Lecture 7.pptx LEKEMIA PHCL 414 Pharmacotherapy-VIII

PHCL 414 Pharmacotherapy-VIII

1. Leukemia Dr. Zabih Ullah Ph.D., EFRE (Belgium & Netherlands) Assistant Professor Email: [email protected]

2. Introduction is a cancer of the blood, characterized by the rapid growth of abnormal blood cells. This uncontrolled growth occur in the bone marrow.Leukemia cells are usually immature (still developing) white blood cells. The term leukemia comes from the Greek words for “white” ( leukos ) and “blood” ( haima ). Unlike other cancers, leukemia doesn’t generally form a mass (tumor) .

3. Pathophysiology of Leukemia Leukemia starts when the DNA of a single cell in the bone marrow changes (mutates) and can’t develop and function normally. Leukemia cells often behave like abnormal white blood cells. Leukemia begins in bonemarrow , Blood cells go through multiple stages before reaching their fully mature forms. Mature, normal blood cells include: Red blood cells: Cells that carry oxygen and other vital materials to all tissues and organs in your body. White blood cells: Cells that fight infection. Platelets: Cells that help your blood clot. These blood cells start as hematopoietic stem cells. The stem cells develop into either myeloid (MAI-uh- loyd ) cells or lymphoid (LIM- foyd ) cells.

4. Pathophysiology of Leukemia If blood cells were to continue to develop normally the mature forms of these cells are as follows: Myeloid cells develop into red blood cells, platelets and certain types of white blood cells (basophils, eosinophils and neutrophils). Lymphoid cells develop into certain white blood cells (lymphocytes and natural killer cells). However, if leukemia appear, one of the developing blood cells begins to multiply out of control. These abnormal cells — called leukemia cells — begin to take over the space inside of your bone marrow. They crowd out the cells trying to develop into healthy red blood cells, white blood cells and platelets

5. Diagnosis Physical exam. look for physical signs of leukemia, such as pale skin from anemia, swelling of your lymph nodes, and enlargement of your liver and spleen. Blood tests . CBC Count Bone marrow test. a procedure to remove a sample of bone marrow from your hipbone. The bone marrow is removed using a long, thin needle. The sample is sent to a laboratory to look for leukemia cells. Specialized tests of your leukemia cells may reveal certain characteristics that are used to determine your treatment options.

6. Signs Fever or chills Persistent fatigue, weakness Frequent or severe infections Losing weight without trying Swollen lymph nodes, enlarged liver or spleen Easy bleeding or bruising Recurrent nosebleeds Tiny red spots in your skin ( petechiae ) Excessive sweating, especially at night Bone pain or tenderness

7. Risk Factors - Previous cancer treatment. Past cancer treatments involving radiation or chemotherapy may increase the likelihood you’ll develop some types of leukemia -Smoking specially for AML (acute myeloid leukemia) -Exposure to industrial chemicals. Benzene and formaldehyde are known cancer -Certain genetic disorders. (Schwachman-Diamond syndrome and Down syndrome) -Family history of leukemia -

8. Treatment options

9. Chemotherapy. Chemotherapy is the major form of treating leukemia. This drug treatment uses chemicals to kill leukemia cells. Depending on the type of leukemia a single chemotherapeutic drug or a combination of chemotherapy , These drugs can be in form of pill, or they may be injected directly into a vein.

10. Radiation therapy. It damage leukemia cells and stop their growth. directing the radiation to precise points on the body where there is a collection of leukemia cells, or radiation over the whole body. Radiation therapy may be used to prepare for a bone marrow transplant.

11. Bone marrow transplant. a stem cell transplant, helps reestablish healthy stem cells by replacing unhealthy bone marrow with leukemia-free stem cells that will regenerate healthy bone marrow. * Prior to a bone marrow transplant , a very high doses of chemotherapy or radiation therapy is recommended to destroy leukemia-producing bone marrow. Then ,receive an infusion of blood-forming stem cells that help rebuild your bone marrow.

