Stem cell transplantation

Question 1

what is an autologous stem cell transplant (SCT)?

Answer 1

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

Question 2

where are Haematopoietic stem cells harvested from?

Answer 2

bone marrow
peripheral blood (G-CSF priming)

Question 3

describe bone marrow HSC harvesting

Answer 3

invasive procedure

HSC( Hematopoietic stem cells)

Question 4

describe peripheral blood HSC harvesting

Answer 4

(G-CSF priming)
endogenous hormone = drive WBC proliferation

Question 5

how long does it take for stem cells to repopulate after inf?

Answer 5

10-14 days

Question 6

why is autologous (SCT) better than chemo?

Answer 6

less toxicity than large dose of chemo

Question 7

What is an allogeneic SCT?

Answer 7

Haematopoietic stem cells harvested FROM A DONOR AND TRANSFERRED TO THE PT

Question 8

who can be a donor in allogeneic SCT?

Answer 8

sibling (1 in 4 chance of match)
unrelated
parent
child

MUST BE A SIMILAR MATCH

Question 9

what can be a source for stem cells?

Answer 9

PB
bone marrow
umbilical cord

Question 10

what are complications of allogenic SCT?

Answer 10

rejection rarely occurs due to immunosuppression

1. graft vs host disease
2. infection - opportunistic

Question 11

what is graft vs host disease?

Answer 11

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

Question 12

how can graft vs host cells be prevented?

Answer 12

decrease T CELL activity

Question 13

name some opportunistic infections and treatment prophylaxis

Answer 13

cytomegalovirus - LETERMOVIR
pnuemonia - co-trimoxazole
candida - fluconazole
Herpes - aciclovir

Question 14

when is prophylaxis given to opportunistic infections

Answer 14

where there is an increase in risk

Question 15

what is cytomegalovirus/CMV?

Answer 15

herpes virus - latent virus
affects 70% of the population

Question 16

what is CMV a complication of ?

Answer 16

allogeneic SCT

Question 17

what can CMV cause?

Answer 17

GVHD
bacterial/fungal infections

Question 18

what is given for CMV prophylaxis?

Answer 18

letermovir

Question 19

Why is an allogeneic SCT better than an autologous SCT?

Answer 19

No risk of stem cell infusion containing malignant cells (e.g. myeloma)
Immune mediated effects

Question 20

Consider what is the main cause of death in those patients who are not cured by an allograft?

Answer 20

• 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

Question 21

what is the GVL effect?

Answer 21

graft vs leukaemia effect

immune system attacks and kills residual cancer cells remaining post transplant = increase survival rates

Question 22

what drugs prevent GVHD/suppress T cells?

Answer 22

• Ciclosporin / Tacrolimus
  – Methotrexate
  – Mycophenolate mofetil
  – Alemtuzumab
  – ATG

Question 23

what Drugs to treat GVHD?

Answer 23

corticosteroids

Question 24

what is ciclosporin?

Answer 24

GVHD prophylaxis
4-6month treatment; start 1 day prior to transplant
NTW drug

suppress T cell activation

Question 25

what are side effects of ciclosporin?

Answer 25

1. Nephrotoxicity – worse if concurrent amphotericin, vancomycin, gentamicin 2. Hypertension – manage with Ca-channel blocker e.g. amlodipine 5-10mg od 3. Hypomagnesaemia – very common. Give Mg aspartate sachets or Mg citrate table 4. hepatotoxicity 5. neurological syndromes 6. Anorexia, nausea, vomiting, tremor – common but if severe, suggest high levels 7. hirsutism

Question 26

what are the drug interactions for ciclosporin?

Answer 26

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

Question 27

MTX dosing for GVHD

Answer 27

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

Question 28

what are side effects of Mycophenolate?

Answer 28

GI risk of infection thrombocytopenia

Question 29

what is Alemtuzumab?

Answer 29

prophylaxis and treatment of GVDH monoclonal antibody (anti-CD52)

Question 30

what is ATG/ALG?

Answer 30

anti-lymphocyte immunoglobin reduces systemic lymphocytes from rabbits

Question 31

whats first line treatment of GVDH?

Answer 31

corticosteriods - prednisolone - methylprednisolone - dexamethasone

Question 32

what are the side effects of corticosteroids?

Answer 32

adrenal suppression/endocrine effects - diabetes musculoskeletal effects - muscle wasting GI effects - GI bleeding mood disturbances - psychosis