SPECIFIC MANAGEMENT OF HAEMATOLOGICAL MALIGNANCIES

DR ODE I C

HAEMATOLOGICAL MALIGNANCIES

• Haematological malignancies are malignant disorders of the blood or the blood forming organs or in simple terms, are cancers of the blood and the blood forming organs

HAEMATOLOGICAL MALIGNANCIES

• Management of haematological malignancies include specific and nonspecific
• The two management protocols complement one another with none superior to the other (debatable)

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SPECIFIC MANAGEMENT OF HAEMATOLOGICAL MALIGNANCIES

• This can be defined as a precise, particular and distinct care and treatment of patients, as well as the pre- and post- treatment assessment of patients with tumors or malignancies arising from the blood and (or) blood forming organs

SPECIFIC MANAGEMENT OF HAEMATOLOGICAL MALIGNANCIES

• AIM is to improve the quality of life (QOL)and increase overall survival of the patient, tumor bulk reduction and achievement of a cure

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SPECIFIC MANAGEMENT OF HAEMATOLOGICAL MALIGNANCIES

• The time and type of specific management depends on the time of patient’s presentation, the clinical state, age and sex of the patient, the diagnosis (type of malignancy) and the available treatment options

TYPES OF SPECIFIC MANAGEMENT

• These include:
• Pre-management evaluation of patient
• Treatment
• Post-treatment evaluation

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PRE-MANAGEMENT EVALUATION

• Pre-management evaluation involves;
• Counseling
• Explain in simple terms to the patient what the diagnosis is

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PRE-MANAGEMENT EVALUATION

• Let the patient know the treatment options and the one he will eventually receive and why
• The patient should be made to understand the financial implication of the treatment

PRE-MANAGEMENT EVALUATION

• Explain in clear terms the short and long term side effects of the treatment
• Obtain consent from the patient

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PRE-MANAGEMENT EVALUATION

• Do baseline investigations
• These baselines will establish the fitness of the patient for a particular chemotherapy or treatment protocol

PRE-MANAGEMENT EVALUATION

• Baselines help detect complication(s) that may arise from treatment
• Baselines help in monitoring patient’s recovery or response

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PRE-MANAGEMENT EVALUATION

• Some of the baseline investigations include:
• Full blood count (FBC)
• Liver function test (LFT)
• Electrolyte, urea and creatinine (E,U,Cr)

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PRE-MANAGEMENT EVALUATION

• Fasting blood glucose (FBG)
• Serum uric acid levels
• BMA
• Ultrasound scan
• CTScan

PRE-MANAGEMENT EVALUATION

• NOTE that some of these investigations may not be applicable in all cases depending on the diagnosis and the treatment modality

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POST-TREATMENT EVALUATION

• This involves re-assessing the patient after treatment using laboratory parameters and other investigative tools as well as clinical assessment

POST-TREATMENT EVALUATION

• This aims at establishing the current state of patients health compared with his pre-treatment status
• It also helps in assessing tumor bulk

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POST-TREATMENT EVALUATION

• It helps detect therapy related complications
• It gives you an insight to the next line of action in the management of the patient

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TYPES OF SPECIFIC MANAGEMENT

• Chemotherapy
• Radiotherapy
• Stem cell transplantation
• Single therapeutic modality or combination therapy could be used

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CHEMOTHERAPY

• Chemotherapy was coined by Paul Ehrlich in 1854-1915, and in its original meaning or sense refers to a chemical which when administered, binds to and specifically kills microbes or tumor cells.

