Guideline sources The following summarized guidelines for the evaluation and management of acute myeloid leukemia (AML) are prepared by our editorial team based on guidelines from the American Society of Hematology (ASH 2020), the International Society on Thrombosis and Haemostasis (ISTH 2020), the European Society of Medical Oncology (ESMO 2020), the Congress of Neurological Surgeons (CNS 2018), the Infectious Diseases Society of America (IDSA/ASCO 2018), the American Society of Hematology (ASH/ACP 2017), the British Society for Haematology (BSH 2017), the British Committee for Standards In Haematology (BCSH 2015), and the Infectious Diseases Society of America (IDSA 2011). 1 2 3 4 5 7 9 10 11 12 12 13 13 13 Definition AML is a hematopoietic stem cell malignancy associated with abnormal differentiation and proliferation of myeloid clone cells. 12 Epidemiology AML is caused by malignant transformation of hematopoietic progenitor cells secondary to genetic mutations that can be inherited or occur sporadically. 13 Pathophysiology https://web.pathway.md/diseases/recgmiUKfU5PnO7Ja 1/6 6/23/23, 1:58 AM Acute myeloid leukemia Pathway The age-adjusted incidence of AML in the United States is 4.3 per 100,000 person-years. 13 Disease course The oncogenic transformation of hematopoietic progenitor stem cells leads to the production of malignant clones causing increased myeloid blasts (myeloblasts, monoblasts, megakaryoblasts) in the bone marrow and peripheral blood, multiorgan infiltration by blast cells, bone marrow failure, and death. 12 Prognosis and risk of recurrence The median overall survival of AML is 8.5 months, with 2-year and 5-year overall survival being 32.0% and 24.0%, respectively. 13 Calculator Calculator Calculator CIBMTR score for acute myeloid Eastern Cooperative Oncology G Karnofsky Guidelines 1. Classification and risk stratification Classification: use the current WHO terminology for the final diagnosis and classification of acute leukemia. A 2. Diagnostic procedures Tissue biopsy: perform a fresh bone marrow aspiration in all patients with suspected acute leukemia, and use a portion of aspirate to prepare smears for morphologic evaluation. Evaluate an adequate bone marrow trephine core biopsy, bone marrow trephine touch preparations, and/or marrow clots, in conjunction with the bone marrow aspirates, if performed. A Show 2 more Ancillary testing: obtain sufficient samples and conduct conventional cytogenetic analysis (karyotype), appropriate molecular genetic and/or fluorescent in situ hybridization testing, and flow cytometric immunophenotyping in addition to morphologic assessment (blood and bone marrow). Ensure that the flow cytometry panel is sufficient to distinguish AML (including acute promyelocytic leukemia), T-cell acute lymphoblastic leukemia (including early T-cell precursor leukemias), B-cell precursor acute lymphoblastic leukemia, and acute leukemia of ambiguous lineage in all patients diagnosed with acute leukemia, and to allow subsequent detection of minimal residual disease. Recognize that molecular genetic and/or fluorescent in situ hybridization testing does not replace conventional cytogenetic analysis. A https://web.pathway.md/diseases/recgmiUKfU5PnO7Ja 2/6 6/23/23, 1:58 AM Acute myeloid leukemia Pathway Show 5 more 3. Medical management Induction chemotherapy, patients eligible for standard treatment: As per ASH 2020 guidelines, initiate antileukemic therapy over best supportive care in older adult patients with newly diagnosed AML being candidates for antileukemic therapy. B Show 3 more As per ESMO 2020 guidelines, consider discussing the requirement of cytoreduction in patients with non-acute promyelocytic leukemia AML with a WBC count > 100 10 /L and signs of leukostasis. Offer hydroxycarbamide 50-60 mg/kg/day or if the patient cannot swallow either IV or SC cytarabine or IV daunorubicin for cytoreduction. C Show 10 more Induction chemotherapy (patients ineligible for standard treatment): offer hypomethylating agents azacitidine or decitabine as first-line therapy in newly diagnosed unfit patients with AML. B Show 4 more Consolidation therapy: As per ASH 2020 guidelines: Consider initiating postremission therapy in older adult patients with AML achieved remission after at least a single cycle of intensive antileukemic therapy and not being candidates for allogeneic HSCT. C Consider continuing therapy indefinitely until progression or unacceptable toxicity in older adult patients with AML achieved a response after receiving less-intensive therapy. C As per ESMO 2020 guidelines, initiate consolidation therapy as soon as patients achieve complete remission/complete remission with incomplete hematological recovery after 1 or 2 induction cycles. B Show 11 more Management of relapsed/refractory disease: offer allogeneic hematopoietic cell transplantation in an attempt to provide long-term survival in patients with primary refractory AML. B Show 7 more Management of thrombocytopenia: administer empiric platelet transfusion (one standard adult unit) for a daily platelet count < 10 10 /L in patients with acute leukemia without active bleeding or coagulopathy. Consider using a higher transfusion threshold (such as 20 10 /L) in patients with active bleeding, as determined by clinical factors, including the degree of hemorrhage, site of hemorrhage, and responsiveness to platelet transfusion. B Show 4 more Management of DIC: ensure a high level of vigilance for DIC in patients with acute leukemia. Obtain systemic evaluation for coagulopathy (including platelet counts and routine coagulation https://web.pathway.md/diseases/recgmiUKfU5PnO7Ja 3/6 