Leukemia Flashcards
Describe acute leukemias in general terms
cancers of the hematopoeitic progenitor cells
Describe chronic leukemias in general terms
cancers involving proliferation of more fully differentiated myeloid and lymphoid cells
What is myelogenous leukemia?
characterized by proliferation of myeloid tissue (as of the bone marrow and spleen) and an abnormal increase in the number of granulocytes, myelocytes, and myeloblasts in the circulating blood
What are lymphocytic leukemias?
characterized by immature lymphocytes and their progenitors that originate in the bone marrow, but infiltrate the spleen, lymph nodes, CNS, and other tissues.
What are the 3 purposes of combination chemotherapy?
decrease drug resistance, decrease drug toxicity to the patient by using multiple drugs w/varying toxicities, and interrupt cell growth at multiple points in the cell cycle
What is induction therapy?
high-dose therapy used before bone marrow transplant
What is consolidation/intensification therapy?
May be given after induction therapy. Purpose is to eliminate remaining leukemic cells that may not be evident
How does bone marrow and stem cell transplantation work?
Eradicates patient’s hematopoietic stem cells and
replaced with those of an HLA-matched (Human Leukocyte Antigen), MLC (mixed Leukocyte Culture) donor
What is AML?
neoplasms affecting myeloid precursor cells in the bone marrow. normal cells are replaced by undifferentiated blast cells leading to anemia, neutropenia, thrombocytopenia
What are risk factors for AML?
age > 60, benzene or radiation exposure, tobacco, down syndrome, previous breast/ovarian ca or lymphma
What laboratory and radiographic work-up should you do for AML?
CBC with manual differential, Uric Acid level, Clotting studies (PT, PTT, D-dimer, fibrinogen), Bone marrow aspirate and biopsy
What are hematological findings for AML?
Anemia (normochromic, normocytic), Leukocytosis (median = 15,000), Thrombocytopenia (< 100,000)
What morphology and cytology changes do you see with AML?
> 20% myeloblasts in blood and/or bone marrow, Auer Rods (cytoplasmic granules), hypercellular bone marrow
What are the treatments for AML?
Chemotherapy: Phase One – Induction therapy. Phase Two – Intensification therapy. Phase Three – Maintenance. Radiation therapy for certain cases. Bone marrow transplantation
What are complications of AML treatment?
Anemia, Infection, Bleeding, Metabolic abnormalities, Ocular, Venous thromboembolus
What is the prognosis for AML?
Five year survival rate in adults under 65 is 33%. Five year survival rate in adults >65 is 4%
What is ALL?
Clonal proliferation and accumulation of blast cells in blood, bone marrow and other organs. Disorder originates in single B or T lymphocyte progenitor
What is proposed etiologies of ALL?
Genetic - Philadelphia chromosome, Viral infection (EBV, HIV), Exposure to high energy radiation (T-cell ALL), Toxic chemical exposure
What is laboratory and radiographic work-up for ALL?
CBC with manual differential, Chemistry studies to check for organ dysfunction, Bone marrow aspirate and biopsy Genetic/Immunological studies, Lumbar puncture
What are hematological findings associated with ALL?
Anemia (normochromic, normocytic), WBC < 5,000 (or > 25,000), Leukocytosis (median = 15,000), Thrombocytopenia, Smear-Blast cells
What do you need in order to do ALL staging?
Bone marrow biopsy, Cytogenic studies, Lumbar puncture, CT scans
What does the treatment strategy for ALL depend on?
- Risk qualification 2. Immunophenotype of leukemic cells- T lineage, early B lineage, mature B lineage 3. Age and biological condition
What classifies someone as high risk ALL?
Age > 35 years, WBC > 30 G/L in B-ALL, > 100 G/L in T-ALL. No remission after 4 weeks of induction therapy
What classifies someone as very high risk ALL?
Chromosome Philadelphia - positive or BCR/ABL(+)
What is treatment strategy for ALL?
