they develop into macrophages .Both types of cell produce
interleukin 1, which
 Act on the hypothylamus , causing the rise in the body temperature
associated with microbial infections
 Stimulates the production of some globulins by the liver
 Enhance the production of activated T-lymphocytes

 Lymphocytes – Lymphocytes are smaller than monocytes and have large

nuclei .They circulate in the blood and are present in great numbers in
lymphatic tissue such as lymph nodes and the spleen .Lymphocytes develop
from pluripotent stem cells in red bone marrow and from precursors in
lymphoid tissue , then travel in the blood to lymphoid tissue elsewhere in the
body where they are activated ,i.e they become immunocompetent which
means they are able to respond to antigens .

d)Platelets ( thrombocytes) – platelets are small , spherical ,non-nucleated mass of

protoplasm with a diameter of 2-4µm and derived from the cytoplasm of megakaryocytes in
red bone marrow .They contain a variety of substances that promote blood cloting ,which
causes haemostasis .Platelets donot have DNA and RNA .Therefore , there can be no protein
synthesis inside the platelet. The life span of platelets is between 8 to 11 days , after that they
destroyed in spleen .Normal platelets count is 1.5 to 2 lakh .

Blood cells are synthesised in red bone marrow .Some lymphocytes , additionally are
produced in lymphoid tissue .In the bone marrow , all blood cells originate from pluripotent
stem cells and go through several development stages before entering the blood .Different
types of blood cell follow separate line of development .The process of blood cell formation
is called haemopoiesis

FUNCTION OF BLOOD
 Transport of respiratory gases
 Excretory function
 Nutritional function
 Acid base balance
 Transport of hormones
 Protection of Defense
 Temperature regulation
 Water balance
 Osmotic pressure

INTRODUCTION

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 Leukemia is a malignant disease of the blood –forming organs . Leukemia is the most
common malignancy in children and young adults .Half of all leukemia are classified as acute
,with rapid onset and progression of disease resulting in 100% mortality within days to
months without appropriate therapy .The remaining classified as chronic ,have a more
indolent course .Bone marrow produces blood cells . Leukemia can happen when there is a
problem with production of blood cells .Leukemia is a cancer of the body’s blood –forming
tissues ,including the bone marrow and the lymphatic system .

DEFINITION
Leukemia is a group of cancers that usually begins in the bone marrow and result in high
members of abnormal white blood cells .Leukemia is a cancer which start in blood forming
tissue ,usually bone marrow .It leads to the over production of abnormal white blood cells
,the part of the immune system which defend the body against infection

INCIDENCE
 In 2010 ,globally , approximately 281,500 people died of leukemia
 In the United State ,62,130 people are expected to receive a diagnosis of leukemia
in 2017, and around 24,500 deaths is likely due to this didease
 It is most likely to affect people over the age of 55years,but it is also the most
common cancer in those aged under 15 years
 The annual mortality rate per 100,000 people from leukemia in India has decreased
by 4.6% since 1990 an average of 0.2% a year
 Acute leukemia develops quickly and worsens rapidly but chronic leukemia get
worse over time

TYPES OF LEUKEMIA
Clinically and pathogically , leukemia is subdivided into a variety of large groups.The
first division is between its acute and chronic forms :

 Acute leukemia
 Chronic leukemia

Another subdivided according to which kind of blood cell is affected

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  Lymphoblastic or lymphocystic leukemia
 Myeloid or myelogenous leukemia

Combining the acute and chronic categories with the cells type involved , there are four major
type of leukemia

 Acute lymphocytic leukemia

 Acute myeloid leukemia
 Chronic lymphocytic leukemia
 Chronic myeloid leukemia

 Acute lymphocytic leukemia (ALL) – Acute lymphocytic leukemia is a cancer

of the lymphoid line of blood cells characterised by the development of large
numbers of immature lymphocytes .As an acute leukemia ,ALL progresses
rapidly and its typically fatal within weeks or months.

