University of Wisconsin Hematology

Acute Leukemia

Biology of acute leukemia

  1. Dores et al. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood 2012;119:34
  2. The Cancer Genome Atlas Research Network. Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia. NEJM 2013;368:2059 (At least one “driver” mutation found in almost every case; average number of mutations per case around 13)
  3. Lindsley and Ebert. The biology and clinical impact of genetic lesions in myeloid malignancies. Blood 2013;122:3741
  4. Bodini et al. The hidden genomic landscape of acute myeloid leukemia: subclonal structure revealed by undetected mutations. Blood 2015;125:600
  5. Thomas and Majeti. Biology and relevance of human acute myeloid leukemia stem cells. Blood 2017;129:1577
  6. Ediriwickrema et al. Single-cell genomics in AML: extending the frontiers of AML research. Blood 2023;141:345
  7. Lane et al. The leukemic stem cell niche: current concepts and therapeutic opportunities. Blood 2009;114:1150
  8. Ferrando and López-Otín. Clonal evolution in leukemia. Nat Med 2017;23:1135
  9. Stauber et al. Preleukemic and leukemic evolution at the stem cell level. Blod 2021;137:1013
  10. Chen et al. Myelodysplastic syndrome progression to acute myeloid leukemia at the stem cell level. Nat Med 2019;25:103
  11. Ho et al. Evolution of acute myelogenous leukemia stem cell properties after treatment and progression. Blood 2016;128:1671
  12. Parkin et al. Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia. Blood 2013;121:369 (Relapse is due to incomplete eradication of AML “founder clones”)  
  13. Peterson et al. Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts. Blood 2007;110:799
  14. Wang et al. The Leukemogenicity of AML1-ETO Is Dependent on Site-Specific Lysine Acetylation. Science 2011;333:765 (“Lysine acetyltransferases represent a potential therapeutic target in AML”)
  15. Mardis et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. NEJM 2009; 361:1058
  16. Patel et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. NEJM 2012; 366:1079
  17. Sachs and Lotem. Control of programmed cell death in normal and leukemic cells: new implications for therapy. Blood 1993;82:15
  18. Pedersen-Bjergaard et al. Genetic pathways in therapy-related myelodysplasia and acute myelogenous leukemia. Blood 2002;99:1909
  19. Link et al. Identification of a Novel TP53 Cancer Susceptibility Mutation Through Whole-Genome Sequencing of a Patient With Therapy-Related AML. JAMA 2011;305:1568 (Inherited mutation predisposing to therapy-related AML)
  20. Wong et al. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukemia. Nature 2014;518:552 (TP53 mutations present in a subset of hematopoietic stem cells prior to therapy predispose to t-AML)
  21. Wolfraim et al.  Loss of Smad3 in Acute T-Cell Lymphoblastic Leukemia.  NEJM 2004;351:552
  22. Mullighan et al. CREBBP mutations in relapsed acute lymphoblastic leukemia. Nature 2011;471:235
  23. Roberts et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. NEJM 2014;371:1005
  24. Godley and Le Beau. The histone code and treatments for acute myeloid leukemia. NEJM 2012;366:960
  25. Eppert et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 2011;17:1086 (Expression of “stem cell” genes by blasts associated with worse prognosis in AML)
  26. Abdel-Wahab and Levine. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood 2013;121:3563
  27. Li et al. Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat Med 2016;22:792(With editorial)
  28. Delhommeau et al. Mutation in TET2 in myeloid cancers. NEJM 2009;360:2289 (Mutation an early event in AML, MDS, MPD. See also the accompanying editorial)
  29. Dey et al. Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 2012;337:1541(With editorial)
  30. Wang et al. Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation. Science 2013;340:622(with editorial)
  31. Chan et al. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat Med 2015;21:178(potential “synthetic lethal” treatment approach; with editorial)
  32. Swaminathan et al. BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint. Nat Med 2013;19:1014(Identification of an important safeguard against leukemogenesis in B cells)
  33. Chantepie et al. Hematogones: a new prognostic factor for acute myeloblastic leukemia. Blood 2011;117:1315
  34. Gurbuxani et al.  Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome.  Blood 2004;103:399
  35. Hole et al. Do reactive oxygen species play a role in myeloid leukemias? Blood 2011;117:5816
  36. Dawson et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 2011;478:529
  37. Placke et al. Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood 2014;124:13
  38. Chen et al. DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia. Nat Med 2015;21:335
  39. Liang et al. Therapeutic Targeting of MLL Degradation Pathways in MLL-Rearranged Leukemia. Cell 2017;168:59(Stabilizing wild-type MLL protein inhibits leukemia cell proliferation; see also NEJM commentaryon this research)
  40. Walter et al. Clonal architecture of secondary acute myeloid leukemia. NEJM 2012;366:1090(85% of marrow cells clonal; founding clone with hundreds of mutations and subclones with many more)
  41. Makishima et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood 2012;119:3203
  42. Damm et al. Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes. Blood 2012;119:3211
  43. Senapati et al. Venetoclax abrogates the prognostic impact of splicing factor gene mutations in newly diagnosed acute myeloid leukemia. Blood 2023;142:1647
  44. Mansour et al. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science 2014;346:1373(Mutation enhances binding of MYB transcription factor, enhancing TAL1 expression in T-ALL; with editorial)
  45. Esposito et al. Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors. Nat Med 2015;21:1481(With editorial)
  46. Fucikova et al. Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients. Blood 2016;128:3113
  47. Schneider et al. SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia. Nat Med 2017;23;250
  48. Herold et al. Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies. Nat Med 2017;23:256
  49. Göllner et al. Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia. Nat Med 2017;234: 23:69
  50. Guryanova et al. DNMT3A mutations promote anthracycline resistance in acute myeloid leukemia via impaired nucleosome remodeling. Nat Med 2016;22:1488
  51. Vu et al. The N6-methyladenosine (m6A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nat Med 2017;23:1369(With editorial)
  52. Colom Díaz et al. Hematopoietic stem cell aging and leukemia transformation. Blood 2023;142:542

