ACUTE LEUKEMIA Flashcards
_______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
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
Classification Schemes for Acute Leukemia
FAB
WHO
/acute leukemias was devised in the 1970s (morphologic examination and cytochemical stains)
• The French-American-British (FAB) classification
/ 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
- initial diagnosis
- follow-up
- prognostication
Flow cytometry
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)
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
______is primarily a childhood and adolescent disease, accounting for:
• 25% of all childhood cancers
• Up to 75% of childhood leukemias
Acute lymphoblastic leukemia (ALL)
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
- evaluation of blast population and maturing myeloid component > mandatory
Stem cell disorders
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
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
• 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
- most common type in adults (less common in children)
• incidence increases with age
AML
_______
/ Morphology & cytochemistry
_______
/ molecular characterization & cytogenetics
• FAB classification
• WHO classification
presents with nonspecific symptoms that result from a decrease in normal bone marrow function due to the proliferation of leukemic cells.
AML
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
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%
• 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
Other Clinical Manifestations
• Infiltration of malignant cells into the:
• ums and mucosal sites → leads to gingival hyperplasia.
• Skin → presents as leukemia cutis.
AML
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)
- Complete Blood Count (CBC)
- Peripheral blood smear examination
- 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
- Acute Myeloid Leukemia with Recurrent Genetic Abnormalities
- Acute Myeloid Leukemia with Myelodysplasia-Related Changes
- Therapy-Related Myeloid Neoplasms
- Acute Myeloid Leukemia, Not Otherwise Specified (NOS)
- Myeloid Sarcoma
- Myeloid Proliferations Associated with Down Syndrome
- Blastic Plasmacytoid Dendritic Cell Neoplasm
- 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.
Acute Promyelocytic Leukemia (APL) with PML-RARA
Morphology:
• Abnormal hypergranular promyelocytes (some with Auer rods).
• Microgranular variant:
• Granules are too small to be seen under light microscopy, making the cells appear agranular.
• Accounts for 30%–40% of APL cases.
• Can be mistaken for other types of AML.
• Nuclear features:
• “Butterfly” or “coin-on-coin” nucleus.
Acute Promyelocytic Leukemia (APL) with PML-RARA
Clinical Features:
• High risk of disseminated intravascular coagulation (DIC) due to procoagulant activity of granules.
• Thromboembolic events may occur at diagnosis and during treatment.
Acute Promyelocytic Leukemia (APL) with PML-RARA
Acute Promyelocytic Leukemia (APL) with PML-RARA
Treatment:
•______ and _____
•_______ → induces differentiation of malignant promyelocytes.
All-Trans Retinoic Acid (ATRA) and Arsenic Trioxide (ATO)
ATRA (Vitamin A analogue)
Prognosis:
• Favorable prognosis in adults who achieve complete remission.
• Variant RARA translocations may cause ATRA resistance, leading to worse outcomes.
Acute Promyelocytic Leukemia (APL) with PML-RARA
Diagnostic Criteria:
• Detection of t(15;17) translocation is sufficient for diagnosis, regardless of blast count.
Acute Promyelocytic Leukemia (APL) with PML-RARA
Acute Myeloid Leukemia with t(9;11)(p22;q23); KMT2A (MLL)-MLLT3
• Prevalence: _____of AML cases.
6%
• Morphology:
• Increase in monoblasts and immature monocytes.
• Blasts:
• Large cells with abundant cytoplasm and fine nuclear chromatin.
• Granules and vacuoles may be present.
• Pseudopodia (cell motility structures) are frequently seen.
Acute Myeloid Leukemia with t(9;11)(p22;q23); KMT2A (MLL)-MLLT3
Clinical Features:
• More common in children.
• May involve the skin and gums.
• Disseminated intravascular coagulation (DIC) may occur.
Acute Myeloid Leukemia with t(9;11)(p22;q23); KMT2A (MLL)-MLLT3
Diagnostic Criteria:
• AML with t(9;11) is distinct from other AMLs with KMT2A (MLL) abnormalities.
• Should not be grouped with other 11q23 abnormalities.
Acute Myeloid Leukemia with t(9;11)(p22;q23); KMT2A (MLL)-MLLT3
Acute Myeloid Leukemia with Gene Mutations
• Frequently associated with monocytic differentiation.
• Better prognosis compared to other AML subtypes
Acute Myeloid Leukemia with Mutated NPM1
Acute Myeloid Leukemia with Gene Mutations
• Associated with a favorable prognosis
Acute Myeloid Leukemia with Biallelic Mutations of CEBPA
Acute Myeloid Leukemia with Gene Mutations
• Associated with worse overall survival.
Acute Myeloid Leukemia with Mutated RUNX1
requires urgent diagnosis due to its risk of DIC and unique treatment approach (ATRA + ATO).
APL with PML-RARA
Overview
• Primarily affects older adults.
• Associated with a poor prognosis.
• Characterized by at least 20% blasts and evidence of multilineage dysplasia.
Acute Myeloid Leukemia with Myelodysplasia-Related Changes
- Significant morphology includes
‹ pancytopenia with neutrophil hypogranulation or hypergranulation
‹ pseudo-Pelger-Huet cells
‘ unusually segmented nuclei
Acute Myeloid Leukemia with Myelodysplasia-Related Changes
Erythroid precursors:
• Vacuolation.
• Karyorrhexis (nuclear fragmentation).
• Megaloblastoid features (abnormally large, immature erythroid precursors).
• Ring sideroblasts (iron-laden erythroid precursors).
Acute Myeloid Leukemia with Myelodysplasia-Related Changes
Therapy-Related Myeloid Neoplasms (t-MNs)
Overview
• Subtypes:
• Therapy-related MDS (t-MDS).
• Therapy-related AML (t-AML).
• Therapy-related MDS/MPN (t-MDS/MPN).
