Acute Leukemias Flashcards by Iseoluwa Ojo

ACUTE LEUKAEMIAS: INTRODUCTION

______ of hematopoietic precursor cells, characterized by the accumulation of _______ in the ______

Neoplasms

excess blasts

bone marrow.

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ACUTE LEUKAEMIAS: INTRODUCTION

Malignant _______ and _____ of ______ haemopoietic cells.

proliferation and accumulation

immature

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ACUTE LEUKAEMIAS: INTRODUCTION

They are usually of (slow or rapid?) onset & are (slowly or rapidly?) fatal.

Rapid

rapidly

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ACUTE LEUKAEMIAS: INTRODUCTION

They are subdivided into acute _______ and acute __________

lymphoblastic leukaemia (ALL)

myeloblastic leukaemia (AML).

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ALL and AML can be further classified into subtypes

T/F

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PATHOPHYSIOLOGY OF CLINICAL FEATURES of Acute leukemias

Pathophysiology follows:
1.______ failure due to _________ of its normal elements

2.________ of other _____

leuko______

4.________ symptoms

5.other

Marrow failure; infiltration/ replacement

infiltration; organs

Stasis

Constitutional

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PATHOPHYSIOLOGY OF CLINICAL FEATURES of Acute leukemias

Symptoms onset over _____ to ____ typically

days to weeks

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PATHOPHYSIOLOGY OF CLINICAL FEATURES of Acute leukemias

Pathophysiology follows:

Marrow failure-

_______
————
________

anaemia
thrombocytopenia
neutropenia

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PATHOPHYSIOLOGY OF CLINICAL FEATURES of Acute leukemias

Pathophysiology follows:Infiltration of other organs

-_____,______ ,______ (particularly in ALL): - _____,______ ,_______ , _____ masses (T-ALL)

gums: -________(_____ subtype of ____)

-_____ pain especially in children with ____

any organ or tissue

liver, spleen, lymph nodes; hepatomegaly, splenomegaly, lymphadenopathy

mediastinal

gum hypertrophy; monocytic; AML

bone; ALL

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PATHOPHYSIOLOGY OF CLINICAL FEATURES of Acute leukemias

Pathophysiology follows: leukostasis

•only seen with WBC&raquo_space;____ x 109/L

•in CNS: - ______

• in lungs: - ______,______

strokes

pulmonary infiltrates, hypoxemia

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PATHOPHYSIOLOGY OF CLINICAL FEATURES of Acute leukemias

Pathophysiology follows: Constitutional symptoms

-______,_____are common

-_______ is relatively uncommon

fevers, sweats

weight loss

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LABORATORY & DIAGNOSTIC INVESTIGATIONS of acute leukemia

Approach:

______ tests
_______ test
_______ tests

Initial

Confirmatory

Further

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LABORATORY & DIAGNOSTIC INVESTIGATIONS of acute leukemia
Approach

Initial tests: ______ and __________ to determine ______ and the presence of _____

Complete blood count

peripheral blood smear

WBC count; blasts

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LABORATORY & DIAGNOSTIC INVESTIGATIONS of acute leukemia

Approach

Confirmatory test: _______ and ______ to examine morphology, histochemistry, cytogenetics, and immunophenotyping

bone marrow aspiration and biopsy

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LABORATORY & DIAGNOSTIC INVESTIGATIONS of acute leukemia

Approach

Further tests: if ______ is suspected (e.g., _____, _____ analysis, biochemistry – renal and liver function tests etc)

organ involvement

imaging

CSF

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LABORATORY FEATURES: Hematologic indices:

Leukocytes: The white blood cell count (WBC) may be elevated, normal, or low and is a reliable diagnostic marker.

T/F

It is not

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LABORATORY FEATURES : Hematologic indices

Anaemia – usually _____cytic

normo

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LABORATORY FEATURES : Hematologic indices

Peripheral blood smear: presence of _____

blasts

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LABORATORY FEATURES: Hematologic indices:

Coagulation studies: to rule out ____ especially in the _____ subtype _______ leukemia.

DIC

AML

promyelocytic

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Features of acute leukaemia on bone marrow:

__________ marrow

Excess number of ______

Hypercellular

blasts

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Acute Leukaemia is diagnosed when over _____% of nucleated cells in the bone marrow are blasts.

