Acute Leukemia modified.pptx presentation

A powepoint lecture about acute leukemia

1. Acute Leukemia Specialist Physician, Thumbay Hospital, Ajman

2. Leukemia Basic physiology of Blood cells and WBCs What is Leukemia ? How common is the problem ? What are different types ? How do they present to the hospital ? How do we evaluate and confirm the diagnosis ? What are the treatment principles ? What are the prognostic factors ?

3. WBCs Granulocytes  (includes Neutrophils, Eosinophils and Basophils) Agranulocytes   (includes Lymphocytes and Monocytes).

4. Neutrophils This shows a neutrophil in a blood smear. The neutrophils are 12-14 µm diameter, and so look bigger than the surrounding red blood cells. There is a single nucleus, which is multilobed , and can have between 2 and 5 lobes . The chromatin in the nucleus is condensed. This means that there isn't protein synthesis. There are few organelles in the cytoplasm.

5. Neutrophil Functions Neutrophils are the commonest type of white blood cell found in a blood smear. They make up 60-70% of the total amount of white blood cells. Neutrophils have 3 types of granules: azure granules (lysosomes), secretory granules in salmon pink cytoplasm, anti-microbial enzymes. have glycoproteins and gelatinase .

6. Function:   Neutrophils are born in the bone marrow. They circulate in the blood for 6-10 hours, and then enter the tissues. They are motile, and phagocytic and will destroy damaged tissue and bacteria. They self destruct after one burst of activity . They are important in  inflammatory reactions

7. Eosinophils This picture shows an eosinophil in a blood smear. These cells are 12 - 17 µm in diameter - larger than neutrophils, and about 3 times the size of a red blood cell. You can see that eosinophils only have two lobes to their nucleus . These cells have large acidophilic specific granules - these stain bright red, or reddish-purple . These granules contain proteins that are 'destructive' and toxic.

8. Eosinophil Functions Eosinophils are fairly rarely found in blood smears - making up 1-6% of the total white blood cells. Function  :  These cells are born in the bone marrow, and migrate from the peripheral blood system after a few hours, into loose connective tissue in the respiratory and gastrointestinal tracts. Eosinophils are important in allergic reactions and killing parasitic worms

9. Basophils This photo shows a picture of a basophil. They are 14-16 µm in diameter, contain lots of deep blue staining granules (basic) and a bilobed nucleus.The granules contain heparin, histamine and serotonin. prostaglandins and leukotrienes .

10. Basophil Functions Basophils are the rarest type of white blood cell, making up only 1% of the white blood cells found in a blood smear. Function : These cells are involved in immune responses to parasites. They have IgE receptors and the granules are released when the cells bind IgE . The degranulation - release of histamine also plays a role in allergic reactions such as hay fever.

11. Lymphocyte This is a photo of a lymphocyte in a blood smear. Most of the lymphocytes are small; a bit bigger than red blood cells, at about 6-9µm in diameter The rest (around 10%) are larger, about 10-14µm in diameter. These larger cells have more cytoplasm, more free ribosomes and mitochondria. Lymphocytes can look like monocytes, except that lymphocytes do not have a kidney-bean shaped shaped nucleus, and lymphocytes are usually smaller. Larger lymphocytes are commonly activated lymphocytes. They have a small spherical nucleus and has abundant dark staining condensed chromatin. Not much cytoplasm can be seen, and it is basophilic (pale blue/purple staining).

12. Lymphocyte Function These are the second most common white blood cell (20-50%), and are easy to find in blood smears. Although the cells look similar there are two main types, B-cells and T-cells. B-cells develop in the bone marrow. T cells are born in the bone marrow, but are matured in the Thymus. There will be more on this in the section on the immune system. Function :  The B-cells develop into plasma cells which make antibodies, The T-cells attack viruses, cancer cells, and transplants .

13. Monocyte This is a photo of a monocyte in a blood smear . These are the largest type of white blood cells, and can be up to 20µm in diameter . They have a large eccentrically placed nucleus, which is kidney bean shaped . They have abundant cytoplasm, and some fine pink/purple granules in cytoplasm .

14. Monocyte Function Monocytes are the third most common type of white blood cell; about 2-10% of leucocytes are monocytes. Function:   Monocytes in the circulation are precursors of tissue macrophages that are actively phagocytic. Monocytes circulate in the blood for 1-3 days, and then migrate into body tissues, where they transform into macrophages. They will phagocytose dead cells and bacteria. Some monocytes can also transform into osteoclasts. Monocytes are important in the  inflammatory response.

