acute myeloid leukemia (AML)
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Introduction
Malignancy of myeloid cells; clonal expansion of myeloblasts in bone marrow, blood or other tissue.
Classification
World Health Organization (WHO)
- acute myeloid leukemia with recurrent genetic abnormalities
- AML with t[8;21][q22;q22]; AML1/ETO
- AML with abnormal bone marrow eosinophils, inv(16)(p13.1;q22.1) or t[16;16][p13;q22]; CBF-beta/MYH11
- acute promyelocytic leukemia (AML-M3) (AML with t[15;17][q22;q12]; PML/RAR-alpha and variants)
- AML with 11q23 (MLL) abnormalities
- AML with mutated RUNX1[15]
- AML with BCR-ABL1[15]
- acute myeloid leukemia with myelodysplasia-related changes
- following myelodysplastic syndrome/myeloproliferative disorder
- without preceding myelodysplastic syndrome
- acute myeloid leukemia, therapy related
- alkylating agent related
- topoisomerase type 2 inhibitor related
- other
- acute myeloid leukemia not otherwise categorised
- acute myeloid leukemia minimally differentiated (AML-M0)
- acute myeloid leukemia without maturation (AML-M1)
- acute myeloid leukemia with matuation (AML-M2)
- acute myelomonocytic leukemia (AML-M4)
- acute monoblastic & monocytic leukemia (AML-M5a, 5b)
- acute erythroid leukemia (AML-M6a, 6b)
- acute megakaryoblastic leukemia (AML-M7)
- acute basophilic leukemia
- acute panmyelosis with myelofibrosis
- myeloid sarcoma
French-American-Brittish (FAB) classification:
- acute myeloid leukemia minimally differentiated (AML-M0) 3-5%
- acute myeloid leukemia without maturation (AML-M1) 15-20%
- acute myeloid leukemia with matuation (AML-M2) 25-30%
- acute promyelocytic leukemia (AML-M3) 10-15%
- acute myelomonocytic leukemia (AML-M4) 20-30%
- acute monoblastic leukemia (AML-M5a) 2-9%*
- acute monocytic leukemia (AML-M5b) 2-9%*
- acute erythroid leukemia (AML-M6a, 6b) 3-5%
- acute megakaryoblastic leukemia (AML-M7) 3-5%
* combined incidence AML-5 (AML-M5a + AML-M5b) 2-9%
Etiology
(risk factors):
- age is greatest risk factor
- prior alkylating agent therapy
- benzene exposure
- radiation
- type 2 topoisomerase inhibitors
- Fanconi's anemia
- Bloom syndrome
- Down syndrome
- neurofibromatosis
- myeliproliferative neoplasm
Epidemiology
- worldwide, approximately 2.8/100,000 population per year
- most cases diagnosed in January, implying seasonal factors such as infectious agents or environmental triggers[32]
- more common in adults
- mean age at presentation is 67 years[7]
- in adults, 90% of acute leukemia is myeloblastic, 10% is lymphoblastic[7]*
* the reverse is true of children & adolescents[7]
Pathology
- bone marrow is hypercellular
- monomorphic population of cells, arrested development
- proliferation of myeloblasts & or promyelocytes in bone marrow & peripheral blood
- WHO recommendation for diagnosis: myeloblasts >= 20% in blood or bone marrow
- may evolve from myelodysplastic syndrome
- leukemic myeloblasts divide hourly & the patient becomes symptomatic over days to weeks[7]
- functional neutropenia due to myeloblast replacement of normal bone marrow
Genetics
> 20 known genetic aberrations associated with AML
- chromosomal abnormalities generally involve chromsomes 5 & 7
- mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, & IDH2, are commonly acquired early & are present in the founding clone[15] typically are secondary events that occur later during leukemogenesis[15]
- constitutively-activated FLT3 associated with poor prognosis
- mutations involving NPM1 or signaling molecules (FLT3, RAS)
- ~1/4 of adult AML patients with FLT3-ITD (Internal Tandem Duplication)
- defects in NPM1 most common genetic defect in AML (30%)[35]
- KMT2A rearrangements in 15% of childen & adults with AML[35]
- early-onset AML may be associated with germline defects in MBD4[18]
- overexpression of ZFP91, MSI2
