ACUTE LEUKEMIAS Flashcards
What is required for diagnosis of majority of acute leukemias
Finding at least 20% of blast ( blast cells are immature stem cells that give rise to different specialized cells)
What is acute lymphoblastic leukemia
Acute Lymphoblastic Leukemia (ALL) is a type of cancer that affects the blood and bone marrow.
What percentage of children diagnosed with ALL experience complete remission
- Children with ALL have a good prognosis Over 80% of pediatric patients are cured and the remission rate is 95%
Explain the chromosomal abnormalities of ALL
- Philadelphia chromosome is seen in about 20% of adults with ALL and 2% to 5 % of children with ALL
- t(4;11) translocation is commonly found in infants with ALL( t(4;11) means translocation between chromosome 4 and 11/genes transferred from gene 4 and 11)
How can the chromosome number in children be used to to predict the severity of ALL
Higher numbers of chromosomes have best prognosis for complete recovery with therapy. Greater than 50 chromosomes
- What is the significance of chromosome number in childhood ALL?
- The chromosome number is critical for predicting the severity of childhood ALL. Specifically, children whose leukemic cells contain more than 50 chromosomes have the best prognosis for complete recovery with therapy.
- How are recurring translocations observed in ALL associated with prognostic outcomes?
- Recurring translocations observed in ALL, such as t(4;11)(q21;q23), t(12;21)(p13;q22), and t(1;19)(q23;p13.3), are associated with prognostic outcomes.
- These translocations help determine patient therapy and play a crucial role in predicting the course of the disease.
Provide examples of recurring translocations observed in ALL and explain their implications on patient therapy.
- t(4;11)(q21;q23): Associated with the MLL gene, this translocation is often seen in infants and has a poor prognosis.
* t(12;21)(p13;q22): Commonly found in children, this translocation involves the TEL-AML1 fusion gene and is associated with a favorable prognosis.
* t(1;19)(q23;p13.3): Linked to the E2A-PBX1 fusion gene, this translocation occurs in adolescents and has an intermediate prognosis
Explain the importance of the subtype of ALL as a prognostic indicator for survival.
- The subtype of ALL is a significant prognostic indicator for patient survival.
- Different subtypes may have varying responses to treatment, affecting overall outcomes.
What are 3 things to look fro to rule out if the patient has leukemia
- Neutropenia
- Thrombocytopenia
- Anaemia
With reference to leukemia triad How to check if the patient has thrombocytopenia
The patient will have mucocutaneous bleeding
With reference to leukemia triad how to check for anaemia
Fatigue
With reference to leukemia triad how to check for neutropenia
Fever
What are the characteristics of ALL
- Lymphadenopathy ( disease of the lymph nodes in which they are enlarged)
- Splenomegaly and hepatomegaly (enraged spleen and enlarged river respectively)
- Bone pain
- Infiltration of malignant cells into meninges
What is lymphadenopathy, and how is it related to ALL?
Lymphadenopathy refers to the enlargement of lymph nodes. In the context of ALL, it is often a symptom due to abnormal proliferation of lymphoblasts in the lymph nodes.
Describe the symptoms of splenomegaly and hepatomegaly in patients with ALL.
- Splenomegaly: Enlargement of the spleen. In ALL, the spleen may become enlarged due to infiltration by leukemic cells.
- Hepatomegaly: Enlargement of the liver. Hepatomegaly can occur in ALL as malignant cells infiltrate the liver tissue.
Explain the cause of bone pain in patients suffering from ALL.
Bone pain results from the infiltration of leukemic cells into the periosteum (the outer covering of bones). This infiltration disrupts normal bone function and causes pain.
How do malignant cells infiltrate into the meninges, testes, or ovaries in ALL?
- Meninges: Leukemic cells can infiltrate the meninges (the protective membranes around the brain and spinal cord), leading to central nervous system involvement.
- Testes and Ovaries: ALL cells may infiltrate the testes or ovaries, affecting reproductive organs.
What are lymphoblasts, and where can they be found in cases of ALL?
Lymphoblasts are immature white blood cells (precursors to lymphocytes). In ALL, they proliferate abnormally. They can be found in the bone marrow, blood, and other tissues.
