Acute leukemia


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Acute leukemia

  2. 2. What is leukemia? • Leukemia is a type of cancer that occurs in blood forming tissues, such as the bone marrow and the lymphatic system. • It is characterized by an abnormal increase of white blood cells.
  3. 3. Signs & Symptoms • Leukemia symptoms vary on the type of leukemia, but a few common symptoms include: – Fever or chills – Persistent fatigue or weakness – Bone pain or tenderness – Excessive sweating – Frequent infections
  4. 4. Four Types of Leukemia: Leukemia Chronic Chronic Lymphocytic Leukemia (CLL) Chronic Myeloid Leukemia (CML) Acute Acute Lymphocytic Leukemia (ALL) Acute Myeloid Leukemia (AML)
  5. 5. Acute leukaemia is a clonal ( derived from a single cell) malignant disorder characterised by the accumulation of immature blast cells in the BM, which replace normal marrow tissue, including haemopoietic precursor cells. This results in BM failure, reflected by peripheral blood cytopenias and circulating blast cells. Infiltration of various organs is also a feature of some forms of leukaemia
  6. 6. (a) acute lymphoblastic leukemia (ALL), in which the abnormal proliferation is in the immature lymphocytes (b) acute myeloid leukemia (AML), which involves the myeloid lineages ( cells from which neutrophils, eosinophils, monocytes, basophils, megakaryocytes, etc. are derived). • The distinction between the two leukemias is based on morphological, cytochemical, immunological and cytogenetic differences and is of paramount importance as the treatment and prognosis are usually different
  7. 7. Subclassification • It is further subdivided on the basis of morphological criteria: • ALL into FAB (French-American-British) subtypes L1, L2, and L3, and • AML into FAB subtypes M0 to M7
  8. 8. FAB for AML M0 AML with minimal differentiation M1 AML without maturation M2 AML with maturation M3 Acute promyelocytic leukaemia M4 Acute myelomonocytic leukaemia M5 Acute monocytic/monoblastic leukaemia M6 Acute erythroleukaemia M7 Acute megakaryoblastic leukaemia
  9. 9. FAB Classification of ALL L1: Small homogeneous blasts; mostly in children L2: Large heterogeneous blasts; mostly in adults L3: “Burkitt” large basophilic B-cell blasts with vacuoles
  10. 10. Incidence for ALL ALL is most common in the age 2-10 years, ( peak at 3-4). Secondary rise after 40 years. In children it is the most common malignant disease and accounts for 85% of childhood leukaemia
  11. 11. Incidence for AML AML accounts for 10-15% of childhood leukemia, but it is the commonest leukaemia of adulthood. The incidence increases with age, and the median age at presentation is 60 years.
  12. 12. Acute myelogenous leukemia • (AML) is a clonal hematopoietic disorder resulting from genetic alterations in normal hematopoietic stem cells. • These changes alter normal hematopoietic growth and differentiation, resulting in an accumulation of large numbers of abnormal, immature myeloid cells in the bone marrow and peripheral blood. • These cells are capable of dividing and proliferating, but cannot differentiate into mature hematopoietic cells. • AML is more common in men than women. • AML is the most common acute leukemia affecting adults, and its incidence increases with age.
  13. 13. Pathogenesis • The malignant cell in AML is the myeloblast. • In normal hematopoiesis, the myeloblast is an immature precursor of myeloid white blood cells; a normal myeloblast will gradually mature into a mature white blood cell. • In AML, though, a single myeloblast accumulates genetic changes which "freeze" the cell in its immature state and prevent differentiation.
  14. 14. Chromosomal translocation The translocation fuses the AML1 gene (also called RUNX1) on chromosome 21 with the ETO gene (also referred to as the RUNX1T1 gene that encodes the CBFA2T1 protein) on chromosome 8.  CBFA2T1 protein - This protein has multiple effects on the regulation of the proliferation, the differentiation, and the viability of leukemic cells.
