Leukaemia, Lymphoma and Other Blood Related Disorders

Clinical haematology is the study of diseases of the blood and bone marrow, and how to treat them. Clinical haematologists diagnose and look after people with these diseases.

Red blood cells, platelets and plasma are called blood components. They can all be given as transfusions if necessary. The blood components come from blood donations from members of the public. After blood is donated, it is tested to check the blood group and screened for infections such as hepatitis and HIV.

Blood is then processed into separate parts; red blood cells, platelets and plasma. If you need a “blood” transfusion, what you actually get is red blood cells. Platelets and plasma can also be given as transfusions. Occasionally people can have reactions to blood, usually causing shivers and a temperature. We can use various medicines to help ease these symptoms if they occur.

What is bone marrow?

Bone marrow is the spongy inner part of bones. It acts as a “factory” to make blood cells. Many diseases of the blood are also diseases of the bone marrow. Often blood diseases can be diagnosed by taking a small sample of bone marrow and examining it under the microscope.

Bone Marrow Transplant (BMT)

Also referred to as a Stem Cell Transplant (SCT).

One DEFINITION of stem cell transplant is:  ‘The intravenous administration of healthy blood stem cells to patients in order to re-establish bone marrow functions where it is failing.’

When the bone marrow fails the patient will experience persistent infections, anaemia and increased bleeding, this is why a transplant is necessary if the patient is well enough.

If a patient is being matched with a donor the process of stem cell transplantation firstly involves tissue typing. Donors are often siblings but can also be an anonymous donor from a donor panel. The stem cells are harvested from either the bone marrow or from peripheral blood. This process is the same for both the donor and the patient. Stem cells can also be taken from a new born baby’s umbilical cord but there are limited numbers of these available as yet.

In order for the body to accept the stem cells the immune response needs to be depressed, as the body’s natural response is to attack the transplanted stem cells as they are not recognized as self. The patient is given strong radiotherapy and chemotherapy to depress the immune system.

There is more than one type of transplant, AUTOLOGOUS transplants use the patient’s own stem cells, for patients with chronic leukaemia, lymphoma and myeloma this is a viable treatment. Any malignant cells are purged before the stem cells are returned to the patient; however there is a higher risk of relapse. The risks of becoming infected, rejecting the cells, and graft failure with autologous transplants is lower.

A transplant where the stem cells come from a donor is called an ALLOGENEIC transplant; these donors must be from a person whose tissue typing is closely matched to the patient. The closer the match the less likelihood of the patients cells rejecting the graft. With allogeneic transplants the immune cells in the stem cell transplanted to the patient can attack the patient’s own cells, this is called graft versus host disease (GVHD), this can be a life threatening condition.

A SYNGENEIC transplant is between identical twins, there is only a minimal risk of graft versus host disease.

If a patient has no family members who are matches a matched unrelated donor (MUD) can sometimes be found. Donors can be found through services such as the Welsh Blood Service, or other UK National Blood services or charitable organisations such as the Anthony Nolan trust.

The most well known inherited blood disorder is Haemophilia

Introduction

Haemophilia is an inherited bleeding disorder, which results in a deficiency of one of the coagulation factors in the blood clotting process. The defective gene is carried on the X chromosome and results in males being affected with the disorder and females being carriers. There are three different degrees of clinical severity of haemophilia – severe, moderate and mild. Haemophilia is commonly accepted as referring to a deficiency of factor VIII known as haemophilia A, but a smaller number of cases are caused by a deficiency of factor IX, known as haemophilia B.

Clotting Factors

Normal coagulation occurs after damage to a blood vessel, which causes leakage and bleeding into the surrounding tissues. The first stage of the clotting process is vasoconstriction of the blood vessels, which slows the blood flow and prevents excess bleeding occurring. Platelets accumulate and a fibrin mesh is formed at the site of the breakage forming an occlusive plug, which seals the wound. The final stage of the process is that thrombin then converts the soluble plasma protein fibrinogen to fibrin, which stabilises the platelet plug. This enmeshed fibrin and platelet plug is the result of a complex biochemical process involving the clotting factors (Howard and Hamilton 1997).

