Leukemias Flashcards
Chronic Leukemia deals with what type of cells?
Acute Leukemia deals with what types of cells?
more mature cells
young cells
What is the pathology behind acute leukemia?
3
What places will the cells infiltrate?
3
Malignancy of the hematopoietic progenitor cell
- Progenitor cells proliferate in an uncontrolled fashion and replace normal bone marrow
- The cells spill out into the blood were they are seen in large numbers
These cells may also infiltrate the liver,
spleen, and
lymph nodes causing enlargement
Etiology of acute leukemia?
6
The cause is unkown
Exposure to
- radiation,
- benzene,
- chemicals, and
- gases have increase incidence
- agressive treatment of hogdkins lymphoma with chemo
- Dysregulation of genes that regulate blood cell development and homeostasis
HOw are leukemias classified and what are those classifications?
2
Classified by their cell type and if they are “acute or chronic”
Lymphocytic and Myelogenous
Describe acute lymphocytic leukemia?
Involves immature lymphocytes and their progenitors that originate in bone marrow, but infiltrate the spleen, lymph nodes, and CNS
Describe acute Myelogenous leukemia?
Involves pluripotent myeloid stem cells in bone marrow and interfere with maturation of all blood cells including granulocytes, erythrocytes, and thrombocytes
Whats more common ALL or AML?
ALL five times more common
WHo is ALL most common in?
4
Peak incidence occurs between 2-5 years of age
More common among boys
Incidence is higher in Hispanic whites
Genetic and immunodeficiency syndromes increase risk
Contains a group of neoplasms composed of precursor B or T lymphocytes referred to as?
lymphoblasts
Where does the cancer occur in the line of cell production?
the common lymphoid progenitor stage
-both B and T lymphocytes
Early signs and symptoms of ALL?
4
- Fever
- Bleeding/Bruising
- Bone pain
- lymphadenopathy (50% of cases)
Why is there bone pain in ALL?
(accumulation of cells are multiplying and multiplying in the bone and it starts to spill out into the peripheral blood)
How is ALL different from lymphoma?
lymphoma does not deal with immature cells (lymphoblasts)
Where is the bone pain felt in ALL?
2
Bone pain to long bones Joint pain (rheumatologic vs leukemia)
As ALL progresses what symptoms present?
6
- headache
- continued bone pain
- lymphadenopathy
- Testicular enlargement
- mediastinal mass
- Peripheral blood abnormalities (anemia and/or thrombocytopenia)
How would we work up the testicular enlargement caused by ALL?
2
US and Bx(just take the whole thing out and biopsy it from there)
What is a complication that could occur with the mediastinal mass caused by ALL?
Large masses can narrow trachea
When working up the anemia/thrombocytopenia that is caused by ALL what should we look at in the lab?
4
- Need for bone marrow examination
- Atypical cells in peripheral blood
- Unexplained decrease in >1 peripheral blood element
- Unexplained lymphadenopathy or hepatosplenomegaly
HOw would we intially evaluate ALL?
3
Referral to pediatric cancer center
Bone marrow aspiration
Peripheral blood
How would we treat ALL?
3
- Remission induction (kill off all cancer cells with chemo)
- Consolidation/intensification
- Maintenance (low dose chemo just to maintain)
What are the three types of standard treatment for ALL?
3
Whats the prognosis for someone with ALL?
Chemotherapy
Stem cell transplant (only if chemo doesnt work)
Targeted therapy
5-year survival rate is about 85%
What is acute myelogenous leukemia characterized by?
- Group of hematopoietic neoplasms involving precursor cells committed to the myeloid line of cell development
- Characterized by clonal proliferation of myeloid precursors with reduced capacity to differentiate into more mature cellular elements
Where does the cancer occur in the line of cell production for AML?
Myleoblasts
What are the risk factors for AML?
3
- Environmental factors
- Genetic abnormalities
- Benign and malignant (mylodisplastic) hematologic diseases
What are the signs and symtpoms related to with AML?
Generally present with symptoms related to complications of pancytopenia
What body structures can be affected with symptoms of AML?
7
Fever Skin Eyes Oropharynx Organomegaly Joints Lymph
WIth AML what is the cause of symptoms associated with skin?
2
Reveals pallor (anemia) Petechiae or ecchymoses (thrombocytopenia)
WIth AML what is the cause of symptoms associated with eyes?
2
Fundus reveals hemorrhages or whitish plaques
Conjunctivae may be pale
WIth AML what is the cause of symptoms associated with the mouth?
Gingival hypertrophy
WIth AML what is the cause of symptoms associated with organomegaly?
Joints?
Lymph?
Liver and spleen
Polyarthritis/arthralgia
Palpable adenopathy is uncommon and significant lymph node enlargement is rare (compared to ALL)
WIth AML what is the cause of symptoms associated with fever?
almost always an infection
What diagnostic tests should we do for AML?
2
Peripheral blood smear
Bone marrow biopsy and aspirate
What would the peripheral blood smear show for AML?
3
- Usually shows a normocytic normochromic anemia
- A majority will have circulating myeloblasts seen on peripheral smear
- Auer rods!!!!!!!!!!
What does the diagnosis for AML require?
2
- Documentation of bone marrow
- Blast forms count for 20% of total cells - Leukemic cells must be of myeloid origin
What are the treatment phases for AML?
2
Induction of remission
Postremission therapy
What are the 4 standard types of treatment for AML?
- Chemo
- Radiation (kids less than 5 cant do radiation)
- Stem cell transplant (usually successful if chemo doesnt work)
- Drug therapy
What drugs would be involved in the therapy of AML?
