Medicine Marrow Pg 121-130 (Hematology)
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Medicine Marrow Pg 121-130 (Hematology)

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Questions and Answers

Which classification does NOT provide prognostic information for AML?

  • WHO classification
  • WHO-5 classification
  • ICC classification
  • FAB classification (correct)

    • Acute Promyelocytic Leukemia (APML) is classified under the WHO classification as having a bad prognosis.

    False

    What type of cell abnormality requires a minimum of 20% blasts for diagnosis in the context of poor prognosis AML?

    t(BCR; ABL)

    AML defined by differentiation falls under the ______ classification.

    <p>FAB</p> Signup and view all the answers

    Match the following recurrent genetic abnormalities with their prognosis:

    <p>t(15; 17) = Good prognosis t(BCR; ABL) = Bad prognosis FLT3-ITD = Very bad prognosis t(8; 21) = Good prognosis</p> Signup and view all the answers

    Which of the following diagnostic methods is NOT part of the 5-point diagnosis of a hematological disorder?

    <p>Ultrasound imaging</p> Signup and view all the answers

    Hyperviscosity is present in acute myeloid leukemia (AML).

    <p>False</p> Signup and view all the answers

    What is the most common cell type found in myeloblastic leukemia?

    <p>myeloblast</p> Signup and view all the answers

    In general, leukemia is characterized by the clonal proliferation of cells of the _____ lineage in marrow or blood.

    <p>WBC</p> Signup and view all the answers

    Match the hereditary conditions to their associated risks for acute myeloid leukemia (AML):

    <p>Bloom syndrome = Defective DNA repair Ataxia-telangiectasia = Defective DNA repair Fanconi's anemia = Inherited causes of aplastic anemia Shwachman-Diamond syndrome = Inherited causes of aplastic anemia</p> Signup and view all the answers

    Which of the following features is NOT associated with Fanconi's anemia?

    <p>Dystrophic nails</p> Signup and view all the answers

    Shwachman-Diamond syndrome is characterized by ribosomopathy.

    <p>True</p> Signup and view all the answers

    What are the common causes of acquired aplastic anemia?

    <p>Idiopathic causes, drugs, toxins (like benzene), viruses, and autoimmune disorders.</p> Signup and view all the answers

    Dyskeratosis Congenita involves a defect in __________ repair.

    <p>Telomere</p> Signup and view all the answers

    Match the following conditions with their associated features:

    <p>Fanconi's anemia = Cafe au lait macules and short stature Dyskeratosis Congenita = Pancreatic exocrine insufficiency and reticular skin pigmentation Shwachman-Diamond syndrome = Metaphyseal dysplasia and pancreatic insufficiency</p> Signup and view all the answers

    Which of the following is a congenital cause of pure red cell aplasia?

    <p>Diamond blackfan syndrome</p> Signup and view all the answers

    MDS and MPN overlap is known as chronic myelomonocytic leukemia.

    <p>True</p> Signup and view all the answers

    What is the most common symptom associated with pancytopenia?

    <p>Fatigue</p> Signup and view all the answers

    The condition characterized by sudden reticulocytopenia due to parvovirus B19 infection is called __________.

    <p>transient aplastic crisis</p> Signup and view all the answers

    Match the following blood parameters with their significance:

    <p>Ringed sideroblasts = SF3B mutation in MDS Oval macrocytes = Most common presentation Giant pronormoblasts = Transient aplastic crisis Howell Jolly bodies = Post-splenectomy or splenic dysfunction</p> Signup and view all the answers

    What does a 5q deletion indicate in terms of prognosis?

    <p>Good prognosis</p> Signup and view all the answers

    The presence of Dohle bodies in the WBC indicates a good prognosis.

    <p>False</p> Signup and view all the answers

    Name one treatment option for trilineage bone marrow failure syndromes.

    <p>Bone marrow transplantation</p> Signup and view all the answers

    The presence of ____ bodies is commonly associated with toxic granulation in white blood cells.

    <p>Dohle</p> Signup and view all the answers

    Match the following diagnostic features with their corresponding prognostic outcomes:

    <p>Pancytopenia: &gt; 10%; dysplastic cells = Poor prognosis Cytogenic abnormality = Good prognosis No AML = Best prognosis No other cause = Indeterminate prognosis</p> Signup and view all the answers

    What is the most common hematological abnormality seen at birth?