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Although blasts are often readily identifiable in the peripheral blood, the key investigation to make the diagnosis of acute leukaemia before committing the patient to chemotherapy is __________________________

the bone marrow investigation

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LABORATORY FEATURES

Bone marrow aspiration & biopsy is also helpful to:

_________ acute leukaemia

Obtain samples for _______

Sub-classify

cytogenetic analysis

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Bone marrow aspirate and biopsy have only diagnostic value but no prognostic value

T/F

They have prognostic value in addition to diagnostic value

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LABORATORY FEATURES Other lab findings: Electrolytes and metabolic markers: ___ PO42- ___ Ca2+ ___ K+ ___ Lactate dehydrogenase ____ uric acid

↑ ↓ ↑ ↑ ↑

LABORATORY FEATURES Other lab findings: X-ray may show ________ and _________ due to enlargement of the ____ and/or ________ in ALL

lytic bone lesions and mediastinal mass thymus mediastinal lymph nodes

DISTINCTION BETWEEN ALL AND AML Who has Auer rods Who has cytoplasmuc granules

only AML blasts only AML blasts

DISTINCTION BETWEEN ALL AND AML -ALL is primarily a (pediatric or adult?) disease -AML is primarily a (pediatric or adult?) disease

pediatric adult

DISTINCTION BETWEEN ALL AND AML: Histochemistry PAS TdT Myeloperoxidase

Positive ; negative Positive ; negative Negative ; positive

DISTINCTION BETWEEN ALL AND AML: morphology Auer Rods granules Nucleoli

None; present Coarse; fine Inconspicuous; fine

ALL Immunophenotyping by flow cytometry B-ALL is usualy positive for ?? T-ALL is usualy positive for ???

B-ALL is usualy positive for CD10 (CALLA), CD19, and CD20 T-ALL is usualy positive for CD2-CD8, especialy CD3

AML Immunophenotyping by flow cytometry

The majority of subtypes are positive for CD13, 33. 34, 117, and HLA-DR

ACUTE LYMPHOID LEUKAEMIA (ALL) A malignant transformation of a clone of ___________ cells leading to a proliferation and accumulation of _________.

lymphoid stem lymphoblasts

ALL can occur both in adult and children. T/F

_______ is the most common malignancy of childhood constituting about _____% of childhood leukaemias.

ACUTE LYMPHOID LEUKAEMIA (ALL) 80

ALL - Aetiology ____________ cause or risk factors in most cases

No identifiable

ALL - Aetiology Environmental risk factors - prior bone marrow damage due to _______, ________ and electromagnetic fields

alkylating chemotherapy ionizing radiation

ALL - Aetiology Adult T-cell leukemia/lymphoma is linked to infection with ______

HTLV

ALL - Aetiology Genetic or chromosomal factors •Down syndrome - risk of ALL is ___-___ times higher in patients with Down syndrome •—————- type 1 •___________

10–20 Neurofibromatosis Ataxia telangiectasia

ALL Classification Classification may be based on ______ _________ The current ____ Classification (2016)

Morphology Immunological markers - WHO

ALL Classification Classification may be based on Morphology - the __________________ classification of ALL

French-American-British (FAB) historical

ALL Classification Classification may be based on Immunological markers - Immunophenotype classification of ALL: based on the ____ (B cell or T cell) and _____ of the leukemic cells

origin Maturity

ALL Classification Classification may be based on The current WHO Classification (2016) classifies ALL into subtypes of _________________/________ based on ______ and _______ factors

precursor lymphoblastic leukaemia/lymphoma morphologic and genetic

ALL Morphologic classification (FAB) L1: Blasts are ___genous, (small, larger or large?) , with (scant or prominent?) nucleoli and ___ nucleo-cytoplasmic ratio. L2: Blasts are (small, larger or large?), ____geneous with (scant or prominent?) nucleoli and _______ cytoplasm L3: Blasts are (small, larger or large?) with ____philic cytoplasm and cytoplasmic vacuoles

homo; small; scant ; high Larger; hetero; prominent ; more abundant Large; baso

ALL Morphologic classification (FAB) L1: ___-__% ALL L2: ____% ALL L3:____% ALL

20-30 70 1-3

ALL - Immunologic classification 1. _______ types 2._____ ALL 3. _____ ALL

Precursor B-cell B-cell T-cell

ALL - Immunologic classification 1. Precursor B-cell types •Pro B (CD ____) •Early Pre B (CD ___) •Pre B (CD ____, intracytoplaasmic μ+)

10- 10+ 10+/-

ALL - Immunologic classification B-cell ALL - ____ immunoglobulin (Sig+) – related to __________ (Mature B-cell ALL)

surface Burkitt’s lymphoma

ALL - Immunologic classification T-cell ALL - (CD__/ CD__) – Adolescent (males or females?) , thymic mass Early (pro-T) ALL Intermediate-T ALL Mature T-cell ALL

3; 7+ Males

ALL - Incidence •Common in ____ with incidence highest at ___-___ years. •The ____, early pre-B (CD10+) is most usual in _____ and has _____ incidence. •T – ALL has a (male or female?) preponderance. •In adults, the peak incidence is in those older than ____ years.