 Acute myeloid leukemia (AML) –It is also called as acute myelogenous

leukemia .It involves the rapid growth of myeloid cells , it occurs more
commonly in adult than in children and more commonly in men than
women .It usually begins in cells that run into white blood cells. Sometimes
,AML can start in other types of blood forming cells.

 Chronic lymphocytic leukemia(CLL)-Chronic Lymphocytic leukemia (CLL)

is a type of cancer in which the bone marrow makes too many lymphocytes.
Early there are no typically symptoms , later non- painful lymph nodes
swelling ,feeling tired ,fever ,weight loss may occur .Enlargement of the
spleen and anaemia may also occur

 Chronic myeloid leukemia (CML)- In CML the bone marrow produces too
many white cells ,called granulocytes .These cell, sometimes called blast or
leukemic blast .Gradually ,crowd the bone marrow ,interfering with normal
blood cell production .They also spill out of the bone marrow and circulate
around the body in the blood stream .Because they are not fully mature, they
are unable to fight the infections .Over time ,a shortage of red blood cells and
platelets can cause anaemia , bleeding and bruising

Others types :
Less common types of leukemia account for about 6,000 cases of leukemia
each year in the U.S
 Hairy cell leukemia is an uncommon type of chronic anaemia
 Chronic myelomonocytic leukemia (CMML) is another type of chronic
leukemia that develops from myeloid cells

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  Juvenile myelomonocytic leukemia (JMML) is a type of myeloid
leukemia that usually occurs in children under 6years of age
 Large granular lymphoticytic leukemia ( LGLL) is a type of chronic
leukemia that develops from lymphoid cells .It can be slow or fast
growing
 Acute promyelocytic leukemia( APL) is a type of AML

ETIOLOGY
There is no single known cause for any of the different types of leukemia.
Other factors that have been known to be associated in the cause are :
 Exposure to radiation or carcinogenic substances
 Natural and artificial ionising radiation
 A few viruses such as human virus
 Chemicals ,e.g benzene
 Alkylating chemotherapy agents for previous malignancy
 Genetics

RISK FACTOR
 Previous cancer treatment
 Genetic disorder
 Exposure to certain chemicals
 Smoking
 Family history of leukemia
 Genetic predisposition
 Down syndrome

PATHOPHYSIOLOGY

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 Etiological factors

Maturational arrest of bone marrow cells

Production of normal blood cells markedly decreases

Rapid proliferation of the abnormal white blood cells

Accumulation in the bone marrow , blood and frequently the spleen and liver

Fig. Pathophysiology of leukemia

CLINICAL MANIFESTATION
 Fever or chills
 Persistent fatigue ,weakness
 Frequent or severe infections
 Losing weight
 Swollen of lymph nodes , enlarged liver or spleen
 Bleeding or bruising
 Recurrent nose bleed
 Tiny red spots in the skin
 Excessive sweating ,especially at night
 Bone pain or tenderness

DIAGNOSTIC EVALUATION

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  Through history and physical examination
 Blood test : a complete blood count determines the numbers of RBCs , WBCs and
platelets in the blood
 Peripheral blood smear to assess the shape of the cells and helps to determine if
the cells have an abnormal appearance
 Blood chemistry and coagulation testing :to assess for underlying liver or kidney
problems
 Bone marrow test : Bone marrow biopsy and aspiration can be done ,These small
samples can identify the type of leukemia and its growth rate
 Lymph node biopsy : To diagnose certain types of leukemia
 Flow cytometry examines the DNA of the cancer cells and determine their growth
rate
 Liver function test show whether leukemia cells are affecting or invading the liver
 Lumbar puncture is performed by inserting a thin needle between the vertebrae of
your lower back .This allows doctor to collect spinal fluid and determine if the
cancer has spread to the central nervous system
 Imaging test such as x-ray ,ultrasounds ,and CT scan help doctor look for any
damage to other organs that caused by the leukemia

MANAGEMENT
Treatment for leukemia depends on many factors such as age , overall health , type of
leukemia and malignancy state .In general ,treatment falls into two phases

 Remission induction therapy : The purpose of the first phase of treatment is to

kill the leukemia cells in the body and bone marrow . However , remission
induction usually doesn’t swipe out all of the treatment cells ,so you need
further treatment to prevent the disease from returning .

