ACUTE LEUKEMIA Flashcards by Kyra Catedral

_______is characterized by the rapid, clonal proliferation of lymphoid or myeloid progenitor cells in the bone marrow:

• _______→ precursors of lymphoid cells
• ________ precursors of myeloid cells

Acute leukemia

Lymphoblasts

Myeloblasts

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Causes of Acute Leukemia

(1)
• Radiation exposure
• Organic solvents (e.g., benzene)

(2)
• Familial cancer predisposition syndromes (rare cases)
• Alkylating agents and chemotherapy → induce DNA damage in hematopoietic cells → leading to therapy-related leukemias

Environmental Exposures
Genetic and Therapy-Related Causes

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Classification Schemes for Acute Leukemia

FAB
WHO

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/acute leukemias was devised in the 1970s (morphologic examination and cytochemical stains)

• The French-American-British (FAB) classification

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/ at least 20% blasts in the bone marrow (diagnosis of the majority of acute (eukemias)

/ Undergo testing - detect the presence or absence of genetic anomalies

WHO classification

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initial diagnosis
follow-up
prognostication

Flow cytometry

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This system classifies acute leukemias based on:
• Morphology (cell shape and structure)
• Cytochemical stains (biochemical reactions of cells)

The French-American-British (FAB) Classification (1970s)

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Key Diagnostic Criteria (______Update)

• ≥ 20% blasts in the bone marrow → required for diagnosing most acute leukemias.

• Genetic testing is necessary to determine the presence or absence of genetic anomalies.

WHO 2017

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______is primarily a childhood and adolescent disease, accounting for:

• 25% of all childhood cancers
• Up to 75% of childhood leukemias

Acute lymphoblastic leukemia (ALL)

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Incidence by Age Group

• The peak incidence of ALL in children occurs between ____of age.

• ALL is rare in____, but the risk increases with age, with most adult cases occurring in individuals older than 50 years.

2 to 5 years

adults

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evaluation of blast population and maturing myeloid component > mandatory

Stem cell disorders

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Acute Myeloid Leukemias With Recurrent Cytogenetic Abnormalities

immature myeloid immunophenotype
highdensity CD34
coexpression of CD19
CD13, myeloperoxidase and often weak CD33
CD34 and CD15: coexpression
TdT is commonly present.

AML with t(8;21)(q22;q22.1); RUNX1/RUNX1T1

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Diagnose_______
• Immunophenotypic features
- lack of CD34, HLA-DR and leukocyte integrin antigens (CD11a, CD11b, CD18)
- presence of CD33 with myeloperoxidase and CD117
- variable CD13 and CD15

Acute Promyelocytic Leukemia

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• AML with minimal differentiation and AML without maturation

Presence of blast - in low-density CD45 antigen Vlow SS - agranular cytoplasm.

Acute Myeloid Leukemias, Not Otherwise Specified

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most common type in adults (less common in children)

• incidence increases with age

AML

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_______
/ Morphology & cytochemistry

_______
/ molecular characterization & cytogenetics

• FAB classification

• WHO classification

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presents with nonspecific symptoms that result from a decrease in normal bone marrow function due to the proliferation of leukemic cells.

AML

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Hematologic Findings
• Total White Blood Cell (WBC) Count
• Typically ranges from 5 to 30 × 10⁹/L but can vary from 1 to 200 × 10⁹/L.
• Myeloblasts are present in the peripheral blood in 90% of cases.

AML

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AML

Hematologic Findings
• Total White Blood Cell (WBC) Count
• Typically ranges from______ or _____
• Myeloblasts are present in the peripheral blood in_____ of cases.

5 to 30 × 10⁹/L but can vary from
1 to 200 × 10⁹/L.

90%

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• Anemia, thrombocytopenia, and neutropenia lead to the following symptoms:
• Pallor and fatigue → due to decreased red blood cell production.
• Fever → due to neutropenia and increased susceptibility to infections.
• Bruising and bleeding → due to thrombocytopenia.
• Disseminated intravascular coagulation (DIC) and other bleeding disorders can also occur.

AML

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Other Clinical Manifestations
• Infiltration of malignant cells into the:
• ums and mucosal sites → leads to gingival hyperplasia.
• Skin → presents as leukemia cutis.

AML

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Other Clinical Manifestation • Splenomegaly occurs in 50% of cases. • Lymphadenopathy (lymph node enlargement) is rare in AML. • Cerebrospinal fluid (CSF) involvement is rare and does not cause as many neurologic symptoms as in acute lymphoblastic leukemia (ALL).

AML

Clinical Presentation • Presence of ***splenomegaly*** • ***Rare*** lymph node enlargement and CSF involvement • few symptoms related to the CNS • Hyperuricemia • Hyperphosphatemia • Hypocalcemia - Hypokalemia

AML

Laboratory Abnormalities (AML) • → due to increased cellular turnover. • → due to cell lysis. • → contributes to progressive bone destruction. • is also commonly observed.