  15. 15. • P. Smear AML • The numerous myelocytes have abundant cytoplasm with prominent specific granulation
  16. 16. • Auer Rods in Leukemia cells
  17. 17. Presentation FOR AML • • • • • • • • • • • • Epistaxis Bleeding gums Bruising/contusions Bone pain or tenderness Fatigue Fever Heavy menstrual periods Pallor Shortness of breath (gets worse with exercise) Skin rash or lesion Swollen gums (rare) Weight loss
  18. 18. Patients with Aml
  19. 19. Blood film of patient with ALL large homogenous lymphoblasts, prominent nucleoli,round nuclei
  20. 20. Presentation for ALL Organ infiltration: in ALL is bone pain, superficial lymphadenopathy, abdominal distension due to abdominal lymphadenopathy and hepatosplenomegaly, respiratory embarrassment due to a large mediastinal mass, testicular enlargement, or a meningeal syndrome. Gum hypertrophy and skin infiltration are more commonly seen in AML than in ALL
  21. 21. DIAGNOSIS • Physical exam • CBC(Complete Blood Count) usually but not invariably shows reduced Hb conc. and platelet count. The WBC can vary from 1000 to 200000, and the differential WBC is often abnormal, with neutropenia and the presence of blast cells. The anaemia is a normochromic, normocytic anaemia, and the thrombocytopenia may be severe
  22. 22. • Bone marrow aspiration: with or without trephine bx is essential to confirm acute leukaemia. The marrow is usually hypercellular, with a predominance of immature (blast) cells
  23. 23. Jamshidi trephine & Salah aspiration needle used for bone marrow aspiration
  24. 24. Biochemical screening • when the leucocyte count is very high, there may be evidence of renal impairment and hyperuricaemia
  25. 25. TREATMENT • Immediate (same day) referral to specialist • Prompt diagnosis • Intensive supportive care • Systemic chemotherapy • Treatment directed at CNS (in children and in adult ALL) • Minimising early and late toxicity of treatment
  26. 26. • Prophylactic PLT transfusions are given if PLT count is 10000. • Clotting abnormalities may result from a DIC where infusions of FFP and cryoprecipitate may be beneficial. • Packed red cell transfusions are given for symptomatic anaemia, though these are contraindicated if the WBC is extremely high. In most patients a central venous catheter is inserted to facilitate blood product support, administration of chemotherapy and antibiotics, and frequent blood sampling
  27. 27. Chemotherapy In AML: • treated with 4 or 5 courses of intensive chemotherapy when there is intent to cure. Each course consists of 10 days of chemotherapy. Subsequent courses are started after cell counts have recovered and response to treatment is established. In AML M3 the drug ATRA (all-transretinoic acid) is used as an adjunct to chemotherapy as it causes differentiation of the malignant clone.
  28. 28. • In ALL the induction course is followed by two or more consolidation periods and by treatment directed at the CNS, followed by long term maintenance or continuation treatment for up to two years. This has been shown to improve long term cure rates in ALL, though not in AML
  29. 29. Distinguishing AML from ALL – AML: Auer rods, cytoplasmic granules – ALL: no Auer rods or granules.
  30. 30. Prognosis • Poor prognosis in ALL Age < 1 year or > 10 years Sex Male Presenting WBC 50000 CNS disease at presentation Presence of blasts in CSF Remission problems Failure to remit after first induction treatment Cytogenetics Philadelphia positive—that is, t(9;22)or t(4;11) ALL
  31. 31. Poor prognosis in AML • Age • Sex > 60 years Male or female Presenting WBC >50000 CNS disease at presentation Remission problems Presence of blasts in CSF 20% blasts in BM after 1st course Cytogenetics Deletions or monosomy of chromosome 5 or 7 or complex chromosomal abnormalities
  32. 32. Survival Type Childhood ALL Adult ALL AML, aged < 60 yr AML, aged > 60 yr At 5 years 65-75% 20-45% 35-40% 10%