 Consodilation therapy : Also called post remission therapy ,maintenance

therapy or intensification , this phase of treatment is aimed at destroying the
remaining leukemia cells . Its considered crucial to decreasing the risk of relapse

Therapies used in these phases include :

a) Chemotherapy : pharmaceutical medication , typically combined into multi drug

chemotherapy regimen

b)Biological therapy : Biological therapy is any treatment that uses living organisms
,substances that come from living organisms , or synthetic various of these substances to

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treat cancer .These treatment help the immune system recognize abnormal cells and then
attack them .Biological therapies for various types of cancer can include antibodies ,tumor
vaccines or cytokines

c)Targeted therapy : Targeted therapies are drugs that interfere with one specific property or
function of a cancer cells , rather than acting to kill all rapidly growing cells
indiscriminately .Targeted cancer therapies are also reffered to as molecularity targeted drugs
,molecularly targeted therapies , or procession medicines . Imatinih ( Gleevec ) and dasatinib
(Sprycel ) are examples of targeted therapies that are used to treat CML , some cases of ALL
and some other cancers

d)Radiation therapy : Radiation therapy uses high energy radiation to target cancer cells
.Radiation therapy may be used in the treatment of leukemia that has spread to the brain , or it
may be used to target the spleen or others area where leukemia cells have accumulated

e)Stem cell transplant : In stem cell transplantation ,high doses of chemotherapy and radiation
are given to destroy leukemia cells along with normal bone marrow .Then ,transplant stem
cells are delivered by an intravenous infusion .The stem cells travel to the bone marrow and
Begin producing new blood cells .Stem cells may come from the patient or from a donor.

SUPPORTIVE TREAMENT
Types of supportive and preventive treatment that can be for patients undergoing
treatment for leukemia include the following:

 Vaccines against the flu or pneumonia

 Blood or platelet transfusion
 Anti biotics or antiviral medication to treat or prevent infection
 White blood cell growth factors to stimulate white blood cell production
 Red cell growth factors to stimulate red blood cell production
 Intravenous injection of immunoglobulin to help fight infection

SURGICAL MANAGEMENT
 Surgical resection of an infected organ –segmentectomy (rarely used) and
lobectomy in lung , pneumonectomy ,splenectomy

NURSING MANAGEMENT

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 A)Assessment
 Obtain thorough history and perform physical examination
 Assess pain : duration ,location ,intensity ,characteristics
 Assess and monitor vital sign’s
 Assess and monitor laboratory reports
 Assess nutritional status
 Assess anxiety level
 Assess activity level

B) Nursing diagnosis and Nursing intervention

a) Acute pain related to swelling of lymph node as evidence by discomfort

Nursing intervention

 Assess the patient pain level ,duration , intensity , frequency

 Provide comfort
 Provide comfortable position and change the position frequently
 Provide divertional therapy
 Evaluate with patient health care team about the effectiveness of pain control
measure
 Teach non pharmacological techniques e.g relaxation
 Provide analgesics as prescribed by the physician

b)Imbalanced nutrition less than body requirements related tohyper-metabolic state , anorexia
as evidence by weight loss

