Adult Leukemias Flashcards
When you have an abnormality i the blood cells that causes either uncontrollable proliferation, or stops cell regulated cell death, it is called…
Leukemia. Characterized by growth (Acute=fast, Chronic=slow) and type of cell affected.
What is not normal on a peripheral smear?
Blasts- REFER!
Erythrocytes, megakaryocytes, monocytes, and granulocytes come from what stem cell lineage?
Myeloid. T lymphocyte, NK Lymphocyte, and B lymphocyte come from lymphoid stem cell.
Most common pediatric cancer
Acute lymphocytic leukemia (ALL)
T/F: Most Adults with ALL are cured while children relapse?
False: Switch
Presenting signs/symptoms of ALL
- Bone marrow failure- Anemiam Thrombocytopenia, neutropenia
- Leukemic infiltration- Bone pain, HA, organomegaly, neurologic symptoms, lymphadenopathy
Diagnostics for ALL
- CBC with manual diff
- Tumor lysis labs
- Coags
- CXR/CT
- Bone marrow aspirate
- Spinal tap
ALL is characterized by the uncontrolled proliferation of ________. This limits the production of other cells by overcrowding and inhibits cell growth and differentiation.
Lymphoblasts
Most common type of cell in ALL
Precursor B-Cell
Burkit-cell leukemia and frequently occurs in HIV patients involves what cell line
Mature B cell
A poor prognosis and associated with HTLV-1 infection. WHat type of cell in ALL?
T-cell
3 phases in ALL treatment
1) Induction- includes vincristine, CCS, anthracycline
2) Post-remission consolidation- rotational consolodation, stem cell transplant
3) Maintenance therapy: Includes Methotrexate, 6-mercaptopurine
ALL: Prognostic factors
- Age
- Leukocyte count at presentation
- Time to achieve CR
- Immunophenotype
- Cytogenic abnormalities
A High WBC at presentation in AML means what?
Poor prognostic factor- WBC100k association with induction death
Treatment of choice for ALL
Bone marrow transplant
T/F: The incidence of AML is 5X greater than ALL
True
Describe the clinical presentation of AML
Abrupt onset (1-6 month prodromal period)
- Similar symptoms to ALL- fatigue, flulike, bleeding, petechiae, purpura, gingival bleeding, GI bleeding, urinary tract bleeding due to decreased platelets.
- Increased susceptibility to infections due to neutropenia
- Enlarged spleen
Detection and Dx for AML
- Blood counts, abnormal blood counts lead to detection of AML: Thrombocytopenia, anemia, increased leukocytes.
- Chromosomal abnormalities
- Presence of Auer rods (structres found in myeloblasts, myelocytes, and monoblasts)
- Bone marrow aspiration biopsy for definitive diagnosis.
True/False: If 30% blast cells are present, acute leukemia is confirmed?
True- DDX is made from staining procedure. Immunophenotyping as in ALL establishes diagnosis in 90% of cases.
Pathology of AML
- Proliferation of precursor cells that have lost the ability to differentiate.
- It involved the hematopoietic stem cells or pluripotent cells
- Results in the gradual accumulation of undifferentiated cells in marrow or other organs.
French-American-British Classification of AML
M0- Undifferentiated (MPO negative) M1- Without maturation M2- With granulocytic maturation M3- Acute promyelocytic M4- Myelomonocytic M5- Monocytic M6- Erythroleukemia M7- Magakaryoblastic
Treatment of AML
- Intensive Chemo: Induction, consolidation
- Stem cell transplant
A distinct clinical and biologic subtype of AML.
- The most curable AML.
- Separate treatment algorithim from other AML subtypes
- T (15:17) results in fusion transcription gene (PML-RAR a)
WHAT IS IT?
Acute Promyelocytic leukemia (APL)
T/F: AML M3 is initially treated differently?
True
T/F: Cytogenetics provides critical prognostic info but it is not used to dictate treatment.
False- It now dictates treatment
T/F: Chronic Leukemias is the overproduction of blood cells, may not need immediate treatment, and is sometimes found on routine health care maintenance?
