Kumar and Clark Haemato-oncoloy Flashcards
What are the investigations in the Dx in acute leukaemia ?
FBC: To check Hb, WBC, Platelets
Blood filim: To identify morphology of cells.
Bone marrow aspiration: For immunophenotyping.
Cytogentics:FISH analysis and Molecular gentics: Prognostication.
Whole body PET or C-XR or CT CAP : To ruleout mediastinial or orther involvement.
CSF: for ALL CNS involvement.
Coagulation profile: To identify risk for DIC as in ApML.
Step in planning acute Leukemia therapy are ?
Biochemistry: Serum urate, LDH, LFT and RFT.
Cardiac function: ECG and Echo
HLA Phenotyping: for SCT
Viral testing: HIV, HBV, HCV
Factors of acute Leukemia supportive or active care?
Avoidance of symptoms of anaemia (keeping haemoglobin <80–100 g/L)
Prevention and control of bleeding
Correction of coagulation abnormalities
Factors affecting SCT decion making in ALL ?
Relapse risk and Transplant-related mortality (TRM)
What are the factors that determine the prognosis of AML ?
- Age
- Cytogentics
- gene mutations
- Presense of Minimal residual disease (MRD) after initial therapy.
What are the good risk or good prognosis indicators of AML?
- Denovo disease
- Favourable cytogenetics: t(15; 17) t(8; 21) or inv(16) or its variant t(16; 16)
- CEBPA bi-allelic mutation
- NPM1 mutation with FLT3 wild type
What are the poor risk or bad prognosis indicators of AML?
-Age >60
-Male gender
-Secondary disease, e.g. prior MDS or MPN
-High WCC
-Adverse cytogenetics: −5, del(5q), −7, abnormal 3q26 or a complex karyotype
-FLT3 internal tandem duplication mutation.
-MRD positivity post induction chemotherapy
APML caused by t(15,17) trasnlocation produces what gene ?
PML- RARA fushion gene.
Presentation pattern of acute Lymphoblastic Leukemia ?
-may present in leukaemic phase with significant marrow involvement (acute lymphoblastic leukaemia, ALL)
-May present as localized bulky disease, typically a mediastinal mass (lymphoblastic lymphoma).
Management of Acute Lymphoblastic Leukeima (ALL)
- Remission indcution Chemotherapy
- Remission consolidation Chemotherapy
- Allogenic SCT in patients with high relapse risk. or Remission maintainance chemotherpay as in AML.
what is the Philadelphia chromosome distribution in CML?
Cytogentical distribution = 95%
Molecular distribution = 5%
CML epidemiology ?
- CML accounts 14% of all leukaemias
- It is an adult onsent male predominat disease ( age 40-60)
- It belongs to the family of myeloproliferative neoplasms (MPNs).
what is the Blast crisis pattern in CML?
- Myloid crisis = 75%
- Lymphoid crisis = 25%
CML is often asymptomatic, when symptomatic what is the presentation?
- symptomatic anaemia
- abdominal discomfort due to splenomegaly.
-weight loss
-Fever and sweats in the absence of infection.
-headache (occasionally) or priapism due to hyperleucocytosis.
What are the signs of CML ?
- Pallor and cynosis
-Massive splenomegaly. - Lymphadenopathy suggests blast crisis.
-extramedullary soft tissue leukemic deposit – ‘chloroma’ (indicates blast crisis).
-retinal haemorrhage due to leukostasis
What are the investigations in CML ?
FBC: Often variable platelets, low HB.
Blood filim: significant Leukocytosis with Neutrophila, eosinophila or baseophelia.
Bone marrow aspirate: Increased cellularity is seen, with greater numbers of myeloid precursors.
Management of CML ?
-Imatinib is the firstline to indcue inhibition of enzymatic activity of BCR-ABL thyrosine kinase.
- If resistance to imatinibe due to seconadry mutations, second-generation TKI, such as dasatinib, nilotinib or bosutinib, should be commenced.
How dose chronic lymphocytic Leukemia or CLL occur ?
It is the most common Leukemia in elderly and occurs due to clonal expansion of small B lymphocytes.
What is the symptomatology and epidemiology of CLL?
- Most patients are asymptomatic and is diagnosed incidently.
- Median survival is 10 years
What are the symptomatic forms of CLL?
-Leukaemic phase with significant marrow/blood involvement (CLL)
- Localized disease (small lymphocytic lymphoma, SLL)
CLL in all cases are prceeded by what condition?
Monoclonal B-cell lymphocytosis (MBL) where there are fewer than 5 × 10 ^9 /L circulating clonal B cells.
Rai staging system of CLL?
Stage 0: Low risk, Lymphocytosis alone. Therefore watch and wait.
Stage 01: Intermideiate risk, Lymphadenopathy, treat only with progression.
Stage 02: Intermediate risk- Splenomegaly- Lymphadepathy or both- treat only with progression.
Stage 03 and 4: High risk- Anemia, organomegaly and or Thrombocytopenia - treat in most cases.
Typical clinical features of CLL progression?
a )Lymphocytosis is present in all stages of the disease.
b) Progression is defined by weight loss, fatigue, fever, massive organomegaly and a rapidly increasing lymphocyte count.
c )Lymphoid areas include the cervical, axillary and inguinal lymph nodes, the spleen and the liver.
What are the investigations in CLL?
- FBC: vairable Hb, Increased WBC, variable plateletes.
- Blood Film: May show smudge cells, no blasts.
-Bone marrow reflects peripheral blood, often very heavily infiltrated with lymphocytes.
-Direct Coombs’ test may be positive if there is haemolysis.
- Immunoglobulins are low or normal.
What is the Lymphocytosis criteria for CLL?
WBC > 5x 10 ^9 / L
What is the prognosis of CLL?
The clinical course of CLL is variable. Prognosis is influenced by age and clinical stage, as well as pace of disease, measured by doubling time.
What is the Managment approach in CLL ?
- The major consideration is when to treat as 30% will not require any treatment.
- Advanced stage disease is treated immediatly.
- Intermediate stage disease has variable treatment approach.
What is the Supportive or active treatment in CLL
- Anaemia due to haemolysis is treated with steroids.
-Anaemia and thrombocytopenia caused by marrow infiltration are treated with chemotherapy and, when necessary, transfusion. ( EPO may avid the need for transfusion).
- Infection active treatment and prophylaxis should be done.
What is the first line treatment of CLL?
Fludarabine + Cyclophosphamide and Rithuximab.
what kind of Richter trasformation is seen in CLL?
- 5 to 10% of cases to DLBCL.
What are Myeloproliferative neoplasms?
These are stem cell disorders characterized by uncontrolled proliferation of erythroid, myeloid and/or megakaryocyte lines.
What are the main types of Myeloproliferative diseases ?
- polycythaemia vera (PV)
- essential thrombocythaemia (ET)
- myelofibrosis
- chronic myeloid leukaemia (CML).
What is polycythaemia Vera ?
It is a clonal stem cell proliferative disorder in which there is an excessive proliferation of erythroid, myeloid and/or megakaryocytic progenitor cells.
What is the most common mutation in Polycythemia Vera ?
JAK2V617F in which there is point mutation causing substitution of phenylalanine for valine at position 617.