    <p>Transient abnormal myelopoiesis</p> Signup and view all the answers

    Environmental factors such as radiation and benzene can increase the risk of hematological diseases.

    <p>True</p> Signup and view all the answers

    What mutation is associated with transient abnormal myelopoiesis?

    <p>GATA-1</p> Signup and view all the answers

    Myelodysplastic syndromes (MDS) can progress to acute myeloid leukemia (AML) when there are at least _____ blast cells.

    <p>20%</p> Signup and view all the answers

    Match the following inherited syndromes with their associated hematological condition:

    <p>Kostmann syndrome = Congenital agranulocytosis Noonan syndrome = Myeloproliferative neoplasms Down syndrome = Potential increased risk of leukemias</p> Signup and view all the answers

    What percentage of acute leukemias in adults is Acute Myeloid Leukemia (AML)?

    <p>80%</p> Signup and view all the answers

    In acute leukemia, children and adolescents show a predominance of Acute Myeloid Leukemia (AML).

    <p>False</p> Signup and view all the answers

    What is the time frame for the short history of acute leukemia symptoms?

    <p>2-3 months</p> Signup and view all the answers

    Acute Myeloid Leukemia (AML) is characterized by the complete arrest of differentiation of _______ in the bone marrow.

    <p>myeloblasts</p> Signup and view all the answers

    Match the precursor cells with their associated leukemia types:

    <p>Myeloblast = Myeloblastic leukemia Monoblast = Monoblastic leukemia RBC precursor = Erythroleukemia Platelet precursor = Megakaryocytic leukemia</p> Signup and view all the answers

    What is the most common cause of Aplastic Anemia?

    <p>Drug dependency</p> Signup and view all the answers

    Myelodysplastic syndrome (MDS) is characterized by hypocellular marrow.

    <p>False</p> Signup and view all the answers

    What age group is primarily affected by inherited Aplastic Anemia?

    <p>Under 20 years</p> Signup and view all the answers

    Pancytopenia with hypercellular marrow is a characteristic of __________.

    <p>Aplastic Anemia</p> Signup and view all the answers

    Match the following conditions with their associated features:

    <p>Aplastic Anemia = Bimodal age distribution Hairy cell leukemia = Massive splenomegaly Myelodysplastic syndrome = Hypercellular marrow Primary myelofibrosis = Pancytopenia + Fibrosis</p> Signup and view all the answers

    Which of the following drugs is associated with dose-dependent aplastic anemia?

    <p>Fluorouracil</p> Signup and view all the answers

    Bleeding is the most common clinical presentation of aplastic anemia.

    <p>True</p> Signup and view all the answers

    Name two drugs that can cause aplastic anemia in a dose-independent manner.

    <p>Chloramphenicol and Sulfonamides</p> Signup and view all the answers

    The most common clinical presentation of aplastic anemia is __________.

    <p>bleeding</p> Signup and view all the answers

    Match the following drugs with their classification as dose-dependent or dose-independent in causing aplastic anemia:

    <p>Fluorouracil = Dose-Dependent Chloramphenicol = Dose-Independent Daunorubicin = Dose-Dependent Gold = Dose-Independent</p> Signup and view all the answers

    Which of the following is the most common complication of acute myeloid leukemia (AML)?

    <p>Abnormal bleeding due to thrombocytopenia</p> Signup and view all the answers

    Meningeal involvement is a common presentation in acute myeloid leukemia (AML).

    <p>False</p> Signup and view all the answers

    What is a common site for myeloid sarcoma in patients with acute myeloid leukemia?

    <p>Orbit</p> Signup and view all the answers

    Acute myeloid leukemia can lead to _____ pain, although it is rare.

    <p>bone</p> Signup and view all the answers

    Match the following presenting features of acute myeloid leukemia with their descriptions:

    <p>Pancytopenia = Decrease in red blood cells, white blood cells, and platelets Anemia = Symptoms such as pallor, fatigue, and weakness Life-threatening hemorrhage = Can occur specifically in acute promyelocytic leukemia Bone pain = Commonly associated with acute lymphoblastic leukemia (ALL)</p> Signup and view all the answers