Inherited myeloid malignancy

  1. Brown et al. Secondary leukemia in patients with germline transcription factor mutations (RUNX1, GATA2, CEBPA). Blood 2020;136:24
  2. Godley and Shimamura. Genetic predisposition to hematologic malignancies: management and surveillance. Blood 2017;130:424
  3. Yang et al. Identification and prioritization of myeloid malignancy germline variants in a large cohort of adult patients with AML. Blood 2022;139:1208 (13.6% of adult AML patients have potentially pathogeneic germline variants)
  4. Kohlmann and Schiffman. Discussing and managing hematologic germ line variants. Blood 2016;128:2497
  5. Drazer et al. How I diagnose and manage individuals at risk for inherited myeloid malignancies. Blood 2016;128:1800
  6. Churpek et al. Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia. Blood 2015;126:2484
  7. Shinawi et al. Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood 2008;112:1042
  8. Homan et al. Hereditary platelet disorders associated with germ line variants in RUNX1, ETV6, and ANKRD26. Blood 2023;141:1533
  9. Simon et al. High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML. Blood 2020;135:1882
  10. Cunningham et al. Natural history study of patients with familial platelet disorder with associated myeloid malignancy. Blood 2023;142:2146 (RUNX1)
  11. Wahlster et al. ANKRD26-related thrombocytopenia 2 with a baseline increase in blasts: implications for clinical surveillance. Blood 2025;146:254 (Increased marrow blasts without progression to myeloid malignancy)
  12. Crispino and Horwitz. GATA factor mutations in hematologic disease. Blood 2017;129:2103
  13. Spinner et al. GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity. Blood 2014;123:809
  14. Calvo and Hickstein.  The spectrum of GATA2 deficiency syndrome. Blood 2023;142:1524
  15. Vinh et al. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 2010;115:1519 (GATA-2 deficiency)
  16. Dickinson et al. Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency. Blood 2011;118:2656 (mycobacterial infection, pulmonary alveolar proteinosis, MDS and AML)
  17. Hsu et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 2011;118:2653
  18. Ganapathi et al. GATA2 deficiency-associated bone marrow disorder differs from idiopathic aplastic anemia. Blood 2015;125:56
  19. Schratz et al. Cancer spectrum and outcomes in the Mendelian short telomere syndromes. Blood 2020;135:1946
  20. Duployez et al. Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study. Blood 2022;140:756 (Male predominance, older, low WBC, better response to intensive chemo; with commentary)
  21. Makishima et al. Germ line DDX41 mutations define a unique subtype of myeloid neoplasms. Blood 2023;141:534 (Lifelong risk of AML 50%; explains 80% of germ line predisposition to AML)
  22. Makishima et al. DDX41-associated susceptibility to myeloid neoplasms. Blood 2023;141:1544
  23. Kovilakam et al. Prevalence and significance of DDX41 gene variants in the general population. Blood 2023;142:1185
  24. Kraft and Godley. Identifying potential germline variants from sequencing hematopoietic malignancies. Blood 2020;136:2498
  25. Bick et al Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 2020;586:763
  26. Feurstein et al. Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages. Blood 2022;140:2533 (7% of MDS patients had potentially pathogenic germline variants)
  27. Reilly and Shimamura. Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: biological insights and clinical advances. Blood 2023;141:1513
  28. Hakkarainen et al. The clinical picture of ERCC6L2 disease: from bone marrow failure to acute leukemia. Blood 2023;141:2853
  29. Zerella et al. Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition. Blood 2024;144:1765

AML: General

  1. Arber et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391
  2. Döhner et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022;140:1345
  3. Arber et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood 2022;140:1200
  4. DiNardo et al. Acute myeloid leukaemia. Lancet 2023;401:2073
  5. Döhner et al. Acute myeloid leukemia. NEJM 2015;373:1136
  6. Walter et al. Significance of FAB subclassification of “acute myeloid leukemia, NOS” in the 2008 WHO classification: analysis of 5848 newly diagnosed patients. Blood 2013;121:2424(Morphology does not provide independent prognostic information in AML if molecular features are known)
  7. Kern et al.  Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial.  Blood 2003;101:64
  8. Elliott et al. Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival. Blood 2007;110:4172
  9. Buccisano et al. Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. Blood 2012;119:332
  10. Jourdan et al. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia. Blood 2013;121:2213(MRD best predictor of relapse)
  11. Ivey et al. Assessment of Minimal Residual Disease in Standard-Risk AML. NEJM 2016;374:422(With editorial)
  12. Schuurhuis et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood 2018;131:1275
  13. Jongen-Lavrencic et al. Molecular Minimal Residual Disease in Acute Myeloid Leukemia. NEJM 2018;378:1189(MRD found during CR, but not persistence of mutations associated with clonal hematopoiesis, predicted relapse; with editorial)
  14. Dillon et al. DNA Sequencing to Detect Residual Disease in Adults With Acute Myeloid Leukemia Prior to Hematopoietic Cell Transplant. JAMA 2023:329:745 (Marked increase in relapse rate and decreased survival if MRD detected prior to HSCT)
  15. Hasserjian et al. Clonal hematopoiesis and measurable residual disease assessment in acute myeloid leukemia. Blood 2020;135:1729
  16. Wang et al. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood 2014;124:1880
  17. Derolf et al. Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005. Blood 2009;113: 3666(5 yr “relative survival” rates 65% for age <18, 58% for ages 19-41, 36% for ages 41-60, 15% for ages 61-70, 5% for ages 71-80, 1% for age >80)
  18. Kayser et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. Blood 2011;117:2137
  19. Voso et al. What’s new in the pathogenesis and treatment of therapy-related myeloid neoplasms. Blood 2021;138:749
  20. Morton et al. Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, 1975-2008. Blood 2013;121:2996
  21. Nardi et al. Acute Myeloid Leukemia and Myelodysplastic Syndromes After Radiation Therapy Are Similar to De Novo Disease and Differ From Other Therapy-Related Myeloid Neoplasms. J Clin Oncol 2012;30:2340
  22. Matutes et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 2011;117:3163(MPAL is a poor risk disease; authors recommend transplantation in 1st remission)
  23. Vasu et al. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood Adv 2018;2:1645(16.6% of patients < 60 and 2.4% of those >60 disease free at 10 yrs; disease free survivors usually had CBF mutations)
  24. Mishra et al. Metabolism in acute myeloid leukemia: mechanistic insights and therapeutic targets. Blood 2023;141:1119

