Acute leukemias
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Transcript of Acute leukemias
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Acute Leukemias
Dr. Syed Muhammad Ali Shah
RMO/PGR
Dept. of Medicine
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What are leukemias???
• Leukaemias are malignant disorders of the haematopoietic stem cell compartment, characteristically associated with increased numbers of white cells in the bone marrow and/or peripheral blood.
• The course of leukaemia may vary from a few days or weeks to many years, depending on the type.
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Epidemiology
• ALL, comprises 80% of the acute leukemias of childhood.
• Peak incidence is between 3 and 7 years of age.
• Appr. 20% of adult acute leukemias is ALL.
• AML - median age at presentation of 60 years
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RISK FACTORS
• Environmental factors– Radiation
– Benzene
– Alkylating agents, topoisomerase II inhibitors, and other cytotoxic drugs
– Tobacco smoke
• Acquired diseases– Clonal myeloid diseases
– Chronic myelogenousleukemia
– Primary myelofibrosis
– Essential thrombocythemia
– Polycythemia vera
– Myeloma
• Other disorders– Human immunodeficiency virus
infection
– Thyroid disorders
– Polyendocrine disorders
• Inherited or Congenital Conditions
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Signs and Symptoms
GENERAL
• Due to anemia pallor, fatigue, weakness, palpitations, and dyspnea on exertion.
• Weakness, loss of sense of well-being, and fatigue on exertion can be disproportionate to the severity of anemia.
• Easy bruising, petechiae, epistaxis, gingival bleeding, conjunctival hemorrhages, and prolonged bleeding from skin injuries reflect thrombocytopenia.
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• Pustules or other minor pyogenic infections of the skin and of minor cuts or wounds are most common.
• The most common pathogens are gram-negative bacteria (Escherichia coli, Klebsiella, Pseudomonas) or fungi (Candida, Aspergillus)
• Major infections, such as sinusitis, pneumonia, pyelonephritis, and meningitis, are uncommon at presentation
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• Anorexia and weight loss are frequent findings.
• Fever is present in many patients at the time of diagnosis.
• Palpable splenomegaly or hepatomegalyoccurs in approximately one-third of patients.
• Lymphadenopathy is extremely uncommon except in the monocytic variant of AML.
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Systemic Involvement
• Skin involvement may be of three types: – nonspecific lesions– leukemia cutis– granulocytic (myeloid) sarcoma of skin and subcutis
• Sensory organ involvement is very unusual, but retinal, choroidal, iridial, and optic nerve infiltration can occur
• Oral manifestations– Gingival or periodontal infiltration– Dental abscesses may lead to an extraction– Prolonged bleeding of an infected tooth socket
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• The respiratory tract can be involved by:– Infiltrates or tumors leading to laryngeal obstruction– Parenchymal infiltrates– Alveolar septal infiltration– Pleural seeding.
• Central or peripheral nervous system - meningealinvolvement is an important consideration in the treatment of the monocytic type of AML.
• Osteoarticular symptoms– Bone pain– Joint pain– Bone necrosis – Crystal-induced arthritis
• Calcium pyrophosphate dihydrate (pseudogout)• Monosodium urate (gout)
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LABORATORY FEATURES
BLOOD PICTURE:
• The hallmark of acute leukemia is the combination of pancytopenia with circulating blasts.
• Anemia is a constant feature - inadequate production of red cells
• Thrombocytopenia is nearly always present -inadequate production and decreased survival of platelets.
• The TLC is < 5000/ L (5 x 109 /L) & absolute neutrophilcount is < 1000/ L (1 x 109 /L) in approximately half of patients at the time of diagnosis.
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Blood film of AML without maturation (acute myeloblastic leukemia). Five myeloblasts are evident. High nuclear-to-cytoplasmic ratio. Agranularcells.
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ALL with large blasts showing prominent nucleoli, moderate amounts of cytoplasm, and an admixture of smaller blasts
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Typical lymphoblasts with scanty cytoplasm, regular nuclear shape, fine chromatin, and indistinct nucleoli
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Bone Marrow Findings
• The marrow always contains leukemic blast cells
• The bone marrow is usually hypercellular and dominated by blasts.