    Study Notes

    AML Classification

    • FAB classification (Does not give prognosis):
      • m2: myeloblast
      • m3: Promyelocyte
      • m4: myelomonocyte
      • m5: monocyte
      • m6: erythroid
      • m7: megakaryocyte
    • WHO classification (2016):
      • AML with recurrent genetic abnormalities (Blasts ≥ 20%): Poor prognosis
      • AML - MDS related
      • AML - therapy related (m6)
      • AML - not otherwise specified (m2, m3, m4): Poor prognosis
      • myeloid sarcoma
    • Recurrent genetic abnormalities:
      • Good prognosis:
        • t(15; 17) / t(PML; RARα): Acute Promyelocytic Leukemia (APML)
        • t(8; 21) / t(RUN X1; RUN X1)
        • t(16; 16) / Inversion 16: Involves CBFB (core-binding factor B)
        • Mutations:
          • Nucleophosmin (NPM)
          • CEBPA
      • Bad prognosis: t(BCR; ABL) / t(9; 22)
        • Very bad prognosis: FLT3-ITD (Inverse tandem duplication of FMS-like tyrosine kinase)
    • WHO-5 classification (2023):
      • AML with recurrent genetic abnormalities. Blasts ≥ 20% not required except in some cases
      • AML-MDS
      • AML-therapy related
      • AML defined by differentiation (FAB classification)

    5 Point Diagnosis of Hematological Disorder

    • Morphology
    • Cytology/Cytochemistry: of bone marrow/blood cells. Myeloperoxidase/Sudan black
    • Immunophenotyping: using Flow cytometry CD markers
    • Cytogenetics: Recurrent genetic abnormalities. Inversion/deletion
    • Molecular Genetics

    AML Definition

    • Generalised neoplastic (clonal) proliferation: of immature leucocytes with/without involvement of peripheral blood and non-hematopoietic tissues.
    • Leukemia: Clonal proliferation of cells of WBC lineage in marrow/blood.
    • Most common cell type: myeloblast (myeloblastic leukemia)
    • Median age: 65 years, but seen in all ages.
    • Gender Predominance: Male > Female (All acute leukemias)

    5-Year Survival Rates of AML

    • >75 years: Almost NIL
    • >50 years: ~20% with transplant

    Risk Factors of AML

    • Hereditary Conditions:
      • Defective DNA repair
      • Bloom syndrome
      • Ataxia-telangiectasia
      • Inherited cause for pure red cell aplasia: Diamond-Blackfan syndrome
      • Inherited causes of aplastic anemia
      • Fanconi's anemia
      • Dyskeratosis congenita
      • Shwachman-Diamond syndrome
    • Environmental factors:
      • Radiation
      • Benzene
    • Drug-induced leukemias:
      • Alkylating agents (after 5-6 years of therapy)
      • Topoisomerase II inhibitors (after 1-3 years of therapy) - etoposide
    • Hematological diseases:
      • Myeloproliferative neoplasms (MPN)
        • Polycythemia vera
        • Primary myelofibrosis
        • Essential thrombocythemia
      • Chronic myeloid leukemia (CML)
      • Paroxysmal nocturnal hemoglobinuria (PNH)
      • Aplastic anemia
      • Myeloma
    • Progression:
      • 25% cases of myelodysplastic syndromes (MDS) can progress to acute myeloid leukemia (AML)
      • (20% blast cells)
      • (10-19% blast cells)

    Aplastic Anemia

    • Inherited:
      • Fanconi's anemia:
        • Defect: Autosomal recessive FANCA gene mutation > FANCB, FANCC
        • Features:
          • Short stature
          • Cafe au lait macules
          • Gonadal dysgenesis
          • Increased risk of AML & SCC (Head & neck)
          • Esophageal atresia
    • Acquired:
      • Dyskeratosis Congenita:
        • Defect: DKC, mutation, Telomere repair, Complex defect
        • Features:
          • Reticular skin pigmentation
          • Dystrophic nails
          • Pancreatic exocrine insufficiency
          • Metaphyseal dysplasia
      • Shwachman-Diamond syndrome:
        • Features:
          • Pancreatic exocrine insufficiency
          • Metaphyseal dysplasia
          • Ribosomopathy

    Acquired Aplastic Anemia

    • Causes:
      • Idiopathic
      • Drugs
      • Toxins: Benzene
      • Virus: Non A, B, C hepatitis virus
      • Others: PNH (Paroxysmal nocturnal hemoglobinuria)
      • Autoimmune: Eosinophilic fasciitis (Scleroderma mimic)