In cases of T-cell ALL, where might a mass be located within the body?
T-cell ALL can present with a mass in various locations, including the mediastinum (the area between the lungs), thymus, and other lymph nodes. It may also affect structures like the trachea and esophagus.
Outline the laboratory investigations of ALL
- Morphology
- Flow cytometric analysis
- Cytochemical stain
Explain the morphology of lymphoblasts in ALL investigations
- Small lymphoblast- the cost common type 1.0 to 2.5 times the size of a nomal lymphocyte scant blue cytoplasm and in distinct nucleoli
- Large lymphoblast- 2 to 3 times the size of a normal lymphocyte with prominent nucleoli and nuclear membrane
Morphological difference between a small lymphoblast and a large lymphoblast
- in lymphoblast has a loose chromatin ( there are many soaces) unlike in the large lymphoblast
- Lymphoblast has a small nucleus to cytoplasm ratio while large lymphoblast has a big nucleus to cytoplasm ratio
- What is the purpose of flow cytometric analysis in the context of laboratory investigation of ALL?
Flow cytometric analysis is used to identify and quantify specific cellular markers expressed by B cells and T cells. It helps characterize cell populations and diagnose diseases like acute lymphoblastic leukemia (ALL).
Which markers are generally expressed by B cells according to the image?
- General B cells express the following markers:
* CD19
* CD20
* CD24
* CD79a
* CD10
* Cytoplasmic µ (mu)
* PAX-5 (B-cell-specific activator protein)
What markers are expressed by blasts (immature B cells) as per the information in the image?
- Blasts express the following markers:
* CD19
* Cytoplasmic CD79a
* Cytoplasmic CD22
* Nuclear TdT (terminal deoxynucleotidyl transferase)
Identify common T cell markers mentioned in the image.
- Common T cell markers include:
* CD2
* CD4
* CD5
* CD8
* Additionally, cells may express other markers like CD3 and CD1a.
What was the ALL reaction to Myeloperoxidase (MPO) in the CYTOCHEMICAL STAIN reaction chart?
The ALL reaction to Myeloperoxidase (MPO) was negative
Which cytochemical stain had a varied ALL reaction?
Periodic acid-Schiff (PAS) had a varied ALL reaction.
How did Factor VIII antibodies react in the CYTOCHEMICAL STAIN test for ALL?
Factor VIII antibodies had a negative reaction.
What are the treatment modalities for ALL Therapy?
The treatment modalities include remission induction therapy, followed by consolidation (intensification), and then continuation therapy to eliminate residual disease.
What is Methotrexate, and what is its role in ALL Therapy?
Methotrexate is a folate antagonist that is commonly used to treat ALL. It causes megaloblastosis on blood film or bone marrow smear and rapid severe leukocytopenia and thrombocytopenia.
What chemical is used to treat ALL in adults
- Daunorubicin
- Vincristine
- Prednisone
What complications comes with using daunorubicin
It causes cardiac complications, as a result routine cardiac assays are required
Wich treatment is the last line of treatment for unresponsive and relapsed ALL
Peripheral blood stem cell transplantation
- What is the most common family of leukemias in children younger than 1 year of age?
Acute Myeloid Leukemia (AML) is the most common family of leukemias in children younger than 1 year of age.
Does the incidence of AML increase or decrease with age in adults?
The incidence of AML increases with age in adults.
On what criteria was the 2008 WHO classification for AML based?
The 2008 WHO classification for AML was based on cytogenetics
What is the clinical presentation of acute myeloid leukemia
Decreased production of normal bone marrow elements
What is the expected number of WBC in an AML patient
Ranges between 5 and 30x10^9/L, though it may range from 1 to 200x10^9/L. Normal range is 4 to 11
What does the clinical presentation of AML reflect?
The clinical presentation of Acute Myeloid Leukemia (AML) reflects decreased production of normal bone marrow elements.
What is the range of WBC count for most patients with AML?
Most patients with AML have a WBC count between 5 and 30 x 10^9/L, although it may range from 1 to 200 x 10^9/L.
Are myeloblasts present in the peripheral blood of AML patients?
Yes, myeloblasts are present in peripheral blood in 90% of AML patients.