6/23/23, 1:58 AM Acute myeloid leukemia Pathway parameters, such as PT, activated partial thromboplastin, and fibrinogen) at least daily until normalization and use at least one of the standardized scores to diagnose DIC. B Show 7 more 4. Therapeutic procedures Leukapheresis: Do not perform leukapheresis in patients with non-acute promyelocytic leukemia AML. D Avoid performing leukapheresis for hyperleukocytosis in patients with acute promyelocytic leukemia because it may exacerbate coagulopathy. D Blood transfusion: consider ensuring the availability of RBC transfusions for older adult patients with AML no longer receiving antileukemic therapy (including patients receiving end-of-life care or hospice care). C 5. Specific circumstances Pregnant patients (diagnosis): use the WHO classification for diagnosing AML in pregnant patients as for nonpregnant patients. A Pregnant patients (general principles of management): manage pregnant patients with a multidisciplinary team including hematologists, obstetricians, neonatologists, and anesthesiologists. B Show 3 more Pregnant patients (chemotherapy): balance the risks of fetal chemotherapy exposure against risks of prematurity following elective delivery at 24-32 weeks of gestation. B Show 3 more Pregnant patients (supportive therapy): avoid using quinolones, tetracyclines, and sulphonamides during pregnancy. D Show 2 more Pregnant patients (delivery): consider administering a course of corticosteroids over a 48-hour period during the week before delivery, if delivery is anticipated at 24-35 weeks of gestation. B Show 6 more Patients with acute promyelocytic leukemia (induction and consolidation therapy): initiate immediate treatment with all-trans-retinoic acid in patients with suspected acute promyelocytic leukemia, until confirmatory molecular and/or cytogenetic results are available. B Show 7 more Landmark trials: Lo-Coco 2013 In patients with acute promyelocytic leukemia classified as low-to-intermediate risk, ATRA- arsenic trioxide was superior to ATRA-chemotherapy with respect to a event-free survival at 2 https://web.pathway.md/diseases/recgmiUKfU5PnO7Ja 4/6 6/23/23, 1:58 AM Acute myeloid leukemia Pathway years. Lo-Coco F et al. N Engl J Med. 2013 Jul 11. Patients with clonal eosinophilia: offer standard induction therapy in patients with AML with clonal eosinophilia and no molecular or cytogenetic abnormality suggesting a likely response to a TKI. A Patients with CNS involvement: consider administering comprehensive radiotherapy to the CNS in patients with AML with a history of CNS involvement undergoing allogeneic HSCT. E 6. Preventative measures Antibiotic prophylaxis: administer antibiotic prophylaxis with a fluoroquinolone in most patients with AML/myelodysplastic syndromes being at high risk for febrile neutropenia or profound, protracted neutropenia. B Antifungal prophylaxis: As per ASCO 2018 guidelines, administer antifungal prophylaxis with an oral triazole or parenteral echinocandin in most patients with AML/myelodysplastic syndromes being at high risk for profound, protracted neutropenia. Antifungal prophylaxis is not routinely recommended for patients with solid tumors. B As per IDSA 2011 guidelines, consider administering antifungal prophylaxis with posaconazole against invasive Aspergillus infections in selected patients 13 years of age undergoing intensive chemotherapy for AML, if the risk of invasive aspergillosis without prophylaxis is substantial. B References 1. Pinnix CC, Yahalom J, Specht L et al. Radiation in Central Nervous System Leukemia: Guidelines From the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2018 Sep 1;102 1 53 58. Open 2. Randy A Taplitz, Erin B Kennedy, Eric J Bow et al. Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update. J Clin Oncol. 2018 Oct 20;36 30 3043 3054. Open 3. Sahra Ali, Gail L Jones, Dominic J Culligan et al. Guidelines for the diagnosis and management of acute myeloid leukaemia in pregnancy. Br J Haematol. 2015 Aug;170 4 487 95. Open 4. Mikkael A Sekeres, Gordon Guyatt, Gregory Abel et al. American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020 Aug 11;4 15 3528 3549. Open 5. 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 https://web.pathway.md/diseases/recgmiUKfU5PnO7Ja 5/6 6/23/23, 1:58 AM Acute myeloid leukemia Pathway 6. Amanda S Davis, Anthony J Viera, Monica D Mead. Leukemia: an overview for primary care. 2014 May 1;89 9 731 8.2014 May 1;89 9 731 8. Open 7. 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 8. 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 9. 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 10. Freifeld AG, Bow EJ, Sepkowitz KA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011 Feb 15;52 4):e56 93. Open 11. Butt NM, Lambert J, Ali S et al. Guideline for the investigation and management of eosinophilia. Br J Haematol. 2017 Feb;176 4 553 572. Open 12. Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018 Aug 18;392 10147 593 606. Open 13. Shallis RM, Wang R, Davidoff A et al. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev. 2019 Jul;36 70 87. Open 14. Tallman MS, Wang ES, Altman JK et al. Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019 Jun 1;17 6 721 749. Open 15. Michel Duval, John P Klein, Wensheng He et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010 Aug 10;28 23 3730 8. Open 16. Val rie de Haas, Nofisat Ismaila, Anjali Advani et al. Initial Diagnostic Work-Up of Acute Leukemia: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists and American Society of Hematology Guideline. J Clin Oncol. 2019 Jan 20;37 3 239 253. Open https://web.pathway.md/diseases/recgmiUKfU5PnO7Ja 6/6