    Hematology

    • Germline susceptibility:
      • Very minimal familial inheritance
      • Germline CEBPA mutation
      • Germline GATA2 mutation
    • Inherited syndromes:
      • Kostmann syndrome (congenital agranulocytosis)
      • Noonan syndrome
      • Down syndrome
    • Transient abnormal myelopoiesis:
      • Most common hematological abnormality
      • Seen at birth and resolves spontaneously within 2-3 months
      • Mutation in GATA-1
    • Acute myeloid leukemia (AML):
      • Occurs in approximately 20% of cases
      • Typically develops within 4 years of age
      • Megakaryocytic (M7) subtype
      • Better prognosis than in children without this subtype

    Bone Marrow Failure Syndromes

    • Other conditions:

      • Howell Jolly body: Post splenectomy
      • Basophil stippling: 5' nucleotidase deficiency

    • WBC:

      • Blasts cells 5-19%
      • Pseudo pelger huet (2 lobes)
      • Hypersegmented
      • Toxic granules
      • Dohle bodies
      • Platelet:
      • Pawn ball (multiple nuclear lobes)
      • Binucleate megakaryocyte

    PROGNOSTIC SCORING for Bone Marrow Failure Syndromes

    Diagnostic Features Prognosis Gene
    Pancytopenia: > 10%; dysplastic cells Poor Tq deletion, monosomy 7
    Cytogenic abnormality Good 5q deletion, 20q deletion
    No AML Best 11q deletion
    No other cause

    TREATMENT for Bone Marrow Failure Syndromes

    • Single lineage:
      • 5q deletion → 
    • Trilineage:
      • Bone marrow transplantation → Hypomethylating agent → Azacytidine → Decitabine
      • Present: Lenalidomide
      • Absent: Erythropoietin
      • Luspatercept: SMAD signaling inhibitor

    PURE RED CELL APLASIA

    • Causes:
      • Diamond blackfan syndrome (Congenital)
      • Thymoma/CLL (Acquired)
      • Transient aplastic crisis:
        • Seen in hereditary spherocytosis d/t parvovirus B19 infection.
        • Sudden reticulocytopenia.
        • Smear: Giant pronormoblasts.
        • Rx: IVIG.
        • Post EPO administration → D/t anti-EPO antibodies.

    Myelodysplastic Syndrome

    • AKA myeloid neoplasm
    • Terminal mature cell proliferation: myeloproliferative neoplasm.
    • Dysplasia + Ineffective erythropoiesis: myelodysplastic syndrome.
    • MDS + MPN overlap: Chronic myelomonocytic leukemia.
    • Myeloblast proliferation (Immature myeloid cell): Acute myeloid leukemia.

    Presentation of Myelodysplastic Syndrome

    • Global:
      • 70 yrs
      • m > F
      • Single/multilineage disease
    • India:
      • 40-60 yrs (D/t sq deletion)
      • Female predominance
      • RBC lineage disease
      • Lenalidomide (Good response)
    • Pancytopenia:
      • Hypercellular (80%), hypocellular (20%)
      • Progresses to AML (25%)
      • No extramedullary hematopoiesis
      • m/c symptom: Fatigue

    BLOOD PARAMETERS of Myelodysplastic Syndrome

    • RBC:
      • Anemia (m/c presentation)
      • Ringed sideroblasts (SF3B mutation MDS)
      • Oval macrocytes (m/c)
      • Megaloblasts, nucleated RBC
      • Howell Jolly body, basophil stippling, cabots ring

    Acute Leukemia

    • Classification:
      • Adults: 80% AML, 20% ALL
      • Children/Adolescents: 90% ALL, 10% AML

    Acute Myeloid Leukemia (AML) Pathogenesis

    • Involves:
      • Clonal proliferation of myeloid precursors:
        Precursor Cell Leukemia Type Percentage of Leukemias
        Myeloblast (m/c) Myeloblastic leukemia (70-80%)
        Monoblast Monoblastic/myelomonocytic leukemia
        RBC precursor Erythro-leukemia
        Platelet precursor Megakaryocytic leukemia
      • Complete arrest of differentiation: Myeloblast takes over the marrow.

