Haematological Cancer: Focus on Leukaemia

Question 1

What are the main differences between leukaemia and lymphoma?

Answer 1

Leukaemia is a ‘liquid’ tumour that arises in the bone marrow and usually spills into the blood, while lymphoma is a ‘solid’ tumour that arises in the lymph nodes and may spread into the bone marrow. Lymphoma may also involve other non-lymphatic tissues.

Question 2

What are the two types of leukaemia?

Answer 2

Leukaemia can be either lymphoid or myeloid in origin.

Question 3

What are some examples of non-lymphatic tissues that may be involved in lymphoma?

Answer 3

Lymphoma may involve tissues such as bone, adrenals, testicles, breast, renal, etc. This is known as extra-nodal disease.

Question 4

What is an oncogene and how does it contribute to cancer development?

Answer 4

An oncogene is a mutated gene that contributes to the development of cancer. It is triggered by exposure to genetic modifiers and/or environmental modifiers.

Question 5

What is a tumour suppressor gene?

Answer 5

A tumour suppressor gene is a gene that acts as an “anti-oncogene” by preventing the development of cancer. It plays a role in regulating cell growth and division.

Question 6

Where does leukaemia occur?

Answer 6

Leukaemia occurs primarily in the bone marrow, where abnormal cells crowd out healthy blood cells.

Question 7

What are the main classifications of leukaemia based on cell proliferation?

Answer 7

Leukaemia can be classified as acute or chronic. Acute leukaemia involves the rapid proliferation of immature cells (blasts), while chronic leukaemia involves the proliferation of mature cells.

Question 8

What are the typical characteristics of acute leukaemia?

Answer 8

Acute leukaemia has a rapid onset and can have a devastating course if left untreated. It primarily affects younger patients and is characterized by the presence of immature cells (blasts) in the blood and bone marrow.

Question 9

What are the typical characteristics of chronic leukaemia?

Answer 9

Chronic leukaemia has a gradual onset and follows an indolent (slow-progressing) course. It primarily affects older patients and is characterized by the proliferation of mature cells in the blood and bone marrow.

Question 10

What are the two main types of cells involved in leukaemia classification?

Answer 10

Lymphoid leukaemia involves cells from the lymphocyte line, while myeloid leukaemia involves cells from other lineages, including granulocytes, monocytes, red blood cells (RBCs), and megakaryocytes.

Question 11

What are some common presentations of leukaemia related to bone marrow failure?

Answer 11

Bone marrow failure in leukaemia can present with bruising, bleeding (especially gums), petechiae (tiny red or purple spots on the skin), anemia (resulting in fatigue and breathlessness), and thrombocytopenia (low platelet count).

Question 12

What is neutropenic infection?

Answer 12

Neutropenic infection occurs when an individual produces too few neutrophils, which are a type of white blood cell responsible for fighting bacterial infections.

Question 13

What are some examples of bacterial infections commonly seen in individuals with leukaemia?

Answer 13

Bacterial infections in individuals with leukaemia can manifest as chest infections, tonsillitis, or cellulitis (skin infection).

Question 14

What are some examples of viral infections commonly seen in individuals with leukaemia?

Answer 14

Viral infections in individuals with leukaemia can result in the development of ulcers and sores.

Question 15

What are some examples of fungal infections commonly seen in individuals with leukaemia?

Answer 15

Fungal infections, such as candida or disseminated fungal lung infections, can occur in individuals with leukaemia.

Question 16

What are some tissues that can be infiltrated by leukaemia cells?

Answer 16

Leukaemia cells can infiltrate various tissues, leading to enlargement of lymph nodes, spleen, liver, gums, nervous system, and testicles.

Question 17

What is leukostasis?

Answer 17

Leukostasis refers to the increased viscosity of blood due to the accumulation of leukemia cells, which can result in impaired blood flow and organ dysfunction.

Question 18

What are some manifestations of leukaemia-related lung involvement?

Answer 18

Lung infiltrates can cause breathlessness in individuals with leukaemia.

Question 19

What are some manifestations of leukaemia-related cerebral vessel congestion?

Answer 19

Cerebral vessel congestion can lead to symptoms such as headache and confusion in individuals with leukaemia.

Question 20

What are some complications that can arise when leukaemia cells release their contents into the blood?

Answer 20

The release of leukaemia cell contents into the blood can cause kidney failure, which, in turn, can lead to a condition called disseminated intravascular coagulation (DIC).

Question 21

What are some components of the diagnostic process for leukaemia?

Answer 21

The diagnostic process for leukaemia includes obtaining a detailed patient history, conducting a physical examination, performing blood tests (including blood count and blood biochemistry), and considering virology studies.

Question 22

What is the significance of morphology in leukaemia diagnosis?

Answer 22

Morphology refers to the examination of cells under a microscope and plays a crucial role in leukaemia diagnosis. It involves the visual assessment of cell characteristics and can help determine if leukaemia cells are present.

Question 23

What is the definitive diagnostic test for leukaemia?

