Stem cell transplantation Flashcards
what is an autologous stem cell transplant (SCT)?
Haematopoietic stem cells harvested FROM PT
Administer high dose chemotherapy to patient
– BEAM or LEAM for lymphoma
– Melphalan for myeloma
* “Rescue” bone marrow by re-infusing stem cells after chemo has finished
where are Haematopoietic stem cells harvested from?
bone marrow
peripheral blood (G-CSF priming)
describe bone marrow HSC harvesting
invasive procedure
HSC( Hematopoietic stem cells)
describe peripheral blood HSC harvesting
(G-CSF priming)
endogenous hormone = drive WBC proliferation
how long does it take for stem cells to repopulate after inf?
10-14 days
why is autologous (SCT) better than chemo?
less toxicity than large dose of chemo
What is an allogeneic SCT?
Haematopoietic stem cells harvested FROM A DONOR AND TRANSFERRED TO THE PT
who can be a donor in allogeneic SCT?
sibling (1 in 4 chance of match)
unrelated
parent
child
MUST BE A SIMILAR MATCH
what can be a source for stem cells?
PB
bone marrow
umbilical cord
what are complications of allogenic SCT?
rejection rarely occurs due to immunosuppression
- graft vs host disease
- infection - opportunistic
what is graft vs host disease?
graft stem cells form a new immune systems that attacks the host cells
driven by T cells
occurs to 50% of pts
chronic/acute forms
commonly affects skin/gut/liver
how can graft vs host cells be prevented?
decrease T CELL activity
name some opportunistic infections and treatment prophylaxis
cytomegalovirus - LETERMOVIR
pnuemonia - co-trimoxazole
candida - fluconazole
Herpes - aciclovir
when is prophylaxis given to opportunistic infections
where there is an increase in risk
what is cytomegalovirus/CMV?
herpes virus - latent virus
affects 70% of the population
what is CMV a complication of ?
allogeneic SCT
what can CMV cause?
GVHD
bacterial/fungal infections
what is given for CMV prophylaxis?
letermovir
Why is an allogeneic SCT better than an autologous SCT?
No risk of stem cell infusion containing malignant cells (e.g. myeloma)
Immune mediated effects
Consider what is the main cause of death in those patients who are not cured by an allograft?
- infection
- relapse of malignancy
- graft vs host disease
- donor lymphocyte infusion (DLI) = increase remission
- pts with mild GVDH better outcome than those who do not
- low ciclosporin levels
what is the GVL effect?
graft vs leukaemia effect
immune system attacks and kills residual cancer cells remaining post transplant = increase survival rates
what drugs prevent GVHD/suppress T cells?
- Ciclosporin / Tacrolimus
– Methotrexate
– Mycophenolate mofetil
– Alemtuzumab
– ATG
what Drugs to treat GVHD?
corticosteroids
what is ciclosporin?
GVHD prophylaxis
4-6month treatment; start 1 day prior to transplant
NTW drug
suppress T cell activation
what are side effects of ciclosporin?
- Nephrotoxicity – worse if concurrent amphotericin, vancomycin, gentamicin
- Hypertension – manage with Ca-channel blocker e.g. amlodipine 5-10mg od
- Hypomagnesaemia – very common. Give Mg aspartate sachets or Mg citrate table
- hepatotoxicity
- neurological syndromes
- Anorexia, nausea, vomiting, tremor – common but if severe, suggest high levels
- hirsutism
what are the drug interactions for ciclosporin?
Enzyme inhibitors will ↑ levels:
– Azoles, clarithromycin, grapefruit juice
Enzyme inducers will ↓ levels:
– Phenytoin, rifampicin, carbamazepine, St John’s wort
As its METABOLISED BY CYTO P450
MTX dosing for GVHD
8mg/m2 on days +2, 4, 8, 12
omit day 12 dose if mucositis is SEVERE
- Give 3 doses of folinic acid 15mg, starting 12 hours after MTX
what are side effects of Mycophenolate?
GI
risk of infection
thrombocytopenia
what is Alemtuzumab?
prophylaxis and treatment of GVDH
monoclonal antibody (anti-CD52)
what is ATG/ALG?
anti-lymphocyte immunoglobin
reduces systemic lymphocytes
from rabbits
whats first line treatment of GVDH?
corticosteriods
- prednisolone
- methylprednisolone
- dexamethasone
what are the side effects of corticosteroids?
adrenal suppression/endocrine effects - diabetes
musculoskeletal effects - muscle wasting
GI effects - GI bleeding
mood disturbances - psychosis