AML: clinical implications of molecular and cytogenetic changes

Prognosis

  1. Grimwade et al. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood 2016;127:29
  2. Döhner and Gaidzik. Impact of genetic features on treatment decisions in AML. Hematology 2011;36
  3. Rockova et al. Risk stratification of intermediate-risk acute myeloid leukemia: integrative analysis of a multitude of gene mutation and gene expression markers. Blood 2011;118:1069
  4. Damm et al. Integrative prognostic risk score in acute myeloid leukemia with normal karyotype. Blood 2011;117:4561
  5. Klco et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811(Persistence of AML-assosiated mutations in remission marrow → worse prognosis)
  6. Mrózek and Bloomfield. Chromosome Aberrations, Gene Mutations and Expression Changes, and Prognosis in Adult Acute Myeloid Leukemia. Hematology 2006;169-77
  7. Mrózek et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood 2007;109:431
  8. Welch and Link. Genomics of AML: clinical applications of next-generation sequencing. Hematology 2011;30
  9. Pikman and Stegmaier. Targeted therapy for fusion-driven high-risk acute leukemia. Blood 2018;132:1241
  10. Østgård et al. Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study. J Clin Oncol 2015;33:3641(AML following CMML or MPD has dismal prognosis)
  11. Röllig et al. Does time from diagnosis to treatment affect the prognosis of patients with newly diagnosed acute myeloid leukemia? Blood 2020;136:823(No)

Cytogenetics

  1. Moorman et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 2007;109:3189
  2. Byrd et al.  Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461).  Blood 2002;100:4325
  3. Marcucci et al.  Abnormal Cytogenetics at Date of Morphologic Complete Remission Predicts Short Overall and Disease-Free Survival, and Higher Relapse Rate in Adult Acute Myeloid Leukemia: Results From Cancer and Leukemia Group B Study 8461.  J Clin Oncol 2004;22:2410
  4. Farag et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood 2006;108:63
  5. Perrot et al. Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities. Blood 2011;118:679
  6. Haferlach et al. Prognostic value of monosomal karyotype in comparison to complex aberrant karyotype in acute myeloid leukemia: a study on 824 cases with aberrant karyotype. Blood 2012;119:2122(Monosomy or 4 or more cytogenetic abnormalities associated with very poor outcome)
  7. Kayser et al. Monosomal karyotype in adult acute myeloid leukemia: prognostic impact and outcome after different treatment strategies. Blood 2012;119:551(Poor response to induction therapy, 9% 4-year survival)
  8. Medeiros et al. Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. Blood 2010;116:2224(3% 4 yr survival!)
  9. Bacher et al. Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood 2012;119:4719
  10. Grimwade et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010;116:354
  11. Middeke et al. Outcome of patients with abnl(17p) acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation. Blood 2014;123:2960(High relapse rate, low 3 year OS)
  12. Herold et al. Isolated trisomy 13 defines a homogeneous AML subgroup with high frequency of mutations in spliceosome genes and poor prognosis. Blood 2014;124:1304

