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Haematology > Stem cell Transplantation > Flashcards

Stem cell Transplantation Flashcards

1
Q

How do we choose a donor?

A
  • Well matched for tissue type - also known as HLA type
  • Ideally a sibling (one in four chance of matching with each sib)
  • If not, a volunteer unrelated donor or minimally mismatched family member
  • More recently, increased use of haploidentical family member – almost every patient has a donor
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2
Q

What is the HLA system?

A

A person’s tissue type comprises a set of distinct proteins called Human Leukocyte Antigens (HLA), found on the surface of most nucleated cells.

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3
Q

What HLA molecules are relevant in transplantation?

A

•HLA-A, -B, -C, (class I), present peptide to CD8+ (cytotoxic T-cells)•HLA-DP,-DQ and -DR (class II), present peptide to CD4+ (helper T-cells)

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4
Q

Where is HLA encoded?

A

HLA encoded by the Major Histocompatibility Complex, MHC, on chromosome 6

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5
Q

What is the function of HLA?

A

•Function – present foreign peptides to T cells

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6
Q

What HLA do we type in transplantation?

A

•Routinely, HLA-A, -B and DR are typed for compatibility purposes.

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7
Q

What is the chance of an HLA match within siblings?

A

Each sibling has a 35% chance of being HLA identical with the patient

Given n siblings the probability that at least one with be HLA0identical is given by the formula 1 – 3n/4n

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8
Q

What is autologous transplantation?

A
  1. Stimulate with GCF by SC injection
  2. Collect stem cells and freeze
  3. Thaw and rein fuse after chemotherapy

Good use: Multiple Sclerosis

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9
Q

What is allogeneic transplantation?

A
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10
Q

What are the principles of transplantation?

A
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11
Q

Where do we get stem cells from?

A
  • Bone marrow
  • Peripheral blood - done more now
  • Umbilical cord

We need 2 million/kg CD34+ cells - easier to get this for BM and PB

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12
Q

What are the complications of SCT?

A
  • Graft Failure
  • Infections
  • Graft-versus-host disease (GVHD):allografting only
  • Relapse
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13
Q

What is GvHD?

A
  • An immune response when donor cells recognise the patient as ‘foreign’•
  • Acute GvHD affects skin, gastrointestinal tract and liver•
  • Chronic GvHD affects skin, mucosal membranes, lungs, liver, eyes, joints - very like an AI disease like scleroderma
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14
Q

What has happened?

A

GvHD

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15
Q

What is the pathophysiology of GvHD?

A
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16
Q

What are the risk factors for acute GvHD?

A
  • Degree of HLA disparity
  • Recipient age
  • Conditioning regimen
  • R/D gender combination (male patients with female donors)
  • Stem cell source
  • Disease phase
  • Viral infections
17
Q

What is the treatment of acute GvHD?

A
  • Corticosteroids
  • Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
  • Mycophenylate mofetil
  • Monoclonal antibodies
  • Photopheresis
  • Total lymphoid irradiation
  • Mesenchymal stromal cells
18
Q

How do we prevent acute GvHD?

A
  • Methotrexate
  • Corticosteroids
  • Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
  • CsA plus MTX
  • T-cell depletion•Post-transplant cyclophosphamide
19
Q

What are the consequences of chronic GvHD?

A
  • Immune dysregulation
  • Immune deficiency,
  • Impaired end-organ function
  • Decreased survival.
20
Q

What is the prognosis of chronic GvHD?

A
  • Diagnosis within 6 months of transplant, lasts 2-5 years
  • 85% of survivors can discontinue treatment at that time
  • 5-year survival is 70–80%, in persons with low risk cGVHD and those responding to corticosteroids.
  • Five-year survival is 30–40% for those with high-risk disease +/- failure of steroids
21
Q

What are the signs of chronic GvHD?

A
22
Q

What are the RFs for chronic GvHD?

A
  • Prior acute GvHD
  • Increased degree of HLA disparity
  • Male recipient: female donor
  • Stem cell source (PB>BM>UCB)
  • T-cell replete
  • Older donor age
  • Use of DLI
23
Q

When do patients tend to get the infections?

A

Bacterial - early when pt is neutropenic

Viruses - much later - more to do with macrophages

Fungi - some very early like candida but aspergillus develops a little later

Pneumocystis - any time in the first couple of years

24
Q

What are the main sources of infection in neutropenic patients?

A
25
Q

Describe bacterial infections in transplants? Who are tested? Which bacteria are usually isolated? What are most deaths caused by?

A
  • In neutropenic patients, the causative organism is identified in approximately one third of patients•
  • The most frequently isolated organisms are gram positive eg, staph epidermidis
  • Most deaths from sepsis are due to gram negative organisms eg e.coli, pseudomonas aeruginosa
  • Reduced incidence of infection using isolation measures and broad spectrum oral antibiotics
26
Q

How do we manage neutropenic sepsis in these patients?

A

Emergency situation

  • Defined as temperature >38 sustained for one hour, or single fever >39, in a patient with neutrophils <1.0 x 109/L
  • Assess patient: temperature, pulse, oxygen saturation and blood pressure. History and examination for evidence of source
  • Blood cultures, MSU, CXR•
  • Initiate empirical broad spectrum antibiotics and supportive care
27
Q

Describe fungal acquisitions in these patients? Where do they come from?

A
  • Yeasts from translocation from the intestinal mucosa, or indwelling catheters•
  • Moulds: inhalation, chronic sinusitis, skin, mucosa
28
Q

What is the time scale for viral infections?

A
29
Q

Describe the CMV in these patients?

A
  • Member of herpes virus family: primary infection usually as a child, remains latent•
  • Can be reactivated if immunosuppressed•
  • Reactivation does not always result in infection
30
Q

What is the manifestation of CMV disease in these patients?

A
  • Pneumonitis•
  • Retinitis•
  • Gastritis – colitis•
  • Encephalitis
31
Q

How can CMV disease be prevented?

A
  • Twice weekly quantitative monitoring of peripheral blood viraemia to day 100•
  • Thresholds for treatment together with evidence of increasing viral load•
  • Ganciclovir/valganciclovir: oral and IV preparations.•
  • Minimum of 2/52 treatment with clear evidence of reduction in viral load
32
Q

Name other viral complications of SCT.

A
  • EBV: acute infection, PTLD•
  • Respiratory viruses: influenza, parainfluenza, respiratory syncytial virus, rhino, metapneumovirus, COVID-19•
  • PAPOVA viruses: BK and haemorrhagic cystitis•
  • Adenovirus
33
Q

What affects the outcome of transplant?

A
34
Q

Question

A
35
Q
A

Prior acute GVHD

Haematology (16 decks)

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