In 1933, Janet Vaughan, said, “Haematology has advanced more rapidly in the last 10 years more than any branch of medicine. Current haematological literature is so prolific that it is increasing difficult for anyone but a specialist to keep up to date7.” In 2019, this is even more so.
Haematology is the study of blood in health and disease. It includes diseases of red blood cells, white blood cells, platelets, blood vessels, the bone marrow, lymph nodes, the spleen and the proteins involved in bleeding and clotting.
There are many different haematological diseases. These are broadly divided into malignant (cancerous) diseases and non-malignant diseases. The malignant diseases, or haematological cancers, include leukaemias, lymphomas and myeloma. There are other rare forms of haematological cancers which fit into other categories.
The non-malignant diseases of blood and bone marrow are quite varied and may affect any component of the haematological system in a variety of ways. All blood diseases may potentially have far-reaching consequences and may lead to complications involving other organs.
The haematological system
Understanding what haematology is requires some understanding of the role of the components of the haematological system.
White blood cells (leukocytes) come in many different forms. Collectively, white blood cells are an important component of the immune system and are vital to fighting infections.
Red blood cells (erythrocytes) contain an important molecule, called haemoglobin. Red blood cells use haemoglobin to transport oxygen from the lungs to the body’s tissues.
Platelets (thrombocytes, though this is an uncommon term) are an important part of the clotting system of blood. In close collaboration with proteins, called clotting factors, they form clots (thrombosis) at the sites of injury to prevent blood loss (haemostasis).
The bone marrow is where white blood cells, red blood cells and platelets are formed.
Blood cell formation is a complex process. Maturation of blood cells, from their most basic ancestors (blood or haemopoietic stem cells) to mature blood cells found circulating in our blood vessels, is a multi-step process which occurs within the bone marrow.
Blood cells go through various stages of development within the bone marrow which may be thought of as a nursery. Once cells have fully matured, they exit the marrow into the blood vessels where they are able to carry out the above-mentioned functions.
A haemopoietic stem cell is the most primitive form of blood cell and can transform into any type of white or red blood cell, or platelets.
What is a haematologist?
A haematologist is a medical specialist who diagnoses and treats haematological diseases. Laboratory haematologists perform bone marrow tests and mainly carry out diagnostic work while clinical haematologists primarily treat patients.
After completing undergraduate medicine, doctors train either as specialist physicians or as laboratory haematologists and they then sub-specialise in clinical haematology. There are some haematologists who do both laboratory and clinical work.
Clinical haematologists use chemotherapy, immunotherapy, and special targeted therapies (and often a combination of these) to treat patients with leukaemias, lymphomas, myeloma and other haematological diseases. Some clinical haematologists perform stem cell transplantation which is required for the treatment of certain haematological cancers.
What is leukaemia?
Leukaemia is a broad term encompassing several diseases. In general, leukaemias are a type of cancer which originate in the bone marrow from immature white blood cells. An error occurs in their development, resulting in abnormal cell growth and accumulation of abnormal, cancerous white blood cells in the bone marrow. These may in turn spill over into the bloodstream, resulting in a high white blood cell count on blood tests.
The acute types of leukaemia are rapidly-evolving diseases and tend to cause complications very quickly after initially developing (usually within weeks to months). They quickly fill the bone marrow with abnormal, cancerous white blood cells which in turn results in the bone marrow’s failure to produce normal white cells, red cells and platelets.
The decrease in production of normal white cells leads to severe infections; too few red cells (anaemia) results in severe fatigue, dizziness and shortness of breath; and a lack of platelets results in bruising and bleeding. These symptoms are often the initial manifestations of an acute leukaemia. It’s important to note that leukaemias are rare diseases and the above-mentioned symptoms are far more commonly attributable to other, more common problems.
There are two major types of acute leukaemia: acute myeloid leukaemia (AML) (more common in older patients) and acute lymphoblastic leukaemia (ALL) (more common in children). Both types may occur in all age groups.
Acute leukaemias are treatable and potentially curable with intensive chemotherapy, provided that the patient is young enough and otherwise healthy enough to undergo intensive treatment. Some types of acute leukaemia require treatment with bone marrow transplantation to prevent patients from relapsing in the future.
For older patients or for patients who have other diseases preventing them from receiving intensive chemotherapy, there are newer, non-chemotherapy treatments available. These hold a lot of promise and while often not curative may provide a reasonable amount of control of the disease.
