What is Leukaemia?

Leukaemia is a cancer of the white blood cells and these cells are produced by the bone marrow. There are many different types of leukaemia and it is identified by which type of white blood cell is affected and whether it is chronic or acute. Acute leukaemia comes on suddenly, often within days or weeks, progressing quickly and need to be treated urgently. Chronic leukaemia may develop more slowly, often over many months or years. These are the four most common types;

  • Acute Myeloid Leukaemia (AML)

Acute myeloid leukaemia (AML) goes by many names, including acute myelocytic leukaemia, acute myelogenous leukaemia, acute granulocytic leukaemia, and acute non-lymphocytic leukaemia. "Acute" means that the leukaemia can progress quickly, and if not treated, would probably be fatal in a few months.

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AML starts in the bone marrow (the soft inner part of the bones, where new blood cells are made), but in most cases it quickly moves into the blood. It can sometimes spread to other parts of the body including the lymph nodes, liver, spleen, central nervous system and testicles.

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  • Acute Lymphocytic Leukaemia (ALL)

Acute lymphoblastic leukaemia (ALL), is a form of leukaemia characterised by excess lymphoblasts.

In ALL, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading to other organs.

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ALL is most common in childhood with a peak incidence at 2-5 years of age, and another peak in old age. The overall cure rate in children is about 80%, and about 45%-60% of adults have long-term disease-free survival.

Acute refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of CLL which has a potential time course of many years.

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  • Chronic Myeloid Leukaemia (CML)

Chronic myeloid leukaemia (CML) is a cancer of the white blood cells. It is a form of leukaemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood.

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CML has a defined genetic abnormality, or chromosomal translocation which invovles parts of two chromosomes (9 and 22) switch places. As a result, one part of a gene called the BCR gene from chromosome 22 is fused with another gene, ABL, on chromosome 9.

This abnormal "fusion" gene generates a protein called p210, which is only found in CML cells.

With improved understanding of the nature of the BCR-ABL protein and its molecular action, specific therapsies have been developed such as Gleevec (also known as imatinib mesylate) which specifically inhibit the activity of the BCR-ABL protein.

CML is often divided into three phases based on clinical characteristics and laboratory findings. In the absence of intervention, CML typically begins in the chronic phase, and over the course of several years progresses to an accelerated phase and ultimately to a blast crisis.

Blast crisis is the terminal phase of CML and clinically behaves like an acute leukaemia.

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  • Chronic Lymphocytic Leukaemia (CLL)

CLL is the second most common type of leukaemia in adults. It often occurs during or after middle age; it rarely occurs in children.

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In CLL, too many blood cells develop into abnormal lymphocytes and do not become healthy white blood cells. The abnormal lymphocytes may also be called leukaemic cells. The lymphocytes are not able to fight infection very well. Also, as the number of lymphocytes increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may result in infection, anaemia, and easy bleeding.

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  • Myelodysplastic Syndromes (MDS)

The myelodysplastic syndromes (MDS) are a diverse collection of haematological conditions united by ineffective production (or dysplasia) of myeloid blood cells and risk of transformation to acute myeloid leukaemia (AML).

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MDS has been found in humans, cats and dogs. Anaemia requiring chronic blood transfusion is frequently present.

MDS are bone marrow stem cell disorders resulting in disorderly and ineffective blood production manifested by defects in blood-forming cells.

In a majority of cases, the course of disease is chronic with gradually worsening cytopenias due to progressive bone marrow failure.

Approximately one-third of patients with MDS progress to AML within months to a few years.

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What is Lymphoma?

 

Lymphoma is a type of blood cancer.

  • Lymphoma occurs when lymphocytes- the white blood cells that help protect the body from infection and disease--begin behaving abnormally. They may grow and divide faster than normal lymphoid cells or they may live longer than they are supposed to by not dying when they should.

  • The two primary types

  • B cells produce proteins that attach to infectious organisms, such as bacteria, and abnormal cells and indicating to the immune system that the infection needs to be destroyed.

  • T cells kill the pathogens directly and serve a function in making sure that the immune system is correctly regulated.

