Stem cell transplantation. Dr Mohammed Karodia NHLS & UP

Transcription

1 Stem cell transplantation Dr Mohammed Karodia NHLS & UP

2 The use of haemopoeitic stem cells from a donor harvested from peripheral blood or bone marrow, to repopulate recipient bone marrow. Allogeneic From one individual to another Usually HLA matched individuals (sibling or MUD) Autologous Utilizes pt s own stem cells Harvested from pt and used to repopulate marrow after further high dose chemo or radiotherapy Cord blood Utilizes fetal stem cells harvested at birth

3 Indications

4 Procedure Treatment with G-CSF combined with chemo (in autologous) is used to mobilize HSC from the BM into the peripheral blood where it is collected by leucopheresis. Can be mobilized from BM by aspirate Collect CD34+ cells Recipient of allogeneic or MUD receives immunosuppressive drugs to reduce the risk of GVHD

5 Complications Side effects of conditioning chemotherapy Bm failure, nausea, alopecia, skin burns etc Rejection Relapse Infection Bacterial, viral, protozoal or fungal. Prophylactic antiviral, antibiotic and antifungals given CMV- pts receive leucodepleted or CMV- blood. Prophylaxis against PCP Metabolic problems Graft vs. Host disease Transplanted lymphocytes recognize host as foreign and mount immunological response. Acute and chronic

6 General aspects of treatment

7 Chemotherapy The use of pharmacological agents to treat malignant or other proliferative diseases. Given orally, by bolus, prolonged subcutaneous or intravenous injection/infusion or intrathecally. Often given as a cycle. Often administered through a central line or indwelling chamber.

8 Side effects of chemotherapy Toxic to normal dividing cells as well as malignant cells. Common side effects Bone marrow failure with increased susceptibility to bleeding and infection Nausea and vomiting Mucositis, abdominal pain and diarrhoea Infertility Tumour lysis syndrome Hyperuricaemia Specific side effects: Neuropathy (vincristine) Cardiomyopathy (anthracyclines) Thrombosis (laspar) Secondary leukaemia (etoposide, alkylating agents) Pulmonary fibrosis (busulphan) Haemorrhagic cystitis (cyclophosphamide)

9 Mechanism of action Affect DNA synthesis or repair and promote cellular apoptosis. Cycle specific agents prevent DNA synthesis and and act on the S phase of the cell cycle. Non-cycle specific agents act at all phases of the cell cycle e.g. alkylating agents which bind to DNA, and anthracyclines, which cause DNA strand braks. Inhibition of the DNA repair enzyme, topoisomrease II is an important component of the action of anthracyclines and etoposide.

10 Biological therapies G-CSF, GM-CSF and EPO Interferons naturally occurring agents which have both antineoplastic and anti-infective properties. Interferon α used in the treatment of Multiple myeloma, CML, non-hodgkin s lymphoma. Monoclonal antibodies targeted therapy

11 Infection Main risk factors: Neutropenia - for bacterial and fungal infections Defected cell mediated or humoral immunity for viral, bacterial or atypical infections Others Indwelling catheters Corticosteroid therapy Mucositis Organisms Splenectomy, impaired splenic function Commensal organisms Bacterial, fungal, virusses, protozoan

12 Prevention Hygiene Barrier nursing Filtered air at positive pressure Cooked foods Antibiotics Diagnosis Fever Physical signs, absent pus Special tests Treatment Supportive care Antimicrobial treatment

13 Radiotherapy Ionizing radiation, usually derived from an external source causes DNA damage to malignant cells. Commonly used in treatment of haematological diseases Lymphoid leukaemia Lymphoma Myeloma Also used as part of conditioning therapy for bone marrow transplant for malignant diseases Side effects nausea, vomiting, burns, secondary malignancies, alopecia, bone marrow failure, growth retardation

14 Other therapies Blood and blood component therapy Splenectomy Increased risk of infection Not for under 5 years of age Pneumococcal, meningococcal and HIB vaccination Prophylactic antibiotics

15 Counselling Valuable modality Patients and families need emotional support during treatment and or bereavement Practical help housing, transport, welfare benefits Good liason with GP s, terminal care support teams and hospices Genetic counselling for families with haemophilia, thalassaemia, sickle cell disease