Leukemia

Leukemia

1. Leukemia Dentaltutor.in

2. Neoplastic proliferations of white blood cells— leukaemias . Incidence is higher in men than in women Classified on the basis of cell types predominantly involved – myeloid or lymphoid Acute: predominance of undifferentiated leucocyte precursors or leukaemic blasts Acute myeloblastic leukaemia (AML) - at all ages Acute lymphoblastic leukaemia (ALL) – primarily a disease of children and young adults Chronic: late precursor series of leucocytes Chronic myeloid leukaemia (CML) – middle age C hronic lymphocytic leukaemias (CLL) - elderly www.facebook.com/notesdental Introduction

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4. www.facebook.com/notesdental Classification

5. Heredity Infections: Human T cell leukaemia -lymphoma virus I (HTLV-I ) Environmental factors Ionising radiation Chemical carcinogens Certain drugs. Association with diseases of immunity: Immunodeficiency diseases like AIDS and iatrogenic immunosuppression induced by chemotherapy or radiation , www.facebook.com/notesdental Etiology

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7. heterogeneous disease characterised by infiltration of malignant myeloid cells into the blood, bone marrow and other tissues mainly a disease of adults (median age 50 years ) develops due to inhibition of maturation of myeloid stem cells due to mutations - induced by several etiologic factors www.facebook.com/notesdental ACUTE MYELOID LEUKAEMIA

8. French-American-British (FAB) CLASSIFICATION Based on morphology and cytochemistry , It divides AML into 8 subtypes (M0 to M7 ) WHO CLASSIFICATION (2002 ) differs from revised FAB classification limited reliance on cytochemistry for making the diagnosis of subtype of AML B ased on clinical , cytogenetic and molecular abnormalitie www.facebook.com/notesdental Classification

9. www.facebook.com/notesdental FAB CLASSIFICATION

10. AML with recurrent cytogenetic abnormalities AML with multilineage dysplasia AML and MDS ( Myelodysplastic Syndrome), therapy-related AML, not otherwise categorised www.facebook.com/notesdental WHO CLASSIFICATION (2002)

11. AML and ALL share many common clinical features - difficult to distinguish on clinical features alone. 25% of patients with AML : preleukaemic syndrome with anaemia may be present for a few months to years prior to the development of overt leukaemia . Clinical manifestations of AML are divided into 2 groups due to Bone marrow failure Organ infiltration www.facebook.com/notesdental Clinical Features

12. Anaemia producing pallor, lethargy, dyspnoea . Bleeding manifestations due to thrombocytopenia causing spontaneous bruises, petechiae , bleeding from gums and other bleeding tendencies . Infections are quite common and include those of mouth , throat , skin, respiratory, perianal and other sites . Fever : no obvious source of infection can be found and may occur in the absence of infection . www.facebook.com/notesdental Clinical Features: Bone marrow failure

13. due to replacement of the marrow and other tissues by leukaemic cells . Pain and tenderness of bones (e.g. sternal tenderness) - bone infarcts or subperiosteal infiltrates by leukaemic cells. Lymphadenopathy and enlargement of the tonsils may occur Splenomegaly of moderate grade may occur – Splenic infarction , subcapsular haemorrhages , and rarely, splenic rupture may occur. Hepatomegaly www.facebook.com/notesdental Clinical Features: Organ infiltration

14. Gum hypertrophy due to leukaemic infiltration of the gingivae is a frequent finding. Chloroma or granulocytic sarcoma : localised tumour forming mass occurring in the skin or orbit - greenish in appearance due to the presence of myeloperoxidase . Meningeal involvement manifested by raised intracranial pressure , headache, nausea and vomiting, blurring of vision and diplopia Sudden death from massive intracranial haemorrhage as a result of leucostasis may occur. Other organ infiltrations include testicular swelling and mediastinal compression www.facebook.com/notesdental Clinical Features: Organ infiltration

15. www.facebook.com/notesdental Clinical Features: Organ infiltration

16. The diagnosis of AML is made by a combination of routine blood picture and bone marrow examination , coupled with cytochemical stains and other special laboratory investigations . BLOOD PICTURE. Anaemia . Thrombocytopenia: moderately to severely reduced (below 50,000/ μl ) but occasionally it may be normal. White blood cells: ranges from subnormal-to-markedly elevated values 25 % of patients – reduced to 1,000-4,000 / μl . More often, however, there is progressive rise in white cell count which may exceed 100,000/ μl in more advanced disease . Majority of leucocytes in the peripheral blood are blasts and there is often neutropenia due to marrow infiltration by leukaemic cells . www.facebook.com/notesdental Laboratory Findings

