Leukaemia Flashcards
What is the long term survival for Hodgkin’s & DLBCL (treated)?
HL = 85%
DBLCL = 60%
What are the long-term long case issues in patients with CML or Lymphoma? (5)
Survivals have improved hence many patients live to have late side effects of treatment.
- Secondary malignancies - AML, solid cancers, skin malignancies
- Osteoporosis
- Cardiovascular disease: early CAD, LV dysfunction from anthracyclins
- Pulmonary disease: ILD, bronchiolitis obliterans (BOOP)
- Fertility issues: infertility: ask about ovum or sperm harvesting & storage
What are the clinical features of Leukaemia? (AML, CML, ALL, CLL) - generic symptoms and complications to ask for) - 5 major categories.
Constitutional: fever, fatigue, weight loss
BM failure (main problem): infection (fungal, HSV…etc), bleeding, anaemia.
Leukostasis (myeloid cells can go upto 700): stroke, ICH, thrombosis, expansion of myeloid cells in BM can cause bone pain (can be v. significant), can involve CNS (hence intrathecal therapy), chloroma (solid lump of peukaemia)
Metabolic effects: catabolism (sarcopaenia), DIC, hyperuricaemia (gout), TLS, hypercalcaemia (rare)
Splenomegaly
Questions to ask - have you had;
- Fever, weight loss, fatigue
- Recurrent infections, bleeding
- Blood clots: DVT/PE/Stroke/IHD/ICH/erythromelalgia
- Bone pain, Abdominal pain/swelling***
- Gout
What test would you ask for in a long case to confirm the diagnosis of CML?
FBC + differentials - high WCC (>50) with left shift (inc no of immature leukocytes), basophilia + eosinophilia
Blood film: spectrum of proliferating myeloid cells of all phases of maturation, basophilia and eosinophilia.
BM - hypercellular
Cytogenetics: BCR-ABL (Philadelphia chromosome) - t(9;22)
What are the management options for CML?
What is your approach to pharmacological Mx of CML?
Goal: to achieve MMR (major molecular response): 3-log reduction in BCR-ABL transcript
TKI (choice based on comorbidities: Nilotinib is 1st line. Heart disease → dasatinib, ling disease → imatinib)
Monitor with FBC and peripheral blood BCR-ABL 3 monthly: Aim for molecular milestones at 3,6, 12 months (1-log reduction at each time point)
Monitor for 1) side effects (switch) and 2) imatinib resistance - change to second gen TKI
What is your approach to managing rising BCR-ABL transcript level in patient who is on TKI for CML?
- Check compliance
- Look for mutations
- Some mutations give you some relative resistance which you can overcome with increased dose
- Some mutations give you complete resistance in which case you might need to use a 2nd gen TKI
Would you advise this patient with CML in remission on Imatinib to stop imatinib?
If tolerated, Imatinib should continue indefinitely. TWISTA study demonstrated that when stopped, 70% relapsed (those who was in MMR for 2 years)
What are the main side effects of (1 each)
Imatinib
Dasatinib
Nilotinib?
This trio affects each systems!
Imatinib: GI (diarrhoea, Nausea)/Hepatotoxicity
Dasatinib (Cardiac: IHD, PVD, CVA - most will consider initiating aspirin)
Nilotinib (Pulmonary: pleural effusions, pneumonitis, pulmonary HTN)
When is the Allognic stem cell transplant indicated in CML?
TKI resistant disease
Advanced disease (late accelerated or blast crisis)
Cure-rate still 80%.
What are the 3 phases of CML?
Chronic phase (<15% blasts in BM)
Accelerated phase (15-29% blasts)
Blast crisis (>=30% blasts in blood or BM)
What are the acute complications of Leukaemia (5) and how would you manage them (1 line summary)
- Neutropaenic sepsis: Taz + Gent +/- G-CSF
- TLS: high K, urate, renal failure. Tx = IVF, Allopurinol/Rasburicase
- Hyperviscousity: if WCC >100, high thrombotic risk → leukophresis, hydroxycarbamide
- DIC: low PLT, fibrinogen, high D.dimer, APTT → replace PLT if <50, cryoprecipitate (to replace fibrinogen), FFP (to replace coagulation factors). ATRA in APML.
- Opportunistic infection: consider fluconazole/acyclovir (fungal/HSV/VZV) prophylaxis in high risk patients undergoing induction chemo. Valciclovir for HSCT.
What are the examination findings to report in patients with Leukaemia or Lymphoma?
Pallor, Bruising
Pallor conjunctiva, petechial haemorrhage
Gingival hypertrophy (leukostasis)
Leukaemic deposits (chloromas)
Radiotherapy marks (Lymphoma)
Lymphadenopathy
Hepatosplenomegaly
Focal neurological deficeit (CML with CNS involvement or CNS lymphoma)
How would you investigate patient with suspected acute Leukaemia?
Blood
FBC: Anaemia, Thrombocytopenia, Leukocytosis or leukopenia
EUC, CMP (TLS), uric acid (hyperuricaemia), LDH
Blood film: Myeloblasts with Auer rods in the cytoplasm (Auer rods = myeloblasts)
Bone marrow
- Biopsy: 20% myeloblasts is diagnostic for CML. In ALL >30% Lymphoblasts.
- Flow cytometry: differentiates AML from ALL by looking for myeloid specific markers
- Cytogenetics – helps determine favourable or unfavourable prognosis (inv (3), t(6;9) have bad prognosis)
- Molecular markers: FLT3 (bad prognosis), NPM1, CEBPA = good prognosis
What is your approach to managing newly diagnosed ALL?
Goal is to minimise complications & debulk the number of leukaemic cells.
Stabilise
- IV fluid
- Allopurinol or Rasburicase for hyperuricaemia & TLS
- Maintain platelets >10
- Consider bacterial and fungal prophylaxis
Induction
- Combination chemo: Hyper-CVAD (cyclophosphamide, vincristine, cytarabine & dex)
- Addition of other agents based on cell-markers
- Add imatinib if Ph+
- Rituximab if CD20+
- If B-cell ALL: Blinatumomab
- Alemtuzumab if CD33+
Consolidation
- High dose cytarabine
-
Cranial prophylaxis
- CNS prophylaxis consisting of intrathecal chemotherapy +/- cranial irradiation may be administered to treat potential sanctuary site
Maintenance
- This is given for 2yrs
- Daily PO 6-MP and weekly MTX
