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Haematology > Bone Marrow Transplant > Flashcards

Bone Marrow Transplant Flashcards

1
Q

Fludarabine

  • class
  • use
  • CIs
A

Class: purine analogue
Use: mainly in CLL….
CIs: CrCl <30, haemolytic anaemia, pregnancy, lactation

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2
Q

BMT Conditioning regimens

A

Myeloablative, reduced intensity and nonmyeloablative

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3
Q

Cyclophosphamide
Class
Uses

A

Class - alkylating agent

Uses - myelo/lympho proliferative disorders and other cancers

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4
Q 
In AML, what prognosis is conferred by the involvement of the following genes?
A. FLT3-ITD 
B. EVI-1
C. WT1 
D. NPM1 alone
A

A. very poor prognosis
B & C - no associated prognosis
D. Good prognosis

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5
Q

Flu/mel is an example of which of the following

  • myeloablative
  • Reduced intensity conditioning
  • non myeloablative
A

RIC

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6
Q 
Which of the following could NOT be attributed to endothelial dysfunction?
A. Engraftment syndrome
B. Haemorrhagic cystitis
C. Veno-occlusive disease of the liver
D. Thrombotic microangiopathy
A

B - haemorrhagic cystitis - is a complication of cyclophosphamide (given with mesna to reduce risk)

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7
Q

Out of bone marrow and peripheral blood SCT, which has:
A. Better engraftment
B. Less GvHD
C. Better survival

A

A. Peripheral blood SCT is associated with better engraftment
B. Traditional BM biopsy is associated with reduced GvHD (hence why we still tend to do this in paediatrics - don’t want to commit a young person to GvHD for the rest of their life)
C. Neither has proven to be associated with better survival

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8
Q

Which cell populations recover the earliest post alloSCT?

A

First are monocytes, granulocytes, and NK cells

T and B cells take 1-2 years to recover and a proportion of patients will have ongoing deficits

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9
Q

Why do we discharge patients on phenoxymethylpenicillin?

A

GvHD gives patients functional asplenism
We discharge on phenoxymethylpenicillin as prophylaxis for invasive pneumococcal disease, which is the most likely infection associated with hyposplenism

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10
Q

First line treatment for mild C diff infection

A

PO metronidazole

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11
Q

Why do we give acyclovir prophylaxis post alloSCT?

A

Prevent reactivation of HSV-1 and 2.

AS WELL

As prophylaxis against VZV. VZV can cause severe (potentially fatal) disease including hepatitis & meningoencephalitis late after alloSCT even in the absence of skin lesions. Risk of reactivation is high especially later i.e. >3 months, post transplantation.

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12
Q

CMV in alloSCT?

Highest risk for reactivation?
How do we detect and prevent?

A

Common for either donor or recipient, or both, to be seropositive.

Highest risk of reactivation when donor is negative and recipient is positive (because you delete your own immune cells and the CMV you already have can reactivate).

Do CMV viral loads weekly. Prophylactic valganciclovir is given until D-2, then ceased and switched to valaciclovir until engraftment (count recovery), then switched back to valganciclovir to D+100. Not given whilst counts low because it can cause BM suppression/failure, hence the reason for the switch.

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13
Q

PJP prophylaxis surrounding BMT?

A

Give bactrim until D-2, withhold until neutrophil count recovers >1.0 – can cause pancytopenia (withhold whilst counts low)

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14
Q 
The HLA locus with the least evidence for the importance of matching on clinical outcome is:
A/ HLA-A
B/ HLA-C
C/ HLA-DRB1
D/ HLA-DQB1
A

D. HLA DQB1 is the least important

HLA-A and C and both MHC class I

The others are both MHC class II

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15
Q 
GvHD is the main risk factor for which of the following:
A. Cataract formation
B. Bronchiolitis obliterans syndrome 
C.  Secondary  breast cancer
D. Thyroid dysfunction
A

B - bronchiolitis obliterans

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16
Q

Causes of haemorrhagic cystitis in BMT patients?

A

Cyclophosphamide

and

BK (polyoma) virus - latent virus in uroepithelium. GvHD is a risk factor for BK-associated haemorrhagic cystitis.

17
Q

What is bronchiolitis obliterans?

A

Clinical syndrome associated with small airways injury. Can be caused by inhalational, infectious, drug exposures AND following lung or haematopoietic SCT

Symptoms: dyspnoea, airflow limitation (obstructive pictures)

18
Q

What is engraftment post BMT defined as?