- mutations in RUNX1, ASXL1, TP53
- translocation t(5;11)(q35;p15.5), NUP98 & NSD1 genes
- translocation t(6;9)(p23;q34) involving DEK with NUP214/CAN
- translocation t(7;11)(p15;p15) involving HOXA9 with NUP98
- translocation t(8;11)(p11.2;p15), WHSC1L1 & NUP98 genes
- translocation t(8;16)(p11;p13) involving MYST3 with CREBBP
- t(8;21)(q22;q22) (AML/ETO) involving AML1 & ETO (favorqble prognosis)
- translocation t(8;22)(p11;q13) involving MYST3 with EP300
- translocation t(12;22)(q13;q11) involving MN1 & TEL genes
- translocation t(11;17)(q23;q25) involving SEPT9 & MLL genes
- translocation t(11;17)(q23;p13) involving GAS7 with MLL genes
- translocation t(4;12)(q12;p13) involving CHIC2 & ETV6 genes
- translocation t(9;11)(q34;q23) involving DAB2IP & MLL genes
- translocation t(11;17)(p15;p13) involving PHF23 & NUP98 genes
- translocation t(3;21)(q26;q22) involving EVI1 & RUNX1/AML1
- translocation t(3,11)(q25,q23) involving GMPS with MLL
- translocation t(1;3)(p36;q21) involving PRDM16
- translocation t(16;21)(p11;q22) involving FUS with ERG
- inversion inv(8)(p11;q13) generates the MYST3-NCOA2 oncogene
- inversion inv(16) (favorable prognosis)[7]
- other implicated genes:
Gene expression profiling clusters[8]
non-coding RNA profiles may provide prognostic information[19]
- some such non-coding RNAs may be located in close proximity to hematopoietic coding genes[19]
* multiple (> 5 genetic aberrations) associated with poor prognosis[7]
Clinical manifestations
- AML-related bone marrow failure
- fatigue (anemia)
- dyspnea
- mucosal & cutaneous bleeding (thrombocytopenia)
- gingival hyperplasia (monocytic leukemias)
- leukemia cutis
- extramedullary tumors
- develops over weeks to months
- fever
- opportunistic infections (neutropenia)
- skin & mucous membrane lesions[3]
- petechiae when platelet count < 20,000/uL[7]
- gingival hypertrophy & leukemia cutis common
- most likely among leukemias to develop petechiae, bruising, bleeding, & infection[7]
- sternal tenderness (bone marrow expansion)
- hepatosplenomegaly uncommon, suggests another diagnosis[7]
- lymphadenopathy uncommon, suggests another diagnosis[7]
Laboratory
- complete blood count (CBC)
- leukocytosis with circulating blasts[7]
- absolute neutrophil count may be low[7]
- anemia
- thrombocytopenia
- in the elderly, typically long-standing pancytopenia
- leukocytosis with circulating blasts[7]
- peripheral blood smear*
- Auer rods in myeloblasts pathognomonic
- >= 20% blasts is diagnostic
- bone marrow aspiration & bone marrow biopsy
- Auer rods in myeloblasts pathognomonic
- >= 20% blasts is diagnostic
- flow cytometry: CD33[7], CD117[5]
- cytogenetics (only definitive diagnosis)
- gene expression profiling using microarray technology predicts prognosis[8]
- detection of mutations during AML remission with targeted next-generation sequencing, excluding mutations associated with age-related clonal hematopoiesis, predicts likelihood of relapse[20]
- specific mutation testing
- C5-cytosine DNA methyltransferase-3A (DNMT3A) gene mutation testing (see NGC guideline, Program in Evidence-based Care)
- reduction of ERK 1/2 & p38 MAPK phosphorylation in the myeloid cell compartment 24 hour post-chemotherapy predicts 5-year overall survival[34]
- see ARUP consult[9]
* image of myeloblasts in a patient with refractory acute myeloid leukemia[29]
* images of myeloblast in mitosis & in apoptosis[29]
Complications
- leukostasis & hyperviscosity syndrome (WBC count is > 50,000/uL)
- tumor lysis syndrome may occur spontaneously or especially with treatment[7]
- may be 1st manifestation of AML[7]
Differential diagnosis
- acute lymphoblastic leukemia (children, adolecents)
- acute promyelocytic leukemia (DIC)
Management
- within 1st 24 hours of diagnosis
- confirm acute leukemia
- confirm AML vs ALL
- exclude acute promyelocytic leukemia