Hyperuricemia Hyperphosphatemia Hypocalcemia Hypokalemia

Occurs during induction chemotherapy, especially in patients with high WBC counts.

Tumor Lysis Syndrome (TLS) in AML

metabolic complications (in patients with malignancy) caused by the breakdown products of dying cancer cells acute uric acid nephropathy renal failure

Tumor lysis syndrome

A life-threatening condition caused by massive cancer cell breakdown, leading to: • Hyperkalemia • Hyperphosphatemia • Hyperuricemia and hyperuricosuria • Hypocalcemia

Tumor lysis syndrome

Complications: • Acute uric acid nephropathy • Renal failure • Severe cardiac arrhythmias due to hyperkalemia • Prevention: • Aggressive prophylactic measures (hydration, allopurinol, rasburicase).

Tumor Lysis Syndrome

Subtypes of AML and Related Precursor Neoplasms • Diagnosis begins with: (3)

1. Complete Blood Count (CBC) 2. Peripheral blood smear examination 3. Bone marrow aspirate and biopsy

Findings: • WBC count can be normal, increased, or decreased. • Anemia is present in most cases. • Significant thrombocytopenia is also common. • Bone marrow is usually ***hypercellular, with >20% marrow blasts*** (except when certain genetic abnormalities are present, in which case the 20% threshold is not required).

Subtypes of Acute Myeloid Leukemia and Related Precursor Neoplasms

2017 WHO Classification of Myeloid Leukemia and Related Precursor Neoplasms

1. Acute Myeloid Leukemia with Recurrent Genetic Abnormalities 2. Acute Myeloid Leukemia with Myelodysplasia-Related Changes 3. Therapy-Related Myeloid Neoplasms 4. Acute Myeloid Leukemia, Not Otherwise Specified (NOS) 5. Myeloid Sarcoma 6. Myeloid Proliferations Associated with Down Syndrome 7. Blastic Plasmacytoid Dendritic Cell Neoplasm 8. Acute Leukemias of Ambiguous Lineage

AML with Specific ***Chromosomal Translocations:***

• AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 • AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 • Acute Promyelocytic Leukemia (APL) with PML-RARA • AML with t(9;11)(p21.3;q23.3); KMT2A(MLL)-MLLT3 • AML with t(6;9)(p23;q34.1); DEK-NUP214 • AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM (RPN1-EVI1) • AML with t(1;22)(p13.3;q13.3); RBM15-MKL1 • AML with BCR-ABL1

AML with Gene Mutations:

• AML with Mutated NPM1 • AML with Biallelic Mutation of CEBPA • AML with Mutated RUNX1

Acute Myeloid Leukemia with **t(8;21)(q22;q22.1); RUNX1-RUNX1T1*** • Prevalence: Found in____ of AML cases. Demographics: • Seen predominantly in____ nd ___

~5% children and young adults.

Morphology: • Myeloblasts have ***dysplastic granular cytoplasm and Auer rods.*** • Cells show some degree of maturation, ***resembling FAB M2 (AML with maturation).*** • **Pseudo–Pelger-Huët cells*** and hypogranulation may be present. • Eosinophilia is possible.

Acute Myeloid Leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1

Acute Myeloid Leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 Prognosis: • Generally favorable, but worsens if additional unfavorable abnormalities (e.g.,______) occur.

monosomy 7

Acute Myeloid Leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 Diagnostic Criteria: • The presence of the_____genetic abnormality is sufficient for diagnosis, regardless of blast count.

t(8;21)

presence of the t(8;21) genetic abnormality is sufficient for diagnosis, regardless of blast count.

Acute Myeloid Leukemia with t(8;21)(q22;q22.1); RUNX1-RUNX1T1

Acute Myeloid Leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 • Prevalence: _____of all AML cases. • Demographics: • Occurs at all ages but is more common in_____

5%–8% younger patients.

Morphology: • Peripheral blood and bone marrow contain ***myeloblasts, monoblasts, and promyelocytes.*** • Bone marrow eosinophilia with dysplastic changes is observed.

Acute Myeloid Leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

Clinical Features: • Higher incidence of ***extramedullary disease*** (involvement outside the bone marrow). • ***Central nervous system (CNS) involvement*** is common → frequent site of relapse.

Acute Myeloid Leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

Prognosis: • High remission rate, but only 50% of patients achieve a cure.

Acute Myeloid Leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

• Diagnostic Criteria: • Presence of inv(16) or t(16;16) is sufficient for diagnosis, regardless of blast count.

Acute Myeloid Leukemia with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

Acute Promyelocytic Leukemia (APL) with PML-RARA Prevalence: _____of AML cases. • Demographics: • Occurs in all age groups, most commonly in_____

5%–10% young adults.

Pathogenesis: • ***Differentiation block at the promyelocytic stage*** → leads to ***accumulation of abnormal promyelocytes.***