acute leukemias

Definition of Acute Leukemias

Neoplastic diseases of undifferentiated or partially differentiated stem cells, characterized by halted differentiation and accumulation of blasts in bone marrow and tissues; aggressive due to acquired somatic mutations.

Pathological Characteristics of Acute Leukemias

Clonal diseases; loss of differentiation; bone marrow failure; extramedullary infiltration; anemia, infection risk, hemorrhage due to decreased hematopoiesis; immortal in vitro.

Incidence of AML

Higher with age, especially after 60 years; more common in men; average age at diagnosis is 70 years.

Pathogenesis of Acute Leukemias

History of hematological disease, exposure to radiation, chemotherapy, toxins; malignant proliferation of immature progenitor cells, blocking differentiation, infiltrating BM and organs.

WHO Classification of Acute Leukemias (2016)

Based on genetic abnormalities; AML and ALL subtypes defined by cytogenetics, immunophenotype, morphology; critical for therapy decisions.

FAB Morphological AML Classification

AML 0-7 including AML M3 (promyelocytic), M4 (myelomonocytic), M5 (monocytic), M6 (erythroleukemia), M7 (megakaryoblastic).

Modern AML Classification

Includes AML with genetic abnormalities, myelodysplasia-related changes, therapy-related, NOS, ambiguous lineage types like MPAL, etc.

ALL Classifications

FAB: L1, L2, L3; WHO: based on genetic abnormalities (e.g., BCR-ABL); Romania uses older FAB classification due to limited genetic testing.

Etiological Factors in Acute Leukemias

Viruses, hereditary syndromes (e.g., Down syndrome), radiation, chemicals (benzene), medications, smoking; germline mutations (e.g., CEBPA).

Clinical Signs: Bone Marrow Failure

Infections (neutropenia), anemia (pallor, dyspnea), bleeding (purpura, epistaxis); caused by infiltration of BM with blasts.

Clinical Signs: Infiltrative Proliferation

Bone pain, lymphadenopathy, splenomegaly, CNS symptoms, gingival hypertrophy; organ infiltration (CNS, testes, etc.).

Peripheral Blood Findings in ALs

Leukocytosis or cytopenias; presence of blasts; leukemic hiatus; left shift with immature cells; Auer rods in AML.

Bone Marrow Findings in ALs

Hypercellular marrow with >20% blasts; essential for diagnosis; cytochemistry and immunophenotyping used for classification.

Immunophenotyping in AL

Identifies blast lineage (myeloid vs lymphoid); crucial for classification; performed on blood or bone marrow.

Cytogenetics & Molecular Testing

Used for classification, prognosis, and targeted therapies (e.g., BCR-ABL, PML-RARA, FLT3); includes FISH, PCR, NGS.

What is a "leukemic hiatus"?

Absence of intermediate forms in leukocyte maturation; only blasts and mature cells are present in blood.

What is left shift in leukocyte diff?

Presence of immature myeloid cells in peripheral blood; pathological in leukemias.

Positive Diagnosis of Acute Leukemia

Suggested by anemia, infection, bleeding; confirmed by >20% blasts in bone marrow and specific cytochemical, immunophenotypic, genetic tests.

Differential Diagnosis of Acute Leukemias

Includes leukemoid reaction, aplastic anemia, MDS, viral infections, megaloblastic anemia, marrow metastases.

Prognosis Factors in Acute Leukemias

Depends on age, performance status, cytogenetics, molecular markers; favorable: t(15;17), t(8;21), inv(16); poor: -7, -5, complex karyotypes.

Special Case: AML M3 (Promyelocytic)

Highly curable with early therapy; needs immediate treatment; characterized by PML-RARA gene fusion.

ECOG Performance Status

0–4 scale evaluating physical function; helps decide eligibility for aggressive therapy (0=fully active, 4=bedridden).

Treatment Strategy in AL

Includes induction, consolidation, maintenance, CNS prophylaxis; depends on subtype and patient fitness.

Chemotherapy Regimens in AL

LAL: complex polychemotherapy; AML: "3+7" regimen (cytarabine + anthracycline), targeted agents for mutations.

Role of Allogeneic Stem Cell Transplant

Performed post-consolidation in eligible patients; depends on risk stratification.

Minimal Residual Disease (MRD) Assessment

Detects residual leukemia after treatment via immunophenotyping and molecular tests; guides further therapy.