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YEAR 5: Haematology SM > Haem: Bone Marrow Transplantation > Flashcards

Haem: Bone Marrow Transplantation Flashcards

1
Q

Which organ in the body is most resistant to radiation?

A

CNS

NOTE: bone marrow is very vulnerable to radiation

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2
Q

What is the main cellular marker of stem cells?

A

CD34

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3
Q

What is the risk of dying from bone marrow transplant?

A

More than 50%

It is the most expensive and risky elective procedure

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4
Q

Outline the process of autologous stem cell transplantation.

A
  • Growht factor is given to the patient to stimulate the production of cells from the bone marrow
  • Cells are sampled from the patient’s bone marrow (some of them will be CD34+ stem cells)
  • These are preserved in a freezer
  • High-dose chemotherapy is given to the patient to eradicate their bone marrow
  • Stem cells are re-infused
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5
Q

What are the most common reasons for autologous stem cell transplantation?

A
  • Myeloma
  • Lymphoma
  • CLL
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6
Q

When is allogeneic bone marrow transplantation used?

A
  • When it is very unlikely that the patient’s disease will be eratdiacted from the bone marrow by standard chemotherapy

NOTE: suitable for acute leukaemia, chronic leukaemia, myeloma, lymphoma, bone marrow failure, congenital immune deficiencies

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7
Q

List some parameters used to gauge outcome of transplantation techniques.

A
  • Overall survival
  • Disease-free survival
  • Transplant-related mortality
  • Relapse incidence
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8
Q

State an equation that relates the probability of having a sibling with a matching tissue type to the number of siblings a patient has.

A

Probability of match = 1 — (3/4)number of siblings

NOTE: there is a 25% chance that your sibling has the same tissue type as you

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9
Q

What are the main classes of HLA based on?

A
  • Serological reactions (e.g. HLA-A)
  • It can be increasingly specified by DNA sequencing
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10
Q

HLA molecules relevent for transplantation

A

HLA-A, -B, -C : Class I - Present to CD8+ (cytotoxic T cells)

HLA- DP, -DQ, -DR: Class II - Present peptide to CD4+ (Helper T cells)

6 HLAs, 2x Parents = MAtch rated /12

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11
Q

Name three ways of harvesting stem cells.

A
  • Bone marrow sampling
  • Peripheral blood sampling
  • Umbilical cord stem cells
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12
Q

Why is bone marrow sampling a difficult process?

A
  • It involves anaesthetising the patient and sampling bone marrow from the pelvis
  • Puncturing the bone causes damage and only sampling a small number of stem cells means that re-puncturing of the bone is necessary
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13
Q

Outline the process of peripheral blood sampling for stem cells.

A
  • Hormones (e.g. G-CSF) is given to stimulate granulocyte production
  • This leads to the bone marrow producing some stem cells along with the granulocytes
  • G-CSF is given for 5 days and stem cells are harvested on the 5th day
  • The donor is connected to a centrifuge which spins the blood, removes the white cell component, reassembles the red cells and plama and reinfuses it into the patient
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14
Q

What proportion of a sample taken during stem cell sampling actually contains stem cells?

A

1%

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15
Q

What factor (related to stem cell harvesting) does the success of a bone marrow transplant depend on?

A

Number of CD34 cells per kg of weight of the recipient

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16
Q

List some complications of stem cell transplantation.

A
  • Graft failure
  • Infections
  • GvHD
  • Relapse
17
Q

Describe Process of Autologous Transplantation

A
  1. Pt given Growth factor + irradiated to threshold
  2. Collect and freeze stem cells
  3. Continue irradiation past threshold
  4. Replace stem cells with autologous
18
Q

When are autologous stem cell transplants suitable

A

In Myeloma - Elderly - cant handle GvHd

Acute Leukaemia

Solid tumours

Germ cell tumours

Lymphoma

CLL

19
Q

Describe Allogenic Transplantation

A
  1. Identify disease unlikely to respond to standard treatment
  2. Treat patient into remission
  3. Identify donor and collect stem cells
  4. Give patient myeloablative therapy
  5. Infuse stem cells
  6. Continue immunosuppression and support patient through period of cytopenia
20
Q

Listsome other factors affecting the outcome of a bone marrow transplant.

A
  • Age
  • Disease phase (early or late)
  • Gender of recipient and donor
  • Time to BMT
  • Donor (sibling or not)

NOTE: this is used to calculate the EBMT risk score

21
Q

List some risk factors for infection that are related to bone marrow transplantation.

A
  • Neutropaenia
  • Breakdwon of protective barriers
  • Decreased antibody levels
  • Depressed T cell responses
22
Q

What are the risk factors for CMV infection following bone marrow transplantation?

A
  • Patient and donor serological status
  • Type of stem cells
  • Type of transplant
  • CMV viral load
23
Q

Which parts of the body are affected in acute graft-versus-host disease?

A
  • Skin - % Surface / Erythroderma / Bullae
  • GI tract - Diarrhoea ± Abdo pain / ileus
  • Liver - Bili
24
Q

Which parts of the body are affected in chronic graft-versus-host disease?

A
  • Skin - sclerosis, ulcers
  • Mucosal membranes - bronchiolitis obliterans
  • Lungs
  • Liver - loss bile ducts
  • Eyes - dry
  • Joints
  • Nail dystrophy
25
Q

Why must patients receiving chemotherapy or radiotherapy have a treatment-free interval before stem cell transplantation?

A

Chemotherapy and radiotherapy can damage tissues leading to the release of loads of cytokines which activate antigen-presenting cells which present antigens to donor lymphocytes.

26
Q

List some risk factors for acute graft-versus-host disease.

A
  • Degree of HLA disparity
  • Recipient age
  • Conditioning regimen
  • Recipient and donor gender combination (male donors with female patients have worse GvHD)
  • Stem cell source
  • Disease phase
  • Viral infections
27
Q

List some treatment options for GvHD.

A
  • Corticosteroids
  • Ciclosporin A
  • FK506
  • Mycophenolate mofetil
  • Monoclonal antibodies
  • Photophoresis
  • Total lymphoid irradiation
28
Q

List some drugs used to prevent GvHD.

A
  • Methotrexate
  • Corticosteroids
  • Ciclosporin A
  • FK506
  • T cell depletion - monoclonal antibodies
  • Post-transplant cyclophosphamide (chemo - will target rapidly dividing, activated, lymphocytes)
29
Q

Which component of the transplanted cells is responsible for GvHD?

A
  • It is the mature lymphocytes within the cell population (i.e. not the stem cells) that are responsible for GvHD
  • You cannot, however, remove these mature lymphocytes from the sample because they are important in preventing relapse
30
Q

Effects of Chonric GvHD

A

Immune Dysregulation

Immune Deficiency

Impaired End-organ function

Decreased survival

31
Q

Effects of Chonric GvHD

A

Immune Dysregulation

Immune Deficiency

Impaired End-organ function

Decreased survival

32
Q

Survival in chronic GvHD

A

gnosis wihtin first 6mo post transplant

85% of survivors can. discontinue treatment

5-year survival is 70-80% in low risk ± repsonding to steroids , 40-50% in high risk / not responding

33
Q

Management neutropenic spesis

A

Emergency

Temp >38, sustained for 1 hour or single fever >39, with neutrophils <1 x10^9

Inv - Blood cultures, MSU, CXR

EMperical treatment

Broad spectrum antibiotics

34
Q

Role of CMV and transplantation

A

Almost everyone is seropositive - reactivation if immunocompromised

Preventing disease - PCR twice per week

YEAR 5: Haematology SM (19 decks)

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