Haemotology/Oncology Flashcards
Post transplant lymphoproliferative disease related to what medication
T-cell suppression (especially with tacrolimus) is associated with a higher risk
of PTLD.
How much iron in 250ml blood unit
250mg
Vincristine and vinblastine mechanism of action
Inhibit mitosis by binding tubulin (minimal myelosuppression) METAPHASE
(Asparginase stops rna into tubulin protein)
Doxorubicin and doaunorubicin mechanism of action
Stops DNA replication by inhibiting topoisomerase and is a DNA intercalator (inserts into DNA) G2 phase
(Antibiotic) and also free radical damage like bleomycin
Cyclophosphamide and platinum mechanism of action
alkalynisation of DNA
Forms DNA cross links leading to apoptosis
Also ifosfamide
Cause of short stature with cranio-spinal radiotherapy
Failure of spinal growth
Highest incidence of secondary malign
Hodgkin lymphoma (10% at 20y)
Diamond-Blackfananaemia
Ribosomal protein disease
Dysmorphic, short, cleft, thumbs weird
Under 1, isolated MACROCYTIC anaemia from marrow failure (therefore no retics )
Bone marrow with decreased erythroid precursors but normal marrow
cellularity
(TEC also low retics but normocytic)
Bone marrow dysfunction with pancreas insufficiency and growth failure ? Cause and uss finding
Fatty infiltrate pancreas
Shwachman syndrome
Tumour lysis syndrome mx
Hyperhydrate Allopurinol xanthine oxidase inhibitor Risk of xanthine nephropathy Rasburicase (0.2 mg/kg) Urate oxidase Contraindicated in G6PD deficiency Risk of rash, hemolysis, anaphylaxis, methemoglobinemia
Drugs associated with mucositis
Bleomycin, Daunomycin, Methotrexate, Mitozantrone, Thioguanine,
Thiotepa, Vinblastine, Idarubicin, Mercaptopurine, Melphalan, 5‐
Fluorouracil, Hydroxyurea, Doxorubicin.
No or minimal BM suppression with which drugs
Cisplatin Asparginase Dacarbazine Procarbazine mercaptopurine Mitomycin C Lomustine Melphalan New monoclonals thioguanine
Haemorrhaging cysitis is SE of which chemo agents
Alkylating agents: Cyclophosphamide / Ifosfamide
At risk groups for secondary malignancy
Radiation exposure: AML, sarcomas
Etoposide exposure: AML, sarcomas
Hodgkins: mantle field irradiation
Genetic predispositons: retinoblastoma, fanconi anaemia, TP53 et
Warm autoimmune haemolytic mx
Supportive with folic acid. Avoid transfusing if possible
Warm antibody mediated responds to steroids
Dyskeratosis congenita (zinsser-Cole-England syndrome)
One of the disorders associated with short telomeres (Flow
FISH test). Others include Hoyeral Hreidisson and n Revesz
Syndrome)
• Genes TERT, TERC
• Ectodermal dysplasia
• Diagnostic “triad’: dystrophic nails, oral leucoplakia, reticular
pigmentation
• May present with pulmonary or liver fibrosis
• SCT for marrow failure. High morbidity and mortality
• Long term screening for oral, naso-pharyngea, vulval cancers
HLH
Hyper inflammation
High TG and high ferritin classic
Mild haemophilia A and VWD management
DDAVP in most instances - Works by releasing endogenous FVIII
Transenamic acid
Term male infant notice to have prolonged oozing from heel prick
site. No family history of bleeding.
Normal platelet count, PT, APTT and fibrinogen
Family reassured and baby discharged.
Mother re-presents in two weeks because umbilical stump oozing.
diagnosis?
Factor 13 deficiency
Defects in fibrinogen
Medulloblastoma predisposed conditions
Gorlin syndrome (basal-cell carcinoma nevus syndrome)
– 3% children with MB
– PTCH pathway mutation
• Turcot’s Syndrome
– Mismatch repair cancer syndrome (Lynch, HNPCC)
– Brain tumour and colorectal polyposis/cancer
– Usually HGG’s or MB in childhood/adolescence
• Li-Fraumeni Syndrome
– TP53
– Bimodal peak <10 years and 20-40 years
– Astrocytomas»_space; MB
Medulloblastoma groups
Genetically defined subgroups
1. WNT-activated – monosomy 6, classic histology, excellent
outcome (EFS >90%)
2. SHH-activated – PTCH pathway, lateral tumours, nodular
desmoplastic, infants have excellent outcome, TP53 mutated
tumour have very poor prognosis
3. Non-WNT/non-SHH
Group 3 – MYC amplification, large cell anaplastic
histology (LCA), poor outcome
Group 4 – MYCN amplification, classic or LCA,
intermediate outcome
ATRT (atypical teratoid rhabdoid tumour
Poor prognosis
Supratentorial
• Highly malignant • Usually occurs before 2 years age • ~15% children <3 years with malignant CNS tumour • Short clinical history • Anywhere in brain and spine • Disseminated disease in 20% • Biallelic inactivation of SMARCB1 in majority
Ependymoma mx
Surgery and focal radiation
High grade glioma
Small round blue cell tumours
Recent discovery of driver
mutations in histone H3.3 and
chromatin remodeling genes in
HGG
Craniopharyngioma MRI findings
Suprasellar
Calcification
Cysts
TS cancer type
Subependymal giant cell astrocytomas (SEGAs ) in 5-20%
Juvenile Pilocystic astrocytoma mx
Observe
Common late effect after brain tumour
GH deficiency
AML related to which syndrome
Downs (<3y, better survival and ALL worse survival)
Familial RUNX1 mutations
Aplastic anaemia
Myelodysplastic syndrome
Myeloproliferative disorders
Extramedullary haematopoesis (skin) think..
