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74 Cards in this Set

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General features of acute leukemia?
First defined:
Cases of leukemia in which death occurred w/in days to a few weeks w/o treatment

Now Used:
-- designate leukemis in which there is little to no cellular maturation
-- predom cell in the periph blood and BM is a blast
Dx of acute leukemia requires...?
presence of at least 20% blasts in the BM
Etiology of leukemia?
heredity
toxic exposures - radiation, chemicals, drugs
possibly viruses
Which acute leukemia occurs predominantly in children? adults?
ALL is seen most often in children w/ 75% of cases under age 6

AML occurs predom in adults at median age of 60
Clinical findings in acute leukemia?
1. DECREASED ERYTHROPOIESIS
-- decreased RBC, Hb, and HCT
-- pts almost always anemic at time of presentation w/ various levels of severity

2. DECREASED NORMAL MYELOPOIESIS
-- peripheral count of normal WBC is low, although total WBC is increased due to leukemic cells
-- decreased normal WBC leads to infections
-- pts may present w/ various infectious d/o including perirectal abcess, bacterial pneumonia, etc

3. DECREASED MEGAKARYOPOIESIS
-- leads to thrombocytopenia of varying severity
-- pt may present w/ bleeding d/o's such as increased bruising, nose bleeds, etc

4. TISSUE INFILTRATION BY BLASTS
-- localized symptoms and signs as blasts infiltrate various organ sites
-- ALL more likely to involve CNS
-- AML more likely to involve gingiva
How are leukemias classified?
LYMPHOCYTIC
- ALL, acute lymphocytic leukemia, acute lymphoblasic leukemia

MYELOCYTIC
- AML, acute myelocytic leukemia, acute myeloblastic leukenia
- ANLL, acute non-lymphocytic leukemia

Within the categories of ALL and AML, subclassif are determined based on:
-- morphology
-- cytochemical stains
-- cell surface markers (immunophenotypes)
-- cytogenetics
-- molecular DNA studies
List the cytochemical stains used in subclassifying AML and ALL.
sudan black

myeloperoxidase

specific esterase

non-specific esterase

PAS

TdT
Sudan black
stains the mbrn of the primary granule
--myeloid, monocytic
Myeloperoxidase
stains the content of the primary granule
-- myeloid, monocytic
Specific esterase
stains enxyme specific to myeloid series
Non-specific esterase
stains enzyme presnet in monocytes
PAS
periodic-acid-Schiff

Stains glycogen in the cytoplasm
-- many types of blasts will stain
-- lymphoblasts tend to have a "chunky" positivity
-- other blasts tend to have finely granular or diffuse staining
TdT
terminal deoxynucleotide transferase
-- enzyme present in the nucleus of T and B lymphoblasts
Myeloid cell markers
CD13, 33, 11c, 34
Pre-B-lymphoblastic cell markers
CD19, 20, 10, 34
T-lymphoblastic cell markers
CD2, 5, 7
B-lymphoblastic cell markers
CD19, 20, 10, monoclonal SIg
Three main categories of AML classification?
1. AML w/ recurrent genetic abnormalities

2. AML w/ multilineage dysplasia

3. AML and myelodysplastic syndromes, therapy related

Also: AML not otherwise categorized
Incidence of AML w/ t(18;21)(q22;122)?
approx 5-12% of all AML cases

usually occurs in younger patients
Morphology of AML w/ t(18;21)(q22;122)?
BM shows maturation of myeloid series w/ at least 10% of cells being:
-- promyelocytes
-- myelocytes
-- metamyelocytes

Auer rods are infrequent
Genetics of AML w/ t(18;21)(q22;122)?
t(18;21) results in fusion of genes AML1 and ETO
-- few cases have been described that show the gene rearrangement w/o cytogenetic evidence of translocation
Prognosis of AML w/ t(18;21)(q22;122)?
usually good response to chemo w/ high rate of first remission and long-term remissions
Incidence of AML w/ abnormal BM eosinophils w/ inv(16)(p13;q22) or t(16;16)(p13;q22)?
approx 10-12% of all AML

usually younger patients
Morphology of AML w/ abnormal BM eosinophils w/ inv(16)(p13;q22) or t(16;16)(p13;q22)?
leukemic blasts show evidence of monocytic and PMN maturation

BM shows increased numbers eosinophils and precursors w/ abnormal granules
Genetics of AML w/ abnormal BM eosinophils w/ inv(16)(p13;q22) or t(16;16)(p13;q22)?
chromosome abnormalities result in rearrangements of:
-- gene CBFβ (core binding factor β) at 16q22 TO
-- MYHII (smooth muscle myosin heavy chain) at 16p13
Prognosis of AML w/ abnormal BM eosinophils w/ inv(16)(p13;q22) or t(16;16)(p13;q22)?
relatively better w/ high rates of complete remission and long-term remission
Incidence of AML w/ t(15;17)(q22;q12), acute promyelocytic leukemia?
approx 5-8% of all AML cases

predominantly middle aged adults
Morphology of AML w/ t(15;17)(q22;q12), acute promyelocytic leukemia?
-- malignant promyelocytes have a variable shaped nucleus, "kidney bean" shape