Molecular analysis

  1. The Cancer Genome Atlas Research Network. Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia. NEJM 2013;368:2059(At least one “driver” mutation found in almost every case; average number of mutations per case around 13)
  2. Papaemmanuil et al. Genomic classification and prognosis in acute myeloid leukemia. NEJM 2016;374:2209(>5000 driver mutations identified; with editorial)
  3. Kewan et al. Molecular patterns identify distinct subclasses of myeloid neoplasia. Nat Comm 2023;14:3136
  4. Itzykson et al. Genetic identification of patients with AML older than 60 years achieving long-term survival with intensive chemotherapy. Blood 2021;138:507
  5. Metzeler et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood 2016;128:686(NPM1, FLT3, CEBPA, TP53, DNMT3A and RUNX1 most important risk factors)
  6. Klco et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811(Persistence of AML-assosiated mutations in remission marrow → worse prognosis)
  7. Grossman et al. A novel hierarchical prognostic model of AML solely based on molecular mutations. Blood 2012;120:2963
  8. Ommen et al. Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias. Blood 2010;115:198
  9. Lindsley et al. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 2015;125:1367(Mutations in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 associated with secondary AML, worse prognosis)
  10. Cairoli et al. Prognostic impact of c-KIT mutations in core binding factor leukemias: an Italian retrospective study. Blood 2006;107:3463
  11. Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology 2013:220
  12. Gale et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008;111:2776(high FLT3 mutant level a strong negative prognostic factor)
  13. Ostronoff et al. Prognostic Significance of NPM1 Mutations in the Absence of FLT3–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report. J Clin Oncol 2015;33:1157 (NMP1 positive, FLT3-ITD negative genotype has favorable impact in patients 55-65, not in older patients)
  14. Bacher et al. Prognostic relevance of FLT3-TKD mutations in AML: the combination matters—an analysis of 3082 patients. Blood 2008;111:2527
  15. Bullinger et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML. Blood 2008;111:4490(gene expression signature associated with FLT3 gene mutation a better predictor of outcome than FLT3 mutation status itself)
  16. Kayser et al. Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood 2009;114:2386
  17. Levis M. FLT3/ITD AML and the law of unintended consequences. Blood 2011;117:6987
  18. Falini et al.  Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype.  NEJM 2005;352:254
  19. Schnittger et al. Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 2005;106:3733
  20. Schlenk et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. NEJM 2008;358:1909(mutations of nucleophosmin or CEBPA genes in the absence of FLT3-ITD mutations conferred better prognosis; with editorial)
  21. Falini et al. Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood 2011;117:1109
  22. Falini et al NPM1-mutated acute myeloid leukemia: from bench to bedside. Blood 2020;136:1707
  23. Gaidzik et al. RUNX1 Mutations in Acute Myeloid Leukemia: Results From a Comprehensive Genetic and Clinical Analysis From the AML Study Group. J Clin Oncol 2011;29:1364
  24. Sood et al. Role of RUNX1 in hematological malignancies. Blood 2017;129:2070
  25. Shen et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood 2011;118:5593
  26. Wouters and Delwel. Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia. Blood 2016;127:42
  27. Marcucci et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. NEJM 2008;358:1919(microRNA signature identified that gave improved prognosis in AML patients with high-risk molecular features; with editorial)
  28. Marcucci et al. The prognostic and functional role of microRNAs in acute myeloid leukemia. Blood 2011;117:1121
  29. Allan et al. Genetic variation in XPD predicts treatment outcome and risk of acute myeloid leukemia following chemotherapy. Blood 2004;104:3872
  30. Zuber et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011;478:524
  31. Kharas et al. Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nat Med 2010;16:903
  32. Ley et al. DNMT3A mutations in acute myeloid leukemia. NEJM 2010;363:2424(DNA methyltransferase gene mutations found in one-third of those with intermediate-risk cytogenetic profile and were an independent predictor of poor outcome)
  33. Schnittger et al. IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with intermediate risk karyotype and unfavorable prognosis in adults younger than 60 years and unmutated NPM1 status. Blood 2010;116:5486
  34. Chou et al. TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics. Blood 2011;118:3803
  35. Metzeler et al. TET2 Mutations Improve the New European LeukemiaNet Risk Classification of Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study. J Clin Oncol 2011;29:1373
  36. Quek et al. Clonal heterogeneity of acute myeloid leukemia treated with the IDH2 inhibitor enasidenib. Nat Med 2018;24:1167(Relapse via clonal evolution or selection of resistant clones, not via new IDH2 mutations)
  37. Tyner et al. Functional genomic landscape of acute myeloid leukaemia. Nature 2018;562:526(Response to specific drugs linked to mutational status)

Gene expression profiling

  1. Gentles et al. Association of a Leukemic Stem Cell Gene Expression Signature With Clinical Outcomes in Acute Myeloid Leukemia. JAMA 2010;304:2706
  2. Eisfeld et al. miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia. Blood 2012;120:249.
  3. Gönen et al. CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900. Blood 2012;120:2297
  4. Bullinger et al.  Use of Gene-Expression Profiling to Identify Prognostic Subclasses in Adult Acute Myeloid Leukemia.  NEJM 2004;350:1605
  5. Haferlach et al. Global approach to the diagnosis of leukemia using gene expression profiling. Blood 2005;106:1189
  6. Valk et al.  Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia.  NEJM 2004;350:1617
  7. Wouters et al. A decade of genome-wide gene expression profiling in acute myeloid leukemia: flashback and prospects. Blood 2009;113:291