Children; 3 – 7 cALL; children; equal sex Male 65

Laboratory investigations of ALL Cytochemical staining: - Strongly ______ PAS stain and ______ sudan black & peroxidase reaction.

positive negative

In Laboratory investigations: Biochemical tests for ALL, ______ and ______ tests are preformed as baseline investigations before treatment begins.

Renal and liver functions

Laboratory investigations of ALL: Radiology Ultrasound may show organ infiltrates T/F

ALL – Morphology (FAB ___ ) is the leukemic counterpart of Burkitt’s lymphoma

ALL – Morphology (FAB L3) Is endemic in parts of ______ _____ sized cells with ____ colored vacuolated cytoplasm Express _____ immunoglobulin ____ chain (usually _____) t(__:__), c-myc oncogene

Africa Large; blue monoclonal; light; gamma 8:14

ALL Cytochemistry ______ for TdT _______ for Myeloperoxidase

Positive Negative

ALL Cytogenetics 90% have ______ abnormality Hyperdiploidy (>___ chromosomes) ________ (eg t(9;22 )

chromosomal 50 Translocation

ALL Cytogenetics has no Prognostic significance T/F

F It does

Only B-ALL cells express TdT T/F

F Both T-ALL and B-ALL cells express TdT (terminal deoxynucleotidyl transferase) a marker present early in T and B cell development.

TdT is involved in _______ of the T cell receptor (TcR) and immunoglobulin (Ig) genes.

somatic mutations

B-ALL variably expresses CD__ , and CD___

10 19

CD ____ is a a pan-B cell marker.

19 And maybe 10?

B-ALL cells do not express surface immunoglobulin except _______

mature B-ALL.

T-ALL cells variably express T-cell related antigens CD___, CD__, CD__, and CD__, in addition to Tdt

1a 7 4 8

T-ALL cells express the T cell receptor on their surface. T/F

F They do not

ALL Management _____,______,________

Supportive, Definitive & Curative

ALL Management Supportive Administration of _____,_____,______, and _____ Manage ____________ with ______ and ______ support ______ to prevent ______ and _____ induced nephropathy

fluid, antibiotics, red cell and platelet transfusion side effects of drugs; antiemetics, nutritional support Allopurinol; hyperuricemia and urate

ALL Management Initial therapy may be complicated by _____ syndrome which is characterized by rapid development of hyper____, hyper____, hyper________, hypo____, ______ nephropathy and acute renal failure. The patient should therefore be given ______ before starting therapy and be well hydrated.

tumour lysis uricaemia; kalaemia phosphataemia; calcaemia uric acid allopurinol

ALL Management Definitive - divided into: 1._____ therapy (Remission induction) 2. ____/_____ 3._________ 4.______ prophylaxis

Induction Consolidation /Intensification Maintenance CNS

ALL Management Definitive - 1. Induction therapy (Remission induction)– • ____ weekly and ______ daily. •High dose ______ •Give until ___________ and Patient is clinically ____. Haematological values return to normal. Less than ___% blasts in the bone marrow. _____ in the peripheral blood.

vincristine; prednisolone chemotherapy patient goes into full remission; normal 5; No blast

ALL Management Consolidation /Intensification:- it makes use of (low or high?) dose of _____ therapy. Patient may need a lot of supportive care. Drugs include cytosine arabinoside, daunorubicin, vincristine etc.

High Multidrug

ALL Management Maintenance- ________,_______ for ___yrs in adults and girls and ___ yrs in males.

6-mercaptopurine, methotrexate 2 3

ALL Management CNS prophylaxis: ____________ or_________

intrathecal methotrexate or radiation.

ALL Management Curative treatment – _______________

Allogeneic Stem cell transplantation.

ALL is curable in (children or adults ?) but difficult to treat in (children or adults?)

Children Adults

ALL Prognosis : Prognostic factors – Haematological factors - poor with very _____,_______, and ______ involvement Sex – poor in _____ due to _____ involvement

high WBC, low platelet count and CNS involvement males; testicular

ALL Prognosis Prognostic factors – Race – Poor in _______ Genetics: Hyperdiploidy (more than ___ chromosomes in metaphase) is associated with a ____ prognosis, while the presence of the _____ chromosome t(9;22);BCR/ABL is associated with a very ____ outcome.

blacks 46; better Philadelphia; poor

The Philadelphia chromosome is more frequent in (childhood or adult?) than (childhood or adult?) B-ALL.

