Stem cell transplantation Flashcards
What is the first line treatment for Hodgkin Lymphoma?
ABVD Adriomycin Bleomycin Vinblastin Dicarbazine
What is an autologous stem cell transplant (SCT)?
Haematopoietic stem cells harvested from patient and stored Bone marrow (from ileac crest) or peripheral blood (G-CSF priming – growth factor stimulates stem cells to come out of bone marrow and into peripheral circulation) High levels of stem cells in peripheral blood of patient, and then hook them up to a machine (similar to a dialysis machine) – cannulate patient, take blood out of one arm and then spin it through this machine and pull off cells that you want and then place rest of blood in other arm. It’s a way of harvesting the particular cells you want (haematopieoc stem cells).
What does “rescuing” of a patient involves? This is seen in myelosuppression.
• “Rescue” bone marrow by re-infusing stem cells after high dose chemo has finished – infusion of stem cells after chemo into veins through blood into bone marrow and then produce new blood cells.
Where can the stem source be for an allogenic SCT?
Stem cell source: PB (peripheral blood), bone marrow, umbilical cord (high concentrations of stem cells – for adult need two cords but for child only need one)
What are the complications of an allogenic SCT?
Graft versus host disease – new immune system recognises the patient as foreign
Infection
Rejection not seen becuase you have wiped out the immune system with chemo therefore not able to reject the new immune cells given.
What are the common infections seen after an allogenic SCT?
Cytomeglovirus – don’t know if you have it but if you are severely immunosuppressed then it can lead to death so prevent giving antiviral
Epstein barr virus – may develop
glandular fever. Can cause PTLD – form of lymphoma
At risk of fungal and bacterial infections – aspergillus, candidias, Pneumacytisis – oportuic infection particualry affecting the lungs
Why is an allogenic SCT better than an autologous SCT? (2 REASONS)
As you got the cells from a donor rather than a patient there is no risk of stem cells being containing malignant cells (e.g. myeloma) – multiple myeloma. But can’t cure these patient, only improve their survival. Within the stem cells that we collect from the patient there are a few myeloma cells in there. So disease will come back. Very rarely used in leukaemia – disease of bone marrow. Lymphoma is better choice giving autologous transplant with a curative intent.
Immune mediated effect
What is Graft vs Leukaemia (GVL) effect?
As well as attacking the patient’s healthy cells and causing GVHD, the new immune system can also attack and kill any residual cancer cells remaining after the transplant.
What immunosupressants are used to prevent GVHD?
prevent GVHD
- Ciclosporin / Tacrolimus
- Methotrexate
- Mycophenolate mofetil
- Alemtuzumab
- ATG
What drugs are used to treat GVHD?
Corticosteroids
How is ciclosporin administered?
Usually started on day before transplant
Starting dose 5mg/kg/day, as continuous infusion for 1 day, then as 2.5mg/kg bd (twice daily) over 4 hours (slow infusion may ↓ flushing, tremor, nausea) Given IV until mucositis resolved and taking medication oral form
What are the side effects of Ciclosporin?
- Nephrotoxicity – worse if concurrent (currently on) amphotericin, vancomycin, gentamicin
- Hypertension – manage with Ca-channel blocker e.g. amlodipine 5-10mg od – best class of drug to treat with
- Hypomagnesaemia – very common – increase in magnesium excretion. Give Magnesium oxide capsules (4mmol) or Mg citrate tablets (8mmol) (IV or tablets)
- Hepatotoxicity
- Neurological syndromes (e.g. fits)
- Anorexia, nausea, vomiting, tremor – common but if severe, suggestive of high levels of cyclosporine
- Hirsutism (excessive hair growth) and gum hypertrophy with prolonged use
What drug interactions are there with Ciclosporin?
- Ciclosporin metabolised by cytochrome P450 system of enzymes in the liver
Enzyme inhibitors will ↑ levels:
- Azoles, clarithromycin, do not drink grapefruit juice or eat!
Enzyme inducers will ↓ levels:
- Phenytoin, rifampicin, carbamazepine, St John’s wort
Describe methotrexate for GVHD.
Methotrexate
- Conventional chemo agent but given at very low doses to prevent GVHD:
- 8mg/m2 on days +2, 4, 8, 12
- Give 3 doses of folinic acid 15mg, starting 12 hours after MTX
- Commonly causes side effect of mucositis:
- Consider omitting day 12 dose if severe
- Can Rx folinic acid mouthwash (7.5mg qds) to rescue
Describe Mycophenolate for GVHD.
- Works by inhibiting DNA production in lymphocytes
- Commonly used in solid organ transplantation
- Side effects
Gastrointestinal, ↑ risk of infection, ↓ counts