AML in the elderly

  1. Ossenkoppele and Löwenberg. How I treat the older patient with acute myeloid leukemia. Blood 2015;125:767
  2. Appelbaum et al. Age and acute myeloid leukemia. Blood 2006:107:3481 (Poor performance status + advanced age = 80% mortality within 30 days of starting Rx)
  3. Walter et al. Prediction of Early Death After Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia With Pretreatment Risk Scores: A Novel Paradigm for Treatment Assignment. J Clin Oncol 2011;29:4417 (PS and age most important predictors of early death; in a multicomponent model age appears to be a surrogate for other risk factors)
  4. Bazinet et al. Evolving trends and outcomes in older patients with acute myeloid leukemia including allogeneic stem cell transplantation. Am J Hematol 2023;98:1383 (Adding venetoclax to low-intensity therapy increases CR rate from 48% to 72%. Frontline SCT improved OS in this retrospective single center study)
  5. Klepin et al. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood 2013;121:4287
  6. Fröhling et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B.  Blood 2006;108:3280(Patients >70 and those with unfavorable karyotype had median survival of 7 mo, 3 year overal survival 6%)
  7. Döhner et al. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations. Blood 2024;144:2169
  8. Döhner et al. Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine. Blood 2024;144:2211
  9. Löwenberg et al. High-Dose Daunorubicin in Older Patients with Acute Myeloid Leukemia. NEJM 2009;361:1235(Higher CR rate, no more toxicity with 90 mg/m2 daunorubicin vs 45 mg/m2)
  10. Gardin et al. Superior Long-Term Outcome With Idarubicin Compared With High-Dose Daunorubicin in Patients With Acute Myeloid Leukemia Age 50 Years and Older. J Clin Oncol 2013;31:321
  11. Fehniger et al. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood 2011;117:1828(30% response rate)
  12. Cashen et al. Multicenter, Phase II Study of Decitabine for the First-Line Treatment of Older Patients With Acute Myeloid Leukemia. J Clin Oncol 2010;28:556(24% CR rate; medial OS 7.7 mo)
  13. Fenaux et al. Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients With Low Bone Marrow Blast Count Acute Myeloid Leukemia. J Clin Oncol 2020;28:562(Azacitidine prolonged survival and reduced time spent in hospital)
  14. Dombret et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 2015;126:291(Azacitidine increased median OS by about 4 mo compared to standard AML Rx)
  15. Nand et al. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood 2013;122:3432(44% of good-risk, 35% of poor-risk patients had CR)
  16. Huls et al. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients. Blood 2019;133:1457
  17. Burnett et al. Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Blood 2013;122:1384
  18. Attar et al. Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502. J Clin Oncol 2013;31:923(65% CR rate)
  19. Erba H. Prognostic factors in elderly patients with AML and the implications for treatment. Hematology 2007:429
  20. Krug et al. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet 2010;376:2000(Web site – requires password)
  21. Prébet et al. Acute Myeloid Leukemia With Translocation (8;21) or Inversion (16) in Elderly Patients Treated With Conventional Chemotherapy: A Collaborative Study of the French CBF-AML Intergroup. J Clin Oncol 2009;27:4747(88% CR rate, 31% 5 year OS)
  22. Juliusson et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 2009; 113:4179(“Most AML patients up to 80 should be considered for intensive therapy”)
  23. Kantarjian et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010;116:4422(Median survival 4.6 mo, 8-week mortality 36%, 1-year survival 28%)
  24. Rowe et al.  A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood 2004;103:479 (No difference among three different anthracyclines; no benefit from GM-CSF priming)
  25. Sekeres et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood 2009;113;28(Delaying treatment not harmful in elderly patients)
  26. Gardin et al. Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy:results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial. Blood 2007;109:5129(6 cycles of outpatient treatment more successful than single course of high dose consolidation treatment)
  27. Clavio et al. Adding low-dose gemtuzumab ozogamicin to fludarabine, Ara-C and idarubicin (MY-FLAI) may improve disease-free and overall survival in elderly patients with non-M3 acute myeloid leukaemia: results of a prospective, pilot, multi-centre trial and comparison with a historical cohort of patients. Br J Haematol 2007; 138:186
  28. Burnett et al. Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia. J Clin Oncol 2012;30:3924
  29. Amadori et al. Sequential Combination of Gemtuzumab Ozogamicin and Standard Chemotherapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia: Results of a Randomized Phase III Trial by the EORTC and GIMEMA Consortium (AML-17). J Clin Oncol 2013;31:4424(Adding GO produced no apparent benefit)
  30. Kadia et al. Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Lancet Haematol 2018;5:e411(58% CR rate, well-tolerated)
  31. Quintás-Cardama et al. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood 2012;120:4840
  32. Tassara et al. Valproic acid in combination with all-trans retinoic acid and intensive therapy for acute myeloid leukemia in older patients. Blood 2014;123:4027(No difference in EFS or OS, but better PFS with addition of valproate)
  33. DiNardo et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol 2018;19:216
  34. DiNardo et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. NEJM 2020;383:617(With editorial)
  35. Dinardo et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood 2019;133:7(67% CR rate, median OS 17.5 mo)
  36. Pollyea et al. Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia. Nat Med 2018;24:1859
  37. Wei et al. Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. J Clin Oncol 2019;37:1277
  38. Pigneux et al. Improved Survival by Adding Lomustine to Conventional Chemotherapy for Elderly Patients With AML Without Unfavorable Cytogenetics: Results of the LAM-SA 2007 FILO Trial. J Clin Oncol 2018;36:3203
  39. Swords et al. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. Blood 2018;131:1415
  40. Fathi et al. A phase 1 trial of vadastuximab talirine combined with hypomethylating agents in patients with CD33-positive AML. Blood 2018;132:1125(70% CR rate in intermediate- and high risk AML, median age 75)
  41. Amadori et al. Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. J Clin Oncol 2016;34:972(GO prolonged survival with “manageable” toxicity)
  42. de Botton et al. Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial. Blood 2023;141:156 (Modest improvement in OS)
  43. DiNardo et al. Mutant Isocitrate Dehydrogenase 1 Inhibitor Ivosidenib in Combination With Azacitidine for Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol 2021;39:57
  44. Pigneux et al. Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study. J Clin Oncol 2017;35:387(Adding androgen improved 5 year OS from 17% to 26% in patients 60+)

AML variants/subtypes

  1. Olopade et al. Clinical, morphologic and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Blood 1992;80:2873
  2. Roumer et al.  M0 AML, clinical and biologic features of the disease, including AML1 gene mutations: a report of 50 cases bye the Groupe Francais d’Hematologie Cellulaire (GFHC) and the Groupe Francais de Cytogenetiquie Hematologique (GFCH).  Blood 2003;101:1277
  3. Hasserjian et al. Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood 2010;115:1985
  4. Oki et al. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood 2006;107:880
  5. Weinberg et al. Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system. Blood 2009;113:1906
  6. Wolach and Stone. How I treat mixed-phenotype acute leukemia. Blood 2015;125:2477
  7. Surapally et al. Emerging therapies for inv(16) AML. Blood 2021;137:2579

