MALIGNANT-LEUKOCYTE-DISORDERS

Malignant Leukocyte Disorders Overview

Presented by: Lars Andreille R. Gata, RMT

Leukemia


Recognition:First recognized by Rudolf Virchow (1839-1845) as a distinct clinical disorder, naming it "leukemia," which relates to the white appearance of blood in febrile patients.

Characteristics:

  • Abnormal proliferation and accumulation of hematopoietic cells.

  • Major symptoms include persistent fever, significant weight loss, and increased sweating, which can interfere with daily activities.

  • Possible enlargement of the liver (hepatomegaly), spleen (splenomegaly), and lymph nodes (lymphadenopathy), especially pronounced in chronic leukemia.

Additional Symptoms:

  • Elevated basic metabolic rate leading to fatigue and malaise.

  • Possible hemorrhagic tendencies due to marked thrombocytopenia, which increases bleeding risk.

  • Bone pain is typical in acute leukemias, resulting from a large mass of leukemic cells infiltrating the bone marrow, causing discomfort and limiting mobility.

Differentiating Leukemia from Other Disorders

Leukemia:

  • A hematopoietic malignancy primarily affecting white blood cells in the bloodstream and bone marrow.

  • Characterized by overproduction of either immature or mature leukocytes, leading to dysfunction in normal blood cell production.

Lymphoma:

  • A general term for malignancies originating in the lymphatic system, predominantly in lymph nodes.

  • Types include Hodgkin lymphoma, recognized by Reed-Sternberg cells, and Non-Hodgkin lymphoma, which encompasses a diverse group of blood cancers.

Myeloma:

  • A cancer of plasma cells, leading to tumors (plasmacytomas) that can disrupt normal hematopoiesis in bone marrow.

Classification of Leukemia

Duration:

  • Acute Leukemia: Symptoms develop rapidly, lasting from days to 6 months.

  • Subacute Leukemia: Symptoms present over a duration of 2 to 6 months with evolving characteristics.

  • Chronic Leukemia: Symptoms develop slowly, with a duration of 1 to 2 years or more, often discovered incidentally.

White Blood Cell Count (WBC CT):

  • Aleukemic Leukemia: WBC CT < 15,000 cells/μL without immature or abnormal cells.

  • Subleukemic Leukemia: WBC CT < 15,000 cells/μL with the presence of immature or abnormal forms.

  • Leukemic Leukemia: WBC CT > 15,000 cells/μL with abundant immature and abnormal forms of leukocytes present in circulation.

Types of WBC Involved:

  • Acute Leukemia: Predominance of immature (blast) cells indicative of an aggressive disease state.

  • Chronic Leukemia: Predominance of mature or older white blood cells, reflecting slower disease progression.

Major Types of Leukemia

Acute Lymphoblastic Leukemia (ALL)

  • Primarily affects children and adolescents, accounting for approximately 25% of all childhood cancers and about 75% of childhood leukemias.

  • Subtypes:

    • Early Pre-B cell or Common ALL (60-70% of cases).

    • T-cell ALL (10-20%) - Associated with mediastinal masses and may present with respiratory difficulties due to mass effect.

    • Rare B-cell ALL variants with distinct molecular characteristics.

Acute Myeloid Leukemia (AML)

  • The most common form of leukemia in adults; incidence increases with age, especially after 60.

  • Common abnormalities include hyperuricemia due to increased cell turnover, electrolyte imbalances (calcium, potassium, phosphate), and coagulopathy.

Chronic Lymphocytic Leukemia (CLL)

  • Predominantly involves B lymphocytes and is more common in men, particularly those over 65.

  • Clinical signs include lymphadenopathy, fatigue, significant weight loss, splenomegaly, and hepatomegaly.

  • Features include fragile lymphocytes on smears, leading to the appearance of "smudge cells" and potentially contributing to immunodeficiency.

Chronic Myelogenous Leukemia (CML)

  • Characterized by marked pancytosis and the presence of the Philadelphia chromosome (t(9;22)) in 90% of cases, which is associated with a poor prognosis if untreated.

  • Patients may present with symptoms of hyperviscosity or splenic complications.

Potential Predisposing Factors for Leukemia & Lymphoma

  • Chemicals: Benzene, hydrocarbons, certain hair dyes.

  • Environmental Factors: Ionizing radiation exposure, insecticides, herbicides.

  • Drugs: Alkylating agents, chloramphenicol, and other chemotherapeutic agents.

  • Viruses: Epstein-Barr virus (EBV), Human Immunodeficiency Virus (HIV), Human T-lymphotropic virus (HTLV).

  • Genetic Syndromes: Down syndrome, Fanconi anemia, and other hereditary predispositions.

  • Hematologic Conditions: Myelodysplastic syndromes, which can progress to acute leukemia.

Organizations Classifying Anemia

French American British (FAB) Classification:

  • The initial system still in use; classifies leukemia based on cellular morphology and cytochemical staining results.

World Health Organization (WHO) Classification:

  • Defines acute leukemia by the presence of ≥20% blasts and categorizes based on cellular morphology, cytochemistry, immunophenotyping, cytogenetic abnormalities, and clinical syndrome, providing a more comprehensive classification framework.

Cytogenetic and Cytochemical Analysis

Cytogenetic Analysis:

  • A laboratory study focusing on chromosome abnormalities such as deletions, translocations, and aneuploidy, which are crucial for prognosis and treatment strategies.

Cytochemistry:

  • Involves specialized stains that identify cellular enzymes and other chemicals; aids clinicians in differentiating various hematologic diseases and specifying leukemia sub-types.

Immunophenotyping (Flow Cytometry):

  • A technique that identifies cells based on surface markers; crucial for determining cell lineage and guiding therapy options.

Acute Lymphoblastic Leukemia (FAB Classification)

  • ALL L1: Small, homogeneous lymphoblasts; scant cytoplasm; high nuclear-to-cytoplasmic (N:C) ratio.

  • ALL L2: Larger, heterogeneous lymphoblasts with prominent nucleoli; typically found in adult presentations.

  • ALL L3: Burkitt-type, characterized by large homogeneous lymphoblasts; generally associated with a poor prognosis and rapid progression.

Acute Myeloid Leukemia (FAB Classification)

  • Includes subtypes M0 through M7, characterized by various levels of differentiation and maturity of myeloid cells, and symptoms can vary from the presence of myeloblasts to effects on overall blood cell counts and morphology.

Other Lymphoproliferative Disorders

  • Hairy Cell Leukemia: Characterized by small B lymphocytes with distinct "hairy" projections; more common in males; symptoms often include fatigue and splenomegaly.

  • Burkitt Lymphoma: Notable for medium-sized, rapidly proliferating lymphoid cells, producing a "starry sky" pattern under microscopy, associated with translocations involving MYC.

  • Mycosis Fungoides & Sézary Syndrome: Cutaneous T-cell lymphoma recognized by irregular nuclear outlines and varying skin-related symptoms; can progress to systemic disease.

  • Hodgkin’s Lymphoma: Distinguished by the presence of Reed-Sternberg cells; classified into Classical and Nodular lymphocyte predominant types, each with distinctive clinical and histological features.

Conclusion


Abnormal Hematopoiesis:Myelodysplastic syndromes (MDS) and related disorders exhibit dysregulated progenitor cells leading to excessive proliferation and maturation abnormalities, setting the stage for potential progression to acute leukemia.


Clonal Disorders:Characterized by hypercellular marrow, associated with various hematologic malignancies, emphasizing the importance of early detection and intervention for optimizing patient outcomes.