- leukapheresis if WBC count is > 50,000/uL
- chemotherapy induction
- daunorubicin (Cerubidine) for 3 days
- cytarabine (Cytosar) for 7 days
- daunorubicin + cytarabine referred to as "7 + 3 regimen"
- idarubicin may substitute for daunorubicin
- high dose cytarabine (ARA-C) (HiDAC) is used in patients with refractory, relapsed or therapy-related AML
- flotetuzumab may induce remission[14]
- vigorous hydration & pretreatment with allopurinol to prevent tumor lysis syndrome
- urine alkalinization to reduce hyperuricemia
- prophylaxis with posaconazole for aspergillosis[22]
- chemotherapy consolidation & maintenance
- high dose ARA-C 1-3 gm/m2 BID
- addition of sorafenib (Nexavar) in patients < 60 years of age may be of benefit[16]
- oral azacitidine (Onureg) as maintenance therapy after first remission[28]
- consolidation after completed remission for low risk patients
- no prior chemotherapy, candidates for targeted therapy
- allogeneic stem cell transplantation reserved for "salvage therapy" & for first complete remission in younger patients (51 years is younger)[7]
- for patients who fail induction therapy, allogeneic stem cell transplantation without intensive salvage induction may be an option[31]
- targeted therapy
- FLT3 inhibitor midostaurin (Rydapt) in combination with standard cytarabine & daunorubicin induction & cytarabine consolidation for constitutively-activated FLT3 mutation[17]
- gilteritinib (another FLT3 inhibitor) shows promise[17]
- quizartinib (Vanflyta) FDA-approved for adults with FLT3-ITD (Internal Tandem Duplication)[36]
- IDH1 inhibitor ivosidenib for AML patients (6-10%) with IDH1 mutations (FDA-approval pending)[23]
- addition of ivosidenib (Tibsovo) to azacitidine increases survival 3-fold[30]
- IDH2 inhibitor enasidenib (Idhifa) for AML patients (20%) with IDH2 mutations[21]
- response rate ~ 30% + another 30% with stable disease
- investigational menin inhibitor revumenib promising for patients with relapsed or refractory KMT2A-rearranged or NPM1-mutant acute leukemia [35
- CD33(+) AML
- gemtuzumab ozogamicin (Mylotarg)
- may induce remission in elderly patients with CD33(+) AML
- not associated with profound myelosuppression
- more harm than benefit; US market removal June 2010
- FDA approval for CD33+ AML Sept 2017
- gemtuzumab ozogamicin (Mylotarg)
- all trans-retinoic acid for AML-M3 (acute promyelocytic leukemia)
- therapy-related AML or myelodysplasia-related AML
- FLT3 inhibitor midostaurin (Rydapt) in combination with standard cytarabine & daunorubicin induction & cytarabine consolidation for constitutively-activated FLT3 mutation[17]
- considerations in older patients
- older, fit patients pretreated with 10-days of decitabine (Dacogen) prior to allogeneic hematopoietic stem cell transplantation with similar overall survival & fewer severe adverse events vs conventional intensive chemotherapy[33]
- older patients with high-risk AML or comorbidities precluding use of intensive chemotherapy may be treated with supportive care & low-dose outpatient chemotherapy (azacytidine or decitabine)[7]
- supportive care
- blood transfusions
- use only filtered & irradiated blood products
- platelet transfusion
- hemorrhage
- platelet count < 10,000/uL
- leukopheresis & chemotherapy for treatment of leukostasis (WBC > 50,000/uL)
- prophylaxis for invasive fungal disease
- caspofungin more effective than fluconazole[26]
- palliative care integrated with oncology care improves quality of life, psychological distress, & end of life care[27]
- blood transfusions
- autologous vs allogeneic stem cell transplantation
- prognosis:
- 30-50% remission in the elderly with induction therapy
- 10% of elderly who achieve remission sustain remission > 5 years[4]
- a favorable prognosis for AML in patients is