AML treatment

  1. El Chaer et al. How I treat AML incorporating the updated classifications and guidelines. Blood 2023;141:2823
  2. Wei et al. How I treat patients with AML using azacitidine and venetoclax. Blood 2025;145:1237
  3. Issa et al. How I treat acute myeloid leukemia with differentiation therapy. Blood 2025;145:1251
  4. Roboz and Canaani. How I use maintenance therapy in acute myeloid leukemia. Blood 2025;145:1273
  5. DiNardo and Wei. How I treat acute myeloid leukemia in the era of new drugs. Blood 2020;135:85
  6. Green and Wang. How I treat secondary acute myeloid leukemia. Blood 2025;145:1260
  7. Burd et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med 2020;26:1852(No apparent harm from delaying therapy 1 week to obtain mutational profile prior to starting treatment in AML patients aged 60-92)
  8. Ofran et al. How I treat acute myeloid leukemia presenting with preexisting comorbidities. Blood 2016;128:488
  9. Krug et al. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia. Leukemia 2016;30:1230
  10. Rashidi et al. Maintenance therapy in acute myeloid leukemia: an evidence-based review of randomized trials. Blood 2016;128:763
  11. Huls et al. Menin inhibitors in the treatment of acute myeloid leukemia. Blood 2025;145:581
  12. Stein and Tallman. Emerging therapeutic drugs for AML. Blood 2016;127:71
  13. Pratz and Levis. How I treat FLT3-mutated AML. Blood 2017;129:565
  14. Erba et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023;401:1571 (Median OS 32 mo with quizartinib, 15 mo without)
  15. Falini et al. How I diagnose and treat NPM1-mutated AML. Blood 2021;137:589
  16. Othman et al. Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission. Blood 2024;143:1931 (“Postinduction molecular MRD reliably identifies those patients who benefit from allogeneic transplant in first remission”)
  17. Forman and Rowe. The myth of the second remission of acute leukemia in the adult. Blood 2013;121:1077
  18. Venditti et al GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood 2019;134:935
  19. Luskin et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood 2016;127:1551
  20. Lee et al. Prospective Randomized Comparison of Idarubicin and High-Dose Daunorubicin in Induction Chemotherapy for Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol 2017;35:2754(Possible advantage of HD dauno in patients with FLT3 ITD)
  21. Bradstock et al. Idarubicin Dose Escalation During Consolidation Therapy for Adult Acute Myeloid Leukemia. J Clin Oncol 2017;35:1678(Increasing anthracycline dose during consolidation improved leukemia-free survival)
  22. Löwenberg et al. Cytarabine dose for acute myeloid leukemia. NEJM 2011;364:1027(2000 mg/m2 no more effective, and more toxic, than 1000 mg/m2)
  23. Löwenberg B. Sense and nonsense of high-dose cytarabine for acute myeloid leukemia. Blood 2013;121:26
  24. Willemze et al. High-Dose Cytarabine in Induction Treatment Improves the Outcome of Adult Patients Younger Than Age 46 Years With Acute Myeloid Leukemia: Results of the EORTC-GIMEMA AML-12 Trial. J Clin Oncol 2014;32:218(Modest improvement in survival for pts given HDAC vs standard dose cytarabine; benefit more pronounced in younger and high-risk pts)
  25. Ohtake et al. Randomized study of induction therapy comparing standard-dose idarubicin with high-dose daunorubicin in adult patients with previously untreated acute myeloid leukemia: the JALSG AML201 Study. Blood 2011;117:2358(50 mg/m2 daunorubicin x 5 days = 12 mg/m2 idarubicin x 3 days)
  26. Holowiecki et al. Cladribine, But Not Fludarabine, Added to Daunorubicin and Cytarabine During Induction Prolongs Survival of Patients With Acute Myeloid Leukemia: A Multicenter, Randomized Phase III Study. J Clin Oncol 2012;30:2441
  27. Löwenberg et al. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML. Blood 2017;129:1636(Reduces relapse but does not improve survival)
  28. Miyawaki et al. A randomized comparison of 4 courses of standard-dose multiagent chemotherapy versus 3 courses of high-dose cytarabine alone in postremission therapy for acute myeloid leukemia in adults: the JALSG AML201 Study. Blood 2011;117:2366(2 regimens equally effective overall, HiDAC better with favorable cytogenetics)
  29. Hokland and Ommen. Towards individualized follow-up in adult acute myeloid leukemia in remission. Blood 2011;117:2577 (Role of MRD monitoring during remission)
  30. Bradstock et al. A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine. Blood 2005;105:481
  31. Neubauer et al. Patients With Acute Myeloid Leukemia and RAS Mutations Benefit Most From Postremission High-Dose Cytarabine: A Cancer and Leukemia Group B Study. J Clin Oncol 2008;26:4603
  32. Lancet et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol 2021;8:e481(Liposomal dauno+cytarabine superior to 7+3 in patients 60-75)
  33. Castaigne et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 2012;379:1508(3 yr EFS 40.8% with low-dose fractionated Mylotarg, 17.1% without)
  34. Hills et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol 2014;15:986(Significant benefit in patients without advers cytogenetics)
  35. Burnett et al. Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial. J Clin Oncol 2011;29:369(Benefits patients with favorable cytogenetics)
  36. Petersdorf et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 2013;121:4854(Adding gemtuzumab did not improve CR rate or OS)
  37. Fournier et al. Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia. Blood 2020;135:542(GO benefits patients with low- and intermediate-risk genotypes, and those with activating signaling mutations)
  38. Freeman et al. Fractionated vs single-dose gemtuzumab ozogamicin with determinants of benefit in older patients with AML: the UK NCRI AML18 trial. Blood 2023;142:1697
  39. Loo et al. Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML: a randomized, placebo-controlled study by the ALLG. Blood 2023;142:1960  (Pretransplant sorafenib did not improve DFS)
  40. Stone et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. NEJM 2017;377:454(Significant improval in OS and PFS with addition of midostaurin)
  41. Schlenk et al. Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood 2019;133:840(Significant improvement in EFS versus historical controls)
  42. Döhner et al. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 2020;135:371(Midostaurin benefits FLT3-ITD positive patients regardless of prognostic category)
  43. Welch et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. NEJM 2016;375:2023(Presence of TP53 mutation predicted favorable response to treatment; with editorial)
  44. Sekeres et al. A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605. Blood 2011;118:523(14% overall response rate, medial overall survival 2 months in this group of older pts)
  45. Stein et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017;130:722(40% OR rate)
  46. Stein et al. Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib. Blood 2019;133:676
  47. Amatangelo et al. Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood 2017;130:732
  48. Roboz et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood 2020;135:463
  49. Stein et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood 2021;137:1792
  50. Montesinos et al. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. NEJM 2022;389:1519
  51. Illendula et al. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science 2015;347:779(Promising experimental agent – with editorial)
  52. Stein et al. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood 2018;131:387
  53. Konopleva and Letai. BCL-2 inhibition in AML: an unexpected bonus? Blood 2018;132:1007(Venetoclax)
  54. Wei et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood 2020;135:2137 (Adding venetoclax to LDAC improved remission rate from 13% to 48%)
  55. Wang et al. Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial. Lancet Haematol 2022;9:e415 (91% CR rate)
  56. Mantzaris et al. Venetoclax plus daunorubicin and cytarabine for newly diagnosed acute myeloid leukemia: results of a phase 1b study. Blood 2025;145:1870 (High rate of MRD-negative CR)
  57. Senapati et al. Venetoclax abrogates the prognostic impact of splicing factor gene mutations in newly diagnosed acute myeloid leukemia. Blood 2023;142:1647
  58. Xie et al. Venetoclax with decitabine as frontline treatment in younger adults with newly diagnosed ELN adverse-risk AML. Blood 2023;142:1323 (61% EFS @ 12 mo; promising as bridge to transplant)
  59. Thomas et al. Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission. J Clin Oncol 2017;35:1223(2 yr RFS 59% vs 47% with HDAC, but more toxic)
  60. Wei et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. NEJM 2020;383:2526(Median OS 25 mo vs 15 mo with placebo in pts 55+ who were not transplant candidates)
  61. Roboz et al. Oral azacitidine prolongs survival of patients with AML in remission independently of measurable residual disease status. Blood 2022;139:2145
  62. Döhner et al. Prognostic impact of NPM1 and FLT3 mutations in patients with AML in first remission treated with oral azacitidine. Blood 2022;140:1674 (Oral aza benefited patients in remission after intensive chemo regardless of mutation status)
  63. Wang et al. Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy. Blood 2022;140:1845 (Modest improvement in OS in gilteritinib group)
  64. Bakst et al. How I treat extramedullary acute myeloid leukemia. Blood 2011;118:3785

