Acute Promyelocytic Leukemia (APML) .pptx

Acute promyelocytic leukemia is a type of Blood cancer.

1. Nccn guidelines Eln guidelines MANAGEMENT OF APML

2. APML – HISTORY

3. APML – MOLECULAR PATHOGENESIS

4. PML RARA - PATHOGENESIS

5. REASON FOR COAGULOPATHY Pro-coagulant pathways : Different from DIC : no microvascular thrombosis / Protein C,S and anti-thrombin levels are normal – not getting utilised / Fibrinogen levels are lower + FDP levels are higher Levels of TF and Cancer pro-coagulant are higher in APML cells. CP activates factor X directly leading to activation of coagulation pathway and generation of thrombin. Fibrinolytic activity : Hyperfibrinolysis is the primary pathology in APML. Annexin A2 levels are very high in APML – this binds to tPA and activates plasmin to destroy fibrin - - thereby increasing FDP and reducing fibrinogen levels. Increased expression of annexin A2 on cerebral endothelial cells – increase risk of ICH. Also high levels of tPA , uPa and UPAR are seen. Increased levels of elastases degrading fibrinogen. Depletion of plasmin inhibitor (a2 antiplasmin ) and PAI-1 Cytokines : Production of IL-1B and TNFa by APML cells If we switch off fibrinolysis by EACA / tranexemic acid – thrombotic tendencies will increase due to TF/CP.

6. DIAGNOSIS - MORPHOLOGY

7. DIAGNOSIS - MORPHOLOGY

8. DIAGNOSIS - MORPHOLOGY

9. DIAGNOSIS - MORPHOLOGY

10. DIAGNOSIS – AML VS APML

11. DIAGNOSIS – HYPERGRANULAR VS MICROGRANULAR

12. DIAGNOSIS – FAGGOT CELLS

13. DIAGNOSIS – CYTOGENETICS / FISH

14. DIAGNOSIS – PCR

15. DIAGNOSIS – PCR REPORT INTERPRETATION

16. DIFFERENTIATION AGENTS

17. NCCN GUIDELINES

18. NCCN GUIDELINES – LOW RISK

19. NCCN GUIDELINES

20. NCCN GUIDELINES – HIGH RISK (NO CARDIAC ISSUES)

21. NCCN GUIDELINES – HIGH RISK (NO CARDIAC ISSUES)

22. NCCN GUIDELINES – HIGH RISK (CARDIAC ISSUES)

23. NCCN GUIDELINES – RELAPSE

24. ELN GUIDELINES – SALIENT POINTS For genetic diagnosis : RT-QLAMP (reverse transciptase -quenching loop mediated isothermal amplification) Staining with anti-PML monoclonal antibodies : fastest/subjective RT-PCR at diagnosis is must to identify PML RARA isoform FLT3/other mutations need not be tested For coagulopathy – consumptive + fibrinolysis Coagulopathy – same Tranexemic acid - ??? Management of APML thrombosis : high risk / No central catheters due to thrombosis risk / NO LP If using LMWH : dose should be 70% if platelet is 70000, 50% If platelet is 50000, stop if platelet is <30000 Use of recombinant thrombomodulin for DIC : ??? Hyperleucocytosis : WBC > 10000

25. ELN GUIDELINES – SALIENT POINTS Prophylactic corticosteroids : Wysolone / Dexamethasone if WBC > 5-10000 For ATO : Avoid Ciplox, Fluconazole and Emset Avoid Bazetts correction of QTC / use framingham or fridericia If QTC > 500 or symptoms (tachycardia, syncope or arrhythmia) – discontinue ATO (restart at 50% dose and make full dose once QTC < 460) Induction : Low risk – ATRA + ATO / ATRA + chemotherapy arm should have maintenance High risk – no difference between ATRA /ATO and ATRA chemotherapy arms

26. ELN GUIDELINES – SALIENT POINTS For CNS prophylaxis : Recommended for WBC count > 10000, in patients with prior history of CNS haemorrhage No CNS prophylaxis in induction For response assessment: RT-PCR at day 28 may be positive in 76% patients on ATRA/ATO and 63% with ATRA+chemo Continue ATRA/ATO till morphological remission Always repeat PCR within 2-4 weeks if positive No PCR monitoring needed for low risk For high risk - ???

27. ELN GUIDELINES – SALIENT POINTS For maintainence : ATRA + chemotherapy : high risk – yes ….low risk – no ATRA + ATO : High risk - ??? …..low risk – no Tamibarotene ( retinobenzoic acid) for maintenance -- Japan For elderly with co-morbidities : ATRA + ATO (irrespective of risk) For children : COG trial for ATO is underway / Dose of ATRA is 25mg/m 2 For pregnancy : ATRA – 1 st trimester – no ….. 2 nd /3 rd trimester – ok ATO – 1 st /2 nd /3 rd trimester – no 1 st trimester – abort – otherwise – only dauno Monitor fetal cardiac function / antenatal corticosteroids / induced labour No breast-feeding Contraceptives Therapy related APL : same as de novo

28. ELN GUIDELINES – SALIENT POINTS For molecular variants : if ATRA resistant, manage like AML

29. ATRA – SIDE EFFECTS Pregnancy category D RA-APL (Differentiation) syndrome Rapidly evolving leukocytosis during therapy Pseudotumor cerebri – in pediatrics Hypercholesterolemia / hypertriglyceridemia Deranged LFT Others : headache (86%), fever (83%), skin/mucous membrane dryness (77%), bone pain (77%), nausea/vomiting (57%), rash (54%), mucositis (26%), pruritus (20%), increased sweating (20%), visual disturbances (17%), ocular disorders (17%), alopecia (14%), skin changes (14%), changed visual acuity (6%), bone inflammation (3%), visual field defects (3%).

30. ARSENIC TRIOXIDE – SIDE EFFECTS