- a unfavorable prognosis for AML in patients is
- genetic classification of AML may better estimate prognosis & facilitate treatment[10]
- routine medical care of family members
More general terms
More specific terms
- acute basophilic leukemia
- acute eosinophilic leukemia
- acute myeloid leukemia t[16;16][p13;q22] or inv[16][p13;q22];(CBF-beta/MYH11)
- acute myeloid leukemia t[18;21][q22;q22];(AML1/ETO)
- acute myeloid leukemia with myelodysplasia-related changes (AML-MRC)
- acute myeloid leukemia, 11q23 (MLL) abnormalities
- acute myeloid leukemia, therapy related
- acute panmyelosis with myelofibrosis
- AML gene expression profiling clusters
- AML-M0; acute myeloblastic leukemia minimally differentiated
- AML-M1; acute myeloblastic leukemia without maturation
- AML-M2; acute myeloblastic leukemia with maturation
- AML-M3; acute promyelocytic leukemia
- AML-M4; acute myelomonocytic leukemia
- AML-M5; acute monocytic leukemia
- AML-M6; acute erythroblastic leukemia
- AML-M7; acute megakaryoblastic leukemia
- chronic myeloid leukemia (CML) blast crisis
Additional terms
References
- ↑ Cotran et al Robbins Pathologic Basis of Disease, W.B. Saunders Co, Philadelphia, PA 1989 pg 726
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 596
- ↑ 3.0 3.1 Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 539
- ↑ 4.0 4.1 Schiller G, in: UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 5.0 5.1 Naeim F, UCLA Clinical Pathology, weekly conference, Oct 7, 2002
- ↑ WHO Classification of Tumours. Tumors of Haematopoietic and Lymphoid Tissues. Jaffe et al. IARC Press 2001
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 7.20 Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2022
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 8.0 8.1 8.2 Bullinger L et al Use of gene-expression profiling to identify prognostic subclasses in adult acute myeloid leukemia. NEJM 350:1605-1616, 2004 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15084693 <Internet> http://content.nejm.org/cgi/content/short/350/16/1605
Valk PJ et al Prognostically useful gene-expression profiles in acute myeloid leukemia. NEJM 350:1617-1628, 2004 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15084694 <Internet> http://content.nejm.org/cgi/content/short/350/16/1617 supplementary http://content.nejm.org/cgi/content/full/350/16/1617/DC1
Grimwade D, Haferlach T. Gene-expression profiling in acute myeloid leukemia. N Engl J Med. 2004 Apr 15;350(16):1676-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15084701 Liu ET, Karuturi KR. Microarrays and clinical investigations. N Engl J Med. 2004 Apr 15;350(16):1595-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15084689 - ↑ 9.0 9.1 ARUP Consult: Acute Myeloid Leukemia - AML The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/acute-myeloid-leukemia
Acute Myeloid Leukemia Molecular Genetic Testing https://arupconsult.com/ati/acute-myeloid-leukemia-molecular-genetic-testing - ↑ 10.0 10.1 The Cancer Genome Atlas Research Network Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia. N Engl J Med May 1, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23634996 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1301689
Steensma DP The Beginning of the End of the Beginning in Cancer Genomics. N Engl J Med May 1, 2013 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23634995 - ↑ Koreth J, Schlenk R, Kopecky KJ et al Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009 Jun 10;301(22):2349-61 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19509382
- ↑ Borthakur G, Estey AE Therapy-related acute myelogenous leukemia and myelodysplastic syndrome. Curr Oncol Rep. 2007 Sep;9(5):373-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17706165
- ↑ Estey E. Acute myeloid leukemia and myelodysplastic syndromes in older patients. J Clin Oncol. 2007 May 10;25(14):1908-15. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17488990