• More than 20% marrow blasts are required to make a diagnosis of acute leukemia.
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• Hyperuricemia
• If DIC is present– the fibrinogen level will be reduced
– the prothrombin time prolonged
– fibrin degradation products or fibrin D-dimerspresent.
• Patients with ALL (especially T cell) may have a mediastinal mass visible on chest radiograph.
• Meningeal leukemia will have blasts present in the spinal fluid, seen in approximately 5% of cases in monocytic types of AML and can be seen with ALL.
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• The phenotype of leukemia cells is usually demonstrated by flow cytometry or immunohistochemistry.
• AML cells usually express myeloid antigens such as CD 13 or CD 33 and myeloperoxidase.
• ALL cells of B lineage will express CD19, common to all B cells, and most cases will express CD10, formerly known as the “common ALL antigen.”
• ALL cells of T lineage will usually not express mature T-cell markers, such as CD 3, 4, or 8, but will express some combination of CD 2, 5, and 7 and do not express surface immunoglobulin.
• Almost all ALL cells express terminal deoxynucleotidyl transferase (TdT).
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Management
Supportive therapy• Anaemia - red cell concentrate transfusions.• Bleeding
– Thrombocytopenic bleeding requires platelet transfusions, unless the bleeding is trivial.
– Prophylactic platelet transfusion should be given to maintain the platelet count above 10 × 109/L. Coagulation abnormalities
• Infection – Fever (> 38°C) lasting over 1 hour in a neutropenic
patient indicates possible septicaemia
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• Empirical therapy - combination of an aminoglycoside (e.g. gentamicin) and a broad-spectrum penicillin (e.g. piperacillin/tazobactam) or a single-agent beta-lactam (e.g. meropenem)
• The organisms most commonly associated with severe neutropenic sepsis are:– Gram-positive bacteria
• Staphylococcus aureus
• Staph. epidermidis,
– Gram-negative bacteria• Escherichia coli
• Pseudomonas
• Klebsiella spp.
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• Gram-positive infection may require vancomycin therapy.
• If fever has not resolved after 3–5 days, empirical antifungal therapy (e.g. a liposomal amphotericin B preparation, voriconazole or caspofungin) is added.
• Oral and pharyngeal candida infection –fluconazole, itraconazole
• Reactivation of herpes simplex infection
• Herpes zoster– Chickenpox
– Shingles
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• Metabolic problems– Frequent monitoring of fluid balance and renal,
hepatic and haemostatic function is necessary.
– Renal toxicity occurs with some antibiotics (e.g. aminoglycosides) and antifungal agents (amphotericin).
– Cellular breakdown during induction therapy (tumourlysis syndrome)• Hyperkalaemia
• Hyperuricaemia,
• Hyperphosphataemia
• Hypocalcaemia.
– Allopurinol and intravenous hydration are given to try to prevent this
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Specific Treatment
• Remission induction – In this phase, the bulk of the tumour is destroyed by
combination chemotherapy.– The patient goes through a period of severe bone marrow
hypoplasia
• Remission consolidation– If remission has been achieved, residual disease is attacked by
therapy during the consolidation phase. – This consists of a number of courses of chemotherapy, again
resulting in periods of marrow hypoplasia.
• Remission maintenance– If the patient is still in remission after the consolidation phase
for ALL, a period of maintenance therapy is given, with the individual as an outpatient and treatment consisting of a repeating cycle of drug administration.
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Haematopoietic Stem Cell Transplantation
• Transplantation of haematopoietic stem cells (HSCT) has offered the only hope of ‘cure’ in a variety of haematological and non-haematological disorders
• The type of HSCT is defined according to the donor and source of stem cells into:
– Allogenic HSCT
– Autologus HSCT
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• In allogeneic HSCT, the stem cells come from a donor either related (usually an HLA-identical sibling) or a closely HLA-matched volunteer unrelated donor (VUD).
• In an autologous transplant, the stem cells are harvested from the patient and stored in the vapour phase of liquid nitrogen until required.