AML
AML morphology
PB/ BM: Blasts >20%
• Larger blasts
• Nucleus: More irregular, prominent nucleoli
• Cytoplasm: Auer rods, granules
Myeloperoxidase in flow cytomegalovirus
CD numbers for B and T cell ALL
B = 19 T = 3
T call ALL overall higher risk and presentation WCC not related to risk
Which cancer has Reed-Sternberg cell
EBV associated
Hodgkin lymphoma
Radiotherapy in ewings or osteosarcoma
Ewings
Mets of wilms, ewings, osteosarcoma to
Lungs
What tumours can metastasise to marrow
Alveolar Rhabdomyosarcoma can spread to bone marrow
Ewings
Child with spinal cord compression or intractable diarrhea or opsoclonus/myoclonus = jumping eyes think of…
Neuroblastoma
Poor prognostic factors in neuroblastoma
Combineclinicalfeatures(Metastases,unresectable biguglyprimary,age>18mths arebad).
Andlabtests(histology,MYCNamplification 8-200+ even if local disease,11qmissingarebad).
Can neuroblastoma regress by itself
Yes
Diagnosis in baby: Blueberry nodules on baby rapidly followed by expanding liver and respiratory embarrassment
Neuroblastoma
Hepatoblastoma predispositions and mx
Genetic predisposition (~15%)
– Beckwith‐Wiedemann syndrome
• IGF2 (11p15.5) overexpression
• Relative risk 2,280
– Familial adenomatous polyposis
• APC mutations
• 1/250 lifetime risk of HB
• ~1/20 with HB have familial polyps
in colon
– Li‐Fraumeni
– Trisomy 18
– NF‐1
– Ataxia‐telangiectasia
– Fanconi anemia
– Tuberous sclerosis
LBW/prem
Mx: cisPLATIN and carboPLATIN
Beckwith‐Wiedemann Syndrome how many percentage tcsncer and screen til what age
10%
8 years
What syndrome
Macrocephaly, autism/LD, skin lesions, lipomas, AVMs
• Thyroid, breast and endometrial cancer; also colon cancer, melanoma,
renal cell carcinoma
• Thyroid cancer screening starting at 10‐12 yo
PTEN syndrome
What is a nephrogenic rests
Embryonal reminent and may develop into nephroblastoma,
AFP is increased in…
HBL, HCC, and germ cell tumours most notably yolk sac or
endodermal sinus tumour.
Highest risk factor for invasive fungal disease
Prolonged neutropenia
On CT
Small nodules, pleural based lesions with surrounding low
attenuation = halo sign (esp. if neutropenic)
With progression nodules may cavitate (and with neutrophil
recovery = air crescent sign)
? Diagnosis and treatment
Invasive pulm aspergillosis
Voriconazole
High risk neuroblastoma can be treated with
anti-GD2 (ch14.18)
Small round blue cells in which cancers
LERRNN
Lymphoma, ewings, rhabdomyosarcoma, retinoblastoma, nephroblastoma, neuroblastoma
Hallmark of lanherhans cell histocytosis
Tennis racket granule (birbeck granule)
Wide radiotherapy in female most common secondary cancer is
Breast
Emancipation in infant cause?
Diencephalic syndrome (hypothalamus and thalamus lesion)
PHACE syndrome stands for
Posterior fossa malformation Haemangiomas Arterial anomalies CoA (and others) Eye abnormality
Blue dots in RBC indicate
Lead poisoning (basophils stippling)
T-ALL risk of what kind of relapse
testicular
Short, eczema, learning difficulties and skeletal dysplasia
Poor feeding, FTT, greasy fatty diarrhoea, risk of infections (mild neutropenia plus or minus low platelet and Hb)
Increased risk marrow aplasia
Syndrome? (Blood, exocrine pancreas failure, growth)
Schwachman-diamond syndrome
DDx fanconi anaemia and pearson syndrome
Vwd type 1-3
1: most common 75% with reduced amounts
2: some not functioning
3: all defective
Delayed nausea in what chemo agent
Cisplatin
Which one of the following is the most common cause of familial thrombophilia (deep vein thrombosis and pulmonary emboli)? A. Activated protein C resistance. B. Antithrombin III deficiency. C. Protein C deficiency. D. Protein S deficiency. E. Prothrombin gene mutation.