CHEMOTHERAPY

• An ideal chemotherapy should be able to kill only tumor cells with minimal toxicity to normal cells (tissues)
• However such an ideal chemotherapy does not exist

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CHEMOTHERAPY

• Chemotherapy is a treatment modality given to treat malignancies with the aim of reducing tumor burden, improving quality of life (QOL), increase overall survival (OS), achieving remission and a cure

CHEMOTHERAPY

• Chemotherapy may be used in some non malignant disease conditions e.g SCA
• Chemotherapy is not only limited to haematological disorders/malignancies

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ROUTES OF ADMINISTRATION OF CHEMOTHERAPY

• Oral
• Intravenous
• Intra-thecal Parenteral
• Subcutaneous
• Topical

PRINCIPLE OF CHEMOTHERAPY

• The principle behind chemotherapy in haematological malignancies is to reduce cancer cells or completely eliminate the cancer by inhibiting or killing the rapidly replicating cancer cells in other to achieve remission and cure

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MECHANISM OF ACTION OF CHEMOTHERAPY

• Mechanism of action of chemotherapy depends on the type of chemotherapeutic agent
• Mechanism of action differ from one chemotherapeutic agent to the other

CLASSES OF CHEMOTHERAPY DRUGS

• Grouping and classification of chemotherapeutic agent is determined by factors:
• How does the chemotherapeutic agent affect the chemical substances within the cancer cell

CLASSES OF CHEMOTHERAPY DRUGS

• Which activity or process in the cell the drug interferes
• What part of the cell cycle the drug affects

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CLASSES OF CHEMOTHERAPY DRUGS

• Some of the drugs are cell cycle specific, acting on a particular cell cycle phase while the cell cycle non-specific act on all phases of cell cycle

CLASSES OF CHEMOTHERAPY DRUGS

• chemotherapy drugs are given in cycles to allow recovery of normal cells
• Cycles are regular intervals at which chemotherapy is given

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CLASSES OF CHEMOTHERAPY�DRUGS

• A cycle may be a dose of one or more chemotherapy drugs given on one or more days, followed by days or weeks without treatment before the next cycle

CLASSES OF CHEMOTHERAPY�DRUGS

• Course(s) of chemotherapy is the total number of cycles an individual being treated for haematological malignancy may have for a particular treatment plan or chemotherapy regimen

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CLASSES OF CHEMOTHERAPY�DRUGS

• Classes of chemotherapy drugs are:
• Alkylating agents
• The alkylating agents are further grouped into:

CLASSES OF CHEMOTHERAPY�DRUGS

• Mustard gas derivatives e.g Cyclophosphamide, Chlorambucil, Melphalan, Ifosfamide, Mechlorethamine
• Alkylsulfonates e.g Busulphan
• Hydrazines e.g Dacarbazine, Procarbarzine

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CLASSES OF CHEMOTHERAPY�DRUGS

• Nitrosoureas e.g Carmustine, Lomustine
• Metal salts e.g Carboplatin, Cisplatin
• Ethylenamines e.g Thiotepa

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MECHANISM OF ACTION OF ALKYLATING AGENTS

• Alkylating agents acts directly on DNA causing DNA breaks, abnormal base pairing and cross linkage of DNA strands resulting in a damaged DNA that is unable to replicate

�MECHANISM OF ACTION OF ALKYLATING AGENTS

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• Alkylating agents are cell cycle phase nonspecific, meaning that they kill the cell in various and multiple phases of the cell cycle

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ALKYLATING AGENTS IN HAEMATOLOGICAL MALIGNANCIES

• Alkylating agents are used in:
• Leukaemias e.g Acute myeloid leukaemia (AML), Chronic lymphoctic leukaemia (CLL),Acute lymphoblastic leukaemia (ALL) and Chronic myeloid leukaemia (CML)

USES OF ALKYLATING AGENTS

• Lymphomas e.g Cyclophosphamide and Dacarbazine are used in Non Hodgkins lymphoma (NHL) and Hodgkins lymphoma (HL) respectively

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USES OF ALKYLATING AGENTS

• Multiple myeloma e.g Melphalan
• Conditioning for stem cell transplantation

SIDE EFFECTS OF ALKYLATING AGENTS

• Specific side effects of alkylating agents include:
• Haemorrhagic cystitis
• Alopecia
• Nephrotoxicity
• Skin hyperpigmentation
• Myelosuppression

