Bone Marrow Transplant Flashcards

1
Q

What are the indications for BM transplants? (kind of conditions - 5+)

A

Malignant & Non-malignant indications

Malignant: both autologous (more common) or allogenic

  • Acute and Chronic Leukaemia
  • Lymphoma, including Hodgkin’s
  • Multiple Myeloma

Non-malignant: mostly Allogenic, not autologous

  • Aplastic anaemia, Fanconi’s anaemia
  • Thalassaemia
  • Sickle cell dsiease
  • Severe combined immunodeficiency
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2
Q

What are the reasons for conditioning the BM prior to SCT? (3)

A

To kill tumour cells

Prevent GvHD

Create space for new stem cells

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3
Q

Difference between myeloablative vs. non-myeloablative (reduced-regime, aka - reduced intensity regime - RIC) conditioning? What is the main pros + cons for each? (2)

A
  • Myeloablative → wipes out the BM. If they don’t get SCT they will remain aplastic and BM will not recover
    • Reduces GvHD
    • Higher risk of infections
  • Reduced intensity → BM will recover without SCT
    • Reduces life threatening infections
    • HIgher risk of GvHD
    • Allows us to offer allogeneic transplants to older patients
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4
Q

What are the complications of BM transplant? (6)

A

Specific to BM: Mucositis, GvHD, Cytopaenia

General transplant associated:

Infection - including CMV, EBV, BK, encapsulated bacteria, VZV, PJP, Aspergillous, toxoplasma

Steroid-related complications: diabetes and osteoporosis

VOD (aka SOS) Hepatic Sinosoidal Obstructive Syndrome

Secondary malignancy

Relapse

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5
Q

How WOULD you describe transplant patient in the long case presentation? (must know)

A
  • Up to 100 days since stem cell engraftment (day 0)
  • How many month after this
  • Really helps what could be going wrong
  • E.g. Mr Jones is 65yo male who is day (X) after his reduced/full intensity regime, matched/unmatched (type of – sibling/MUD/Haplo) transplant for (indication – e.g. high risk AML) that was (in remission or not) at the time of transplant
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6
Q

How does acute GvHD present? (4)

A

Maculopapular rash - in severe cases desquamation

Pruritis

Derranged LFTs

Diarrhoea

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7
Q

Risk factors for GvHD? (5) - what is the prevalence?

A
  1. Degree of HLA mismatch

~40% of recipients of fully matched sibling donor

~70% in those with 1 antigen mismatch from unrelated donor

  1. Previous blood product exposure
  2. Previous pregnancy
  3. Source of graft (risk higher with peripheral blood or BM compared with cord-blood)
  4. GvHD prophylactic regime used
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8
Q

BMT - examination (5)

A

Anaemia, Cachexia

Lymphadenopathies

Signs of infection: especially for HSV, EBV, chest infection

Stigmata of chronic GvHD: skin changes similar to scleroderma, dry eyes, mouth (sicca), alopecia, signs of bronchiolitis obliterans (wheeze)

Hepatomegaly + Ascites (VOD)

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9
Q

How would you support this patient undergoing a BM transplant (3)?

A
  1. Cytopaenia: transfusion support (irradicated blood, PLT - must be CMV -ve if CMV -ve recipient) until the engraftment occur. G-CSF (to support engraftment + speed recovery)
  2. GvHD prophylaxis (allo): Prednisolone + MTX +/- Cyclosporin
  3. Infection prophylaxis: valganciclovir if CMV +ve, use sero -ve blood, fungal (fluconazole/posiconazole), PCP (Bactrim: 6-12 months)
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10
Q

How would you manage complications of BM transplant? (8)

A

ABCDEFG

Acute GvHD: Methylpred + Cyclosporin. If steroid refractory - Rituximab, ATG, Alemtuzumab (anti-CD52)

Chronic GvHD: presents with skin thickening like scleroderma, difficulty eating due to pain, GI upset. Prednisolone, extra-corporial photophresis → WCC isolated and exposed to UVA irradiation then returned.

Bone marrow: cytopaenia support transfusion support + G.CSF in consultation

Cancer surveillance: age-appropriate cancer screening - full skin checks, mamogram, PSA, FOBT/Colonoscopy…etc.

Dry mouth - Mucositis: Big problem (results in feeding difficulties and malnutrition) sodibic mouth wash, LA, analgesia, screen for HSV and Aciclovir if present

EEnfection: Infection: prophylaxis, vaccination, hygiene. Education + Action plan.

