Acute Leukemia PDF

ACUTE LEUKEMIA MEKOYA D MENGISTU MD, INTERNIST, ASSIST PROF OF INTERNAL MEDICINE  ACUTE LEUKEMIA is the result of a malignant event occurring in an early hematopoietic precursor the affected cells fail to differentiate but continue to proliferate in an uncontrolled fashion Bla...

ACUTE LEUKEMIA MEKOYA D MENGISTU MD, INTERNIST, ASSIST PROF OF INTERNAL MEDICINE  ACUTE LEUKEMIA is the result of a malignant event occurring in an early hematopoietic precursor the affected cells fail to differentiate but continue to proliferate in an uncontrolled fashion Blasts—rapidly accumulate and progressively replace the BM, diminishing the production of normal red cells, white cells, and platelets Number of blasts in BM > 20% of the total cells of the bone marrow aspirate OR Number of blasts in PM > 20% of nucleated cells in p/film 2  common clinical complications of leukemia: anemia, infection, and bleeding With time, the leukemic blasts pour out of the blood stream and infiltrating the lymph nodes, spleen, and other vital organs If untreated, acute leukemia is rapidly fatal; most patients die within weeks to months after diagnosis With appropriate therapy many patients can be cured 3  ALL CLL Lymphomas MM naïve B-lymphocytes Plasma Lymphoid cells progenitor T-lymphocytes AML Myeloproliferative disorders Hematopoietic Myeloid Neutrophils stem cell progenitor Eosinophils Basophils Monocytes Platelets Red cells 4 EPIDEMIOLOGY OF ACUTE LEUKEMIA  The annual incidence of AML( in Western pop): 80% of AL  The annual incidence of ALL: 20% of AL  The incidence of AML  Increases with age  Median age at presentation 60-65yrs  The peak incidence of ALL  3-4yrs of age  Incidence decreases after 9yrs of age  Rare after 40 Sex distribution: More common in males The relative frequency of the 4 leukemias in the west  ALL (11%) AML (46%)  CLL (29%) CML (14%)  Ethiopia: CML accounts for 50% of leukemias in our country 5 CLASSIFICATION OF ACUTE LEUKEMIA The classification is based on biological features – Clinical feature – Morphology based on Wright or Giemsa stain – Cytochemical studies – Flow cytometry – Cytogenetics – molecular study 6  1-Morphologic classification (microscopic) Lymphoblast / myeloblast – Blast size :small – Large – Cytoplasm: Scanty – Moderate – Chromatin: Dense – Fine, Lacy – Nucleoli :Indistinct – Prominent – Auer-rods: Never present – Present in 50% 7 Auer-rods 2-Immunological classification (flow cytometry)  can quickly identify the abnormal cell population,  characterize its phenotype, give lineage classification,  make the diagnosis, or narrow down the differential list. Based on this flow cytometry , AL is classified into  Acute Myelogenous Leukemia(AML)  Acute Lymphoblastic Leukemia(ALL)  Biphenotypic Leukemia—have both AML and ALL feature  Undifferentiated leukemia  Based on cell surface markers of ALL  Classifies into B or T cell types  Determines their maturation 8  3-cytochemistry Different chemicals are used to stain enzymes specific to some leukemias e.g. Peroxidase staining, sudan black B, Esterase ↓↓ Positive for myeloblast and negative for lymphoblast Currently not commonly used, and Replaced by immunophenotyping(flowcytometery) 9  4-Cytogenetics In most cases of acute leukemia, an abnormality in chromosome number or structure is detected often they include – gain or loss of whole chromosomes – chromosomal translocations, – deletions, or – Inversions the chromosomal abnormality disappears – when patients receive treatment and enter into complete remission (CR), – when relapse occurs, the abnormality reappears a favorable prognosis is seen in leukemias (AML) with : – t(8;21) – inv(16) – t(15;17), invariably associated with APL unfavorable prognosis seen in leukemias with – Deletions of part or all of chromosomes 5 or 7 10  5-Molecular analysis Used for – diagnosis, – prognosis, – As target for therapy The BCR/ABL fusion (Philadelphia chromosome) can be detected in the lab – ALL with t(9;22) has a poor prognosis when treated with conventional chemotherapy  Ph+ ALL patients are treated with the same regimens as other types of ALL, with poor results.  