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Lymphoma occurs when B or T cells are altered or transformed and begin growing and multiplying uncontrollably. Lymphoma can develop in the lymph nodes in any part of the body and often develop in the spleen, bone marrow, blood or other organs and eventually they form a mass of cells called a tumour. If abnormal lymphocytes travel from one lymph node to the next or to other organs, the cancer can spread or metastasise. Lymphoma development outside of lymphatic tissue is called extranodal disease. The cause of lymphoma is still unknown.

There are two main types of lymphomas:

  • Hodgkin lymphoma (HL) - There is six types of HL, it is an uncommon form of lymphoma that specifically involves the Reed-Sternberg cells.

  • Non-Hodgkin lymphoma (NHL) There are more than 61 types of NHL, some of which are more common than others. Any lymphoma that does not involve Reed-Sternberg cells is classified as non-Hodgkin lymphoma.

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  • Signs and Symptoms

Some symptoms are not specific to lymphoma and are similar to those of many other illnesses such as a cold, flu or some other respiratory infection that does not go away.

Common symptoms may include:

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  • Swelling of lymph nodes, which may or may not be painless

  • Fever

  • Unexplained weight loss

  • Night sweat

  • Chills

  • Lack of energy

  • Itching

Most people who have these non-specific symptoms will not have lymphoma. However, it is important that anyone with persistent symptoms be examined by a doctor to make sure lymphoma is not present.

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  • Lymphoma Treatment

Hodgkin Lymphoma

is usually treated with some type of chemotherapy, radiation therapy, or a combination of the two. Bone marrow or stem cell transplantation may also sometimes be done under special circumstances. Most patients with Hodgkin lymphoma live long and healthy lives following successful treatment.

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Non-Hodgkin lymphoma

lymphoma is usually treated with some form of chemotherapy, radiation therapy, biologic therapy, or a combination of these. Bone marrow or stem cell transplantation may sometimes be used.

Although some forms of non-Hodgkin lymphoma are not currently curable, the outlook is still very good. Patients may live for 20 years or more following an initial diagnosis. Approximately 30 to 60% of patients with an aggressive form of non-Hodgkin lymphoma can be cured.

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  • Hodgkin Lymphoma (HL)

Hodgkin lymphoma is not as common as Non Hodgkin Lymphoma (NHL). Although the cancer can occur in both children and adults, it is most commonly diagnosed in young adults between the ages of 15 and 35 and in older adults over age 50.

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Hodgkin lymphoma is characterized by the presence of very specific large cell type called the Reed-Sternberg (R-S) cells, although other abnormal cell types may be present. HL usually starts in the lymph nodes, and often spreads from one lymph node to another and can also spread to other organs.

Common Types of HL

Hodgkin lymphoma has been divided into two main types; the classical HL (CHL), which accounts for most cases of HL, and nodular lymphocyte predominant HL.

Classical Hodgkin Lymphoma

  • Nodular Sclerosis CHL: the most common subtype of HL, accounting for between 60 and 80% of all cases of HL. This type of HL is more common in women than men, and it usually affects adolescents and adults under 50.

  • Mixed Cellularity CHL: accounts for 15-30% of all cases of HL and is found more commonly in men than women. More advanced disease is usually present by the time this subtype is diagnosed.

  • Lymphocyte-depletion CHL: this type of HL is rare.

  • Lymphocyte-rich CHL: Around 5% of HL cases. This subtype of HL is usually diagnosed at an early stage in adults and has a low relapse rate

Lymphocyte Predominant Hodgkin Lymphoma

  • Nodular Lymphocyte Predominant HL: accounts for 5-10% of all HL cases and affects men more often than women and is usually diagnosed before the age of 35.

Treatment Options

Over 80% of patients with HL are cured and most patients treated for HL will receive some form of chemotherapy, and sometimes radiation therapy, as their first treatment. The recommended first-line therapy for HL is a combination of four drugs: Adriamycin, Bleomycin, Vinblastine & Dacarbazine with or without radiotherapy. Stem cell transplantation is typically used disease returns after treatment or does not respond to treatment.

