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
What is the prognosis of patients with ALL being treated with chemotherapy?
Complete remission rate
5y survival
Complete remission rate is 92%
5y survival rate 50% in <40, only 17% in >60 due to toxicities of chemotherapy.
What is your approach to managing newly diagnosed AML?
Goal is to minimise complications & achieve complete remission (<5% blasts in BM)
Stabilise
- IV fluid
- Allopurinol or Rasburicase for hyperuricaemia & TLS
- Maintain platelets >10
- Consider bacterial and fungal prophylaxis
Induction
- Combination chemotherpy with Cytarabine + Anthracycline (-rubicins)
- 7+3 (cytarabine 7d then daunorubicin for 3d)
Consolidation
- High dose cytarabine
Risk stratification then ASCT
- Allogenic SCT for adverse cytogenetics or molecular markers (e.g. FLT3)
Specific treatment for APML
- Flow cytometry shows a large number of pro-myelocytes
- ATRA +/- Arsenic + steroids
Side effects of Anthracyclines (daunorobucin/idarubicin)? 3
Myelosupression - onset 7d, nadir 10-14, recovery 21-28d
Cardiotoxicity - CHF
Extravasation reaction
Side effects of Cytarabine (3)?
Drug fever (significant)
Myelosuppression
Derranged LFTs
CLL - PRICMCP?
P: asymptomatic, anaemia, infection, lymphadenopathy, hepatosplenomegaly, B-symptoms
R: FH of haematological disorders
I: Had BM aspirate/biopsy? (not always needed)
C: AIHA (15-30% has DAT+ve haemolytic anaemia), ITP, Ritcher’s transformation
Complications of treatment: immunoSx/BM suppression.
M: observation. For older chlorambucil based-regime. For younger, Fludarabine based-regime. Rituximab. Other monoclonals (Ibrutinib - RESONATE2 trial NEJM 2015, increased OS/PFS
C: stable or worried about Ritcher’s. How is patient coping with disease
P: Insight.
How would you investigate patient with CLL?
FBC - lymphocytosis, cytopaenias
Blood film - smudge cells
LDH + B2M + EPG = prognostic markers
Uric acid, Calcium = TLS risks
DAT - AIHA
Flow cytometry: CD5, CD19, CD23
BM Aspirate + biopsy
CT scan for staging the disease
CLL staging? 2 markers of prognosis?
Binet (easiest to remember)
A: <=2 lymph node areas
B: >2 lymph node areas enlarged
C: anaemia (Hb <100) or thrombocytopaenia (plt <100)
Markers of prognosis are LDH and B2M.
CLL - what are indications for treatment? (3)
Consider if:
Binet B or C
AIHA or ITP
Frequent infections
What are essential elements of non-pharmacological therapy for Leukaemia survivors? (2)
High psychosocial burden: frequent, intense treatment with frequent complications. Offer support, regularly screen for depression, help patient to develop supportive network (e.g. blood cancer support groups)
Each patient should receive cancer treatment summary + f/u care plan (called Survivorship care plan) - includes critical information regarding diagnosis, tx, potential late complications, surveillance, preventitive strategies and education.
What are pharmacological & non-pharm treatments for CLL?
Non-pharm: vaccinate, IVIG, antimicrobial prophylaxis, EPO
Pharm: Chlorambucil / Fludarabine, R-CHOP, Allogenic SCT for relapsed disease.
Steroids for AIHA + ITP.
