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Haematology > Bone marrow transplant/ASCT > Flashcards

Bone marrow transplant/ASCT Flashcards

1
Q

What’s the difference between Autologous and allogeneic?

A

Autologous: from self (peripheral blood or BM)
Allogeneic: from another individual

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2
Q

What is graft versus host disease?

A

Donor’s immune system attacks the tissues of the recipient

This is one of the most common complications of BMT

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3
Q

What are risk factors for acute graft versus host disease?

A

Donor related

  • HLA incompatibility
  • Different sex (F/M)
  • Alloimmunity (previous transfusions, pregnancy)
  • Source of stem cells (peripheral blood >BM >cord blood)
  • Positive CMV serology

Recipient related

  • Age
  • Conditioning regime - total body irradiation, myeloablative
  • GvHD prophylaxis regime
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4
Q

Clinical features of acute graft vs host disease

A

Skin - rash
GIT - cramps, nausea, vomiting, diarrhoea, weight loss
Liver - raised bilirubin, cholestatic LFTs
Fever

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5
Q

How to diagnose acute graft vs host disease?

A

Biopsy

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6
Q

How to grade acute graft vs host disease?

A

4 grades
Based on skin, liver and GIT findings
Correlate with mortality

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7
Q

Why is chronic graft vs host disease not a bad thing?

A

Those that survive acute graft vs host disease have lower relapse rates and higher survival
Because it means the donor T cells are also attacking the leukemic cells

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8
Q

List long-term problems of surviving post-BMT

A 
Relapse 
Chronic graft vs host disease
Infection especially viral
Cardio-respiratory disease
Endocrinopathies 
Infertility
Eye disease 
OP
Renal disease
Secondary cancers particularly oesophageal ca
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9
Q

List indications for autologous BMT

A

3 major conditions

Multiple myeloma (gold standard for initial tx)
NHL (at relapse or up front in some high-grade NHL)
HL (relapse)

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10
Q

List indications for allogenic BMT

A

5 major conditions

Acute leukaemia (AML, ALL) - first admission or relapse
MDS
Severe aplastic anaemia
Immunodeficiency e.g. SCID (children)
NHL
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11
Q

List some early complications of autologous BMT

A

Spend a month in hospital post tx
Risk of death is 1%

Early complications

1) Sepsis
- Particularly bacterial, but also respiratory viruses, CMV, VZV, PJP
- Become neutropenic a few days after transfusion, lasts about 7 days, recover at day 10-14
- Risk factors: length of neutropenia, central access, mucositis/enterocolitis, debilitation

2) Mucositis
- Pain, malnutrition, sepsis, delayed resumption of oral intake and prolonged recovery
- Consider TPN or enteral feeding
- Involve APS

Rare

3) ARDS/idiopathic pulmonary syndrome
4) Engraftment syndrome
5) sinusoidal obstructive syndrome (chemo affects venules in the liver –> liver failure)

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12
Q

List some late complications of autologous BMT

A

Late complications

1) Infection
- Viral, PJP
- Need 6/12 prophylaxis of valaciclovir + Bactrim
- Re-vaccinate at 6+ months

2) Secondary cancers
- MDS/AML after 2-5 years
- Skin cancers
- Solid cancers

3) PTSD/psychological

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13
Q

List early complications of allogeneic BMT

A 
Transplant related mortality 
Chemo-radiotherapy toxicity
Hepatic sinusoidal obstructive syndrome
Idiopathic pneumonia syndrome
Diffuse alveolar haemorrhage
TTP/HUS
Infection and neutropenic sepsis
Acute graft vs host disease
Graft failure/rejection
Haemorrhagic cystitis
ICU post BMT
Transfusion and nutritional support
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14
Q

2 Sources of haematopoietic stem cells (autologous and allogeneic)

A

Peripheral blood

  • Dominant source
  • Give CGSF to encourage stem cells to migrate from BM to peripheral blood
  • Collected via leukapharesis - separate stem cells from white cells
  • Associated with faster engraftment but also increased rate of GVHD
  • Easier to collect and transport