Treatment of relapsed or refractory AML

  1. Thol et al. How I treat refractory and relapsed acute myeloid leukemia. Blood 2024;143:11
  2. Gooptu et al. How I treat AML relapse after allogeneic HSCT. Blood 2025;145:2128
  3. Hospital et al. Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML Intergroup. Blood 2014;124:1342(Gemtuzumab ozogamicin given before transplant improves outcome)
  4. Garzon et al. A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Blood 2017;129:3165(“Disease control rate” – improvement or disease stabilization – in 69%)
  5. DiNardo et al. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. NEJM 2018;378:2386(CR rate 22%, OR rate 42%; about a third of patients alive at 1 yr)
  6. Perl et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. Blood 2019;381:1728(Gilteritinib prolonged median OS from 5.6 mo to 9.3 mo with less toxicity)
  7. Daver et al. Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia. J Clin Oncol 2022;40:4048
  8. Perl et al. Follow-up of patients with R/R FLT3-mutation–positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood 2022;139:3366
  9. Uy et al. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood 2021;137:751(Bispecific Ab to CD3 and CD123, 30% OR rate, 12 mo OS 50%)
  10. Daver et al. Venetoclax and idasanutlin in relapsed/refractory AML: a nonrandomized, open-label phase 1b trial. Blood 2023;141:1265