A

Absolute neutrophil count >1.0 OR 3 consecutive days with a count above 0.5

19
Q

DDx for pulmonary complications BEFORE engraftment (i.e. in the first 30 days)

A
  • Infection
  • Pulmonary oedema
  • Sepsis
  • Aspiration
  • Engraftment syndrome
20
Q

DDx for pulmonary complications AFTER engraftment (i.e. 30 days onwards)

A
  • Infection
  • Pulmonary oedema less common although can occur
  • Diffuse alveolar haemorrhage
  • Idiopathic pneumonia syndrome (non infectious widespread alveolar injury)
  • Pulmonary alveolar proteinosis
21
Q

What is engraftment syndrome?
Timeframe?
Symptoms?
What test may predict engraftment syndrome?

A

Non infectious complication of alloSCT seen in about 15-20% of recipients

  • Develops approx 10 days post alloSCT in time of neutrophil recovery (within 3 days of engraftment)
  • Symptoms are typically mild and include fever, rash (diffuse erythema), with variable presence of dyspnoea/hypoxemia, weight gain, diarrhoea and altered mental status

A rapid fall in phosphate may predict engraftment syndrome

22
Q

Engraftment syndrome radiological appearances

A

Bilateral ground glass
Hilar or peribronchial consolidation
Thickening of septa

23
Q

What are the diagnostic criteria for engraftment syndrome?

How do we treat it

A

Three major or two major AND one minor criteria

Three major:

  • Non infectious fever > 38
  • Erythematous maculopapular rash (not due to drug/acute GvHD)
  • Diffuse pulmonary opacities consistent with non cardiogenic pulmonary oedema

Minor criteria:

  • Liver dysfunction
  • Renal failure
  • Transient encephalopathy

TREATMENT: STEROIDS

24
Q

Hyperacute and acute GVHD timeframe

A
  • Hyperacute - within the first 2/52 post transplant. 88% have skin involvement and non-cardiogenic pulmonary oedema
  • Acute - in first 100 days following alloSCT. Rarely affects lungs directly.
25
Q

Which of the following is not a clinical manifestation of VOD?
Weight gain, ascites, platelet refractoriness or diarrhoea

A

Diarrhoea is not a feature

Weight gain, ascites both result from endothelial dysfunction and leaky vessels

Platelet refractoriness is from post transplant micro-angiopathy associated with endothelial damage/dysfunction

26
Q

BPT exam question

What is the correct test for comparing two Kaplan-Meier survival curves?

A

Log-rank test

27
Q

Who gets alloSCTs?

A

The most common patient group to get alloSCTs are the acute leukaemias (AML/ALL)
- AlloSCTs for AML/ALL are given POST intensive chemo and BEFORE there is any evidence of relapse, to reduce the risk of disease recurrence, which is associated with a terrible prognosis - i.e. 6 months.
Currently, whether or not you get an allo is mainly based on high risk mutations. We don’t know if a patient is cured or not before they have the alloSCT (i.e. they could be in the proportion of adverse risk patients are actually cured from chemo, but you can’t take that chance). AlloSCT is not without risks, so it’s a bit of a gamble.

For the more indolent conditions, like CML, alloSCT used to be the mainstay before new treatments arrived. Now, we give alloSCTs to CML/lymphomas etc. if they have failed the other treatments. BMTs are risky and have high mortality so you want to avoid it if there are other options.

AlloSCT remains the only curative treatment for myelofibrosis.

28
Q

Acute vs chronic GvHD timeline

A

Acute generally before 100 days, chronic >100 days

29
Q

Most common cause of death post stem cell transplant?

A

Recurrence of disease

Other causes of death include infection, second cancers and organ dysfunction

30
Q

How long does immune reconstitution take post transplant?

A

18 months to 2 years

31
Q

Why might immune reconstitution take longer than normal in certain patients?

A

Slower in alloSCTs than autos

Slower in HLA mismatched, T cell-depleted grafts and in the presence of cGvHD

32
Q

Cardiovascular disease post transplant?

A

2-10% of SCT survivors will die from CV causes. Greater risk than in matched non-transplant population.

More likely to get diabetes, HTN, chol, etc. cGVHD and chemo are also risk factors.

33
Q

What’s the greatest cause of late non-relapse mortality in autoSCTs?

A

Pulmonary complications! (although the chance of pulm cx with autos is still lower than in alloSCTs).

34
Q

What kidney problems can you get post SCT?

A
  • Thrombotic microangiopathy
  • Drug toxicity
  • Nephrotic syndrome
  • Membranous GN
35
Q

Fertility after SCT?

A

Myeloablatative allo almost always causes sterility…

Auto and allo (due to conditioning or cGVHD) very commonly have temporary/permanent infertility.

36
Q

Other long term endocrinology cs of SCT

A

Hypoadrenalism, hypothyroidism (a third!), OP, avascular necrosis…

37
Q

Which organ is most commonly involved in GVHD?

A

Skin!

Skin, liver and GI tract are the most common

Haematology (8 decks)

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