17. www.facebook.com/notesdental Laboratory Findings

18. www.facebook.com/notesdental Laboratory Findings

19. Cellularity : Typically , the marrow is hypercellular but sometimes a ‘blood tap’ or ‘dry tap’ occurs. Leukaemic cells generally tightly packed with leukaemic blast cells Romanowsky stains: cytochemical stains may be employed to know the type of leukaemia . Erythropoiesis . Erythropoietic cells are reduced . Megakaryocytes . They are usually reduced or absent. Cytogenetics : shows karyotypic abnormalities in 75% of cases which may have a relationship to prognosis. Immunophenotyping . AML cells express CD13 and CD33 antigens. M7 shows CD41 and CD42 positivity. www.facebook.com/notesdental Laboratory Findings: BONE MARROW EXAMINATION

20. www.facebook.com/notesdental Laboratory Findings: BONE MARROW EXAMINATION

21. CYTOCHEMISTRY: Commonly employed cytochemical stains, as an aid to classify the type of Myeloperoxidase : Positive in immature myeloid cells containing granules and Auer rods Sudan Black Periodic acid-Schiff (PAS): Positive in immature lymphoid cells and in erythroleukaemia ( M6) Non-specific esterase (NSE): Positive in monocytic series (M4 and M5 ). Acid phosphatase : Focal positivity in leukaemic blasts in ALL and diffuse reaction in monocytic cells (M4 and M5). BIOCHEMICAL INVESTIGATIONS: may be of some help Serum muramidase : elevated in myelomonocytic (M4) and monocytic (M5) leukaemias . Serum uric acid: frequently increased www.facebook.com/notesdental Laboratory Findings

22. TREATMENT OF ANAEMIA AND HAEMORRHAGE. Anaemia and haemorrhage are managed by fresh blood transfusions and platelet concentrates. Patients with severe thrombocytopenia (platelet count below 20,000/ μl ) require regular platelet transfusions haemorrhage is an important cause of death in these cases TREATMENT AND PROPHYLAXIS OF INFECTION www.facebook.com/notesdental Treatment and Complications

23. CYTOTOXIC DRUG THERAPY Aim : firstly induce remission , secondly to continue therapy to reduce the hidden leukaemic cell population by repeated courses of therapy. The most effective treatment of AML is a combination of 3 drugs: cytosine arabinoside , anthracyclines ( daunorubicin , adriamycin ) and 6-thioguanine . Another addition is amsacrine (m-AMSA) administered with cytosine arabinoside , with or without 6-thioguanine. www.facebook.com/notesdental Treatment and Complications

24. BONE MARROW TRANSPLANTATION Bone marrow (or stem cell) transplantation from suitable allogenic or autologous donor The basic principle of marrow transplantation is to reconstitute the patient’s haematopoietic system after total body irradiation and intensive chemotherapy – kill the remaining leukemic cell Bone marrow transplantation has resulted in cure in about half the cases. www.facebook.com/notesdental Treatment and Complications

25. Remission rate with AML is lower (50-70%) than in ALL, Often takes longer to achieve remission, and disease-free intervals are shorter. AML is most malignant of all leukaemia Survival with treatment is 12-18 months. www.facebook.com/notesdental Prognosis

26. Most common type of leukemia in children 15% of acute leukemia in adults Immature lymphocytes proliferate in the bone marrow Signs and symptoms may appear abruptly Fever, bleeding Insidious with progressive Weakness, fatigue Central nervous system manifestations www.facebook.com/notesdental Acute Lymphocytic Leukemia (ALL)

27. www.facebook.com/notesdental Chronic Myeloid Leukemia (CML)

28. Excessive development of mature neoplastic granulocytes in the bone marrow Move into the peripheral blood in massive numbers Ultimately infiltrate the liver and spleen Philadelphia chromosome The chromosome abnormality that causes chronic myeloid leukemia (CML) (9 &22) Genetic marker Chronic, stable phase followed by acute, aggressive ( blastic ) phase www.facebook.com/notesdental Introduction