What are the clinical findings associated with anemia, thrombocytopenia, and neutropenia in AML patients?
The clinical findings include pallor, fatigue, fever, infections, bruising, and bleeding.
Besides the common symptoms, what can be significant in AML patients?
In addition to common symptoms, disseminated intravascular coagulation and other bleeding abnormalities can be significant.
Where can infiltration of malignant cells be seen in AML patients?
Infiltration of malignant cells can be seen into gums, other mucosal sites, and skin.
Mention the triad of clinical findings of acute myeloid leukemia
Anaemia
Thrombocytopenia
Neutropenia
Hat does a myeloid stem cell forms
Erythrocytes
Monocytes
Granulocytes
What does the lymphoid stem cell form
B lymphocytes
T lymphocytes
What are blast cells
Less differentiated blood cells
What does breach in differentiation myeloid stem cell line called
Myeloid leukemia
What does the breach in lymphoid stem cell line called
Lymphoblastic leukemia
When leukemia occurs in blast cells the leukemia will be called
Acute
Is the leukemia attacks the nearly mattured cells the leukemia will be called
Chronic
what does the word” infiltration of malignant cells into gums, other mucosal sites and skin mean”
term “infiltration of malignant cells into gums, other mucosal sites, and skin” refers to the spread of cancerous cells from their original location (usually a primary tumor) into nearby tissues such as the gums, other mucosal surfaces (such as the lining of the mouth, throat, or digestive tract), and the skin.
Why is bone and joint pains related with acute myeloid leukemia
AML leads to the accumulation of cancerous white blood cells in the bone marrow. As these abnormal cells multiply, they crowd out normal blood-making cells, causing the bone marrow to expand. This expansion exerts pressure on the nerves within the bone tissue, resulting in soreness, aching, or sharp pain.
What are the symptoms of acute myeloid leukemia
- Bone and joint pain
- Splenomegaly
What are common abnormalities in laboratory tests associated with acute myeloid leukemia
- Hyperuricemia. ( excess uric acid in the blood)
- Hyperphospatemia.( due to cell lysis)
- Hypocalcaemia
- Hypokalemia (low levels of potassium)
What is tumor lysis syndrome associated with?
Tumor lysis syndrome is associated with Acute Myeloid Leukemia (AML).
When can tumor lysis syndrome occur during the treatment of AML?
It can occur during the induction of chemotherapy when the white blood cell count (WBC) is quite elevated.
What complications are caused by tumor lysis syndrome?
The complications are caused by the breakdown products of dying cancer cells, which in turn cause acute uric acid nephropathy and renal failure.
What are the characteristics of tumor lysis syndrome
Hyperkalemia
Hyperphosphatamia
Hyperuricemia
Hypocalcaemia
What are the Chromosome abnormalities in acute myeloid leukemia
- Philadelphia chromosome ( translocation) is observed in 1% of patients with AML
- Disruption of MLL gene is also seen in AML just as in ALL
- Characteristic chromosome translocations are associated with some subgroups and were incorporated into WHO classification
What are the chromosome abnormalities in ALL
- Translocation between long arm of chromosome 8 and the long arm of chromosome 21 t(8;21) (q22;q22) is representative f AML with maturation.
- A translocation between long arms of chromosome 15 and 17, t(15;17), (q24;q21)associated with acute promyelocytic anaemia ( a subtype of cute myeloid leukemia)
- A pericentric inversion of chromosome 16, inv(16) (p13.2q22) is seen in AML with increased eosinophilia
Xplain the laboratory investigation of AML
- Complete blood count, peripheral blood film examination, bone marrow aspirate
- Thrombocytopenia
- Bone marrow is hypercellular and greater than 20% of cells are marrow blast
- Cytochemical stain reaction chart
What are Cytochemical stain and their reaction done on acute myeloid leukemia
Cytochemical stain. AML reaction
1. Myeloperoxide Positive
2. Sudan black. B. Positive
3. Naphthol AS-D Positive
chloroqcetate esterase
4. Apha naththyl butyrate Negative
Esterase ( ANBE)
5. Apha naphthyl acetate Negative
Esterase
6. Factor VIII antibodies. Negative
