Acute Leukemia Characteristics Quiz

Acute Leukemias

• Acute leukemia is a group of malignant blood disorders
• Originates from the clonal proliferation of hematopoietic stem cells in bone marrow
• Accumulation of immature (blast) or abnormal white blood cells in both peripheral blood and bone marrow occurs
• Caused by somatic mutation and malignant transformation of BM pluripotent stem cells
• Neoplastic expansion in the BM leads to abnormal leukemic cells with impaired production of red cells, neutrophils, and platelets
• Unique morphological, cytogenetic, and immunophenotypic features are used for classification, diagnosis, and prognosis
• In acute leukemia, a diagnosis requires 20% or more blasts (immature cells) in the blood and bone marrow

Classification of Leukemia

• Categorized into acute and chronic types
• Further sub-classified based on myeloid or lymphoid origin
• Acute myeloid leukemia (AML)
• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)
• Chronic lymphocytic leukemia (CLL)

AML (Acute Myeloid Leukemia)

• AML is a malignant clonal disorder of the myeloid cell line
• Characterized by accumulation of myeloblasts in blood, bone marrow, or other tissues
• Myeloblasts often show myeloid or monocytic differentiation
• Approximately 80% of AML patients have chromosomal abnormalities
• 20% or more blasts are present in blood and bone marrow

AML Epidemiology

• AML can occur at any age; incidence increases with age
• Accounts for 80% of adult acute leukemias and 20% of childhood acute leukemias
• Predominant form of congenital leukemia, often associated with Down syndrome (Trisomy 21)
• Incidence slightly higher in males compared to females
• Higher incidence in developed and industrialized countries
• Little difference in incidence between blacks and whites at any age

AML Causes

• Idiopathic (most common)
• Underlying hematologic disorders (MDS, PNH, PRV, MF)
• Exposure to chemicals (e.g., benzene, petroleum products)
• Certain drugs (cytotoxic drugs)
• Ionizing radiation
• Viral infections (HTLV-I)
• Genetic conditions (Down syndrome, Turner syndrome, Klinefelter syndrome, Fanconi anemia)
• Primary (de novo AML) or secondary to other conditions (MDS, PNH, MF, PRV) or exposure to chemical/drugs

AML Clinical Features

• Symptoms related to bone marrow suppression and organ infiltration by malignant myeloblasts
• Symptoms due to:
  • Marrow failure
  • Tissue infiltration
  • Leukostasis (excessive WBC accumulation in circulation)
  • Constitutional symptoms (fever, headaches, night sweats, anorexia, nausea, vomiting)
  • Bleeding tendency (thrombocytopenia or DIC)
• Usually short duration of symptoms (weeks/months if untreated)
• Clinical findings: bone marrow infiltration, neutropenia, anemia, thrombocytopenia, medullary infiltration (marrow), extramedullary infiltration (liver, spleen, lymph nodes, central nervous system), gum hypertrophy, purpuric/petechial rashes, subcutaneous nodules,chloromas/granulocytic sarcomas

AML Classification

• Classified based on morphology of myeloblasts, molecular markers, and cytogenetic abnormalities
• Key classification systems include:
  • French-American-British (FAB) classification (divides AML into 8 types; Mo-M7)
  • World Health Organization (WHO) classification (divides AML into 5 categories/groups based on recurrent genetic abnormalities, multi-lineage dysplasia, therapy-related syndromes, not otherwise categorized, and ambiguous lineage)

ALL (Acute Lymphoblastic Leukemia)

• Results from accumulation of lymphoblasts in both peripheral blood and bone marrow
• Most common childhood leukemia, though it can occur in adults
• Accounts for about 76% of all leukemias diagnosed in children below 15 years
• More males are affected than females

ALL Etiology

• Etiology is unknown in most cases
• Environmental factors (ionizing radiation, chemical mutagens)
• Genetic predisposition (e.g., Down syndrome)
• Exposure to childhood infections (mainly viral)

