Oncology Flashcards
(71 cards)
Medulloblastoma fast facts
Most common malignant brain tumour Embryonal neuroepithelial tumour M>F Small round blue cell tumour Associated syndromes: gorlin, Li-Fraumeni, Turcot, Gardner, Cowden Arise from cerebellum, typically vermis. ONLY occurs in the posterior fossa. Spreads along the neuroaxis: metastatic disease 1/3 at presentation Prognosis WNT1: good SHH: intermediate MYC, p52: bad
ATRT (Atypical teratoid/ rhabdoid tumour)
Embryonal malignancy Highly malignant Usually in children <3yrs Short clinical history 90% show loss of INI1 nuclear staining (SMARCB1) Can occur ANYWHERE in the brain or spine Poor prognosis, survival ~ 12 months even with complete resection Check for germline mutation- at risk for renal + soft tissue tumours
Ependymoma fast facts
Tumour originating from the wall of the ventricle or spinal cord composed of neoplastic ependymal cells Slow growing Increased in NF2 Surgery + radiation main treatment. Not usually chemosensitive.
In what tumour do you find rosenthal fibres?
Low grade glioma: astrocytoma
Low grade glioma fast facts
Largest group of CNS tumours- mostly juvenile pilocytic astrocytoma 2/3 occur in posterior fossa Almost ALL tumours involving the optic pathway are juvenile astrocytomas Generally good outcomes
Types of transplants
Autologous = patient receives own cells Syngeneic = use of cells from identical twin Allogenic= cells collected from a relative or unrelated donor
Types of transplant matches
HLA identical Haploidentical: half match Mismatch Matching based on HLA typing. Tested in 2 ways: 1) serologic testing (use antibody assay for HLA antigens) 2) molecular typing (looks at underlying alleles on chromosome)
Preferred characteristics of a transplant donor
Matched sibling= ideal donor CMV negative Males + non-parous women (women may have antibody to Y antigen) ABO + Rh status compatibility NOT required
Graft preparation: What is the purpose of T cell depletion of a transplant recipient / donor
Reduces the risk of GVHD BUT this also increases the risk of recurrence + infection
Describe the graft vs leukaemia effect
In addition to stem cells, the graft contains mature blood cells of donor origin, including T cells, B cells, natural killer cells, and dendritic cells. These cells repopulate the recipient’s lymphohematopoietic system and give rise to a new immune system, which helps eliminate residual leukemia cells that survive the conditioning regimen.
Describe graft vs host disease
Donor alloreactive cytotoxic CD8+ effector T cells may attack recipient tissues, particularly the skin, gastrointestinal (GI) tract, and liver
Who does HLA-A, HLA-B, and HLA-C major histocompatibility complex (MHC) class I molecules, present peptides to?
CD8+ T cells
Who does HLA-DR, HLA-DQ, and HLA-DP MHC class II molecules present peptides to?
CD4+ T cells
Acute vs chronic GVHD
GVHD is caused by engraftment of immunocompetent donor T lymphocytes in an immunologically compromised host who shows histocompatibility differences with the donor. These differences between the donor and the host may result in donor T-cell activation against either recipient major histocompatibility complex (MHC) antigens or minor histocompatibility antigens. Acute: within 3 months of transplant Chronic develops OR persists > 3 months post transplant
Grades of GVHD
Grade I: skin rash (maculopapular) only < 25% BSA Grade II: mod severe multiorgan disease. Rash 25-50% BSA, elevated bili, diarrhoea Grade III: severe multiorgan disease. Rash >50% BSA, elevated bili, diarrhoea (survival 25%) Grade IV: life threatening (survival 5%)
Pharmacological prophylaxis of GVHD
Immunosupression - Cyclosporine or tacrolimus - Methotrexate, prednisolone, MMF Prednisolone remains the most effective 1st line treatment (response ~55%)
What 2 factors have increased the rates of chronic GVHD
Use of MUD Use of peripheral blood as stem cell source
Clinical manifestations + biopsy findings in acute GVHD
SKIN - Maculopapular rash, pain, blisering - Biopsy: apoptotic bodies in the basal layer of epithelium LIVER - Jaundice + deranged LFTs - Biopsy: bile duct destruction with apoptotic bodies GIT: - N+V, diarrhoea, abdo pain, bleeding. - Biopsy: apoptotic bodies in the base of crypts
Primary vs secondary graft failure
Primary graft failure - Failure to achieve a neutrophil count of 0.5 × 109/L after transplantation. Secondary graft failure - Loss of peripheral blood counts following initial transient engraftment of donor cells.
Causes of graft failure
- Inadequate stem cell dose - Viral infections (e.g. CMV, HHV6) which are often associated with activation of recipient macrophages - Immunologically mediated rejection by residual recipient T cells that survive conditioning
Describe veno-occlusive disease (VOD)
AKA sinusoidal obstruction syndrome Injury to hepatic venous endothelium leads to dilation + RBC congestion = obstruction of the sinusoidal blood flow. Venous occlusion –> necrosis of liver –> multi-organ failure Onset usually within 30 days
Risk factors for VOD
- Previous hepatic disease - CXT induction agents: cyclophosphamide, busulphan, MTX - Allogenic graft > autologous graft - Young age - Abdominal radiation - Repeated transplants - HLH
Clinical features of VOD
Weight gain Ascities Tender hepatomegaly Elevated bilirubin (jaundice) Thrombocytopenia Hepatosplenomegaly
Treatment of VOD
Defibrotide Ursodeoxycholic acid
