Bone marrow transplant/ASCT Flashcards
What’s the difference between Autologous and allogeneic?
Autologous: from self (peripheral blood or BM)
Allogeneic: from another individual
What is graft versus host disease?
Donor’s immune system attacks the tissues of the recipient
This is one of the most common complications of BMT
What are risk factors for acute graft versus host disease?
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
Clinical features of acute graft vs host disease
Skin - rash
GIT - cramps, nausea, vomiting, diarrhoea, weight loss
Liver - raised bilirubin, cholestatic LFTs
Fever
How to diagnose acute graft vs host disease?
Biopsy
How to grade acute graft vs host disease?
4 grades
Based on skin, liver and GIT findings
Correlate with mortality
Why is chronic graft vs host disease not a bad thing?
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
List long-term problems of surviving post-BMT
Relapse Chronic graft vs host disease Infection especially viral Cardio-respiratory disease Endocrinopathies Infertility Eye disease OP Renal disease Secondary cancers particularly oesophageal ca
List indications for autologous BMT
3 major conditions
Multiple myeloma (gold standard for initial tx)
NHL (at relapse or up front in some high-grade NHL)
HL (relapse)
List indications for allogenic BMT
5 major conditions
Acute leukaemia (AML, ALL) - first admission or relapse MDS Severe aplastic anaemia Immunodeficiency e.g. SCID (children) NHL
List some early complications of autologous BMT
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)
List some late complications of autologous BMT
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
List early complications of allogeneic BMT
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
2 Sources of haematopoietic stem cells (autologous and allogeneic)
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
Explain HLA matching
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
What are the donor possibilities?
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
What happens in autologous HSCT?
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
3 main roles in allogenic HSCT?
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
2 types of allogenic conditioning regimen types
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
Complications of autologous HSCT
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
Complications of allogenic HSCT
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)
Infectious complications post allogenic HSCT
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)
Infectious disease porphylaxis in Allogenic HSCT
Gram neg bacteria
PJP
Invasive fungal disease
HSV/VZV
CMV
EBV
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.
CMV - what donor and recipient is best?
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)