Individuals with haemophilia, who have a deficiency of the clotting factor VIII or IX, have an incomplete coagulation process, due to low levels of the clotting factors. Although platelet activation prevents excessive superficial bleeding, the blood takes much longer to form a clot.

Haemophilia A

Haemophilia A is often referred to as ‘classical haemophilia’ and relates to a deficiency in the clotting factor VIII. Approximately one in every ten thousand males are affected with up to one third of all newly diagnosed persons being the result of a new genetic mutation with no previous family history of haemophilia. The severity of the condition depends upon the deficiency of the clotting factor, as determined by a clotting assay, and is classified as severe, moderate or mild for both haemophilia A or B.
• Severe- less than 2 iu/dl
• Moderate- 2-5 iu/dl
• Mild- 5- 30iu/dl
(Hoffbrand et al 2001)

Haemophilia B

Haemophilia B, sometimes referred to as Christmas Disease, occurs as a result of a deficiency of factor IX. The incidences of this condition occur in 3-4 per 100,000 live male births (Howard and Hamilton 1997). The inheritance and clinical presentation of haemophilia B are the same as for haemophilia A.

Clinical Features

Bleeding tendency depends upon the severity of the condition and the circulating levels of clotting factors. The most common sites for bleeding are the major joints such as knees, elbows or hips although any joint may be affected. Mucosal bleeding may occur following dental extraction or epistaxis in children may be a problem. Trauma or surgery is the only cause of bleeding for many individuals with the mild form of the condition.

Presentation

In a family with a known history of haemophilia, diagnosis is made at birth. The blood sample may be taken from the cord blood thereby obtaining a diagnosis within hours of birth. If there is no known history of haemophilia, diagnosis is often made when the child becomes mobile around 10-12 months of age and may present with excess bruising or a swollen joint. In a small number of cases bleeding tendency may be established earlier following traumatic birth, bleeding from umbilical cord site or following circumcision. A number of parents may have had the added trauma of being suspected of non-accidental injury to their child before a diagnosis is confirmed (Hoffbrand et al 1999).

Diagnosis

Diagnosis is confirmed by a factor clotting assay which will detect a prolonged activated partial thromboplastin time (APPT) and low levels of the clotting factor VIII or IX.

Prognosis

Prompt treatment with replacement factor concentrates may prevent serious complication occurring. Dosage of treatment depends on the required rise in level of the clotting factors, which varies according to the severity of the bleeding episode. The parents or individual often administers treatment at home themselves, which allows more prompt treatment to be given. Many children with severe haemophilia are treated with prophylaxis factor concentrates 3 – 4 times a week to prevent spontaneous bleeding occurring. This may result in almost total eradication of bleeding and the ability to maintain an improved quality of life.

White blood cells (WBC’s) are less common than red blood cells but are equally important. White blood cells are part of your body’s immune system and their most important job is to fight infections. Different types of white blood cells fight different types of infections.

The most common white blood cells are called neutrophils, and they help to fight off bacterial infections. Lymphocytes are another type of white blood cell, and mostly help to fight viral infections. There are other rarer white blood cells including eosinophils and basophils.
If you have an infection, for example in your lung, white blood cells are attracted to it and start to attack the infection. When you have an infection, your body will normally produce extra white blood cells to help fight it.
Some white blood cells normally only live for a few hours so your body produces new WBC’s every day. In particular, neutrophils often only live for 3 or 4 hours.
Many blood diseases can cause a lack of white blood cells. People who have too few white blood cells tend to be more susceptible to infection than normal. This is particularly the case with low levels of neutrophils, a condition called neutropenia. Because they only live a short time, it is very difficult to give WBC’s in a transfusion and WBC transfusion is not currently available in New Zealand for example. Fortunately, modern antibiotics are usually very effective in fighting infection in people who have low levels of neutrophils.

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What are Platelets?

Platelets are technically not proper cells but little bits broken off big cells. Platelets are part of a system which allows the blood to clot. (Certain chemicals in the plasma, called clotting factors, are also needed for the blood to clot.) If you cut yourself, platelets are attracted to the cut and begin to stick together with the help of the clotting factors, and a blood clot is formed.

People who lack platelets are more likely to bleed and bruise than normal. When necessary, platelets can be given in a transfusion to some people who lack platelets.