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CLASSES OF CHEMOTHERAPY�DRUGS

• Antimetabolites
• These are further grouped into:
• Purine analogues e.g fludarabine 6-Mercaptopurine, 6-Thioguanine

CLASSES OF CHEMOTHERAPY�DRUGS

• Pyrimidine analogues e.g cytosine arabinoside (cytarabine) Folate antagonists e.g Methotrexate
• Inhibitors of de novo DNA synthesis e.g hydroxyurea

MECHANISM OF ACTION OF ANTIMETABOLITES

• Antimetabolites block enzymes or metabolism required for DNA synthesis
• Antimetabolites are cell cycle specific, they impair synthesis of DNA and formation of new cells

USES OF ANTIMETABOLITES IN HAEMATOLOGICAL MALIGNANCIES

• Antimetabolites are used in:
• Leukaemias e.g Acute myeloid leukaemia (AML), Acute lymphoblastic leukaemia (ALL), and Chronic lymphoid leukaemia (CLL)

SIDE EFFECTS OF ANTIMETABOLITES

• Specific side effects of antimetabolites include:
• Pigmentation
• Jaundice
• Nail dystrophy
• myelosuppression

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CLASSES OF CHEMOTHERAPY�DRUGS

• Cytotoxic antibiotics e.g doxorubicin, hydroxodaunorubicin, epirubicin, mitozantrone and bleomycin

MECHANISM OF ACTION OF CYTOTOXIC ANTIBIOTICS

• Cytotoxic antibiotics interfere with DNA replication through intercalating into the DNA and strongly binds to topoisomerase, blocking their activity and impairing DNA replication

MECHANISM OF ACTION OF CYTOTOXIC ANTIBIOTICS

• They generate free radicals that destroys DNA
• They are cell cycle non specific

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CYTOTOXIC ANTIBIOTICS IN HAEMATOLOGICAL MALIGNANCIES

• Cytotoxic antibiotics are used in:
• Leukaemias e.g daunorubicin in AML, ALL
• Lymphomas e.g doxorubicin, epirubicin in Non Hodgkins lymphoma (NHL) and bleomycin in Hodgkins lymphoma (HL)

SIDE EFFECTS OF CYTOTOXIC ANTIBIOTICS

• Specific side effects of cytotoxic antibiotics include:
• Cardiac toxicity
• Skin pigmentation
• Hair loss
• Pulmonary fibrosis

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CLASSES OF CHEMOTHERAPY�DRUGS

• Plant derivatives include:
• Vinca alkaloids e.g Vincristine, Vinblastine
• Podophyllotoxins e.g Etoposide
• Taxanes e.g paclitaxel, docetaxel

MECHANISM OF ACTION OF PLANT DERIVATIVES

• Plant derivatives damage spindle formation, inhibits mitosis and inhibits topoisomerase

PLANT DERIVATIVES IN HAEMATOLOGICAL MALIGNANCIES

• Plant derivatives are used in:
• Leukaemias e.g vincristine in AML, ALL and etoposide in ALL
• Lymphomas e.g vincristine in NHL and vinblastine in HL

SIDE EFFECTS OF PLANT DERIVATIVES

• Specific side effects of plant derivatives include:
• Neurotoxicity
• Hair loss
• myelosuppression

OTHER DRUGS USED IN HAEMATOLOGICAL MALIGNANCIES

• Other drugs used in the management of haematological malignancies include:
• Monoclonal antibodies e.g
• Rituximab (anti-CD20)
• Alemtuzumab (anti-CD52), Mylotarg (anti-CD33)

OTHER DRUGS USED IN HAEMATOLOGICAL MALIGNANCIES

• Immune modulators e.g thalidomide, lenalidomide
• Inhibitors of signal transduction e.g imatinib, nilotinib, dasatinib
• Corticosteriods e.g prednisolone

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