Nursing intervention

 Assess the present of nausea , vomiting and diarrhae

 Monitor weight
 Assess and provide food that patient can tolerate
 Monitor serum glucose levels
 Suggest the patient to have small and frequent meal
 Start intravenous fluid
 Instruct patient to avoid spicy food

c)Hyperthermia related to infection as evidence by fever

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 Nursing intervention

 Monitor vitals signs

 Provide cold sponging
 Switch on the fans and remove excessive clothing
 Administer antipyretics as prescribed by the physician
 Encourage the patient to increase the oral intake to prevent from dehydration

d)Risk of infection related to low immunity as evidence by bleeding gum

Nursing intervention

 Assess the skin for color ,texture ,elascity and moisture

 Routinely monitor the patient’s white blood cell count
 Note the patient’s current medication
 Check the patient’s immunization history
 Monitor the patient for any signs of swelling ,redness
 Explain to the patient’s about the important of hand washing
 Wear gloves during any contact with mucus ,blood and other body fluid

e)Risk of deficient fluid volume related to decrease fluid intake as evidence by intake
output chart

Nursing intervention

 Assess the skin turgor and mucous membranes for signs of dehydration
 Assess vital signs specially BP ,HR
 Assess color, concentration and amount of urine
 Monitor the weight
 Assess for fatigue , sensory deficits and muscle weakness
 Encourage oral fluids as the patient tolerate

COMPLICATION
 Infection
 Leukostasis leading to haemorrhage
 Renal failure
 Tumor lysis syndrome
 Disseminating intravascular coagulation

PROGNOSIS
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 The prognosis of leukemia depends upon the type of leukemia that is present and the age
and health status of the patient .Mortality(death )rates for leukemia are higher in the elderly
than in younger adults and children .In many cases , leukemia can be managed or cured with
treatment available today .In particular , childhood ALL has a very high 5-year survival rate
. Modern treatment have led to a greater than fourfold increase since 1960 in five –year
survival rates for different types of leukemia are approximately :

 CML -66%
 CLL-83%
 AML -27 % overall , 64%for children and teenage younger than 15
 ALL- 71% overall ,over 90% for children

CONCLUSION
WBC’s are a vital part of the immune system,They protect the body from invasion
by bacteria ,viruses, and fungi as well as from abnormal cells and other foreign
substances . In leukemia ,the WBC’s don’t function like normal WBC’s .They can
also divide too quickly and eventually crowd out normal cells

JOURNAL REFERENCE
Leukemia Research 68(2018) 32-39. Bruno C. Medrios. Interpretation of clinical endpoints
trial of acute myeloid leukemia.

ABSTRACT

Treatment regimens for acute myeloid leukemia (AML) have remained largely unchanged
until recently. Molecular advances have opened the door to targeted therapies, many of which
are in late-phase clinical trials. As new therapeutic opportunities arise, it is appropriate to
review key aspects of clinical trial design, statistical interpretation of outcomes, and methods
of data reporting. Complete remission and overall survival (OS) are common primary
endpoints in early-phase AML clinical trials. OS and event-free survival are frequent primary
endpoints in phase 3 trials. Clinical trials are designed to address the primary endpoint using
prespecifiedαand power levels. Interpretation of additional endpoints (eg, secondary
endpoints and subgroup analyses) must be viewed in light of a trial’s statistical design.
Furthermore, variations in reporting of endpoints must be considered in order to understand
trial outcomes. Time-to-event endpoints are typically reported using Kaplan-Meier curves,
which are visually informative. Statistical data derived from these curves can be complex,
and a variety of factors may impact interpretation. The purpose of this review is to discuss the
nuances of common AML trial endpoints and their data presentation to better inform
evaluation and understanding of clinical trial data.

BIBLIOGRAPHY

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 Smeltzer Suzanne C,Bare Brendon G, et al.Brunner and Suddharth’s ,textbook of
Medical surgical nursing- 11 edition .New Delhi ;wolters Kluwer publishers( India)
Pvt Ltd ;2008
 Lewis Sharon L, Driksen Shannon Ruff ,Bucher Linda Medical surgical nursing- 2
edition .New Delhi Reed Elsevier ,India Pvt Ltd ,2015
 Ross and Wilson anatomy and physiology in health and illness -11 edition
 https://www.sciencedirect.com/science/article/pii/S0145212618300304#abs0010

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