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

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

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

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

14. Acute Myeloblastic Leukaemia (AML)

15. Acute Lymphoblastic
Leukaemia
(ALL)

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

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

18. 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/m2-IV-
BD
in AML
 GI disturbances
 Bleeding
 Hepatotoxicity
 Myelosupression
 Oral/anal
Inflammation
Daunorubicin Anti tumor
antibiotics
Inhibit DNA
synthesis by
alkylation and
intercalation
45mg/m2-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/m2-IV-
Daily
in AML
 Leukopenia
 GI disturbances
 Alopecia
 Hepatotoxicity
 Pancytopenia

19. Vincristine Mitotic
inhibitors
Inhibit DNA synthesis
by interrupting
microtubule formation
1.5mg/m2-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 m2-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 m2-oral-
Daily
in ALL
 GI disturbances
 Hepatotoxicity
 Thrombocytopenia
 Stomatitis
 Leukopenia
Prednisolone Corticosteroid Decreases
chemotherapy induced
nausea and vomiting
40mg m2-oral-
Daily
in ALL
 Acne
 Adrenal
suppression
 Delayed wound
healing
 Diabetes

20. L Aspariginase Enzyme Kills cancer cells
by depleting
levels of
asparigine
6000U/ m2-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

21. Resources
• https://ascopubs.org/doi/full/10.1200/JCO.2007.12.90
98
• https://ascopubs.org/doi/full/10.1200/jco.2004.10.050
• https://www.nejm.org/doi/full/10.1056/nejm19941006
3311402
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC55204
00/pdf/bcj201753a.pdf
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC49911
39/