A
Which one of the following is least toxic to bone marrow? A. Carboplatin. B. Cyclophosphamide. C. Doxorubicin. D. Etoposide (VP-16). E. Vincristine.
E
Bad extravasion with what chemo drug
Vincristine
NRAS proto-oncogene associated with
AML
Improved symptoms in spherocytosis from what intervention
Splenectomy
What drug can trigger haemolytic in G6PD?
(Paracetamol NSAIDs)
Antibiotics:
Quinolones - cipro, Nitrofurantoin
Sulpha drugs (cotrimox)
Antimalarials:
Primaquine
Haptoglobin very low from
Intravascular haemolysis
Or wilsons
Causes or prolonged PT
Vit k def/liver disease
Deficient 2,7, 10, 5, fibrinogen
Pain sickle cell drug
Hydroxyurea
Methylene blue used to treat what
Hereditary methaemoglobinemia
Dyskeratosis congenita
Background:
o Multisystem disorder characterized by mucocutaneous abnormalities, bone
marrow failure and a predisposition to MDS and cancer.
o Diagnostic mucocutaneous triad: reticulate skin pigmentation of the upper body,
mucosal leukoplakia, nail dystrophy.
o Aplastic anaemia occurs in 50%.
o X linked recessive inheritance.
Pathology: shortened telomeres.
Treatment: androgens and stero
Most common inherited risk factor for thrombosis
Factor V Leiden
Result of single nucleotide change within the factor V gene. Causes factor Va to become resistant to inactivation by activated protein C.
AML Tx
multiagent chemotherapy (usually cytarabine based)
Favourable features for AML
Downs
t(8;21)
t(15;17)
inv(16)
M3 (Acute promyelocytic leukaemia is characterized by a gene rearrangement
involving the retinoic acid receptor (t(15;17); PML-RARA) and is very
responsive to all-trans-retinoic acid combined with anthracyclines and
cytarabine.)
Unfavourable AML features
monosomy 7 and 5, 5q-, 11q23
Imatinib treatment for?
CML with BCR-ABL
Tumour markers: catecholamine metabolites (homovanillic acid – HVA,
vanillylmandelic – VMA) in urine?
Neuroblastoma
Alkylsulphonate: busulphan
important SE
Pulmonary oedema leading to fibrosis
Chemo agent with SE of chemical conjunctivitis
Cytarabine
Radiation skin reaction from what chemo
Daunorubicin and doxorubicin
Increased risk secondary cancer (AML)
Etoposide
Asparaginase: Side effects:
Venous thrombosis.
Anaphylaxis.
Pancreatitis.
B cell lymphoma primary site
B for belly
T for thorax
Renal tubular toxicity which drug
Ifosfamide
Life of a platelet
10 days
Hb high affinity for o2 (epo and Hb level)
Both high
Two weeks after transplant present with fluid retention, hyperbilirubinemia, and painful hepatomegaly
Veno-occlusive disease (VOD) of the liver remains one of the most feared complications associated with high-dose chemotherapy and hematopoietic stem cell transplantation (SCT)
Target cells and pencil cells mean
Target mean thalassaemia
Pencil means iron deficiency
Atypical teratoid rhabdoid tumour mutation.
INI1
Tumour from forth ventricle
Ependymoma (50% have calcification)
Post op complication post fossa op?
Posterior fossa syndrome cerebellum mutism where mute and ataxia
Most common childhood brain tumour
Astrocytoma
Spherocytes on blood film indicate (2 things)
Autoimmune haemolytic anaemia and hereditary spherocytosis
Child presents with otitis media, HSM, lyric skull lesion and diabetes insipidus (drinks lots)
Investigations and diagnosis
Investigations show birbeck tennis racket shape granule and Langerin CD207 and CD1a
What drug avoid intrathecal?
Vincristine
Gene deletion in short, mesomelia, madelung deformity?
Shox
LERI-WEILL DYSCHONDROSTEOSIS; LWD
Sonic hedge role and importance
Regulates cell differentiation and proliferation and important in embryo development
Related to Gorlin syndrome (craniofacial and skeletal abnormalities and increased risk medulloblastoma and BCC - gene PTCH1)
Child with CD1a positivity, birbeck tennis racket granules and langerin CD207 has?
Langerhands cell histocytosis
HLH mutation
SAP
10% on high dose cytarabine chemotherapy get this?
Cerebelluar toxicity and ataxia
Congenital central hypoventilation syndrome and neuroblastoma gene
PHOX2B
ALK mutation in?
Anaplastic lymphoma kinase
Target for drugs
Neuroblastoma
Lymphoma
Alveolar rhabdomyosarcoma genetics?
T(1:13), t(2:13)
Second most common childhood cancer?
Brain tumour