Treatments Currently Under Investigation

Although the cure rate in HL is already high, research continues to look for ways to treat the small minority of patients who are resistant (refractory) to treatment and those who relapse. Many promising therapies are currently under investigation in clinical trials for HL. Types of therapy under investigation include:

  • Bendamustine (Treanda)

  • Bortezomib (Velcade)

  • Lenalidomide (Revlimid)

  • Panobinostat

  • Temsirolimus (Torisel)

  • Vorinostat (Zolinza)

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  • Non-Hodgkin Lymphoma (NHL)

Non-Hodgkin lymphoma is the most common cancer of the lymphatic system, a part of the immune system. Since the 1970’s, incidence rates for NHL have nearly doubled.

Non-Hodgkin lymphoma is not a single disease, but rather a group of several closely related cancers and the WHO has suggested that there may be at least 61 types of NHL.

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Non-Hodgkin lymphomas are broadly divided into two major groups: B-cell lymphomas and T-cell lymphomas. B-cell lymphomas account for 85% of all NHL; whilst T-cell lymphomas account for the remaining 15%. Non-Hodgkin lymphomas may also be classified as indolent (slow-growing) or aggressive (fast-growing).

Stages

Non-Hodgkin lymphoma is divided into four stages based on how far the disease has spread.

  • Stage I (early disease): the cancer is found only in a single lymph node OR in one organ or area outside the lymph node.

  • Stage II (locally advanced disease): the cancer is found in two or more lymph node regions on one side of the diaphragm.

  • Stage III (advanced disease): the cancer involves lymph nodes both above and below the diaphragm.

  • Stage IV (widespread disease): the cancer is found in several parts of one or more organs or tissues (in addition to the lymph nodes). Or, it is in the liver, blood or bone marrow.

Treatment Options

Many effective treatment options exist for NHL patients, including:

  • watchful waiting

  • chemotherapy

  • radiation therapy

  • stem cell transplantation

  • novel targeted agents

  • newer versions of established agents

The form of treatment chosen depends on the type of lymphoma and the stage of disease, as well as other factors including age, prior therapies received and the patient’s overall health

Some patients may relapse (disease returns after treatment) or become refractory (disease does not respond to treatment). However, numerous treatment options exist for patients with relapsed or refractory NHL, which are often referred to as secondary therapies. Many of the novel therapeutic agents that have been approved by the United States Food and Drug Administration, as well as those being investigated in clinical trials, focus specifically on those with relapsed or refractory disease.

Before starting treatment, patients should discuss all available treatment options with their physician.

Common Types of NHL

AIDS-Related Lymphomasoccur in HIV-positive patients are usually aggressive. It is estimated that as many as 10% of people who are HIV-positive will ultimately develop lymphoma, usually non-Hodgkin lymphomas.

Anaplastic Large-Cell Lymphoma (ALCL)is a rare type of aggressive T-cell lymphoma comprising about 3% of all lymphomas in adults and between 10-30% of all lymphomas in children

Burkitt's Lymphoma, Burkitt-like Lymphoma (Small Non-Cleaved Cell Lymphoma)is an aggressive B-cell form of NHL that occurs most often in children and young adults. Burkitt's lymphoma has a specific chromosomal abnormality called the t(8;14) translocation. There are three main types of Burkitt’s lymphoma.

  • Sporadic Burkitt’s lymphoma occurs throughout most of the world

  • Endemic Burkitt's lymphoma is found mostly in Africa and is often associated with the Epstein-Barr virus (EBV).

  • Immunodeficiency-related Burkitt's lymphoma is diagnosed most often in people infected with HIV/AIDS.

Cutaneous T-Cell Lymphoma (CTCL) arises in the skin and account for approximately 2-3% of all NHL cases.

Diffuse Large B-Cell Lymphoma (DLBCL) is the most common form of NHL, accounting for up to 1/3rd of newly diagnosed lymphoma cases.

Follicular Lymphoma is a relatively common lymphoma, accounting for 20-30% of all NHL, although it typically occurs in middle-aged and older adults, it can affect younger people in their 30s and 40s.