Answer 23

The definitive diagnosis of leukaemia often requires a bone marrow biopsy. Samples obtained from the bone marrow can be analyzed for various purposes, including morphology assessment to detect the presence of leukaemia cells.

Question 24

What types of genetic abnormalities can be evaluated in leukaemia diagnosis?

Answer 24

Genetic testing in leukaemia diagnosis can involve analyzing whole or part of chromosomes for numeric or structural abnormalities, as well as detecting micro deletions or duplications. Additionally, single gene disorders can be investigated using next-generation sequencing, allowing for the screening of specific genes associated with blood cancers.

Question 25

How can mutational profiling be used in leukaemia diagnosis?

Answer 25

Next-generation sequencing can be used to perform mutational profiling by screening for DNA changes in certain genes associated with blood cancers. This information can help with risk stratification, prognosis, and making therapeutic decisions for patients with acute myeloid leukemia (AML).

Question 26

What is immunophenotyping, and how does it aid in the diagnosis of leukaemia?

Answer 26

Immunophenotyping is a technique that looks for the presence or absence of cell antigens (proteins in the cell membrane) to provide clues about the type of blood abnormality. It involves using specific cell markers, often identified by “C numbers,” and flow cytometry to analyze the expression of these markers on the surface or inside the cells.

Question 27

How does flow cytometry work in immunophenotyping?

Answer 27

Flow cytometry utilizes monoclonal antibodies labeled with fluorescent dyes to detect specific proteins or molecules on the cell surface, cytoplasm, or nucleus. A sample of the patient’s cells is mixed with different antibodies, each labeled with a different dye. The flow cytometer then passes individual cells through lasers to excite the fluorescent dyes. Detectors measure the emissions from the dyes, providing information about the amount of each protein expressed on each cell.

Question 28

What is the significance of CD names in immunophenotyping?

Answer 28

Proteins detected through immunophenotyping are assigned CD names, such as CD45. CD stands for “cluster of differentiation” and provides a standardized nomenclature for cell surface markers.

Question 29

What are the characteristics of acute lymphoblastic leukaemia (ALL)?

Answer 29

Acute lymphoblastic leukaemia is the most common malignancy in childhood. It typically presents with bone marrow involvement, bulky disease (e.g., mediastinal nodes), and can be classified as B cell or T cell ALL. There is also a risk of cerebro-spinal fluid (CSF) involvement, which requires CSF analysis and treatment directed at the central nervous system.

Question 30

What are some features of B cell ALL?

Answer 30

B cell ALL is characterized by bone marrow failure and often presents with a large spleen (splenomegaly). It is associated with the expression of CD10 and CD19 cell markers.

Question 31

What are some features of T cell acute lymphoblastic leukaemia (T-ALL)?

Answer 31

T-ALL commonly affects teenage boys and is characterized by thoracic lymphadenopathy and mediastinal widening on chest X-ray. T-ALL is associated with low CD numbers, specifically CD5 and CD7 cell markers.

Question 32

What are some characteristics of acute myeloid leukaemia (AML)?

Answer 32

AML is characterized by the presence of at least 20% blasts in the bone marrow or film. It tends to occur more frequently in older patients, with a median age of 65. Auer rods, which are needle-like cytoplasmic inclusions, are considered diagnostic. AML blasts also exhibit myeloperoxidase-positive granules.

Question 33

What is acute promyelocytic leukaemia (APL), and what are its distinctive features?

Answer 33

APL is a variant of AML. It can be associated with severe coagulopathy, activating the clotting pathway and causing depletion of clotting factors. It is considered a hematological emergency. The specific treatment for APL is all-trans retinoic acid (ATRA), which induces differentiation (maturation) of the promyelocytes.

Question 34

What factors need to be considered in the treatment of acute leukaemia?

Answer 34

When treating acute leukaemia, patient factors (such as age, overall health, and preferences) and disease factors (such as subtype, stage, and genetic markers) are taken into account to determine the appropriate treatment approach.

Question 35

What is the difference between curative and palliative care in the context of acute leukaemia?

Answer 35

Curative care aims to provide treatment with the intention of curing the disease, while palliative care focuses on managing symptoms and improving quality of life without the expectation of a cure.

Question 36

What are some supportive care measures used in the treatment of acute leukaemia?

Answer 36

Supportive care measures in acute leukaemia treatment include managing symptoms, preventing bleeding (through blood and platelet transfusions), correcting coagulation abnormalities (using Fresh Frozen Plasma - FFP), preventing menstruation (using hormone therapy), preventing infections through prophylaxis and hygiene practices, and preserving fertility through options like sperm or egg storage.

Question 37

What is involved in curative treatment for acute leukaemia?

Answer 37

Curative treatment for acute leukaemia typically involves a highly aggressive regimen lasting 6-12 months. It may require multiple prolonged hospital admissions and can have potential long-term effects, such as infertility, bone necrosis, and cardiac/neurological toxicity.

Question 38

What is GCSF (Granulocyte Colony-Stimulating Factor) used for in acute leukaemia treatment?

Answer 38

GCSF is used to stimulate the production of granulocytes (a type of white blood cell) and can be used in acute leukaemia treatment to help boost the immune system.