- ↑ 14.0 14.1 O'Neil A CD123-Targeted Flotetuzumab Induces Some CRs in AML. DART molecule aimed at receptor expressed on most myeloid blast and leukemic stem cells. MedPage Today Oct 11, 2017 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/68470
- ↑ 15.0 15.1 15.2 15.3 15.4 Bullinger L, Dohner K, Dohner H Genomics of Acute Myeloid Leukemia Diagnosis and Pathways. J Clin Oncol. 2017 Mar 20;35(9):934-946 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28297624
- ↑ 16.0 16.1 16.2 O'Neil A, Short NJ AML: TKI Sorafenib Added to '7+3' Equals EFS Benefit. The multiple kinase inhibitor targets several different pathways important for AML development and maintenance. MedPage Today. Jan 11, 2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/70405
Rollig C, et al The addition of sorafenib to standard AML treatment results in a substantial reduction in relapse risk and improved survival. Updated results from long-term follow-up of the randomized- controlled Soraml Trial. American Society of Hematology (ASH) 2017; Abstract 721. - ↑ 17.0 17.1 17.2 O'Neil A, Klil-Drori AJ. AML: FLT3 Inhibitor Shows 'Robust' Activity as Frontline Therapy - Overall response rate 100% in patients with FLT3- mutated disease in early research. MedPage Today. Jan 17, 2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/70559
- ↑ 18.0 18.1 O'Neil A DNA Repair Mutations Lead to AML Predisposition. In early research, germline mutations shut down a mechanism that guards against harmful mutations that increase leukemia risk. MedPage Today, ASCO Reading Room. Feb 21, 2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/71284
Sanders MA, Chew E, Flensburg C et al Germline loss of MBD4 predisposes to leukaemia due to a mutagenic cascade driven by 5mC. bioRxiv preprint first posted online Nov. 1, 2017 https://www.biorxiv.org/content/biorxiv/early/2017/11/01/180588.full.pdf - ↑ 19.0 19.1 19.2 O'Neil A Non-coding RNAs Offer AML Prognosis. Four-gene LincRNA expression signature predicts risk in multiple cohorts. MedPage Today. ASCO Reading Room 03.07.2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/71586
Beck D, Thoms JAI, Palu C et al A four-gene LincRNA expression signature predicts risk in multiple cohorts of acute myeloid leukemia patients. Leukemia volume 32, pages 263-272 (2018) PMID: https://www.ncbi.nlm.nih.gov/pubmed/28674423 https://www.nature.com/articles/leu2017210 - ↑ 20.0 20.1 Jongen-Lavrencic M, Grob T, Hanekamp D et al Molecular Minimal Residual Disease in Acute Myeloid Leukemia. N Engl J Med 2018; 378:1189-1199 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29601269 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1716863
- ↑ 21.0 21.1 Minerd J New Options for Acute Myeloid Leukemia. Targeted therapies improve outcomes in specific patients. MedPage Today. ASCO Reading Room 03.28.2018 https://www.medpagetoday.com/reading-room/asco/hematologic-malignancies/72028
- ↑ 22.0 22.1 Ullmann AJ, Aguado JM, Arikan-Akdagli S et al Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 Mar 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29544767
- ↑ 23.0 23.1 Ingram I. Ivosidenib Induces Deep Remissions in IDH1-Mutant AML On strength of phase I data, drug appears headed for FDA approval. MedPage Today. June 03, 2018 https://www.medpagetoday.com/meetingcoverage/asco/73242
DiNardo CD, Stein EM, de Botton S et al Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. Jun 2, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29860938 https://www.nejm.org/doi/full/10.1056/NEJMoa1716984