Induction/CNS Prophylaxis, Consolidation/intensification, Maintenance
What is included in remission induction therapy in ALL?
- Antineoplastic treatment- Drugs: prednisone, vincristine, asparginase, cyclophosphamide, duanorubicin/adriablastin/epirubicin, cytosine arabinoside, 2. CNS preventative tx 3. Supportive care 4. Treatment of complications
What are induction treatment complications?
Tumor lysis syndrome, Thrombosis, Bleeding, Infection, Anaphylaxis, HPA axis suppression
What is maintenance therapy in standard risk ALL?
low dose chemo: 6-mercaptopurine, methotrexate - for 2-3 years. Intensification treatment periodically repeated: daunorubicin/adriablastin, prednisone, vincristine, cyclophosphamide.
What is the consolidation therapy in high-risk ALL?
. Intensification treatment: amsacrine, mitoxantrone, idarubicine, high dose cytosine arabinoside, high dose methotrexate, high dose cyclophosphamide.Hematopoietic stem cell transplantation - high-dose therapy or reduced intencity conditioning
What is the consolidation therapy in very high risk ALL?
High-dose therapy (reduced-intensity ?) + allogeneic stem cell transplantation
What is prognosis for ALL?
Children-Complete remission (CR) 95-99%, Leukemia-free survival (LFS) ~80%. Adults Complete remission (CR) 80-85% Leukemia-free survival (LFS) 30-40%
What is CML?
Proliferative disorder of hematopoietic stem cells
characterized by proliferation of marrow granulocytes, erythroid precursors, and megakaryocytes.
CML is associated with what chromosomal abnormality?
Philadelphia (Ph) chromosome
CML is associated with what molecular abnormality?
Bcr-Abl tyrosine kinase
What happens as a result of the philadelphia chromosome transloction?
the fusion of BCR-ABL possesses tyrosine kinase activity that lets cells bypass cell growth regulators resulting in malignant transformations.
What is the Philadelphia (Ph) chromosome
Reciprocal translocation of chromosome 22 and chromosome 9. The portion of chromosome 9 contains ABL and it’s received at the BCR site of chromo 22. 90-95% of CML pts have it
What are the phases of CML?
Chronic Phase, Accelerated Phase, Blast Crisis
What are the chronic phase CML clinical features?
40% asymptomatic. Splenomegaly often massive increasing the abdominal girth
What are CML clinical features?
Pallor, dyspnea, tachycardia, Bruising, epistaxis, menorrhagia, Hyperleukocytosis, thrombosis, gout, Visual disturbances, Chronic infection, Fever
How should you work-up CML?
CBC with manual differential. Serum Vitamin B12 and B12 binding capacity. Leukocyte alkaline phosphatase (decreased). Uric acid level. Chromosomal testing - Philadelphia chromosome. Bone marrow biopsy
What are expected hematological findings of CML?
Anemia (normochromic, normocytic). Leukocytosis (median = 20,000). Basophilia. Thrombocytopenia
CML Bone Marrow features
Hypercellular. Myeloid:erythroid ratio – 10:1 to 30:1.
Myelocyte predominant cell, blasts less 10%. Megakaryocytes increased & dysplastic. Increase reticulin fibrosis to 30-40%
Describe the Chronic phase of CML?
3-5 years. Current treatment is with alpha-interferon. Young patients should undergo BMT.
Describe the accelerated phase of CML?
Difficult to control, lasts 6-9 months. Splenomegaly and increasing chemo requirements. Hypermetabolism sx. Lab: blasts >15%, blast and promyelocyte > 30%, basophil > 20%, thrombocytopenia.
Blast phase
> 30% blasts in blood or marrow. Similar to acute leukemia. 2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase. Survival : 3-6 mos
What are CML treatments to control and prolong chronic phase (non-curative)?
-Imatinib mesylate (Gleevec) or other small molecule therapy, Alpha interferon (IFN-), chemotherapy (Hydroxyurea)
What are CML treatments to eradicate malignant clone (curative) in the chronic phase?