Hypergranular form:
-- cytoplasm full of numerous, priminent primary granules,
-- some cells w/ multiple Auer rods

Microgranular variant:
-- "dusty" cytoplasm and inapparent granules w/ typical stain
-- easily demonstrated w/ cytochemistry studies
Genetics of AML w/ t(15;17)(q22;q12), acute promyelocytic leukemia?
Translocation results in fusion of:
-- the gene retinoic-acid-receptor-α (RARα) on 17q12 with
-- a nuclear regulatory gene, PML (promyelocytic leukemia) on 15q22
Prognosis of of AML w/ t(15;17)(q22;q12), acute promyelocytic leukemia?
Patients are at high risk of DIC due to pro-coag activity of granules

Response is favorable to all-trans-retinoic-acid followed by chemo
Incidence of AML w/ 11q23 abnormalities?
approx 5-6% of all AML cases
Morphology of AML w/ 11q23 abnormalities?
-- most show monocytic differentiation, w/ or w/o PMN differentiation

-- Monocytic differentiation can be detected by morphology, cytochem,and immunophenotype
Genetics of AML w/ 11q23 abnormalities?
Most common translocations are:
-- t(9;11)(p21;q23)
-- t(11;19)(q23;p13.1)
Results in rearrangement of gene MLL (developmental regulator) at 11q23
Prognosis of AML w/ 11q23 abnormalities?
Intermediate survival
Incidence of acute myeloid leukemia w/ multilineage dysplasia?
mainly occurs in elderly
Morphology of acute myeloid leukemia w/ multilineage dysplasia?
Dysplastic features are apparent in ≥ 50% of marrow cells in at least 2 different cell lines
Genetics of acute myeloid leukemia w/ multilineage dysplasia?
cytogenetic abnormalities are seen in most cases, and tend to be similar to those seen in MDS such as:
-- -5/del(5q)
-- -7/del(7q)
-- +8
-- +11
Prognosis of acute myeloid leukemia w/ multilineage dysplasia?
poor response to chemo
Incidence of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
When related to alkylating agents/radiation exposure, usually occurs 5-6yrs post exposure

When related to topoisomerase II inhibitor, interval from exposure is 12-130 months
Morphology of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
May present as MDS or AML w/ 20% blasts

Involves all 3 cell lines w/ dysplastic features

Cases assoc w/ topoII inhibitors show monocytic component
Genetics of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
Most cases will have clonal cytogenetic amnormalities, frequently:
-5/5del(q)
-7/7del(q)

Cases assoc w/ topoII inhibitors will have t(9;11)
Prognosis of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
Little or no response to therapy

Cases assoc w/ topoII inhibitors may have prognosis similar to primary acute leukemia
What are the AML's not otherwise categorized?
-- AML, minimally differentiated
-- AML, w/o maturation
-- AML, w/ maturation
-- Acute myelomonocytic leukemia (AMML)
-- Acute monoblastic leukemia, acute monocytic leukemia
-- Acute erythroid leukemia
-- Acute megakaryoblastic leukemia
-- Acute basophilic leukemia
-- Acute panmyelosis w/ myelofibrosis
-- Myeloid sarcoma
AML, minimally differentiated
≥ 20% blasts in the BM that have:
-- no Auer rods
-- negative cytochem stains
-- have myeloid markers by immunophenotyping

Approx 50-75% of cases will have clonal chrom aberrations, but no distinctive cytogenetic or molecular DNA abnormalities are seen
AML, w/ maturation
≥20% blasts and >10% of cells showing maturation to:
-- promyelocytes
-- myelocytes
-- metamyelocytes

Frequent Auer rods seen

Approx 30-45% of all cases of AML

Occurs more often in younger age groups and has relatively better prognosis
Incidence of AML w/ 11q23 abnormalities?
approx 5-6% of all AML cases
Morphology of AML w/ 11q23 abnormalities?
-- most show monocytic differentiation, w/ or w/o PMN differentiation

-- Monocytic differentiation can be detected by morphology, cytochem,and immunophenotype
Genetics of AML w/ 11q23 abnormalities?
Most common translocations are:
-- t(9;11)(p21;q23)
-- t(11;19)(q23;p13.1)
Results in rearrangement of gene MLL (developmental regulator) at 11q23
Prognosis of AML w/ 11q23 abnormalities?
Intermediate survival
Incidence of acute myeloid leukemia w/ multilineage dysplasia?
mainly occurs in elderly
Morphology of acute myeloid leukemia w/ multilineage dysplasia?
Dysplastic features are apparent in ≥ 50% of marrow cells in at least 2 different cell lines
Genetics of acute myeloid leukemia w/ multilineage dysplasia?
cytogenetic abnormalities are seen in most cases, and tend to be similar to those seen in MDS such as:
-- -5/del(5q)
-- -7/del(7q)
-- +8
-- +11
Prognosis of acute myeloid leukemia w/ multilineage dysplasia?
poor response to chemo
Incidence of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
When related to alkylating agents/radiation exposure, usually occurs 5-6yrs post exposure

