Leukemia Flashcards
Pathobiology of Leukemia
- Cell arrest in early phase of maturation
- Accumulation of immature cells (Blasts)
- Abnormal proliferation of blasts
- Crowding of marrow elements
Etiology of Leukemia
*Cause is unknown
-Related to genetic disorders
-Down’s syndrome, Bloom’s syndrome, Fanconi’s sarcoma, Klinefelters syndrome
-55-78% of patients have ACQUIRED chromosome abnormalities
-XRT (atomic bomb survivors)
-Chemicals (Alkylators & antibiotics)
-Chemotherapy (20-25% of cause)
• -Etoposide & Topoisomerase II inhibitors
Viruses:
Adult T-cell leukemia & HTLV-1 virus
Epidemiology of Leukemia
Most common type in adults is AML and CLL
Over 1/2 of cases are acute
Increasing incidence
Clinical Manifestations of Leukemia
Caused by:
• Increased proliferation of blasts in blood forming organs
• Infiltration of blasts into other organs
• Decrease in normal leukocytes, erythrocytes & thrombocytes
• displayed by Granulocytopenia, Anemia, Leukemic Infiltrates, Thrombocytopenia
*Signs & symptoms usually present for
Diagnostic Tests for leukemia
Bone Marrow biopsy is standard
-AML is Myeloid line of cells (myelocytes)
-ALL is Lymphoid line of cells (lymphocytes)
-Usually Hypercellular
-Auer rods are diagnostic of AML
Cytogenetic studies
–2/3 of pt’s have chromosomal abnormalities
prognostic indicators
Flow cytometry
-AML vs. ALL
-lymphoid & myeloid markers= biphenotypic
*Peripheral smear may show blasts
Classification of Leukemia
AML
-malignant clone of myeloid, monocytes, erythroid or megakaryocyte
M1 (Acute Myelocytic Leukemia)
-most common type
M3 (Acute Promyelocytic Leukemia)
• high risk of DIC; best response/prognosis at 95%
-M4 (Acute Myelomonocytic Leukemia)
-extra medullary infiltration
M5 (Acute Monocytic Leukemia)
-extra medullary infiltration
-M7 (Acute Megakaryocytic Leukemia)
◦ rare disease from platelet precursor line
Classification Systems for Leukemia
FAB • Morphology, cell stains and flow cytometry • Myeloid M0-M7 ◦ MDS vs. AML threshold= 30% blasts ◦ Lymphoid L1-L3
WHO • uses prognostic factors ◦ molecular markers ◦ chromosome translocations ◦ dysplasia present? ◦ 17 subclasses ◦ MDS vs. AML threshold= 20% blasts
AML w/ characteristic genetic abnormalities
-chromosome 8 and 21 translocations
-chromosome 15 and 17 translocations
-chromosome 16 inversion
◦ Most favorable; no transplant in first remission
AML w/ multi lineage dysplasia
patients with MDS or MPD
AML and MDS (therapy related)
prior treatment w/ chemo and/or XRT
AML; not otherwise categorized
other subtypes
Acute leukemia w/ ambiguous lineage
-both myeloid and lymphoid cells -or not distinguishable -Mixed or biphenotypic
AML Treatment
Induction -normally 7+3 Evaluation -Day 14 BM Bx -CR =
Classification of APL and treatment
Also called M3
Chromosome 15 and 17 translocation
Treated with Arsenic and Atra
Monitored by PML-RAR alpha
Description of ALL
Originates in thymus, lymph nodes and bone marrow
T-cell, B-cell, or NK cell
CNS disease common
Can be Philly positive (BCR-ABL testing)
ALL Presentation
Lymphadenopathy
Splenomegaly
Induction therapy for ALL?
HyperCvad x8 treatments
A: Cytoxan, vincristine, doxorubicin, decadron
B: MTX, cytarabine, IT MTX
Also use IT Cytarabine
Blinatumomab
TX of Relapse, refractory, Philly negative ALL
CD19 positive cells are attacked by cytotoxic T-cells
*CD19 is a specific B-cell marker
Treatment of Philly + ALL
25% of ALL diagnosis
Need allo transplant
Tx with TKI: dasatinib, ponatinib
How is MDS scored?
The IPSS
- blast percentage
- cytogenetics
- # of cell types affected in circulating blood
- Higher score=decreased survival rate (I.e. >2.5)
Treatment for MDS
Observation Vidaza Growth factors (procrit) Revlimid Decitabine Clinical trial HSCT w/ HLA identical donor
Description of CML
95% of pts Philly +
Chromosome 9 and 22 translocation
BCR-ABL +
S/S of CML
LUQ pain Early satiety Bone, joint pain Abd fullness *MANY ARE ASYMPTOMATIC
Diagnosis of CML
BM BX for FISH and BCR-ABL
- elevated WBC
- Decreased Hgb
- elevated platelets in chronic phase