Fertility: sperm/ovum banking pre-transplant, GnRH agonist for ovarian protection

Hepatic Sinusoidal Obstructive Syndrome (SOS or known as VOD - Veno Occlusive Disease): monitor LFTs, hepatomaly, jaundice and ascites. Prevent with UDCA prophylaxis if having hyeloablative transplant. Tx with Defibrotide. Consider tPA.

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11
Q

What are the BMT details you must obtain in the long-case (P?) 7.

A
  1. Indication - was other treatment unsuccessful? relapse? Important to know as prognosis is worse if BMT was done due to failed tx.
  2. Autologous or allogenic
  3. Who was the donor? parent, sibling or unrelated
  4. HLA match (allogenic, matched out of 8 or 10)
  5. Source (mobilised peripheral blood, BM [aspirate] or cord blood)
  6. Conditioning/Full (or myeloablative - BM wiped out completely with radiation of chemo) or reduced-regime (full or reduced intensity)
  7. Has the patient had GvHD prophylaxis (if allogenic)
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12
Q

BMT - PRICMCP?

A

P: when was it, indication, prior tx, matching, graft source, conditioning vs. reduced regime, GvHD prophylaxis

C: complications - how long was the patient in the hospital?

  • Transplant itself: graft rejection, GvHD (acute <3m or chronic >3m), Hepatic SOS (jaundice, RUQ pain, LFT derrangement), recurrence of original disease
  • Therapy related: mucositis, cytopaenia, infection (PJP, CMV, BK…etc), infertility, steroid complications (DM + OP), secondary malignancy

M:

  • Current medications: ImmunoSx
  • Infection prophylaxis, vaccinations - does patient have an action plan for symptoms of infection?
  • Hepatic SOS prophylaxis (UDCA, defibrotide)
  • Transfusion support
  • Sperm/ovum banking

C: Why is patient in hospital now? ask about symptoms of GvHD and VOD. Does patient feel better after transplant? _How is patient coping (enough support at hom_e)? Infertility is big issue for young patients

P: Insight re: long-term complications of transplant e.g. infection - understand importance of vaccines/hygiens…etc. Insights into prognosis.

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13
Q

Timing of Acute and Chronic GvHD?

A

Acute - by definition, occur within 3 months after transplant.

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14
Q

What are measures to prevent GvHD? (2) what is the problem associated with the latter approach?

A

Prophylaxis: prednislone + immunosuppressives (e.g. MTX and Cyclosporin/tacrolumus)

Donor BM maybe treated to remove T-cells but this increases the risk of Graft rejection

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15
Q

Management of severe acute GvHD?

A

High dose prednisolone

Antithymocyte globulin (ATG)

Monoclonal Ab to T-cells

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16
Q

What is the long-term problem of GvHD?

A

Increased risk of tumour recurrence.

17
Q

Chronic GvHD clinical features?

A

Develops after 3 months following the transplant.

Autoimmune like-illness with sicca, sclerooderma-like skin thickening, arthritis, cholestasis, bronchiolitis obliterans.

18
Q

Why is it important to know indication for BM transplant, whether it was done as a primary or secondary therapy when all else has failed?

A

Because if latter is the case, the prognosis is worse.

19
Q

5yr survival rates of BM transplant patients?

Acute Leukaemia

CLL

CML

Hodgkin’s

NHL

A

Acute Leukaemia ~50%

CLL ~50%

CML ~70% (chronic), 40% (accelerated), 15% (blast crisis)

Hodgkin’s ~50%

NHL ~40%

20
Q

Explain the phases of stem-cell transplant? (4)

A

Conditioning - with chemo or RTx to eliminate malignancy

Neutropaenic phase

Engraftment

Post-engraftment phase (main problems are infection and GvHD)

21
Q

Timing and type of infections following the BMT? (3 time periods)

A

First month (neutropaenc phase): bacterial, fungal

Upto 3 months: viral - CMV, EBV, BK, RSV

After 3 months - Atypicals: PJP, Aspergillous, Toxoplasma, encapsulated bacteria.

Infections are a lot less frequent after 100 days, as immunosuppressive are generally weaned off (if all goes well with minimal GvHD) unless of course, they are being treated for GvHD (chronic) - which may require prolonged immunosuppressive therapy.

