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Year 5 - Pathology > HAEM: Bone marrow transplant > Flashcards

HAEM: Bone marrow transplant Flashcards

1
Q

How resistant is bone marrow to irradiation? How risky is BM transplant? What is the cost of BM transplants?

A
  • CNS is the most resistant to radiation (bone marrow is one of the least)
  • Bone marrow transplant is the most expensive and risky elective procedure offered by the health service
  • Risk of dying from a bone marrow transplant is >50%
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2
Q

What is a CD marker of stem cells?

A

CD34

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3
Q

Which conditions are suitable for autologous BM transplants?

A
  • Acute leukaemia
  • Myeloma
  • Solid tumours
  • Lymphoma
  • Autoimmune disease
  • CLL

In theory should work best in those without BM disease but in practice done mostly in lymphoma and myeloma. Chemo first, then GCSF and extraction once in remission, then myeloablation and reinfusion.

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4
Q

What are the steps invovled in autologous transplants?

A
  • GCSF given and obtain a CD34+ population of cells from the bone marrow (the stem cells)
  • These are preserved in the freezer
  • A high dose of chemotherapy is given to eradicate the bone marrow à reinfuse the stem cells
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5
Q

What conditions are suitable for allogenic BM transplantation?

A
  • Acute leukaemia
  • Chronic leukaemia
  • Thalassaemia
  • Myeloma
  • Lymphoma
  • SCD
  • Bone marrow failure
  • Congenital immune deficiencies
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6
Q

What are the steps involved in allogenic transplantation?

A
  • Used when patient’s disease is unlikely to be eradicated from the bone marrow by standard chemotherapy
  • Give them high dose chemoradiotherapy to ablate the bone marrow (malignant and normal cells)
  • Then give them some bone marrow from a healthy donor

Issue with BM transplantation is that donor immune cells recognise patient as foreign.

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7
Q

What are the chances of matching a BM transplant with a sibling?

A

1 in 4

More recently there has been increased use of haploidentical (half matched) family member - almost every patient has a donor

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8
Q

Where is HLA encoded chromosomally? Which are typed for BM compatibility purposes?

A

Chromosome 6

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

NB:

  • 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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9
Q

How is chance of HLA match within the family calculated?

A

Probability of having match with a sibling is 1-(3/4)^number of siblings

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10
Q

What is the use of serology and DNA matching in HLA matching?

A

Serology gives you the low resolution HLA group e.g. HLA-A2

DNA matching gives you high resolution matching e.g. HLA-A*0203 etc

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11
Q

How many BM cells are required in each BM harvest?

A

2 x 106 CD34+ cells/harvest

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12
Q

What does BM sampling involve?

A
  • Involves anaesthetising the patient and sampling some bone marrow from their pelvis
  • Puncturing the bone and getting into the medulla damages it, meaning that the first few millilitres that you collect will contain stem cells, however, the rest of it will be blood flooding into the damages site
  • So, you keep re-puncturing the bone, collecting a small amount at a time until you have a good harvest

(1.5L, 1% CD34+ = 15mL CD34)

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13
Q

What does peripheral blood sampling for HSC involve?

A
  • Hormones (e.g. G-CSF) can be used to stimulate granulocyte production (given 5 days before)
  • This leads to the bone marrow releasing some white cells as well as some stem cells
  • The donor is connected to a centrifuge device which spins the blood, removes the white cell component, reassembles the red cells and plasma and reinfuses it into the patient

(10L, 1% CD34+ = 100mL CD34)

~200ml of white cells extracted in this way.

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14
Q

What does the success of HSCT depend on regarding the source? What is the disadvantage of umbilical cord stem cell harvesting?

A
  • Important because success of transplant depends on the number of CD34 cells per kg of weight of the recipient
  • Therefore, in cord blood (only harvest 0.1L), there is fewer CD34 cells and so can only really be used for babies
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15
Q

What does umbilical cord stem cell sampling involve?

A
  • Umbilical cord stem cells (0.1L, 1% CD34+ = 1mL CD34)
  • Stem cells can be harvested at the time of delivery

Used for people of a small size as this has highest concentration of CD34+ cell

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16
Q

What are the complications of HSCT?

