What are the guideline sources, guidelines and references for Acute promyelocytic leukemia ?
Guideline sources The following summarized guidelines for the evaluation and management of acute promyelocytic leukemia (APL) are prepared by our editorial team based on guidelines from the International Society on Thrombosis and Haemostasis (ISTH 2020; 2015), the European Society of Medical Oncology (ESMO 2020), the European Leukemia Net (ELN 2019), and the American Society of Hematology (ASH/ACP 2017). 1 2 3 4 5 Calculator Calculator Eastern Cooperative Oncology G Karnofsky performance status s Guidelines 1. Diagnostic investigations Mutational analysis: https://web.pathway.md/diseases/recBNBa37E5DPGci3 1/4 6/23/23, 2:03 AM Acute promyelocytic leukemia Pathway As per ELN 2019 guidelines, obtain molecular testing for the detection of PML-RARA fusion (or rare molecular variants) to confirm the diagnosis of APL. B As per ACP 2017 guidelines: Obtain mutational analysis for NPM1, CEBPA, and RUNX1 in patients other than those with confirmed core-binding factor-acute myelocytic leukemia, APL, or acute myeloid leukemia with myelodysplasia-related cytogenetic abnormalities. A Obtain rapid detection of PML-RARA in patients with suspected APL. A Coagulation studies: obtain appropriate coagulation tests to evaluate for DIC in patients with APL. A 2. Diagnostic procedures Immunostaining: consider obtaining immunostaining with anti-promyelocytic leukemia antibodies (in addition to FISH, reverse transcriptase PCR, real-time quantitative PCR, reverse transcription- quenching loop-mediated isothermal amplification) for rapid diagnosis of APL. C 3. Medical management General principles: manage the diagnosis of APL (once suspected) as a medical emergency. B Show 3 more Initial therapy: As per ESMO 2020 guidelines, initiate immediate treatment with all-trans-retinoic acid in patients with suspected APL, until confirmatory molecular and/or cytogenetic results are available. B Show 2 more As per ELN 2019 guidelines, offer all-trans retinoic acid and arsenic trioxide without chemotherapy as induction therapy in patients with a WBC count 10 10 /L. Initiate all-trans retinoic acid and anthracycline-based chemotherapy as a second option when arsenic trioxide is contraindicated or unaffordable. B Show 6 more Consolidation therapy: offer 4 consolidation courses of arsenic trioxide (0.15 mg/kg/day 5 days/week, 4 weeks on 4 weeks off) and 7 courses of all-trans retinoic acid (45 mg/m /day in adults; 25 mg/m /day in children, 2 weeks on 2 weeks off) in patients treated with chemotherapy- free approaches. B Show 4 more Maintenance therapy: Do not offer maintenance therapy in patients treated with chemotherapy- free approaches (WBC count 10 10 9/L). D Show 4 more https://web.pathway.md/diseases/recBNBa37E5DPGci3 2/4 6/23/23, 2:03 AM Acute promyelocytic leukemia Pathway Management of coagulopathy: As per ISTH 2020 guidelines, do not preclude or delay antineoplastic therapy (such as all-trans retinoic acid or arsenic trioxide) based on the presence of DIC in patients with APL. D Show 2 more As per ELN 2019 guidelines, initiate treatment with all-trans retinoic acid immediately when a diagnosis of APL is suspected. B Show 4 more As per ISTH 2015 guidelines, consider administering 1-2 doses of platelets (commonly from 5 donors or equivalent) in patients with APL and DIC at high risk of bleeding (such as surgery or invasive procedures), if the platelet count is < than 30 10 /L. C Management of differentiation syndrome: Administer corticosteroids (IV dexamethasone 10 mg BID) immediately at the earliest clinical suspicion of incipient APL differentiation syndrome. Consider discontinuing corticosteroids and reinitiating arsenic trioxide/all-trans retinoic acid once the syndrome has resolved. B Consider discontinuing differentiation therapy (all-trans retinoic acid or arsenic trioxide) temporarily only in case of severe APL differentiation syndrome. C 4. Therapeutic procedures Leukapheresis: As per ESMO 2020 guidelines, avoid performing leukapheresis for hyperleukocytosis in patients with APL because it may exacerbate coagulopathy. D As per ELN 2019 guidelines, avoid performing leukapheresis in patients with hyperleukocytosis due to the risk of precipitating fatal hemorrhage. D 5. Specific circumstances Pediatric patients: administer all-trans retinoic acid at a dose of 25 mg/m /day in pediatric and adolescent patients. B Pregnant patients: advise against conceiving while exposed to all-trans retinoic acid and arsenic trioxide for consolidation and maintenance therapy in female patients with APL. B Show 6 more Elderly patients: manage elderly patients in good clinical condition treated with chemotherapy- based regimens similarly to younger patients but slightly attenuated in dose intensity. Consider offering chemotherapy-free approaches in patients with non-high-risk APL. B Patients with comorbidities: consider offering arsenic trioxide-based therapy schedules in young and older patients with severe comorbidities unfit for chemotherapy (especially anthracyclines). C https://web.pathway.md/diseases/recBNBa37E5DPGci3 3/4 6/23/23, 2:03 AM Acute promyelocytic leukemia Pathway 6. Preventative measures CNS prophylaxis: consider administering CNS prophylaxis only in patients with hyperleukocytosis. C 7. Follow-up and surveillance Treatment monitoring: interpret an increase of WBC counts > 10 10 /L after treatment initiation with all-trans retinoic acid and/or arsenic trioxide as a sign of all-trans retinoic acid/arsenic trioxide-induced differentiation and do not reclassify the patient as having high-risk disease. B Show 4 more Management of relapsed/refractory disease: As per ESMO 2020 guidelines, offer arsenic trioxide/all-trans-retinoic acid for reinduction and consolidation until the achievement of second molecular remission in patients relapsing after all- trans-retinoic acid and chemotherapy or relapsing > 24 months after the end of arsenic trioxide/all-trans-retinoic acid treatment. B Show 3 more As per ELN 2019 guidelines, initiate preemptive therapy promptly to prevent frank relapse in patients with confirmed molecular relapse (defined as 2 successive PCR-positive assays, with stable or rising promyelocytic leukemia-retinoic acid receptor alpha transcript levels detected in independent samples analyzed in 2 laboratories). B Show 6 more References 1. Tzu-Fei Wang, Robert S Makar, Darko Antic et al. Management of hemostatic complications in acute leukemia: Guidance from the SSC of the ISTH. J Thromb Haemost. 2020 Dec;18 12 3174 3183. Open 2. Miguel A Sanz, Pierre Fenaux, Martin S Tallman et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019 Apr 11;133 15 1630 1643. Open 3. Arber DA, Borowitz MJ, Cessna M et al. Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017 Oct;141 10 1342 1393. Open 4. J Thachil, A Falanga, M Levi et al. Management of cancer-associated disseminated intravascular coagulation: guidance from the SSC of the ISTH. J Thromb Haemost. 2015 Apr;13 4 671 5. Open 5. M Heuser, Y Ofran, N Boissel et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Jun;31 6 697 712. Open https://web.pathway.md/diseases/recBNBa37E5DPGci3 4/4