Adult Childhood

B-ALL is generally a ____ prognosis leukaemia in children.

good

B-ALL ___% of children with this disease can be cured with multi-agent intravenous, oral, and intrathecal (in the cerebrospinal fluid) Chemotherapy given over a period of _____ years The cure rate among adults is (lower or higher?) at about ______%. This is owing to the presence of __________

80 three Lower; 30 less favourable cytogenetics.

T-ALL in childhood is not treated as high risk disease T/F

F It is

Prognostic factors in ALL( good , bad) Age WBC

2-10 years ; less than 2 or greater than 10 10k or less; more than 50k

Prognostic factors in ALL( good , bad) Gender Type

Female; male L1/CALL; L3/BALL

Prognostic factors in ALL( good , bad) Cytogenetics Remission Extra medullary disease

Hyperdiploidy; Philadelphia Chromosome, Hypodiploidy Early; late Absent; present

ACUTE MYELOID LEUKAEMIA (AML) Accumulation of _____ cells.

primitive myeloid

ACUTE MYELOID LEUKAEMIA (AML) A (benign or malignant?) transformation of a clone of myeloid stem cells leading to a proliferation and accumulation of _____.

malignant myeloblasts

ACUTE MYELOID LEUKAEMIA (AML) AML constitutes ____% of adult leukaemias and about _____% of childhood leukaemias.

80 15 – 20

ACUTE MYELOID LEUKAEMIA (AML) There are two types of AML: _______ AML _______ AML

Denovo Secondary

ACUTE MYELOID LEUKAEMIA (AML) There are two types of AML: Denovo AML – _______________ Secondary AML – following _____, _____ disorders or following treatment of haematological malignancies with ______ e.g. busulphan, melphalan etc

No pre-existing disease MDS; myeloproliferative chemotherapy

CML can cause AML T/F

AML - Classification Classification –Two types of classification exist: _________ and ______

FAB Classification and WHO Classification

AML - FAB classification This is a morphological classification M0 -_______________ leukaemia M1 - ______ leukaemia _____ M2 - ______ leukaemia ______ M3 - ______________ leukaemia M4 - _________ leukaemia M4Eo - Variant: Increase in abnormal marrow ______ M5 - ______ leukaemia M6 - _____leukemia (_______ disease) M7 - ___________ leukaemia

minimally differentiated Myeloblastic ; without maturation Myeloblastic; with maturation Hypergranular promyelocytic Myelomonocytic; eosinophils Monocytic ; Erythro; DiGuglielmo's Megakaryoblastic

DiGuglielmo's disease is ______leukemia( M__)

Erythro M6

AML Incidence The vast majority of AML occur in (children or adults?) ,with the median age being ___ years. AML represents ___% of all cancer deaths.

Adults 60 1.2

AML Clinical features is Essentially same as ALL T/F

AML Haematological investigations is same as in ALL T/F

AML Laboratory investigations Lumbar Puncture is frequently done T/F

F Not done in many cases except when you suspect CNS disease which is commonly seen in M4 and M5.

AML’s Biochemical test is As with ALL T/F

AML Laboratory investigations - diagnosis Cytochemistry Periodic acid-schiff (PAS )–______ or _______ Sudan black and peroxidase – ______ Non specific esterase – ______ in ____ and ——-

Negative or weakly positive positive Positive M4 and M5

AML Laboratory investigations - diagnosis Immunophenotype – myeloid cells have the following CD – CD ___ & CD ____

13 33

AML Cytochemistry Myeloperoxidase -______ TdT -_______

Positive Negative

AML Immunology Positive for myelo/monocytic antigens CD ____ and ___ Negative for B-lineage antigens CD__ and __ Negative for T lineage antigens CD__ and __

13 and 33 10 and 19 3 and 7

AML M3 (Promyelocytic) -Neoplastic ____ -____ Auer rods -treated with _______

Promyelocytes Many Retinoic acid

AML Prognosis Good •BM response : ____% blasts after first course •Age - <___ years Bad • BM response -____% blasts after first course. Age - > ___ years.

<5; 60 >20; 60

Most common translocation in ALL Philadelphia chromosome translocation Translocation in M3 Translocation in M2 Translocation in L3

15:21 9:22 15:17 8:21 8:14

Mo morphologicallu resembles ______