However, tyrosine kinase inhibitors (TKIs) inhibit the bcr-abl fusion protein of Ph+ ALL 11 Acute myeloid leukemia (AML)  AML is a neoplasm characterized by infiltration of the blood, bone marrow, and other tissues by proliferative, clonal, poorly differentiated cells of myeloid line of the hematopoietic system. comprises a spectrum of malignancies that, untreated, are uniformly fatal. AML is the most common acute leukemia in older patients, – median age at diagnosis of 65-67 years. Long-term survival is infrequent; – U.S. registry data report that only 27% of patients survive 5 years.  ETIOLOGY Most cases of AML are idiopathic. AML cases with established etiology are relatively rare. Risk factors implicated in the development of AML are – Genetic predisposition, – radiation, chemical exposures, Exposure to ionizing radiation, benzene, chloramphenicol, phenylbutazone, and other drugs can uncommonly result in BM failure that may evolve into AML. – Drugs Hx- Anticancer drugs are the leading cause of therapy-associated AML. Alkylating agent[eg. Chlorambucil]–associated leukemias – occur on average 4–6 years after exposure Topoisomerase II inhibitors[Eg. Anthracyclines]–associated leukemias – occur 1–3 years after exposure No direct evidence suggests a viral etiology.  CLINICAL PRESENTATION Patients with AML usually present with nonspecific symptoms that begin gradually, or abruptly, – are the consequence of  anemia,  leukocytosis, leukopenia/leukocyte dysfunction, or  thrombocytopenia.  pancytopenia 50% of AML pts have symptoms up to 3 months before the AML diagnosed. – Fatigue is a frequent first symptom among AML patients. – Anorexia and weight loss are common. – Fever with or without identifiable infection is the initial symptom in ~10% of pts. – Bone pain, LAP, nonspecific cough, headache, or diaphoresis may also occur. Signs of abnormal hemostasis (bleeding, easy bruising) are common.  Rarely, patients may present with symptoms from a myeloid sarcoma – Is a tumor mass consisting of myeloid blasts – occur at anatomic sites other than bone marrow most common sites: skin, lymph node, GIT, soft tissue, and testis. – often characterized by chromosome aberrations (e.g., monosomy 7, trisomy 8, 11q23 rearrangement, inv, trisomy 4, t[8;21]), – may precede or coincide with blood and/or BM involvement by AML. Patients who present with isolated myeloid sarcoma typically develop blood and/or marrow involvement quickly thereafter and cannot be cured with local therapy (radiation or surgery) alone.  PHYSICAL FINDINGS Fever, Tachycardia, Tachypenia less commonly: splenomegaly, hepatomegaly, LAP, and “bone tenderness” Hemorrhagic complications are most commonly and, classically, found in APL – APL patients often present with DIC-associated minor hemorrhage – but may have significant GI bleeding, intrapulmonary hemorrhage, or intracranial hemorrhage. – Retinal hemorrhages are detected in 15% of patients. – Likewise, thrombosis is another less frequent but well recognized clinical feature of DIC in APL. Infiltration of gingiva, skin, soft tissues, or meninges with leukemic blasts – is characteristic of the monocytic subtypes (monoblastic leukemia) and – those with 11q23 chromosomal abnormalities. 18  HEMATOLOGIC FINDINGS  CBC: Hb: Anemia is usually present at diagnosis though it is not typically severe. – The anemia is usually normocytic normochromic. – Active blood loss may rarely contribute to the anemia. WBC: 60% of pts have an elevated, 25% low and 15% normal wbc – The median presenting leukocyte count is ~15,000/μL. – 20% have >100,000/μL. – Aleukemic leukemia: 5% of pts have no detectable leukemic cells in the blood. Platelet: