Bone marrow transplantation Flashcards

1
Q
  1. Describe how autologous transplant occurs
  2. Which conditions are autologous transplant useful for?
A
  • Growth factor is given to the patient
  • Stem cells are collected and frozen
  • The stem cells can then be thawed and reinfused when the patient needs them e.g. recieving high dose chemotherapy

Autologous stem cell transplant is when the patient recieves their own stem cells

  1. Acute leukemia, solid tumors, autoimmune diseases, - anything that you can treat into complete remission

Can be used inmyeloma, lymphoma and CLL as a holding therapy but not a cure

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2
Q
  1. What is allogenic transplant?
  2. What are it’s uses?
A
  1. Allogenic transplant is when stem cells/bone marrow is donated from a donor
  2. Suitable for when someone undergoes high dose chemotherapy +/- radiotherapy. Can be used for
  • Acute leukemia
  • Chronic leukemia
  • Myeloma
  • Lymphoma
  • BM failure
  • Congenital immune deficiencies
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3
Q
  1. Which organ in the body is most susceptible to radiation?
  2. Which organ is the least susceptible to radiation?
A
  1. Bone marrow
  2. CNS
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4
Q

What marker which is found on the surface of a human stem cell can be used to identify a stem cell?

A

CD34

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5
Q

How do we choose a donor for stem cell transplantation?

A

Someone who is a well-matched tissue type or HLA type. Ideally a sibling, and if not an unrelated donor with a close match

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6
Q

Describe the process of transplantation

A

Identify disease unlikely to respond to standard treatment

Treat patient to remission

Identify a donor and collect stem cells

Give patient myeloablative therapy - need to remove the current immune system

Infuse stem cells

Continue immunosuppression & support patient through period of cytopenia - to prevent graft vs host disease

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7
Q

Which chromosome is HLA encoded for?

A

Short arm of chromosome 6

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8
Q
  1. What do HLA class 1 present to?
  2. What do HLA class 2 present to?
A
  1. HLA class one presents to CD8+ cytotoxic T-lymphocytes
  2. HLA class 2 presents to CD4 Helper T cells
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9
Q

HLA -A2 alleles. There are several types of HLA-A2, but what are the two genes that are most common that all lineages of HLA-A2 have?

A
  • G62
  • T142-H145
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10
Q

Why would you not want to transfuse someone who A*0201 with someone who is A*0205, even when they are both HLA-A2 positive?

A

Becuase although these subtypes of HLA-A2 have matching genes within them e.g. G62. Individually they have mismatches in their sequences which are unique to them, and these can be recognised by T cells and produce varying levels of graft vs host disease

So even though they are both HLA-A2 matching, there are subtypes within HLA-A2 which makes them less similar, and these can be detected by T cells

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11
Q

What three places can stem cells be harvested from?

A

Bone marrow

Peripheral blood

Umbilical cord

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12
Q

What amount of CD34 cells are needed per kilo of body weight for transplant to be successful?

A

2x106 CD34+ cells per kilo of body weight minimum

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13
Q

What are the complications of stem cell transplant?

A
  • Graft failure
  • Infections
  • Graft versus host disease - allografting only
  • Relapse
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14
Q

What 5 things affects the outcome of transplant?

A

Age <20=0,20-40=1,>40=2

Disease phase Early=0, int=1, late=2

Gender of R/D Female into male = 1

Time to BMT <1 yr = 0, >1 yr = 1

Donor Sib = 0, VUD = 1

High score is bad, and can help predict 5 years survival

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15
Q

What does the cell need to be doing to be targeted by chemotherapy?

A

Chemotherapy will target any cell that it is dividing. Therefore, it will also target healthy cells that rapidly divide e.g. in the GI tract, epithelial cells in the lung, sperm etc.

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16
Q

What are the risk factors for infection following chemotherapy?

A

Neutropenia

Break down of protective barriers

Decreased antibody levels

Depressed T-cell immune responses

17
Q

Which bugs are most likely to cause sepsis when there is neutropenia e.g. following chemotherapy?

A

Gram negative sepsis

18
Q

What family of viruses does CMV belong to?

A

Herpes

19
Q

What are the risk factors for CMV disease?

A

The patient’s serological status

The donor’s serological status

The type of stem cell donor (sibling, unrelated, haplo)

The type of transplant (allogeneic, autologous, reduced conditioning)

The CMV viral load

In a healthy individual, 20% of T cells are working to stop reactivation of CMV. therefore, anyone who has T cells affected by a disease are at risk from CMV e.g. HIV

20
Q

What is graft vs host disease?

A

An immune response when donor cells recognise the patient as ‘foreign’

Acute GvHD affects skin, gastrointestinal tract and liver (within first 100 days)

Chronic GvHD affects skin, mucosal membranes, lungs, liver, eyes, joints

Different variations and severity of GVHD for each organ e.g. liver can cause mild jaundice (stage 1) to liver failure (stage 4)

Staged 1-4 for all organs - 4 the worst

21
Q

What are the risk factors for acute GvHD?

A
  • Degree of HLA disparity
  • Recipient age
  • Conditioning regimen - Immunosuppression
  • R/D gender combination - female cells in males suffer more - could be that female cells react badly to proteins released by the Y chromosome
  • Stem cell source
  • Disease phase
  • Viral infections
22
Q

What are the treatments for GvHD?

A

Corticosteroids

Cyclosporin A

FK506

Mycophenylate mofetil

Monoclonal antibodies

Photopheresis

Total lymphoid irradiation

23
Q

What can be used to prevent GvHD?

A

Methotrexate

Corticosteroids

Cyclosporin A

CsA plus MTX

FK506

T-cell depletion

Post-transplant cyclophosphamide