2
Arsenic trioxide
All-trans retioic acid (ATRA)
What are complcations that can arise with acute leukemia?
3
Leukostasis
Hyperuricemia
Tumor lysis syndrome
Why does AML cause leukostasis? How would you treat it?
Increase blast count causes increase blood viscosity leading to leukoblastic emboli
Treat with apheresis and chemo
Why does AML cause hyperuricemia? How would we treat it?
Breakdown of purine nucleotides secondary to chemo from leukemic cell death
Treat with rasburicase (Elitek)
Why does AML cause tumor lysis syndrome?
How would we treat it?
Necrosis of malignant cells during initial phase of chemo
Leads to life threatening metabolic disorders
Manage hydration with alkaline solution and rasburicase (Elitek)
Chronic Leukemia involves malignancies involving what kinds of cells?
WHat are the two major types?
proliferation of more fully differentiated myeloid and lymphoid cells
Chronic Lymphocytic Leukemia (CLL)
Chronic Myelogenous Leukemia (CML)
What is chronic lymphocytic leukemia caused by?
A clonal malignancy of B lymphocytes
Whats the most common form of leukemia in adults?
Chronic Lymphocytic Leukemia (CLL)
What are the risk factors associated with CLL?
3
Benzene and heavy solvent exposure
Rubber manufacturing workers
Multiple episodes of pneumonia
Signs and symptoms of CLL?
4
Painless swelling of lymph nodes
Fatigue
Enlargement of liver or spleen
Skin abnormalities
What kind of skin abnormalities would we see in CLL?
2
Macules, papules, nodules, ulcers, or blisters
Exaggerated reaction to insect bites
HOw would we diagnose CLL?
3
What are not needed for the diagnosis of CLL?
2
Lymphocytosis
Cytopenias
“smudge” cells
Bone marrow aspirate and biopsy are not required
What are the 5 types of treatment for CLL?
- Watchful waiting
- Radiation therapy
–External or internal - Chemo- able to manage so we don’t really need to do it
- Surgery
–Splenectomy - Targeted therapy
Monoclonal antibody or Tyrosine kinase inhibitor (TKI)
What are the types of targeted therapy that we could use for CLL?
2
What is the surgery that we could do with CLL?
Monoclonal antibody or Tyrosine kinase inhibitor (TKI)
Splenectomy
What is the prognosis for CLL?
Early:
Late:
Early stage survival of 10-15 years
Late stages 2 year survival is >90%
Chronic myelogenous leukemia is a myeloproliferative disorder characterized by what?
It involves the fusion of two genes. WHat are they?
dysregulated production and uncontrolled proliferation of mature granulocytes with fairly normal differentiation
BCR (chromosome 22)
ABL1 (chromosome 9)
What are the signs and symtpoms of CML?
5
20-50% of patients are asymptomatic
Symptomatic patients: Fatigue Malaise Weight loss Excessive sweating Abdominal fullness
What diagnostic tests would we do for CML?
CBC with diff
Bone marrow aspiration & biopsy
What would we see in the CBC with diff for CML?
3
- Leukocytosis
- Absolute basophilia and eosinophilia of granulocytes in 90% of cases
- Platelet count can be normal or elevated
What is a diagnosis of CML confirmed by?
2
- Demonstration of Philadelphia Chromosome
2. BCR-ABL 1 fusion gene
On the genetic level what is telling the cells to reproduce over and over again? And how do we treat it?
tyrosine kinase tells the cell to reproduce over and over again. can treat with a tyrosine kinase inhibitor
What are the three phases of treatment for CML?
Chronic phase
Accelerated phase
Blastic phase (enlarged spleen, fever, fatigue. over 20%)
How would we treat the chronic phase with CML?
3
- Tyrosine kinase inhibitor (TKI)
- -Imatinib mesylate - Interferon or chemotherapy
- Stem cell transplant
How would we treat the accerlated phase of CML?
TKI and other drugs - higher doses
How would we treat the blast phase of CML?
greater than 20%- palliative therapy
Whats the prognosis for CML?
80-95% survival at 9 years (if they can survive the blast phase)
What is Hairy cell leukemia?
What does this pathology result in?
5
Chronic B cell lymphoproliferative disorder characterized by accumulation of small mature B cell lymphoid cells with abundant cytoplasm and “hairy” projections
Results in:
- splenomegaly and
- reduction of normal red cells,
- platelets,
- mature granulocytes, and
- monocytes
What is the clinical presentation of HCL?
- Symptoms of splenomegaly or cytopenias
2. PE finding splenomegaly
What are the symptoms associated with splenomegaly and cytopenias?
2
- Abdominal fullness
2. Usually do not complain of fever or night sweats(like other leukemias)
What are uncommon findings in HCL that are often found in other leukemias?
- Usually do not complain of fever or night sweats
2. Lymphadenopathy is uncommon
What diagnostic tests would we do for HCL?
2
Peripheral blood smear
Bone marrow
What would we find on the peripheral blood smear for hairy cell leukemia?
the hairy cell!
What kind of bone marrow biopsy would we do in HCL pts?
Trephine bx and aspirate with immunophenotyping and flow cytometry
Treatment of HCL?2
How should we treat the return of the leukemia?2
If asymptomatic can observe
- Purine analog drugs
Cladribine and pentostatin - Splenectomy
- Return of leukemia
Purine analog drug
Monoclonal antibody (rituximab) or interferon-alfa
What are the purine analog drugs used for HCL?2
Cladribine and pentostatin
What is the prognosis for HCL?
95% of patients live longer than 10 years