Pollyea DA, et al Ivosidenib (IVO; AG-120) in mutant IDH1 relapsed/refractory acute myeloid leukemia (R/R AML): Results of a phase 1 study. American Society of Clinical Oncology (ASCO) 2018; Abstract 7000 - ↑ 24.0 24.1 Fuerst ML with expert critique by Taylor J New AML Therapeutic Strategy Aims to Make Stealth Leukemia Cells Visible, Interferon gamma induces the cells to re-reveal themselves in relapsed/refractory disease. MedPage Today. ASCO Reading Room, Nov 20, 2018 https://www.medpagetoday.com/reading-room/asco/immunotherapy/76452
- ↑ Dohner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015 Sep 17;373(12):1136-52. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26376137
- ↑ 26.0 26.1 Fisher BT, Zaoutis T, Dvorak CC et al Effect of Caspofungin vs Fluconazole Prophylaxis on Invasive Fungal Disease Among Children and Young Adults With Acute Myeloid Leukemia. A Randomized Clinical Trial. JAMA. 2019;322(17):1673-1681. Nov 5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31688884 https://jamanetwork.com/journals/jama/fullarticle/2753898
- ↑ 27.0 27.1 Annals of Long-Term Care. June 3, 2020 Palliative Care Proves Beneficial in Treatment of Patients With AML. https://www.managedhealthcareconnect.com/content/palliative-care-proves-beneficial-treatment-patients-aml
l-Jawahri A, LeBlanc TA, Kavanaugh A et al. Multisite randomized trial of integrated palliative and oncology care for patients with acute myeloid leukemia (AML). J Clin Oncol. 38: 2020; suppl; abstr 12000. Not indexed in PubMed - ↑ 28.0 28.1 Bankhead C Year in Review: Acute Myeloid Leukemia. MedPage Today November 29, 2020 https://www.medpagetoday.com/hematologyoncology/leukemia/89909
- ↑ 29.0 29.1 29.2 Markewitz RDH, Dargvainiene J Images in Clinical Medicine Mitotic and Apoptotic Figures on a Peripheral-Blood Smear. N Engl J Med. 2021. May 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34014049 https://www.nejm.org/doi/full/10.1056/NEJMicm2033085
- ↑ 30.0 30.1 Ingram I Upfront IDH1 Inhibitor Triples Survival in Older AML. Median OS for ivosidenib-azacitidine reached 2 years in patients ineligible for intensive therapy. MedPage Today December 11, 2021 https://www.medpagetoday.com/meetingcoverage/ashhematology/96149
- ↑ 31.0 31.1 Osterweil N 'Astonishing' Results: Skip Salvage Chemo, Go Straight to HSCT. Medscape. Dec 11, 2022 https://www.medscape.com/viewarticle/985384
- ↑ 32.0 32.1 Cotelo J AML's Seasonal Peak Suggests Viral or Environmental Etiology. Medscape. August 16, 2022 https://www.medscape.com/viewarticle/979272
Sanchez-Vizcaino F, Tamayo C, Ramos F et al Identification of seasonal variation in the diagnosis of acute myeloid leukaemia: a population-based study. Br J Haematol. 2022. Aug;198(3):545-555. ePub: May 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35639095 PMCID: PMC9542150 Free PMC article https://onlinelibrary.wiley.com/doi/10.1111/bjh.18279 - ↑ 33.0 33.1 Melville NA Similar Survival, Less Toxicity With Decitabine vs Chemo in AML. Medscape. June 12, 2022 https://www.medscape.com/viewarticle/975438
- ↑ 34.0 34.1 Tislevoll BS et al Early response evaluation by single cell signaling profiling in acute myeloid leukemia. Nature Communications 2023. 14:115. Jan 7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36611026 PMCID: PMC9825407 Free PMC article https://www.nature.com/articles/s41467-022-35624-4
- ↑ 35.0 35.1 35.2 Brooks M Novel Drug Leads to 'Impressive' Responses in Advanced Leukemia. Medscape. March 20, 2023 https://www.medscape.com/viewarticle/989871
- ↑ 36.0 36.1 Otto MA FDA Approves Quizartinib for Newly Diagnosed AML. Medscape. July 20, 2023 https://www.medscape.com/viewarticle/994618
- ↑ NEJM Knowledge+
- ↑ Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies (PDQ): Treatment http://www.cancer.gov/cancertopics/pdq/treatment/childAML/HealthProfessional
- ↑ Adult Acute Myeloid Leukemia (PDQ): Treatment http://www.cancer.gov/cancertopics/pdq/treatment/adultAML/HealthProfessional
Patient information
acute myeloid leukemia patient information