12. Immunotherapy. This treatment uses certain drugs to boost your body’s defense system your immune system to fight leukemia

13. chimeric antigen receptor (CAR)-T cell therapy Therapy allow the body germ-fighting T cells, engineers them to fight cancer and infuses them back into your body. CAR-T cell therapy might be an option for certain types of leukemia. 76% of patients achieved remission and 33% experienced immune effector cell-associated neurotoxicity syndrome, a common side effect of CAR-T therapy. * CAR IS APPROVED BY FDA FOR TREATING Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

14. Four main types of leukemia • Acute Myeloid Leukemia. • Acute Lymphocytic Leukemia. • Chronic Myeloid Leukemia. • Chronic Lymphocytic Leukemia.

15. Treatment phases Induction, which is short and intensive, usually lasts about a month. Consolidation (intensification), which is also intensive, typically lasts for a few months. Maintenance (post-consolidation), which is less intensive, typically lasts for about 2 years.

16. Chemotherapy for acute lymphatic leukemia

17. Pathophysiology Acute lymphocytic leukemia is the most common type of cancer in children, and treatments result in a good chance for a cure. Acute lymphocytic leukemia can also occur in adults, though the chance of a cure is greatly reduced. is caused by a series of acquired genetic aberrations. Malignant transformation usually occurs at the pluripotent stem cell level, although it sometimes involves a committed stem cell with more limited capacity for self-renewal.

18. Chemotherapy . Chemo for ALL uses a combination of anti-cancer drugs . The most commonly used chemo drugs include: Vincristine or liposomal vincristine ( Marqibo ) Daunorubicin ( daunomycin ) or doxorubicin (Adriamycin) Cytarabine (cytosine arabinoside , ara -C) 6-mercaptopurine (6-MP) Methotrexate Cyclophosphamide Prednisone Dexamethasone

19. Side Effects The side effects of chemo depend on the type and dose of drugs given and the length of time they are taken: Hair loss Mouth sores Loss of appetite Nausea and vomiting Diarrhea or constipation

20. Side effect of certain chemotherapy Cytarabine ( ara -C), especially when used at high doses, can cause dryness in the eyes and can affect certain parts of the brain, which can lead to problems with coordination and balance. Vincristine can damage nerves, which can lead to numbness, tingling, or weakness in hands or feet. Anthracyclines (such as daunorubicin or doxorubicin) can damage the heart, so the total dose needs to be watched closely, and these drugs might not be used in someone who already has heart problems.

21. Chemotherapy for Chronic Myeloid Leukemia

22. Pathophysiology KNOW AS chronic myelogenous leukemia. It's a type of cancer that starts in certain blood-forming cells of the bone marrow. In CML, a genetic change takes place in an early (immature) version of myeloid cells -the cells that make red blood cells, platelets, and most types of white blood cells (except lymphocytes). This change forms an abnormal gene called BCR-ABL, which turns the cell into a CML cell. The leukemia cells grow and divide, building up in the bone marrow and spilling over into the blood. In time, the cells can also settle in other parts of the body, including the spleen. CML is a fairly slow growing leukemia, but it can change into a fast-growing acute leukemia that's hard to treat.

23. Chemotherapy *Any drug used to treat cancer (including tyrosine kinase inhibitors or TKIs) can be considered chemo, - hydroxyurea ( Hydrea ®) is taken as a pill,quickly lower very high white blood cell counts and shrink an enlarged spleen. - cytarabine ( Ara -C). - busulfan . - cyclophosphamide (Cytoxan®). - vincristine ( Oncovin ®). - Omacetaxine ( Synribo ®) is a chemo drug that was approved to treat CML that's resistant to TKIs and progresses to the accelerated phase.

24. Side effects of chemotherapy Hair loss Mouth sores Loss of appetite Nausea and vomiting Low white blood cell counts (leukopenia), which increases the risk of serious infection Low blood platelet counts (thrombocytopenia), which can lead to easy bruising or bleeding Low red blood cell counts (anemia), which can lead to feeling tired and weak

25. Questions ???