Question 39

What are some systemic anti-cancer therapies used in the treatment of acute leukaemia?

Answer 39

Systemic anti-cancer therapies for acute leukaemia include chemotherapy (usually given in combination), immunotherapy (e.g., monoclonal antibodies), radiotherapy, and bone marrow transplantation. These treatments can take months or years and may be intense.

Question 40

What are some risks and complications associated with allogeneic transplantation?

Answer 40

Allogeneic transplantation (a form of bone marrow transplantation) carries risks such as graft failure, graft-versus-host disease (GvHD) affecting the skin, gut, and liver, infections (including atypical and viral reactivation), fertility issues, psychosocial challenges, the burden of follow-up care, morbidity, and the possibility of relapse.

Question 41

What is the prognosis for acute leukaemia?

Answer 41

The prognosis for acute leukaemia varies depending on several factors, including the subtype of leukaemia, patient characteristics, and response to treatment. There are risks associated with treatment, such as graft failure, GvHD, infections, fertility issues, psychosocial challenges, burden of follow-up care, morbidity, and the potential for relapse.

Question 42

What are some key features of chronic lymphocytic leukaemia (CLL)?

Answer 42

CLL is commonly seen in older individuals (median age of 70 years) and has a generally good prognosis with a median survival of 10 years. It involves B lymphocytes and is characterized by a lymphocyte count greater than 5.0 x 10^9/L, which can sometimes be very high (over 100). Small to medium-sized lymphocytes are typically seen in the blood film and bone marrow. Smear cells may also be present on the blood film.

Question 43

How does CLL typically present?

Answer 43

CLL is most commonly an incidental finding. However, it can manifest with a high white cell count on blood count. Patients are often asymptomatic but may have generalized lymphadenopathy, splenomegaly, symptoms of anemia, autoimmune hemolytic anemia, bone marrow failure, and increased susceptibility to infections due to reduced immunoglobulins and decreased white blood cell diversity.

Question 44

What are some special considerations in chronic lymphocytic leukemia (CLL)?

Answer 44

CLL may exhibit positive Coombs test (direct antiglobulin test) if hemolysis is present. It is characterized by CD19+ B cell surface antigens, and genetic analysis can influence treatment decisions. CLL can overlap with lymphoma and has the potential to transform into a high-grade lymphoma. The term “Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)” may be used. In many cases, no treatment is required initially, and a “watch and wait” approach is adopted.

Question 45

What are some screening markers for hemolysis in CLL?

Answer 45

Hemolysis screen in CLL may show increased reticulocytes, positive direct antiglobulin test (DAT) if immune hemolysis is present, increased unconjugated bilirubin, decreased haptoglobin, and elevated lactate dehydrogenase (LDH) levels.

Question 46

What are some characteristics of chronic myeloid leukemia (CML)?

Answer 46

CML is typically seen in older individuals, with a peak incidence around 50 years of age. It is characterized by a mutation in the stem cell affecting the entire myeloid cell line, including granulocytes, monocytes, and megakaryocytes. The disease follows a slow course with three phases: chronic phase (less than 10% blasts), accelerated phase (10-20% blasts), and blast crisis (more than 20% blasts), which has a worse prognosis.

Question 47

How does CML typically present?

Answer 47

CML often presents with a very high white blood cell count, often exceeding 100 x 10^9/L. All granulocyte lines, including immature forms, may be present. Patients are often asymptomatic but can experience symptoms related to bone marrow failure, such as fatigue from anemia. Splenomegaly (possibly massive), fever, sweats, weight loss, headache, retinal bleeding, and priapism (persistent and painful penile erection) are other potential symptoms.

Question 48

What is a highly specific feature on the peripheral blood film that aids in the diagnosis of chronic myeloid leukemia (CML)?

Answer 48

Basophilia (presence of basophilic granules) on the peripheral blood film is highly specific for the diagnosis of CML.

Question 49

What are the different phases of CML defined by blast count?

Answer 49

CML has three phases: chronic phase, accelerated phase, and blast crisis. The chronic phase has less than 10% blasts, the accelerated phase has 10-20% blasts, and blast crisis refers to transformation into acute leukemia, which can be either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).

Question 50

What is the Philadelphia chromosome, and how is it formed?

Answer 50

The Philadelphia chromosome is a characteristic genetic abnormality in CML. It is formed when parts of chromosomes 9 and 22 swap with each other. The exact cause of this chromosomal translocation is not yet fully understood. It’s important to note that CML is not an inherited condition and cannot be passed on to children.

Question 51

What is the specific treatment for CML?

Answer 51

CML is characterized by the overproduction of a tyrosine kinase signaling protein, resulting in increased tyrosine kinase activity and overproduction of myeloid cells. The specific treatment for CML is a tyrosine kinase inhibitor, such as Imatinib. Imatinib induces complete remission in approximately 70% of cases.

Question 52

How are blast crisis and accelerated phase of CML typically treated?

Answer 52

Blast crisis and accelerated phase of CML are typically treated with chemotherapy and stem cell transplantation.