22
Q

DDx for derranged LFTs post BMT? How would you distinguish between them? (3)

A

GvHD - acute <100d (rash, diarrhoea) vs. chronic >100d (scleroderma like skin-thickening)

Hepatic SOS (VOD) - usually within 3 weeks. Ascites & RUQ pain.

So timing is the key and clinical features are quite different.

Medication (MTX - hepatotoxicity, CsA - raised bilirubin/AST)

23
Q

Sibling has what % chance of a 6/6 match?

A

25%

24
Q

What is 10/10, 8/10 match?

A
  • Just means that more of HLA genes, other than A,B,D are tested (e.g. C and DQ)
  • 8/10 match → less well matched (mismatched transplant) → really high risk of GvHD
25
Q

What is Syngeneic vs. Haploidentical transplant?

A

Syngeneic = from identical twin

Haploidentical transplant - 50% exact match.

  • 75% of sibling will have 50% exact match (1/4 sibling will have no match and hence useless)
  • Your parents have 50% HLA types that match (as you have inherited 1 from each)
  • You can extend search to include extended families
  • High-likelihood of finding a match
26
Q

What are indications for autologous SCT?

A
  • MM
  • Lymphoma
  • Follicular
  • Relapsed chemo-responsive DLBCL
  • Hodgkin’s (50% respond even if chemo-refractory)
  • T-cell lymphoma
  • If patient tells you that they had autologous SCT for other disease – may not be true as this is very rare
27
Q

Would you give childhood vaccination to patient who had SCT? Why?

A
  • Yes because the chemotherapy to cook the BM will wipe out memory cells.
  • As per childhood vaccination program
  • PCP and Shigles prophylaxis
28
Q

What is the mortality risk with allogenic transplant? (siblig, haplo and MUD)

A

About 20-25% over 6 months

29
Q

What is the purpose of “conditioning”?

A
  • To allow engraftment
  • Prevent GvHD
  • Not to directly kill tumour cells
  • So over the years we have been using less toxic regime (from whole body radiation + high dose cyclophosphamide* (i.e. full-intensity regime) ⇒ Mephalane + fludarabine) – aka. Reduced Intensity Allograft (RIC)
30
Q

What are the indications of Allogenic SCT?

A
  • Acute leukaemia* (AML, ALL) – high risk cytogenetics
  • MDS* (BM failure) – high risk cytogenetics
  • Aplastic anaemia (5yr survival 90% - particularly good)
  • Refractory lymphoma
31
Q

Pros and cons of BM harvest over peripheral blood? (2)

A

•Advantages

  • Very few lymphocytes → less risk of GvHD
  • Especially important for Aplastic Anaemia**

•Disadvantages

  • Painful
  • Has lot of RBCs – so if ABO incompatible, can incur essentially transfusion reaction
32
Q

What are the clinical features of chronic GvHD? (>100 days) - 5

A

Skin

  • Lichen planus (violaceous papules & plaques)
  • Similar to scleroderma – sclerotic skin changes
  • Wide spectrum

GIT

  • Mouth ulcers – THEY CANT EAT**
  • Dysphagia, weight loss
  • Chronic diarrhoea & malabsorption

Liver: abnormal LFTs (see later – what condition in particular)?

Lung – bronchiolitis obliterans

Renal – nephrotic syndrome

33
Q

What if someone relapse post transplant? – what are tx options? (Leukaemia) - 5.

A
  • Know that there is very high mortality rate
  • Donor lymphocyte infusion (or frozen ones) – idea is to give T-cells to incur Graft versus Leukaemia effect
  • Second allograft
  • Novel chemotherapy – e.g. FLT3 inhibitors, venetoclax
  • CAR-T cell therapy (modified T-cells Taylor made to recognise tumour cells)
34
Q

Allogenic BMT - early graft assessment

A

= Recovery of Neutrophils (>2.0) and PLT (>50)

Assess with FBC

Should recover within 3-4 weeks - if not, failure of engraftment (i.e. rejection). 5%.

35
Q

Is immunosuppressants given long term in patients with allogenic BMT?

A

No.

They are all initially put on ImmSx post transplant but aim to cease ALL immunosuppressants unless there is evidence of ongoing GvHD.

This is to enable Graft-Versus- Tumour effect - so if you suppress immune system too much, you are not treating the Cancer

So the duration of ImmSx therapy for each patient varies - depends on transplant type, underlying disease, degree of GvHD and toxicities.

Those patient who has had GvHD - maybe on immunosuppressants as they are tapering corticosteroids…etc.

So - if they are well maintained, they should not be on any ImmSx