There are two main types of lymphoma:-

Non-Hodgkin’s Lymphoma (NHL)

NHL is a cancer of the lymphatic system (the network of lymph glands which occur throughout the body). Cells within the lymph nodes and other lymphatic tissues play an important part in the immune system and help to keep the body free from infection. The cells called lymphocytes originate in the bone marrow and can be classified as T or B cells. There are many different types of NHL (more than 30).

Hodgkin’s Lymphoma (HL)

Hodgkin’s lymphoma is again a cancer of the lymphatic system. The defining feature of Hodgkin’s lymphoma is the presence of a distinctive abnormal lymphocyte called the Reed-Sternberg cell. Hodgkin’s lymphoma has a high cure rate, especially in younger patients diagnosed with early-stage disease.

Leukaemia is one of the many different types of blood related disorders. The main types of leukaemias, lymphomas and other blood disorders commonly treated on the ward are outlined briefly.

There are many different forms of leukaemia, some are:-

Acute Lymphoblastic Leukaemia (ALL)

This is a cancer that affects the lymphocytes in the bone marrow. Lymphocytes are white blood cells that produce antibodies. In ALL there is an accumulation of immature lymphocyte forming cells called blast cells in the bone marrow. These blast cells affect the production of normal blood cells thus reducing the number of red and white cells and platelets in the blood.

Chronic Lymphocytic Leukaemia (CLL)

This is a slowly progressing form of leukaemia in which there is an excess of mature poorly functioning lymphocytes in the circulating blood. Lymphocytes are white blood cells that produce antibodies and are a vital part of the body’s immune system. The major reason for the build up of tumour cells is the failure of lymphocytes to die at the end of their normal life span.

Acute Myeloid Leukaemia (AML)

AML affects the myeloid blood cells in the bone marrow. Myeloid cells are red blood cells, platelets and all white cells except lymphocytes. In AML production of blood cells is obstructed and immature cells (blast cells) accumulate in the bone marrow. These cells are unable to mature properly leading to a reduction of normal blood cells in the circulation.

Chronic Myeloid Leukaemia (CML)

CML starts in the stem cells in the bone marrow. Throughout most stages of CML the majority of leukaemia cells in the blood and bone marrow are the myeloid cells. Myeloid cells are red blood cells, platelets and all other white cells except lymphocytes. CML is a form of leukaemia that progresses slowly during the chronic phase of the disease. This phase can last from approximately four to six years then it transforms to a more rapidly progressing disease.

Haematology doctors often need to take small samples of bone marrow to help with diagnosis of certain blood disorders, and sometimes other disorders. This is a quick and simple procedure which can be carried out in the out patient clinic. Local anaesthetic is given to numb an area of skin usually over the pelvis (just above the buttock) and a needle is used to take a small sample of bone marrow. The procedure usually only takes about 15 minutes.

Sometimes people are given sedative drugs before the procedure and will need to stay an hour or two afterwards to allow these drugs to wear off. If you are given sedative medicines, you cannot drive for the rest of the day. If not, you can go back to work if you wish and have a normal day after the bone marrow test.
The samples taken are analysed by the haematology doctors. The results are usually available in about one week to ten days, sooner for some tests.

Lupus is an autoimmune disease where the body’s immune system creates antibodies which, instead of protecting the body from bacteria and virus, attack the person’s own tissue.

Over 30,000 people have lupus in the UK of whom 90% are female. The main side effects linked with lupus include; extreme fatigue, joint pain, muscle aches and anaemia. Lupus can mimic other disease such as Multiple Sclerosis and Rheumatoid Arthritis making it difficult to diagnose. There are a number of factors thought to trigger the onset of lupus, or cause lupus to flare, including; exposure to light, certain prescription drugs, infection, certain antibiotics, hormones and possibly stress. The most commonly used treatments for lupus are anti-malarial and steroids. Occasionally immunosuppressive drugs are used.

Sickle cell disease is an inherited disorder that affects red blood cells. People with sickle cell disease have red blood cells that become hard and pointed instead of soft and round. Sickle cells cause anaemia, pain and many other problems.

