A 3yo girl presents with a 10/7 history of fatigue, malaise and easy bruising. O/E you note an enlarged spleen + liver as well as multiple bruises + petechiae.
What is the likely diagnosis and how would you investigate?
ALL
Bloods
- FBC: anaemia, thrombocytopaenia, neutropenia, high or low WCC
- peripheral blood film: blasts
- coagulation screen: high risk of DIC
- U+Es, LFTs, LDH
BMAT: BM blasts 25% or more
- also send for immunophenotyping (determine lineage e.g. AML vs ALL) + cytogenetic analysis
Other
- LP: ?CNS disease
- CXR: ?mediastinal mass typical of T cell disease
- abdo. USS: ?intra-abdominal adenopathy or renal infiltration
Describe the supportive + specific management of a patient newly diagnosed with ALL.
Supportive:
- blood or platelet transfusion: if cytopaenic
- hydration + allopurinol (start 12hrs before chemo) OR rasburicase if high risk of TLS
- CO-TRIMOXAZOLE (2-3 consecutive days weekly): for P. jirovecci prophylaxis
Specific:
1. induction combination chemo (1/12) to include pred/dex
+/- intrathecal chemo e.g. METHOTREXATE if CNS disease
A 3yo child has been diagnosed with ALL (no CNS disease) and received induction combination chemo for 1/12. What will follow up treatment involve?
- consolidation: systemic chemo + intrathecal chemo
2. maintenance: e.g. daily oral mercaptopurine for 2 (F) or 3 (M) yrs
What test should be performed before prescribing mercaptopurine?
TPMT activity
What are the haematological causes of hepatosplenomegaly?
- leukaemias: AML, CML, ALL, CLL
- lymphomas
- myelofibrosis
- myeloproliferative disease e.g. essential thrombocytopaenia, polycythaemia
- haemolytic anaemias e.g. thalassaemia, sickle cell, spherocytosis, G6PD deficiency, pyruvate kinase deficiency
A 36yo woman presents with a 2/52 Hx of fatigue, palpitations and bruising.
What would a peripheral blood film show if the diagnosis is AML?
blasts with Auer rods
Suggest risk factors for the development of AML.
- previous chemo
- radiation exposure inc. radiotherapy
- haematological dyspoiesis e.g. MDS, aplastic anaemia and myeloproliferative disorders
- genetic factors
- age >65yrs
A patient who has been diagnosed with AML has a WCC of 128,000 cells/uL. How would you treat this hyperleukocytosis?
HYDROXYCARBAMIDE
Which mutation is characteristic of CML?
T(9;22) translocation (Philadelphia chromosome) causing BCR-ABL fusion - constitutively active tyrosine kinase (oncogene)
Which signs/symptoms may be present in a patient with AML?
- Sx of anaemia e.g. lethargy
- Sx of thrombocytopaenia e.g. bruising, bleeding
- weight loss + night sweats
- splenomegaly (may be marked) causing abdo. discomfort/fullness
- +/- hepatomegaly or lymphadenopathy
- hyperviscosity (due to leucocytosis) e.g. visual disturbances (due to retinal haemorrhages), confusion, cerebrovascular accident, priapism
A 56yo gentleman presents with fatigue, weight loss + bruising for the past 2/12. There is marked splenomegaly on examination and you suspect CML. How will you investigate and what will these show?
Bloods
- FBC: raised WCC, anaemia, +/- thrombocytopaenia/cytosis
- peripheral blood smear: raised granulocytes (all stages of dev.), >20% basophils, >20% eosinophils
- U+Es: +/- raised urate
- LDH: raised
BMAT:
- aspirate: raised BM blasts
- trephine: hypercellular marrow, raised myeloid + progenitor cells
- cytogenetic analysis: t(9;22)
- qRT-PCR: quantitative detection of BCR-ABL fusion
A 56yo gentleman is diagnosed with chronic phase AML.
What is 1st line treatment?
TKIs: IMATINIB (v. good cytogenetic response) - inhibits BCR-ABL tyrosine kinase and inhibits proliferation/induces apoptosis of AML cells
A 78yo asymptomatic man present with an incidental finding of a lymphocytosis on a recent blood test.
You suspect CLL. How would you confirm diagnosis?
- FBC + differential: raised WCC with lymphocytes
- peripheral blood smear: smudge cells
- peripheral blood flow cytometry: typical CLL cell surface markers
- peripheral blood FISH: to determine prognosis
What are the management options for CLL?
- watch + wait: if asymptomatic with no indications for Tx
- FCR chemotherapy: if favourable cytogenetics + good performance status
- BCR inhibitors e.g. IBRUTINIB + RITUXIMAB: if unfavourable cytogenetics
Indications for immediate Tx include: anaemia or thrombocytopaenia, symptomatic, rapidly progressive disease (<6/12 lymphocyte doubling time, rapidly enlarging lymph nodes or spleen, AIHA or ITP refractory to immunosuppresive therapy
Suggest possible complications of CLL.
- Richter’s transformation: transformation to high-grade lymphoma
- hypogammaglobulinaemia with higher risk of infection
- warm autoimmune haemolytic anaemia (10-15%)
- anaemia or thrombocytopaenia (poor prognosis)
What is your differential for lymphocytosis?
- infection e.g. EBV, CMV, TB, hepatitis
- smoking
- post-splenectomy
- CLL
- ALL
- lymphoma (leukaemic phase)
What is myelodysplastic syndrome?
Haematopoietic stem cell clonal cytogenetic abnormality causing dysplastic haematopoiesis resulting in:
- 1+ cytopenias
- BM dysplasia with <20% blast cells
- risk of AML development (1/3)
A 73 yo man presents with an incidental finding of anaemia + thrombocytopaenia (no bleeding). You suspect myelodysplastic syndrome. How will you investigate?
Bloods
- FBC + differential: 1+ cytopenia
- reticulocyte count: inappropriately normal (if anaemia) or low
- folate + B12: exclude deficiency as cause of anaemia
- iron studies: exclude deficiency as cause of anaemia
- HIV testing: exclude as cause of anaemia
BMAT
- aspiration: single or multilineage dysplasia, BM blasts <20%
- trephine: hypercellular marrow
- cytogenetic analysis: chromosomal abnormalities characteristic of MDS
What are the management option for a patient with myelodysplastic syndrome?
If acute high risk disease with suitable donor + good general health: allogeneic HSCT
If asymptomatic: watch + wait, regular FBC
Symptomatic cytopaenia(s) with chromo. 5q31 deletion:
- LENALIDOMIDE (immunomodulatory agent)
- RBC or platelet transfusions
Symptomatic cytopaenia(s) without chromo. 5q31 deletion:
- G-CSF (e.g. filgrastim) or EPO
- RBC or platelet transfusions
