Leukaemia

Pharmacotherapeutics of leukemia

1. Leukaemia Dr. V. S. Swathi Assistant Professor

2. Definition It is a cancer of body’s blood forming cells including bone marrow and lymphatic system

3. Epidemiology In the world, nearly 3, 00, 000 new cases are diagnosed each year globally In India, more than 10,000 childhood leukaemia cases are reported

4. Types Acute Myeloblastic Leukaemia (AML) Here cells grow quickly Effects immature myeloid cells Commonly affects children and adults Chronic Myelocytic Leukaemia (CML) Here cells grow slowly Effects mature myeloid cells Commonly affects adults Acute Lymphoblastic Leukaemia (AML) Here cells grow quickly Effects immature lymphoid cells Commonly affects children Chronic Lymphocytic Leukaemia (CLL) Here cells grow slowly Effects mature lymphoid cells Commonly affects adults

5. Risk factors Radiation Smoking Family history of leukaemia Down syndrome Exposure to chemicals Exposure to cytotoxic drugs Viral infections- Human T cell lymphotropic virus

6. Etiology Abnormal expression of genes responsible for blood forming cell production on exposure to risk factors

7. Pathogenesis

8. Clinical Presentation Bleeding Symptoms of infection Symptoms of anaemia Head ache Irritable behaviour Persistent fatigue Weight loss Swollen lymph nodes Recurrent nose bleeds Petechiae Excessive sweating during night times Bone pain

9. Complications Infections Cancer of multiple organs like skin, lung, GIT

10. Diagnosis Patient history Clinical presentation Complete blood count Bone marrow aspiration Cytogenetic testing Computed Tomography Magnetic Resonance Imaging

11. Non Pharmacological Treatment Counselling Cognitive behavioural therapy Transcutaneous electrical nerve stimulation (TENS) Acupuncture Physical therapy Radiation Bone marrow transplantation Stem cell transplantation

12. Acute Myeloblastic Leukaemia (AML )

13. Acute Lymphoblastic Leukaemia ( ALL)

14. Chronic Myelocytic Leukaemia (CML ) Hydroxycarbamide Interferon Imatinib Dasatinib Nilotinib

15. Chronic Lymphocytic Leukaemia (CLL) Chlorambucil Corticosteroids Fludarabine Rituximab Cyclophosphomide

16. Drugs used in treatment of Leukaemia Drug Category Mode of action Dose Adverse effect Cytarabine Antimetabolites Inhibit DNA synthesis by acting as false substitutes in the production of nucleic acids 100mg/m 2 -IV-BD in AML GI disturbances Bleeding Hepatotoxicity Myelosupression Oral/anal Inflammation Daunorubicin Anti tumor antibiotics Inhibit DNA synthesis by alkylation and intercalation 45mg/m 2 -IV- Daily in AML GI disturbances Arrhythmias Discoloration of urine Alopecia Hyperurecemia Etoposide Topoisomerase Inhibitor Inhibit DNA replication and synthesis by inhibiting enzyme Topoisomerase 100 mg/m 2 -IV- Daily in AML Leukopenia GI disturbances Alopecia Hepatotoxicity Pancytopenia

17. Vincristine Mitotic inhibitors Inhibit DNA synthesis by interrupting microtubule formation 1.5mg/m 2 -IV- Weekly in ALL Alopecia Peripheral neuropathy Acute uric acid nephropathy Hypertension Myelosupression Methotrexate Antimetabolites Inhibit DNA synthesis by acting as false substitutes in the production of nucleic acids 20mg m 2 -oral-Weekly in ALL Arachnoiditis Encephalopathy Hyperurecemia GI disturbances Intestinal Perforation 6-Mercaptopurine Antimetabolites Inhibit DNA synthesis by acting as false substitutes in the production of nucleic acids 75mg m 2 -oral-Daily in ALL GI disturbances Hepatotoxicity Thrombocytopenia Stomatitis Leukopenia Prednisolone Corticosteroid Decreases chemotherapy induced nausea and vomiting 40mg m 2 -oral-Daily in ALL Acne Adrenal suppression Delayed wound healing Diabetes Hepatotoxicity Osteoporosis

18. L Aspariginase Enzyme Kills cancer cells by depleting levels of asparigine 6000U/ m 2 -IM- Weekly in ALL GI disturbances Oedema Hepatotoxicity Dyspnoea Coagulapathy Hydroxycarbamide Ribonucleotide reductase inhibitor Interferes with DNA synthesis of WBC cells 1.5-2g-Daily for 2 weeks in CML GI disturbances Rashes Infections Vitamin D deficiency Weight gain Chlorambucil Alkylating agent Interferes with DNA synthesis of WBC cells 0.1mg/kg/Day for 3-6 weeks in CLL Bone marrow suppression Seizures Hallucination Peripheral neuropathy GI disturbances Hyperurecemia

19. Resources https ://ascopubs.org/doi/full/10.1200/JCO.2007.12.9098 https://ascopubs.org/doi/full/10.1200/jco.2004.10.050 https://www.nejm.org/doi/full/10.1056/nejm199410063311402 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520400/pdf/bcj201753a.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991139/