These are the most common blood cells. They give the blood its red colour. Red blood cells (RBC’s) are filled with chemical called haemoglobin. The haemoglobin in the red blood cells transports oxygen (from the lungs, where it is breathed in from the air) around the body to all the other tissues like the heart, liver, kidneys and brain. Every tissue in the body (even fat and skin) needs oxygen to make energy so people that are short of haemoglobin feel tired and lacking in energy, because they cannot move the oxygen to where it is needed.

Red blood cells live for about 3 to 4 months, so every day your body produces millions of new red blood cells (from the bone marrow) to replace the ones that have died. This is normal and part of a natural “recycling” process.
Red blood cells make up about 40 – 50% of the volume of blood in your body; most of the rest is the watery plasma. Red blood cells can be given in a transfusion to people who lack them when this is necessary. However, usually, a lack of red blood cells can be treated by other methods. Some people can react to blood transfusions and so they are only used when absolutely necessary.

Platelets are technically not proper blood cells but little bits broken off big cells. Platelets are part of a system which allows the blood to clot. (Certain chemicals in the plasma, called clotting factors, are also needed for the blood to clot.) If you cut yourself, platelets are attracted to the cut and begin to stick together with the help of the clotting factors, and a blood clot is formed.

People who lack platelets are more likely to bleed and bruise than normal. When necessary, platelets can be given in a transfusion to some people who lack platelets.

Administering the Stem Cells

Before a patient receives a stem cell  transplant they will have to undergo a conditioning regime of drugs to destroy their own bone marrow and any residual disease. This will vary depending on the disease; radiation and chemotherapy are usually given. This has a high toxicity and there has to be a careful balance. The levels of chemotherapy are given in lethal doses and in combination with radiotherapy can make the patient very unwell.

The day that the transplant is given is called day 0, this day is often an anticlimax for patients because the actual process is so easy compared to the build up. The stem cells are given directly into the blood stream via a blood administration set into a central venous catheter.

Aplastic anaemia is a rare acquired disorder in which there is a failure of the bone marrow to produce sufficient blood cells for circulation. Aplastic anaemia is not a form of cancer. In AA there is a lack of cells (red cells, white cells and platelets) within the blood. Failure of the stem cells to produce mature blood cells varies from partial to almost complete thus producing a disease of varying severity in different people.

Multiple Myeloma is a blood cancer, which affects plasma cells in the bone marrow. Plasma cells produce antibodies and are a specialised form of blood cell called a B lymphocyte. In myeloma a single cell becomes malignant and produces a very large number of identical cells. Large numbers of a single type of antibody called paraprotein is produced. Normal antibody levels in myeloma are almost always reduced.

Before and after stem cell transplant complications can occur and skilled nursing care is essential. The main issues are preventing complications and if they occur managing them effectively.

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer.

Blood is a transport system for the body, helping to move nutrients and energy to where they are needed and removing waste products from body tissues. Normal blood consists of blood cells, which float around in a watery mixture called plasma. The different types of blood cells and the plasma all have different functions.

Before the patient receives the transplant they will have to undergo a conditioning regime of drugs to destroy their own bone marrow and any residual disease. This will vary depending on the disease; radiation and chemotherapy are usually given. This has a high toxicity and there has to be a careful balance. The levels of chemotherapy are given in lethal doses and in combination with radiotherapy can make the patient very unwell.

 

The myelodysplastic syndromes are a group of diseases in which the production of blood cells by the bone marrow is disrupted. Unlike leukaemia, in which one specific type of blood cell (the white cell) is produced in excessively large numbers, the production of any and sometimes all types of blood cells is affected. Patients with MDS will at some stage transform to acute myeloid leukaemia.

Plasma is the name given to the liquid that the blood cells float in. Plasma is mostly water with chemicals like salt and sugar dissolved in it. It also contains various proteins and other chemicals that are necessary for your body to function properly. Levels of salt, sugar and other chemicals can be abnormal for many reasons, including diseases of the liver or kidneys or other problems like diabetes.

 

One group of chemicals found in plasma are called the clotting or coagulation factors. These work with platelets to allow the blood to clot when necessary. Some people can have abnormal amounts of these clotting factors. In some cases this can lead to a tendency for blood to clot when it should not.

For other people, lack of certain clotting factors can lead to an increased risk of bleeding, for example in haemophilia.
Some people with low levels of clotting factors need plasma transfusions. These are given like a blood transfusion, and have similar possible side effects.