Imatinib mesylate (Gleevec). Thyrosine kinase inhibitor. Allogeneic transplantation. Alpha interferon
What is the CML prognosis?
Median survival 3.5 yrs (range 2-8 yrs). Interferon + chemotherapy :6 years. Transplant : 5+ years. Imatinib mesylate (Gleevec)80% survival – 9 years
What is the most common lymphoid leukemia?
CLL which is a clonal malignancy of B lymphocytes
CLL Epidemiology
Median age at diagnosis is 70 years. Males > Females. Hallmark is isolated lymphocytosis
What is the proposed etiology of CLL?
Genetic, Viral infection (EBV, HIV) - Burkitt’s Lymphoma, Exposure to high energy radiation (T-cell ALL), Toxic chemical exposure, Smoking
What are symptoms of CLL?
Fever, Night sweats, Fatigue, Pallor, Shortness of breath, Easy bruising, Gingival bleeding, Weight loss, Frequent infections
CLL physical findings
Splenomegaly and/or hepatomegaly, Lymphadenopathy, Multiple bruises, Bleeding gingivae, Leukemia cutis
How should you work-up CLL?
CBC with manual differential, Peripheral smear
Chemistry studies to check for organ dysfunction, Flow cytometry, Lymph node biopsy
What is the diagnostic criteria for CLL?
lymphocyte count > 20,000/microL, usually 75-98% lymphocytes. HCT & platelets are normal. bone marrow aspirates showing >30% smudge cells. The cell should have the presence of B-cell specific differentiation antigens
Pretreatment studies of patients with CLL should include examination of:
CBC, peripheral blood smear, reticulocyte count, Coomb’s test, renal and liver fxn tests, serum protein electrophoresis, immunoglobulin levels, plasma 2 microglobulin level, immunophenotyping, CXR
What are treatment options for CLL?
Alkylating agents (chlorambucil, cyclophosphamide). Nucleoside analogs (cladribine, fludarabine). Biological response modifiers. Monoclonal antibodies. Bone marrow transplantation
Describe Hairy Cell Leukemia
2% of all adult leukemias. Usually in males > 40 years old. Chronic disease of lymphoproliferation B lymphocytes that infiltrate the bone marrow and liver
Hairy Cell Leukemia Clinical presentations
Splenomegaly, Pancytopenia, Infection, Vasculitis
What labs should be done w/hairy cell leukemia?
CBC, Liver function tests, Kidney functions
What does Hairy Cell Leukemia treatment consist of?
Chemo-alpha-interferon, pentostatin, cladribine
Rai Classification for CLL
- Lymphocytosis (>5 G/L)
- Lymphocytosis + lymphadenopathy
- Lymphocytosis + splenomegaly +/-lymphadenopathy
- Lymphocytosis + anemia (Hb <100G/L) +/- anemia +/-lymphadenopathy +/- splenomegaly
Binet Classification for CLL
A. < 3 involved areas, Hb > 10g%, Plt > 100G/L
B. > 3 involved areas, Hb > 10g%, Plt > 100G/L
C. Any number of involved areas, Hb < 10g%,
Plt < 100G/L
Name a tyrosine kinase inhibitor and what it is used to treat
imatinib mesylate. treats leukemias that display the philadelphia chromosome translocation (CML)
What are the shared clinical features of ALL and AML?
fatigue, fever, night sweats, weight loss, bleeding, bone pain and tenderness, infections. lymphadenopathy, splenomegaly, hepatomegaly are more common in ALL, but still occurs in AML.
What differentiates ALL from AML clinically?
CNS involvement is more common with ALL: nerve palsies, HA, N/V, papilledema
What can cause hyperuricemia and how is it treated?
occurs as a result of increased proliferation or increased breakdown of purines secondary to leukemic cell death. Treat w/allopurinol which inhibits uric acid synthesis.