Bone marrow
- Stem cells harvested directly from pelvis

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15
Q

Explain HLA matching

A

Inherit one chromosome 6 from mum and one from dad
HLA is located on chromosome 6

Matching major class I (HLA A, B, C) as well as class II (HLA DR, DQ, DP) antigens associated with reduced GVHD

Most important ones to match are HLA A, B, C, DR

Even if you match all major class I and II, and its a “full match”, there are still minor HLA differences within the chromosome that can cause GVHD

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16
Q

What are the donor possibilities?

A

Matched sibling

Matched unrelated donor

Mismatched unrelated donor
- High GVHD but lower relapse risk (this often go hand in hand)

Haploidenitical donor

  • Matched at half (one set) of HLA class I and II
  • Not preferred at the moment
  • Gaining popularity

Umbilical cord blood

  • Cord blood collected soon after delivery
  • Less stringent matching criteria, suitable for patients without related or unrelated donors
  • Reduced GVHD, reduced engraftment
  • Less popular now
17
Q

What happens in autologous HSCT?

A

Extract and conserve your own SCs

Allows delivery of high dose therapy for treatment of malignancies

Infuse back your own SCs so they can work again

Alteration of the adaptive immune system in autoimmune disease

18
Q

3 main roles in allogenic HSCT?

A

3 main roles

1) Deplete resident HSC from the BM niche (so donor cells can come in)
2) Suppress the recipient immune system to prevent graft rejection
3) Deplete any residual malignant cells

19
Q

2 types of allogenic conditioning regimen types

A

Myeloablative conditioning (MAC)

  • Autologous recovery unlikely. Need donor cells/engraftment.
  • Intense
  • Lower relapse rates
  • Increased GVHD
  • Requires fitter, younger patients

Reduced intensity conditioning (RIC)

  • Autologous recovery possible
  • High relapse rate but reduced GVHD
  • Older, less fit patients
20
Q

Complications of autologous HSCT

A

Mortality is rare <1% in haematologic malignancies, however mortality is high if performed on systemic sclerosis

Relapse high and leading cause of death after 100 days

Second malignancies long-term (often exposed to alkylating agents)

Overall survival approaches the general population if you survive 10 years

21
Q

Complications of allogenic HSCT

A

Far more common than autologous HSCG

Transplant related mortality is much higher (14-41% at 2 years)

Relapse 
Infections
GVHD
Organ toxicity
Graft failure

Late effects (not like autologous where the overall survival approaches general population at 10 years, allogenic HSCT always has the potential of late effects)

22
Q

Infectious complications post allogenic HSCT

A

Preengraftment <30 days

  • Neutropenia
  • Mucositis
  • Central catheter e.g. IDC related infections
  • Acute GVHD
  • Bacterial infection - gram neg, gram pos, HSV, candida, early aspergillus

Early postengraftment 30-100 days

  • Less bacterial infections but can still get respiratory infections, pneumonia
  • More viral infections: CMV, VZV (prophylaxis given), RSV, EBV (associated post transplant lymphoproliferative disease; prophylaxis with rituximab?)
  • PJP (prophylaxis given)
23
Q

Infectious disease porphylaxis in Allogenic HSCT

Gram neg bacteria

PJP

Invasive fungal disease

HSV/VZV

CMV

EBV

A

Gram neg bacteria - none given but potentially small survival benefit

PJP - yes, pantamadine during neutropenic phase then transition to bactrim (myelosuppressive effects)

Invasive fungal disease - yes esp targeting aspergillus (leading fungal disease)

HSV/VZV - yes, aciclovir or valciclovir

CMV - traditionally, monitor CMV twice a week and almost always you see a rise in CMV level before CMV disease but not always the case and then treated with ganciclovir. New agent letermovir is now associated with reduced viremia and disease (but no change to survival).