ALL Classification

• Classified based on morphology of lymphoblasts and immunological markers
• Types:
  • FAB (L1, L2, L3) - morphological classification
  • Immunological classification (e.g., B-lineage: pro-B-ALL, common ALL, pre-B-ALL, B-cell ALL; T-lineage: pre-T-ALL, T-cell ALL)

ALL Morphology (FAB)

• L1: Small, homogeneous blasts
• L2: Large, heterogeneous blasts
• L3: Large, homogeneous blasts with abundant basophilic cytoplasm and vacuoles

ALL Clinical Features

• Acute presentation, often critically ill due to bone marrow failure
• Symptoms of anemia, weakness, lethargy, breathlessness, palpitations
• Infections (e.g., Staphylococcus, Pseudomonas, HSV, Candida)
• Bleeding tendencies (purpura, menorrhagia, epistaxis)
• Signs of leucostasis (hypoxia, retinal hemorrhage)
• Mediastinal involvement and CNS involvement are considerations

ALL Investigations and Diagnosis

• Full blood count and blood film (normocytic normochromic anemia, thrombocytopenia, leukocytosis with lymphoblasts)
• Bone marrow aspiration/biopsy (hypercellular marrow with >20% lymphoblasts)
• Bone marrow cytogenetics (to detect chromosomal abnormalities)
• CSF examination to look for CNS involvement
• Biochemical tests (↑ LDH, ↑ uric acid, LFTs, renal function tests)
• X-rays (to detect possible thymic or mediastinal lymph node enlargement)
• Immunophenotyping of blood or bone marrow blasts

ALL Treatment (Supportive and Specific)

• Supportive:

  • Explain diagnosis and offer counseling
  • Central venous catheter for drug and blood product administration
  • Transfusions of RBC and platelets
  • Prophylactic and aggressive treatment of infections (antibiotics, antivirals, antifungals)
  • Allopurinol to prevent hyperuricemia and tumor lysis syndrome
  • Antiemetic drugs to prevent vomiting

• Specific:

  • Induction therapy to achieve complete remission (vincristine, prednisolone, daunorubicin, L-asparaginase)
  • CNS prophylaxis (generally includes cranial irradiation and/or intrathecal chemotherapy)
  • Consolidation therapy to reduce tumor burden and prevent relapse.
  • Maintenance therapy (necessary for those not undergoing stem cell transplant)
  • Allogeneic stem cell transplantation (SCT) in some cases

Prognostic Factors (AML and ALL)

• AML:

  • Cytogenetics (favorable = t(8;21), t(15;17), inv 16; unfavorable = deletions of chromosomes 5 or 7, FLT3 mutation)
  • Age at diagnosis (>60 years is unfavorable)
  • Onset of disease (primary or secondary)
  • Bone Marrow response to induction chemotherapy (CR or <5% blasts after first course vs. >20% blasts)

• ALL:

  • TWBC (Total White Blood Cell Count) at diagnosis (low is good)
  • Sex (female better prognosis)
  • Age (childhood better prognosis)
  • Immunophenotype (certain types of ALL have better prognoses)
  • Cytogenetics (normal or hyperdiploidy is better than Ph+ or hypoploidy)
  • CNS disease (absence preferable)

Biphenotypic Acute Leukemias

• A minority of cases with two distinct leukemia cell populations
• Often expressing both B-lymphoid and myeloid markers
• Variable response rates; treatment protocol selection can be problematic

Tumor Lysis Syndrome (TLS)

• Rapid tumor cell lysis causes release of intracellular substances (potassium, phosphate, nucleic acids) overwhelming the kidneys
• Can occur at presentation with chemotherapies or high-grade lymphomas
• Risk of renal failure, electrolyte imbalances, and hyperphosphatemia
• Usually treated with hydration, allopurinol, and supportive care

Additional Notes

• Presented data is from a series of presentations
• Specifics like patient demographics and detailed clinical findings depend on the specific case studies, and the summary assumes general context from the presentations.

Test your knowledge on acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) with this quiz. Explore topics such as cell markers, clinical features, and classifications of different leukemia subtypes. Answer questions about presentations and findings associated with these hematological malignancies.