Stem Cell Transplantation Flashcards

1
Q

How are donors for stem cell transplantation chosen?

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 are the chances of HLA match within a family?

A

Each sibling has a 25% 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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3
Q

Which patients are autologous stem cell transplants suitable for?

A

Acute leukaemia

Solid tumours

Autoimmune disease

Myeloma

Lymphoma

Chronic lymphocytic leukaemia

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4
Q

Which patients are allogenic stem cell transplants suitable for?

A

Acute leukaemia

Chronic leukaemia

Myeloma

Lymphoma

BM failure

Congenital immune deficiencies

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5
Q

What are the principles 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

Infuse stem cells

Continue immunosuppression & support patient through period of cytopenia

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6
Q

Where do haemopoeitic stem cells come from?

A

Umbilical cord

Plasma

Bone marrow

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7
Q

What are complications associated with stem cell transplant?

A

Graft failure

Infections

Graft-versus-host disease (GVHD): Allografting only

Relapse

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8
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.

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9
Q

What are risk factors for GvHD?

A

Degree of HLA disparity

Recipient age

Conditioning regimen

R/D gender combination

Stem cell source

Disease phase

Viral infections

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10
Q

What is the treatment for acute GvHD?

A

Corticosteroids

Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus

Mycophenylate mofetil

Monoclonal antibodies

Photopheresis

Total lymphoid irradiation

Mesenchymal stromal cells

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11
Q

How can acute GvHD be prevented?

A

Methotrexate

Corticosteroids

Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus

CsA plus MTX

T-cell depletion

Post-transplant cyclophosphamide

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12
Q

What are features of chronic GvHD?

A

Immune dysregulation

Immune deficiency

Impaired end-organ function

Decreased survival

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13
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.

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14
Q

What are risk factors for chronic GvHD?

A

Affects 50% of patients who survive >1 year from transplant.

  • 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
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15
Q

What are the main sources of infection in neutropenic patients?

A

Gram +ve: Vascular access

Gram -ve: GI tract

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16
Q

What are the most common causative organisms of bacterial infections in neutropaenic patients?

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.

17
Q

How is neutropaenic sepsis managed?

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.

18
Q

Which fungal infections are common in neutropaenic patients?

A

Yeasts from translocation from the intestinal mucosa, or indwelling catheters.

Moulds: Inhalation, chronic sinusitis, skin, mucosa.

19
Q

What is the association between CMV and neutropaenia?

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.

20
Q

What are manifestations for CMV?

A

Pneumonitis

Retinitis

Gastritis – colitis

Encephalitis

21
Q

How is CMV 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.

22
Q

Which other viruses can cause complications in stem cell transplants?

A

EBV: Acute infection, PTLD

Respiratory viruses: Influenza, parainfluenza, respiratory syncytial virus, rhino, metapneumovirus, COVID-19

PAPOVA viruses: BK and haemorrhagic cystitis.

Adenovirus

23
Q

What affects the outcome of a 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: <1yr=0, >1yr=1

Donor: Sib=0, VUD=1