ALL in children is a highly treatable and curable disease with cure rates with modern therapies approaching 100%1.
Chronic leukaemia is a more slow-developing disease and may evolve over months to years without the development of symptoms.
Chronic lymphocytic leukaemia (CLL) (occurs predominantly in older adults) is often diagnosed incidentally on routine blood tests. This disease, if no complications or symptoms are present, may require no treatment at all2. These patients are regularly monitored for
the development of symptoms or complications related to the disease and only if symptoms or complications arise, does the disease need treatment.
Chronic myeloid leukaemia (CML) is also a slow-growing disease but all patients diagnosed will need treatment. CML is caused by a very specific genetic abnormality (not hereditary), known as the BCR/ABL fusion gene (also known as the Philadelphia chromosome).
This defect has very successfully been targeted by medications and most patients with this disease are able to live fairly normal lives and have a normal life expectancy3.
There are, however, some patients with chronic leukaemias who experience a more complicated course of disease and require intensive therapies. In some instances, chronic leukaemias may also require treatment with stem cell transplantation3.
What is lymphoma?
Lymphoma is cancer that begins in infection-fighting cells of the immune system, called lymphocytes. Lymphocytes are one of the various types of white blood cell. These cells are found in the lymph nodes, spleen, thymus, bone marrow and other parts of the body. When a patient is diagnosed with lymphoma, lymphocytes change and grow out of control.
There are two main types of lymphoma:
• Non-Hodgkin’s lymphoma (NHL) (the more common type)
• Hodgkin’s lymphoma
It should be noted that non-Hodgkin’s lymphoma is not a specific diagnosis, but rather a very large group of different types of lymphoma which are different to Hodgkin’s lymphoma.
The most common examples of NHL are diffuse large B-cell lymphoma and follicular lymphoma, but there are many more. NHLs may be grouped into high-grade and low-grade, or indolent lymphomas.
High-grade lymphomas (diffuse large B-cell lymphoma) grow rapidly and cause symptoms related to their growth and compression of bodily structures within weeks. They require urgent chemotherapy and often respond very well to treatment4. Many cases are curable with chemotherapy often used
in conjunction with immunotherapy. The outlook for patients is highly variable though and depends upon the specific type of lymphoma, the stage at diagnosis, and the patient’s age and general condition.
Low-grade lymphomas (follicular lymphoma) usually grow slowly with a gradual onset of symptoms and complications. Like CLL, some patients with follicular lymphoma may initially require no treatment at all5.
Others with early-stage asymptomatic disease may be amenable to immunotherapy alone without chemotherapy. Those who are symptomatic will require a combination of chemotherapy and immunotherapy. There are many exciting new developments in the treatment of lymphoma with newer specialised targeted therapies being researched and becoming available with each passing year.
Indolent lymphomas are potentially curable but are more likely to relapse after treatment. Even where relapses of lymphoma occur the condition is still potentially treatable and curable5.
Hodgkin’s lymphoma occurs predominantly in two distinct age groups: young adults and in patients older than 556.
It often behaves like a high-grade lymphoma and most commonly patients have enlarged lymph nodes in the neck and chest.
Over the last four decades, advances in the treatment of Hodgkin’s lymphoma have significantly increased the cure rate of patients. Currently, more than 80% of all newly diagnosed patients younger than 60 years are likely to be cured of their disease6.
- Hunger, Stephen P MCG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015;373(16):1541–52.
- Hallek M. Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. Am J Hematol. 2015 May;90(5):446–60.
- Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol. 2018 Mar;93(3):442–59.
- Li S, Young KH, Medeiros LJ. Diffuse large B-cell lymphoma. Pathology. 2018 Jan;50(1):74–87.
- Freedman A. Follicular lymphoma: 2018 update on diagnosis and management. Am J Hematol. 2018 Feb;93(2):296–305.
- Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol. 2018 May;93(5):704–15.
- The Anaemias by Janet Vaughan, 1st edition, Oxford Medical Publications, 1933.
MEET OUR EDITOR
Dr Michael Cass is a clinical haematologist and stem cell transplant physician at Alberts Cellular Therapy (Dr Brittain and Partners Inc, affiliated to ABJ Oncology) based at Netcare Pretoria East Hospital. He also consults at the ABJ Benoni Oncology Unit and Life Glynnwood Hospital.