EBV - surveillance only. Evidence with rituximab that depletes the B cells (EBV infects B cell machinery to replicate itself). Rituximab is associated with lower rate of post transplant lymphoproliferative disease thought to be due to reducing EBV burden.

24
Q

CMV - what donor and recipient is best?

A

Matching CMV status e.g. positive to positive or negative to negative = better survival

Mismatch donor = worse survival in general
CMV positive recipient + CMV negative donor = worst outcome (donor’s immune system is naive to CMV, highest risk of infection)

25
Q

Acute GVHD is driven by … Cells

A

T cells

26
Q

Chronic GVHD is driven by …. cells

A

T + B cells

27
Q

Acute GVHD and chronic GVHD is classically separated by … days

A

100 days

However features of acute GVHD can still occur after 100 days = “persistent acute GVHD” or “recurrent acute GVHD”

28
Q

GVHD prophylaxis

A

Multiple agents used

  • Calcineurin inhibitors - cyclosporin or tacrolimus
  • Mycophenolate mofetil
  • MTX
  • Post transplant cyclophosphamide
  • Donor T cell depletion (in vivo using anti thymocyte globulin; ex vivo in a lab and physically remove T cells)
29
Q

What’s post transplant cyclophosphamide?

A

Used in mismatched grafts or mismatch haploidentical donors

Deliver donor graft along with T cells –> allow T cells to proliferate –> day 3 deliver cyclophosphamide –> depletes the cells that are starting to react to the donor (does not threaten the HSC)

30
Q

Acute GVHD affects which 3 organs

A

<100 days

1) Skin
Erythematous maculopapular rash often involves palms, soles but also entire body
Severe cases –>bullae –> desquamation

2) Liver
Deranged LFTs

3) GI tract
Anorexia, N&V
Diarrhoea

31
Q

Chronic GVHD manifestations

A

> 100 days

1) Skin
Sclerotic type lesions, plaque like lesions
Hair loss
Presently dry skin

2) Oral mucosa
Reticular changes, ulcers, mucoceles

3) Eyes
Dry eyes

4) liver
5) GI tract

6) lung
Most concerning places
High rates of mortality
Bronchiolitis obliterans = restrictive picture; traction bronchiectasis on CT

7) Joints and fasciae
Sclerosis and reduced range of movement

32
Q

Treatment GVHD

A

1st line: glucocorticoids (if mild, topical)

2nd line/steroid refractory: Ruxolitinib (JAK inhibitor) new
Prior to this, there were lots of treatments with similar efficacy

However in general, steroid refractory is associated with high mortality and difficult to treat

33
Q

What’s sinusoidal obstructive syndrome ie veno-occlusive disease?

A

Immune related damage to endothelial cells –> slough off –> obstruct the sinusoid –> reduces hepatic outflow –> hepatocellular damage

Associated with high mortality

34
Q

Rx veno-occlusive disease

A

Prophylaxis with ursodeoxycholic acid until day 90

Improved survival

35
Q

What’s graft failure?

A

Primary graft failure - never failed to engraft

Secondary graft failure - grafted then failed

Graft failure is higher in haploidentical, mismatched graft or cord blood transplant

Associated with 80% mortality

36
Q

Risk factors for graft failure

A 
Pre-transplant (difficult to modify)
HLA mismatch
Non-malignant disease
Advanced disease
Extensive marrow fibrosis extensive prior treatment
Donor age
Splenomegaly
Iron overload 
HLA antibodies
Transfusion history

Pre-transplant (easy to modify)
Graft source
Conditioning
T cell depletion

Peri-post transplant
CD34+ cell count
Viral infections
GVHD
Drug toxicity
37
Q

Late effects of allogenic HSCT

A

Overall survival is less than general population even if there is no GVHD or relapse

Can affect every organ
Cognitive impairment
Heart failure
Post transplant depression/anxiety/PTSD

Haematology (7 decks)

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