15. Maturation of WBCs

16. Normal Peripheral Smear

17. Leukemia Leukemia is a cancer of the marrow and blood Acute Leukemias are rapidly progressing diseases that affect the cells which are not fully developed In Acute Myeloid leukemia a cancerous change begins in a marrow cell that form certain blood cells In Acute Lympocytic leukemia cancerous change begins in a marrow cell that normally forms Lympocytes

18. Once the cell becomes leukemic it multiplies in to 11 billion or more cells. These cells are leukemic blast cells These Leukemic blast cells do not function normally and it also blocks the production of the other normal cells like RBCs and Platelets

19. How common is the Problem ?

20. AML Incidence increase with age ( 1 in 100,000 from 30 – 34 Yrs to 10 in 100,000) AML is more common form of Leukemia in adults and ALL more common in children

21. Etiology Not known in most of the cases More common with increasing age and higher socio economic status – leading to the hypothesis of less exposure to bacterial diseases during childhood Increased exposure to radiation – based on atomic bomb survivors in Japan Mutatations in gene Life style and environmental factors But the reason is not very clear at this point in time

22. Clinical Manifestations Symptoms of Anemia ( Low RBCs ) – fatigue, exertional dyspnea, looking pale Symptoms of Thrombocytopenia ( Low platelets )– Petechiae , purpura , bleeding from minor cuts Symptoms of Non functioning WBCs – Frequent Infections

23. Symptoms of Rapid WBCs production from BM – Bony pain, joint pain Symptoms due to rapid production and destruction of all the blood cells – Splenomegaly, Hepatomegaly and Lymphadenopathy

24. Classification of leukemias ( acute )

25. Investigations Blood smear Bone Marrow Immunophenotyping – Identifying the cell type by antigens present on the cell surface ( Flow cytometry ) Cytogenetics - Identifying the chromosomes and genes in the cancer cells ( FISH / PCR )

26. Acute Lymphoblastic Leukemia

27. Acute Myeloid Leukemia

28. Normal Smear Acute Myeloid Leukemia Acute Lymphocytic Leukemia

29. Cytogenetics

30. Treatment Principles Chemotherapy Radiotherapy Bone Marrow Transplant

31. Chemotherapy Induction /Remission Consolidation Maintenance

32. Remission goals No evidence of Leukemic blast cells in bone marrow Normal blood cell count production is restored and counts returns to normal Factors which influence the treatment results are age, type of leukemic lymphocytes based on the appearance, immunophotype and chromosome composition Once remission is achieved patient needs Maintenance chemotherapy or Stem cell Transplantation

33. Chemotherapy Antitumor Antibiotics – D aunarubicin , doxorubicin, mitoxantrone DNA Repair Enzyme inhibitors – E toposide , teniposide DNA synthesis inhibitor – Carboplatin DNA damaging agents – Cyclophospamide Tyrosine kinase Inhibitors – Imatinib , dasatinib

34. Anti metabolites – Cladribine , fludaribine , hydroxyurea , methotrexate Monoclonal Antibodies – Alemtuzumab , rituximab Drugs that prevent cell division – Vincristine Enzymes that prevent cell from surviving – Asparginase Synthetic Hormones – Prednisolone, dexamethasone

35. Drugs for Induction Chemotherapy Doxorubicin, Asparaginase , Vincristine, Methotrexate, cytarabine , corticosteroid IV, Oral or in to CSF ( Intrathecal ) Usually 2 or More drugs are given Given for a month ( one cycle ) and if the remission is not achieved then might be repeated again

36. Post remission ( Consolidation and Maintenance ) Aim of the consolidation chemotherapy is to reduce the number of leukemic cells still remaining Given in cycles for 4 – 6 months Multiple drugs are used to prevent resistance

37. Maintenance Aim of the maintenance Therapy is to prevent the disease relapse Maintenance therapy is given for 2 years

38. Chemotherapy related side effects( General ) Mouth ulcers Diarrhea Temporary hair loss Infections Fatigue Rashes Nausea and vomiting Loss of appetite

39. Stem cell transplant Allogenic transplant Autologous Transplant Depends on the patients age, cytogenetic and molecular characteristics, ability to tolerate the chemotherapy, availability of HLA related or unmatched stem cell donar

40. Treatment outcomes 40 percent of adults can expect long term disease free survival In children under 15 years 5 year survival has increased from 3 percent in 1964 to 89 percent in 2006

41. Diagnosis Disease progression Survival rates

42. University of Minnesota, Hematography The histology Guide