Lymphoblastic Lymphoma can effect both B-cells and T-cells, but is much more common in T-cells, comprising 80% of all lymphoblastic lymphomas. This lymphoma is most often diagnosed in children. With intensive chemotherapy, the complete remission rate can be very high.

Mantle Cell Lymphoma is a B-cell lymphoma that affects approximately 6% of all NHL patients.

Marginal Zone Lymphoma is a group of indolent lymphomas whose cells come from B-lymphocytes normally found in the marginal zone of the secondary lymphoid follicles in the spleen and lymph nodes, accounts for approximately 7% of all NHLs. The median age for diagnosis of this type of lymphoma is 65.
Marginal zone lymphomas encompass three basic types:

  • Extranodal or mucosa-associated lymphoid tissue (MALT), occurring outside the lymph nodes

  • Nodal, occurring within the lymph nodes

  • Splenic, occurring mostly in the spleen and blood

Marginal zone and MALT lymphomas vary from other types of B-cell NHLs in a number of ways: (1) their natural history is different; (2) many people who develop MALT lymphoma have a history of inflammation or autoimmune disorders; (3) chronic inflammation is associated with Helicobacter pylori (H. pylori), a microbial pathogen linked to chronic gastritis; and, (4) sometimes, MALT lymphomas can be treated with antibiotics.

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Myeloma

 

Myeloma is also known as multiple myeloma or myelomatosis.

  • Blood cells look and work differently, but they all repair and reproduce themselves in the same way. Normally, new cells are produced to replace old, worn-out cells in an orderly, controlled way. However, in myeloma the process gets out of control and large numbers of abnormal plasma cells – myeloma cells – are produced. These fill up the bone marrow and interfere with production of normal white cells, red cells and platelets.

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The myeloma cells usually produce a large amount of one type of abnormal antibody. This is known as a paraprotein or M protein. This paraprotein cannot fight infection effectively and often reduces the production of normal antibodies.

Myeloma cells have the ability to spread throughout the bone marrow and into the hard outer casing of the bone. Some, or many, areas of bone may be affected. Myeloma can cause thinning of the outer bone and bone pain.

Myeloma usually occurs in middle-aged and older people. It is unusual before the age of 50 and very rare in people younger than 40.

Myeloma is one type of disorder of the plasma cells. Some other conditions of the plasma cells can develop into myeloma but may not necessarily do so. The two most common of these are monoclonal gammopathy of uncertain significance (MGUS) and smouldering myeloma (also known as indolent or asymptomatic myeloma). If you are diagnosed with either of these conditions, you will be monitored with blood tests, but may not need to have any treatment unless the condition progresses.

Sometimes abnormal plasma cells are found in a bone in only one area of the body. This condition is known as a solitary plasmacytoma. It is treated with radiotherapy. Some people with solitary plasmacytoma may go on to develop multiple myeloma, so you will be regularly monitored with blood tests.

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Bone Marrow

  • The bone marrow is the soft inner part of some bones such as the skull, shoulder blades, ribs, pelvis, and backbones. The bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow.

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Blood stem cells go through a series of changes to make new blood cells. During this process, the cells develop into either lymphocytes (a kind of white blood cell) or other blood-forming cells. The other blood-forming cells can develop into 1 of the 3 main types of blood cell components:

Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed. Anaemia (having too few red blood cells in the body) typically causes a person to feel tired, weak, and short of breath because the body tissues are not getting enough oxygen.

Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in plugging up holes in blood vessels caused by cuts or bruises. A shortage of platelets is called thrombocytopenia. A person with thrombocytopenia may bleed and bruise easily.

White blood cells help the body fight infections. Lymphocytes (L) are one type of white blood cell. The other types of white blood cells are granulocytes (G) (neutrophils, basophils, and eosinophils) and monocytes.

Any of the blood-forming or lymphoid cells from the bone marrow can turn into a leukaemia cell. Once this change takes place, the leukaemia cells fail to go through their normal process of maturing. Leukaemia cells may reproduce quickly, but in most cases the problem is that they don't die when they should. They survive and build up in the bone marrow. Over time, these cells spill into the bloodstream and spread to other organs, where they can keep other cells in the body from functioning normally.

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