A
  • Graft failure
  • Infections
  • Graft-versus-host disease (GVHD): allografting only
  • Relapse
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17
Q

Which risk score is used for outcomes of transplants?

A

EBMT risk score

Higher score means less chance of successful outcome: 80% survival in score 0-1, 70% survival in 2 score, 50% survival in 3 score, 30% survival in 4 score, 15% survival in 5-7 score

  • 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

*VUD = Volunteer Unrelated Donor

18
Q

What is the pathophysiology of GvHD?

A
  • Damaging the skin, GI tract and various other tissues by giving chemotherapy will cause the release of cytokines which activates APCs, which then present the antigens to the donor lymphocytes –> immune reaction against the host tissue
  • You could wait for longer after the chemoradiotherapy for the effects to die down before giving the stem cell transplant, however, this increases the time during which they are susceptible to infection
19
Q

What is shown?

A

GvHD maculopapular rash which is widespread

20
Q

How is GvHD staged and graded?

A

Based on skin, liver and GI signs and symptoms.

21
Q

What are the sites affected by acute vs chronic GvHD?

A

Acute GvHD affects skin, gastrointestinal tract and liver

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

22
Q

What are the risk factors for acute GvHD?

A
  • Degree of HLA disparity
  • Conditioning regimen
  • R/D gender combination
  • Stem cell source
  • Disease phase
  • Viral infections
23
Q

What are the available treatments for GvHD?

A
  • Corticosteroids
  • Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
  • Mycophenylate mofetil
  • Monoclonal antibodies
  • Photopheresis
  • Total lymphoid irradiation
  • Mesenchymal stromal cells
24
Q

What can be used to prevent acute GvHD?

A
  • Methotrexate
  • Corticosteroids
  • Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
  • CsA plus MTX
  • T-cell depletion
  • Post-transplant cyclophosphamide
25
Q

List 3 pathological features of GvHD.

A
  • Immune dysregulation
  • Immune deficiency,
  • Impaired end-organ function
  • Decreased survival.
26
Q

What is the 5 year survival in low and high risk chronic GvHD? When is it usually diagnosed?

A

Within 6 months of transplant and lasts 2-5 years.

Low risk - 70-80% survival for 5 years

High risk - 30-40% survival for 5 years

27
Q

List some features of chronic GvHD.

A
28
Q

What are the risk factors 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
29
Q

What is the most important RF for cGvHD?

A

Previous GvHD

30
Q

Which infections occur pre and post engraftment and late phase?

A
31
Q

What is the main source of infection in neutropenic patients?

A

Gram +ve from vascular access

Gram -ve from gastrointestinal tract (of the patient)

*not from those who visit.

32
Q

Do gram + or - cause death in neutropenic patients?

A

Gram -ve most commonly

33
Q

How do you manage neutropenic sepsis?

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
34
Q

How do transplant patients acquire fungal infections? What is the mortality?

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

41% mortality in allo, 59% mortality in auto

35
Q

Which viruses are most common in post-transplant patients?

A
36
Q

What is CMV infection and how does it affect the host?

A

Type of herpes virus, remains laten and can be reactivated in immunosuppression; although reactivation may not result in infection

37
Q

What are 4 manifestations of CMV?

A
  • Pneumonitis
  • Retinitis
  • Gastritis – colitis
  • Encephalitis
38
Q

How do we prevent CMV disease?

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
39
Q

List 4 other viruses affecting HSCT patients.

A

EBV: acute infection, PTLD

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

PAPOVA viruses: BK and haemorrhagic cystitis

Adenovirus

40
Q

What is the effect of removing T cells from HSCT?

A
  • Those with T cell depletion did not have any GvHD
  • But relapsed within about 18 months and had worse survival in those with T cell depletion compared to HSCT without depletion due to lack of graft vs. leukaemia effect.
  • Also get more viral infections with T cell depletion
41
Q
A

2

42
Q
A

About 30 days after

More common in seropositive patients

Cannot be cured by antibacterials

Answer is 3

Year 5 - Pathology (89 decks)

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