Leukemias Flashcards
What is the cause of Myelodysplastic syndrome?
What is observed in the peripheral blood smear?
What is observed in the bone marrow biopsy?
cells that can divide, but not mature
peripheral blood smear: HIGH blasts (immature neutrophils, RBCs, platelets); immature RBCs have basophilic stippling
bone marrow bx: hypercellular, ringed sideroblasts, lots of different types of immature cells
What is the cause of Acute Myeloid Leukemia?
What is observed in the peripheral blood smear?
What is observed in the bone marrow biopsy?
mutations/translocations that result in neoplastic proliferation/accumulation of immature myeloid blast cells
peripheral blood smear: irregular shaped nuclei, prominent nucleoli, auer rods, abnormal budding of class
bone marrow biopsy: hypercellular, monotonous population of immature cells
How does AML arise?
de novo (translocation) or progression from Myelodysplastic Syndrome
What is the prognosis of myelodysplastic syndrome?
depends on
- # of blasts in marrow
- # of cytopenias
- karyotype change
What is the prognosis of acute myeloid leukemia?
prognosis depends on type of translocation:
favorable: Inv(16), t(15,17), t(8,21)
unfavorable: trisomy 8, monosomy 1, del (5)
What is leukostasis?
WBCs are big chunky and sticky, and therefore sludge in the capillaries of the
- brain, leading to mental status changes, stroke
- lungs, causing CHF-like symptoms
- kidneys, resulting in renal damage
What is hyperuricemia and how is this a concern in AML patients? How do you minimize the effects of this?
Hyperuricemia is due to high cell turnover observed in AML, which can harm the kidneys
treat with allopurinol, which blocks the production of uric acid.
What two drugs are used for induction for AML treatment?
daunorubicin + cytarabine
What is the initial management of AML?
- stabilize patients for infections and bleed
- cardiac function - chemoRx can cause cardiac failure
- leukostasis (due to high WBC) - can sludge along the capillaries of the brain, lungs, and kidneys
- hyperuricemia (due to tumor lysis) - treat with allopurinol to minimize uric acid production
What is Acute Promeylocytic Leukemia (APL)?
What’s the clinical presentation of APL?
How is this normally treated?
APL is caused by t(15;17), resulting in the formation of PML:RAR hybrid protein that has reduced affinity to retionic acid but enhanced affinity to DNA promoters, thereby blocking transcription and differentiation of granulocytes.
Clinical Presentation: APL tumor cells have granules that contain plasminogen activators that lead to clot lysis and tumor cell procoagulants, which lead to DIC. Bleeding is usually due to a clot breakdown (rather than inhibition of clot formation), therefore coagulopathies and hyperfibrinolysis are common presentations of APL.
This can be overcome with treatment of all-trans retinoic acid (ATRA), which binds to the altered receptor, thereby allowing the blasts to mature and eventually die.
What are examples of myeloproliferative neoplasms?
Chronic Myeloid Leukemia (CML) Polycythemia Vera (PV) Essential Thrombocythemia (ET) Primary Myelofibrosis (PMF)
What is CML caused by?
What would be the CBC findings?
Bone Marrow biopsy findings?
Peripheral blood smear findings?
How is this treated
Cause: Philadelphia chromosome t(9:21), which creates a Bcr:abl protein
CBC:
- increased WBC, but low levels of blast cells (compared to AML)
- high number of basophils and eosinophils
- may have elevated hemoglobin and platelets
Bone Marrow Biopsy
- hypercellular marrow (low fat spaces)
- increased immature myeloid cells
Peripheral Bood smear:
- high immature myeloid cells with few blasts
- high number of WBC
- high number of basophils/eosinophils
Treatment:
- Hydroxyurea (resistant in 3 years)
- Gleevec (TK inhibitor)
- Dasatinib (TK inhibitor, better survival)
What is Polycythemia Vera caused by?
What would be the CBC findings?
Bone Marrow biopsy findings?
Peripheral blood smear findings?
How is this treated
Cause: JAK2-V617 mutation that results in neoplastic proliferation of mature myeloid cells, particularly RBCs
CBC:
- LOW EPO (problem is not within the kidneys)
- increased WBC,
- increased platelets
- may progress to anemia and thrombocytopenia
Bone Marrow Biopsy
- hypercellular marrow (low fat spaces)
- increased proliferation of erythroid, granulocytic, and megakaryocytic cells
Peripheral BLood smear:
- NORMAL
Treatment:
- Phlebotomy
What is Essential thrombocytopeania caused by?
What would be the CBC findings?
Bone Marrow biopsy findings?
Peripheral blood smear findings?
How is this treated
Cause: JAK2-V617 or W515L/K MPL mutation that results in a neoplastic proliferation of mature myeloid cells, especially megakaryocytes, which increases platelet production
CBC:
- high platelets
- high abnormal megakaryocytes
Bone Marrow Biopsy
- megakaryocyte hyperplasia
Peripheral Blood smear:
- increased number of platelets
Treatment:
- low risk patients (<60yo, no hx of thrombosis, plaletlets under 1000K)
- high risk patients: hydroxyurea (with aspirin and anagrelide)
What is Primary Meylofibrosis caused by?
What would be the CBC findings?
Bone Marrow biopsy findings?
Peripheral blood smear findings?
How is this treated
JAK2-V617 or W515L/K MPL mutation that results in a neoplastic proliferation of mature megakaryotes cells, which produce PDGF that increase fibrosis in the marrow, leading to decreased RBC production
CBC:
- increased atypical megakaryocytes
- Decreased RBC (anemia)
- may see decreased platelets and WBC
Bone Marrow biopsy:
fibrosis that replaces the bone marrow with scattered atypical megakaryocytes
Treatment: splenomeagly: hydroxyurea, irradiation,