    Clinical Presentation of AML

    • Short history (2-3 months)
    • Acute presentation:
      • No involvement of CNS/testes/organs (Spleen/liver/lymph nodes)
      • Pancytopenia manifesting as bleeding
    • High turnover: Leaks out into blood when marrow is completely replaced.
    • Blood blasts: Increased blood blast counts (poor prognosis).
    • CNS involvement (late stages): Decreased blood blast counts (possible prognosis).

    Bone Marrow Failure Syndromes

    • Diseases:
      • Aplastic Anemia
      • Myelodysplastic syndrome/neoplasia (MDS)
      • Pure red cell aplasia
      • Myelophthisis (Secondary myelofibrosis)

    Approach to Pancytopenia

    • Bone marrow aspiration + biopsy

    • Cellularity of marrow:

      • Hypercellular Marrow:

        • 1.Acute Leukemia (unless proven otherwise)
          • (In adults: AML (80%), ALL (20%))
        • 2.Myelodysplastic syndrome (MDS)
        • 3.Primary myelofibrosis (PMF)
        • 4.Hairy cell leukemia (Good prognosis)
        • 5.Megaloblastic anemia (Good prognosis)
        • 6.Paroxysmal nocturnal hemoglobinuria (PNH)
        • 7.Systemic: SLE, HIV, TB, brucellosis, leishmaniasis, sarcoidosis

      • PMF: Pancytopenia + Fibrosis

      • Hairy cell leukemia: Pancytopenia + massive splenomegaly

      • Aplastic Anemia

        • Pancytopenia with hypercellular marrow.
        • Bimodal age distribution (Inherited < 20 years, acquired > 60 years).
        • Most common cause: Drug dependent (Good prognosis).
        • Most common infection: Non A, non-B hepatitis.
        • Poor prognosis.
        • Hypocellular Marrow + Pancytopenia:
          • Aplastic anemia (20% of MDS cases)
          • Aleukemic leukemia
          • Copper deficiency
          • Lymphoma
          • Q fever
          • Legionella
          • Anorexia
          • TB

    Drugs Causing Aplastic Anemia

    • Dose-Dependent:
      • Anticancer drugs
        • Fluorouracil
        • Mercaptopurine
        • Daunorubicin
        • Cyclophosphamide
        • Busulfan
    • Dose-Independent:
      • Chloramphenicol
      • Sulfonamides
      • Gold
      • Acetazolamide
      • Propylthiouracil (PTU)
      • d-Penicillamine

    Clinical Presentation of Aplastic Anemia

    • Bleeding (most common)
    • Anemia
    • Infection
    • Features against diagnosis of aplastic anemia: Hepatomegaly, splenomegaly, lymphadenopathy, fever.

    Investigation for Aplastic Anemia

    • Blood Counts: Hb: #

    Clinical Features of AML

    Presenting Features

    • Acute presentation (3 month history)
    • Pancytopenia
      • m/c complication: Abnormal bleeding d/t prominent thrombocytopenia
        • Bruising
        • Petechiae
        • Epistaxis
        • Gingival bleeds
        • Excess menstrual bleeding
    • Anemia: Pallor, fatigue, weakness, palpitation
    • Absolute Neutrophil Count (ANC): Normal → Only minor infection/pustules.
    • No fever (No cytokine production)/lymphadenopathy
    • No hepatosplenomegaly
    • Bone pains (Rare, m/c in ALL)
    • Life-threatening hemorrhage (in acute promyelocytic leukemia)
    • Meningeal, cardiac, urogenital involvement: Rare
    • Complex infections in:
      • Aplastic anemia (Profound neutropenia)
      • Hairy cell leukemia (Neutropenia, monocytopenia)

    Other Manifestations

    • Myeloid sarcoma/Chloroma:
      • D/t extramedullary blast proliferation
      • Uncommon
      • m/c site: Orbit
      • Can occur independent of bone marrow involvement
      • Associated translocation: t(8; 21)
      • Also seen in children
      • m/c causative cells: myeloblast/monoblast (m4/m5) → Infiltrate
    • Chloroma:
      • Gingiva → Gum hypertrophy/gingivitis
      • Liver → Hepatomegaly
      • Spleen → Splenomegaly
      • Dental abscess
      • Proctitis

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    Description

    This quiz covers the classification of Acute Myeloid Leukemia (AML) including FAB, WHO, and WHO-5 classifications. It explores various subtypes, prognosis indicators based on recurrent genetic abnormalities, and key mutations involved. Test your knowledge of the different categories and prognostic factors of AML.

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