29. 20% of all leukaemias Peak incidence is seen in 3rd and 4th decades of life. A distinctive variant seen in children is called juvenile CML . Both sexes are affected equally. Some of the common presenting manifestations are as under Anemia Hypermetabolism such as weight loss, lassitude, anorexia, night sweats. www.facebook.com/notesdental Clinical Features

30. Splenomegaly is almost always present and is frequently massive. Bleeding tendencies such as easy bruising, epistaxis , menorrhagia and haematomas may occur. Less common features include gout, visual disturbance, neurologic manifestations. Juvenile CML often associated with lymph node enlargement than splenomegaly . Other features are frequent infections, haemorrhagic manifestations and facial rash. www.facebook.com/notesdental Clinical Features

31. The diagnosis of CML is generally possible on blood picture alone. However, bone marrow, cytochemical stains and other investigations are also useful BLOOD PICTURE Anaemia . Anaemia is usually of moderate degree and is normocytic normochromic in type. www.facebook.com/notesdental Laboratory Findings

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33. White blood cells. Characteristically, there is marked leucocytosis (approximately 200,000/ μl or more at the time of presentation). The natural history of CML consists of 3 phases—chronic, accelerated, and blastic . Chronic phase: begins as a myeloproliferative disorder and consists of excessive proliferation of myeloid cells of intermediate grade (i.e. myelocytes and metamyelocytes ) and mature segmented neutrophils . Accelerated phase: increasing degree of anaemia , blast count in blood or marrow between 10-20%, marrow basophils 20% or more, and platelet count falling below 1,00,000/ μl . Blastic phase or blast crisis: blood or marrow blasts >20%. Myeloid blast crisis in CML is more common and resembles AML. Auer rods are not seen in myeloblasts of CML in blast crisis. Platelets. Platelet count may be normal but is raised in about half the cases. www.facebook.com/notesdental Laboratory Findings

34. www.facebook.com/notesdental Laboratory Findings

35. BONE MARROW EXAMINATION Cellularity : hypercellularity with total or partial replacement of fat spaces by proliferating myeloid cells. Myeloid cells: predominate in the bone marrow with increased myeloid- erythroid ratio. The differential counts of myeloid cells in the marrow show similar findings as seen in the peripheral blood with predominance of myelocytes . Erythropoiesis : normoblastic but there is reduction in erythropoietic cells. Megakaryocytes : are conspicuous but lare usually smaller in size than normal. Cytogenetics : the characteristic chromosomal abnormality called Philadelphia (Ph) chromosome ( 90-95%) www.facebook.com/notesdental Laboratory Findings

36. www.facebook.com/notesdental Philadelphia (Ph) chromosome

37. CYTOCHEMISTRY The only significant finding on cytochemical stains is reduced scores of neutrophil alkaline phosphatase (NAP) These helps to distinguish CML from myeloid leukaemoid reaction in which case NAP scores are elevated OTHER INVESTIGATIONS Elevated serum vitamin B 12 and vitamin B12 binding capacity. Elevated serum uric acid ( hyperuricaemia ). www.facebook.com/notesdental Laboratory Findings

38. Knowledge of molecular mechanism of CML has brought about major changes in its therapy. The approach of modern therapy in CML is targetted at removal of all malignant clones of cells bearing BCR/ABL fusion protein, So that patient reverts back to prolonged non- clonal haematopoiesis . This is achievable by the following approaches Imatinib oral therapy Allogenic bone marrow (stem cell) transplantation. Interferon- α . Chemotherapy Others: splenic irradiation, splenectomy and leucopheresis . The most common cause of death (in 80% cases) in CML is disease acceleration and blastic transformation www.facebook.com/notesdental Treatment

39. Production and accumulation of functionally inactive but long-lived, mature-appearing lymphocytes B cell involvement Lymph node enlargement is noticeable throughout the body ↑ incidence of infection Complications from early-stage CLL is rare May develop as the disease advances Pain, paralysis from enlarged lymph nodes causing pressure www.facebook.com/notesdental Chronic Lymphocytic Leukemia (CLL)

40. Robbinson's basic pathology 8 ed Harsh Mohan - Textbook of Pathology 6th Ed. Color atlas of pathology www.facebook.com/notesdental References

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