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review haem > 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

Acute leukaemia, chronic leukaemia, myeloma, lymphoma, bone marrow failure, congenital immune or haematological conditions

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7
Q

What are some advantages of allogenic vs autologous HSCT

A

Autologous
* No GvHD
* No need to wait for match
* No risk of rejection

Allogenic
* Graft vs tumour effect (graft immune cells kill residual cancer cells)
* Reduced risk of disease recurrence (which can happen in autologous HSCT)

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8
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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9
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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10
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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11
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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12
Q

Name three ways of harvesting stem cells.

A
  • Bone marrow sampling
  • Peripheral blood sampling
  • Umbilical cord stem cells
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13
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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14
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
  • Apheresis - 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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15
Q

Describe Process of Autologous Transplantation

A
  1. Patient given growth factor
  2. Collect and freeze stem cells
  3. Myeloablative therapy (high dose chemotherapy or radiotherapy)
  4. Replace stem cells with autologous
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16
Q

When are autologous stem cell transplants suitable

A

In Myeloma - Elderly - cant handle GvHD

Acute Leukaemia

Solid tumours

Germ cell tumours

Lymphoma

CLL

17
Q

List some other factors affecting the outcome of a bone marrow transplant.

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

NOTE: this is used to calculate the EBMT risk score

18
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
19
Q

List some complications of stem cell transplantation.

A
  • Graft failure
  • Infections
  • GvHD
  • Disease relapse
20
Q

What is graft-versus-host-disease and what are the 2 types

A

When mature donor T cells within stem cell graft attack host cells

Two types:
* Acute: occurs within 100 days
* Chronic: occurs after 100 days

21
Q

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

A
  • Degree of HLA disparity
  • Donor and receipent age
  • Donor and recipient sex (male recipients with female donors have worse GvHD)
  • Donor lymphocyte infusion
  • Conditioning regimen type
  • Stem cell source (PB>BM>UCB)
  • Disease phase
  • Viral infections
22
Q

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

A
  • Skin - painful rash and desquamation
  • GI tract - abdominal pain and diarrhoea
  • Liver - jaundice and hepatomegaly
23
Q

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

A
  • Skin - sclerosis, ulcers, nail dystrophy
  • Mucosal membranes - ulcer
  • Lungs - bronchiolitis obliterans
  • Liver - dysfunction and jaundice
  • Dry eyes
  • Polymyositits
24
Q

List some treatment options for acute GvHD.

A
  • Corticosteroids (mainstay)
  • Calcineurin inhibitors: cyclosporin, tacrolismus
  • Mycophenolate mofetil
  • Monoclonal antibodies
  • Photophoresis
  • Total lymphoid irradiation
25
Q

List some drugs used to prevent GvHD.

A
  • Methotrexate
  • Corticosteroids
  • Calcineurin inhibitors

CsA + MTX or mycophenolate is the standard prevention regime

  • T cell depletion - monoclonal antibodies
  • Post-transplant cyclophosphamide
26
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

27
Q

Why can you not just remove mature lymphocytes from donor graft

A

These mature lymphocytes are important in preventing graft rejection, leukaemia relapse, an opportunistic infection

28
Q

What is the prognosis of chronic GvHD

A

Can last up to 5 years with 85% of patients being able to discontinue treatment at that time

29
Q

What are the 2 most common sources of infection in neutropenic patients

A

Gram positive infections: vascular access procedures and lines

Gram negative infections: GI tract

30
Q

Management neutropenic spesis

A

Emergency

  • Definition: temperature >38 sustained for 1 hour or single fever >39, in a patient with neutrophils <1 x10^9
  • Investigations - Blood cultures, MSU, CXR

Emperical treatment

Broad spectrum antibiotics and supportive care

31
Q

Role of CMV and transplantation

A

Nearly everyone is infected with CMV as a child but infection is latent

Reactivation occurs during immunocompromise - e.g. HSCT transplant

32
Q

How can CMV disease manifest

A
  • Pneumonitis
  • Retinitis
  • Colitis
  • Encephalitis
33
Q

How is CMV disease prevented and treated?

A

Monitoring: twice weekly blood PCR to detect viraemia
If detected, treatment is with ganciclovir/valganciclovir

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