When related to topoisomerase II inhibitor, interval from exposure is 12-130 months
Morphology of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
May present as MDS or AML w/ 20% blasts

Involves all 3 cell lines w/ dysplastic features

Cases assoc w/ topoII inhibitors show monocytic component
Genetics of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
Most cases will have clonal cytogenetic amnormalities, frequently:
-5/5del(q)
-7/7del(q)

Cases assoc w/ topoII inhibitors will have t(9;11)
Prognosis of acute myeloid leukemias and myelodysplastic syndromes, therapy related?
Little or no response to therapy

Cases assoc w/ topoII inhibitors may have prognosis similar to primary acute leukemia
What are the AML's not otherwise categorized?
-- AML, minimally differentiated
-- AML, w/o maturation
-- AML, w/ maturation
-- Acute myelomonocytic leukemia (AMML)
-- Acute monoblastic leukemia, acute monocytic leukemia
-- Acute erythroid leukemia
-- Acute megakaryoblastic leukemia
-- Acute basophilic leukemia
-- Acute panmyelosis w/ myelofibrosis
AML, minimally differentiated
≥ 20% blasts in the BM that have:
-- no Auer rods
-- negative cytochem stains
-- have myeloid markers by immunophenotyping

Approx 50-75% of cases will have clonal chrom aberrations, but no distinctive cytogenetic or molecular DNA abnormalities are seen
AML, w/ maturation
≥20% blasts and >10% of cells showing maturation to:
-- promyelocytes
-- myelocytes
-- metamyelocytes

Frequent Auer rods seen

Approx 30-45% of all cases of AML

Occurs more often in younger age groups and has relatively better prognosis
AML, w/o maturation
≥20% blasts in BM w/ <10% cells of myeloid maturation

Auer rods may be seen

Approx 50-75% of cases will have clonal chromosome abnormalities, but no distincive cytogenetic or molecular DNA abnormalities are seen
Acute myelomonocytic leukemia (AMML)
leukemic blasts show myeloid and monocytic differentiation w/ >20% but <80% monocytic cells

No specific clonal aberrations, but many cases involve 11q

Approx 15-20% of cases of AML
Acute monoblastic leukemia

Acute monocytic leukemia
Leukemic blasts show >80% with monocytic differentiation

Monoblastic:
-- predom of monoblasts

Monocytic:
-- some maturation with promonocytes and monocytes

No specific chromosome aberration, but 11q is frequently involved

Approx 5-8% of cases of AML

Clinically, this type of leukemia more often has tissue infiltration, particularly gingival hypertrophy
Acute erythroid leukemia
Rare type of acute leukemia that has a predominance of erythroblasts

Poor prognosis

No specific type of chrom aberration
Acyte megakaryoblastic leukemia
Prolif of megakaryoblasts and abnormal mature megakaryocytes

Freq assoc w/ fibrosis in the BM hampering diagnosis
Acute lymphocytic leukemia (ALL) general info
May occur at any age, but more often in pediatric age groups w/ peak indidence of 4yrs.

WHO classification based on cell surface markers
Types of ALL?
Precursor B lymphoblastic leukemia/lymphoma

Precursor T lymphoblastic leukemia/lymphoma
Incidence of precursor B lymphoblastic leukemia/lymphoma?
Most cases of ALL are precursor-B, and most cases of lymphoma are precursor-T
Morphology of precursor B lymphoblastic leukemia/lymphoma?
Two distinctive morphologies:

1. BLASTS -- small w/ minimal cytoplasm; homogenous in appearance
NUCLEUS -- immature but slightly course chromatin, no nucleoli

2. BLASTS - somewhat larger w/ moderate cytoplasm; more heterogenous in appearance
NUCLEUS - usually 1 to 2 nucleoli
Genetics of precursor B lymphoblastic leukemia/lymphoma?
Cytogenetics are very important for prognosis and determining high-risk vs. low-risk cases

Good prognosis:
-- hyperdiploid >50 chrom
-- normal
-- t(12;21)(p13;q22)

Intermediate to Poor Prognosis:
-- t(9;22)(q34;q11.2)
-- t(v;11)(q23)
-- t(1;19)(q23;p13.3)
-- hypodiploid, <46 chrom
Incidence of precursor T lymphoblastic leukemia/lymphoma?
few cases of ALL, but most cases of lymphoblastic lymphoma are precursor T
Morphology of precursor T lymphoblastic leukemia/lymphoma?
Same as for precursor B

Some cases may show convolutions of the nucleus
Genetics of of precursor T lymphoblastic leukemia/lymphoma?
Many will have abnormal chrom at loci of T-cell receptor genes: 14q11.2, 7q35, 7p14-15
Prognosis of precursor T lymphoblastic leukemia/lymphoma?
Most cases are considered high-risk