True
What is the most common leukemia?
CLL -Accounts for 30% of leukemias -CLL 2X as common as CML -Incidence increases with age, rare under 35 Males more common.
Clinical presentation of CLL
- Usually asymptomatic
- Bruising (thrombocytopenia)
- Early satiety (splenomegaly (late))
- Recurrent infections
- Lymphadenopathy
T/F: Male sex, White ancestry and Family hx are risk factors for CLL
True
CLL Lab Findings:
- Lymphocytosis: NO blasts!! All mature lymphocytes.
- Hypogammaglobinemia
- Smudge cells
CLL Work Up includes
- Adequate Hx/physical
- CBC, Differential, PLT count
- CMET, LDH, B2-microglobulin
- Occasionally: Direct coombs, bone marrow aspirate/biopsy, serum immunoglobulins
- Retic count
- CXR/abdominal/pelvic
- Flow cytometry
- Cytogenetics
- Molecular studies-Ig receptor gene rearrangements
CLL Staging: Rai Staging System
- Low (0)= Lymphocytosis in PB and BM
- Intermediate (I-II)= Lymphocytosis, lymphadenopathy, hepatosplenomegaly
- High (III-IV)= Lymphocytosis, anemia, thrombocytopenia
CLL Staging: Binet Staging
A= HGB >10, PLT>100K, 10, PLT>100k, 3 or more nodal areas involved C= HGB ,10, PLT<100K, or both, independent of nodal ares involved
T/F:
1) CLL is traditionally an illness of younger individuals?
2) CLL well patients do not require therapy?
3) IVIG monthly replacement if hx of bacterial infections (management not treatment)?
4) Earlier/ more aggressive conventional therapy has shown to improve survival or cure of patients?
1) False- older pts
2) True
3) True
4) False: not clearly known to improve
Initial therapies in treatment of CLL include:
- Oral chemo
- Single agent IV chemo
- Combo therapy
- Campath-monoclonal antibody
What is this: Accounts for 20-30% of all leukemias. Rare in children. Uncommon before age 21. Peaks in 40s. Males slightly more common.
CML
The etiology of CML is unknown. Maybe linked to radiation, benzene? What chrmosome is present in 95% of CML patients.
Philadelphia chromosome. Abnormal Ch 22- loss of part of long arm.
What are prognostic indicators dependent on in CML?
- Spleen size
- PLT count
- Hematocrit (% of erythrocytes in blood volume)
- Gender
- % of blood myeloblasts (immature BM cells)
What phase of CML is this: Median survival of 3.5-5 years before transformation. Asymptomatic in 15-40%. May have abdominal complaints/exam consistent with organomegaly.
Chronic phase
What phase of CML is this: Median survival 18 months. Peripheral blasts >15%. Increased basophils. Difficult to control white count. Thromocytopenia. Patient with more symptoms such as fever, night sweats, and wt. loss.
Accelerated phase
What phase of CML is this? Equivalent to AML. Median survival 3-6 months. Signs include peripheral blasts >30%, marrow blasts >30%, clumps of blasts on BM bx, extramedullary chloromas. Symptoms are similar to accelerated phase.
Blast crisis
Lab findings in CML include:
- Leukocytosis
- Thrombocytosis (Sometimes over 1mil.)
CML Diagnostic test:
Peripheral blood or bone marrow
-Philadelphia chromosome- translocation (9;22). Involves bcr/abl. Tested by FISH cytogenetics
How would you treat stable CML?
Gleevec- tyrosine kinase inhibitor
How would you treat unstable CML?
- Admission to control counts- Leukapheresis, hydrea, blast crisis treat as AML.
- Medication failures: Stem cell transplant
What is this: A malignant tumor of myeloid cells. Can be found in kidney, skin, brain, bowel, etc. Solid tumor may be only sight of disease (bone marrow clear). Still treat systemically.
Granulocytic Sarcoma
The take home message with acute leukemia is to not mess around. This means you should…
REFER!