AML: Stem cell transplantation

APML

  1. Lallamand-Breietenbach and de Thé. Retinoic acid plus arsenic trioxide, the ultimate panacea for acute promyelocytic leukemia? Blood 2013;122:2008
  2. Sanz et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood 2019;133:1630
  3. Sanz and Lo-Coco. Modern approaches to treating acute promyelocytic leukemia. J Clin Oncol 2011;29:495
  4. Lo-Coco and Ammatuna. The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment. Hematology 2006;156-61
  5. Wei et al. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer. Nat Med 2015;21:457
  6. Tallman et al. Does microgranular variant morphology of acute promyelocytic leukemia independently predict a less favorable outcome compared with classical M3 APL? A joint study of the North American Intergroup and the PETHEMA Group. Blood 2010;116:5650(No)
  7. Montesinos et al. Clinical significance of CD56 expression in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens. Blood 2011;117:1799(Adverse prognostic feature)
  8. Licht J. Acute Promyelocytic Leukemia — Weapons of Mass Differentiation. NEJM 2009;360:928
  9. Ablain and de The. Revisiting the differentiation paradigm in acute promyelocytic leukemia. Blood 2011;117:5795
  10. Ablain et al. Activation of a promyelocytic leukemia–tumor protein 53 axis underlies acute promyelocytic leukemia cure. Nat Med 2014;20:167(With editorial; suggests inducing differentiation is not the sole basis of APL cure with arsenic or ATRA)
  11. Sanz et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2009;113:1875
  12. Adès et al. Is Cytarabine Useful in the Treatment of Acute Promyelocytic Leukemia? Results of a Randomized Trial From the European Acute Promyelocytic Leukemia Group. J Clin Oncol 2006;24:5703
  13. Adès et al. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood 2008;111:1078(Adding cytarabine to ATRA + ida may be beneficial in APL patients with WBC > 10K)
  14. Lo-Coco et al. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood 2010;116:3171
  15. Chen et al. From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemia. Blood 2011;117:6425
  16. Tallman et al.  All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol.  Blood 2002;100:4298
  17. Tallman et al. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood 2000;95:90
  18. Montesinos et al. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors. Blood 2009;113:775
  19. Sanz and Montesinos. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. Blood 2014;123:2777
  20. Soignet et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. NEJM 1998;339:1341
  21. Sanz et al.  Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood 2004;103:1237
  22. Sanz et al. Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA Group. Blood 2008;112:3130(5 year DFS 84%)
  23. Sanz et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood 2010;115:5137
  24. Avvisati et al. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood 2011;117:4716(12 year EFS 69%; no apparent benefit from maintenance therapy after molecular remission confirmed)
  25. Estey et al. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood 2006;107:3469
  26. Burnett et al. Arsenic trioxide and all- trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol 2015;16:1295
  27. Russell et al. Attenuated arsenic trioxide plus ATRA therapy for newly diagnosed and relapsed APL: long-term follow-up of the AML17 trial. Blood 2018;132:1452
  28. Lo-Coco et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. NEJM 2013;369:111(100% CR, 97% 2-yr EFS; less hematologic toxicity than ATRA+chemo, more liver problems)
  29. Platzbecker et al. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non–High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. J Clin Oncol 2017;35:605
  30. Ravandi et al. Effective Treatment of Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid, Arsenic Trioxide, and Gemtuzumab Ozogamicin. J Clin Oncol 2009;27:504(ATRA + ATO with or without GO can replace chemotherapy-containing regimens)
  31. Iland et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood 2012;120:1570(95% CR, 2 year OS 93%)
  32. Abaza et al. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood 2017;129:1283(5-year OS 88%; relapse is rare)
  33. Zhu et al. Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial. J Clin Oncol 2013;31:4216(Oral arsenic compound as effective and safe as IV ATO)
  34. Asou et al. A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RAR transcript after consolidation therapy: The Japan Adult Leukemia Study Group (JALSG) APL97 study(PCR negative patients had better outcome without maintenance)
  35. Adès et al. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood 2010; 115:1690(10 year survival 77%)
  36. Grimwade et al. Prospective Minimal Residual Disease Monitoring to Predict Relapse of Acute Promyelocytic Leukemia and to Direct Pre-Emptive Arsenic Trioxide Therapy. J Clin Oncol 2009;27:3650 (MRD monitoring was most powerful predictor of relapse. Early treatment with arsenic trioxide prevented frank relapse in most MRD positive pts)
  37. Chendamarai et al. Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy. Blood 2012;119:3413
  38. Au et al. Oral arsenic trioxide–based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study. Blood 2011;118:6535
  39. Mathews et al. Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data. J Clin Oncol 2010;28:3866(80% 5 year DFS)
  40. Powell et al. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood 2010;116:3751
  41. Zhu et al. The simpler, the better: oral arsenic for acute promyelocytic leukemia. Blood 2019;134:597
  42. Echaniz-Laguna et al. Mitochondrial myopathy caused by arsenic trioxide therapy. Blood 2012;119:4272
  43. Yanada et al. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood 2013;121:3095
  44. Zhu et al. Resistance to arsenic in acute promyelocytic leukemia (letter). NEJM 2014;370:1864(PML gene mutations in arsenic-binding domain cause resistance)
  45. Mantha et al. Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era. Blood 2017;129:1763(High white count predicts early hemorrhagic death)
  46. Cao et al. Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia. Blood 2017;129:1855
  47. de la Serna et al. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood 2008;111:3395.(Death during induction due to hemorrhage in 5%, infection in 2.3%, ATRA syndrome in 1.4%)
  48. Park et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011;118:1248(Overall early death rate 17.3%)
  49. Voso et al. Acute promyelocytic leukemia: long-term outcomes from the HARMONY project. Blood 2025;145:234 (ATRA/ATO improves outcomes but early death rate remains high)

ALL: biology/general

  1. Gökbuget et al. Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood 2024;143:1891
  2. Gökbuget et al. Management of ALL in adults: 2024 ELN recommendations from a European expert panel. Blood 2024;143:1903
  3. Malard and Mohty. Acute lymphoblastic leukaemia. Lancet 2020;395:1146
  4. Hunger and Mullighan. Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine. Blood 2015;125:3977
  5. Simonin et al. NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of patients. Blood 2024;144:1570
  6. Passet et al.Genetic subtypes of B-cell acute lymphoblastic leukemia in adults. Blood 2025;145:1451
  7. Pölönen et al. Classification and risk stratification in T-lineage acute lymphoblastic leukemia. Blood 2025;145:1464
  8. Forman and Rowe. The myth of the second remission of acute leukemia in the adult. Blood 2013;121:1077
  9. Gocho and Yang. Genetic defects in hematopoietic transcription factors and predisposition to acute lymphoblastic leukemia. Blood 2019;134:793
  10. Di Paola and Porter. ETV6-related thrombocytopenia and leukemia predisposition. Blood 2019;134:663(Predisposition to B-ALL)
  11. Pullarkat et al. Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood 2008;111:2563. (t(9;22), -7, +8, and 11q23 rearrangement had worse prognosis; cytogenetics most important prognostic factor in adult ALL)
  12. Moorman et al. A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood 2010;115:206
  13. Roberts et al. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. NEJM 2014;371:1005
  14. Asnafi et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood 2009;113:3918
  15. Thomas et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood 2009;113:6330(CD20 expression an independent predictor of poor outcome)
  16. Brüggemann et al. Has MRD monitoring superseded other prognostic factors in adult ALL? Blood 2012;120:4470
  17. Beldjord et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood 2014;123: 3739
  18. Gökbuget et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood 2012;120:1868
  19. Girardi et al. The genetics and molecular biology of T-ALL. Blood 2017;129:1113
  20. Jain et al. Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype. Blood 2016;127:1863
  21. Gökbuget et al. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood 2012;120:2032
  22. Jain et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood 2017;129:572
  23. Tasian et al. Philadelphia chromosome–like acute lymphoblastic leukemia. Blood 2017;130:2064
  24. Safavi and Paulsson. Near-haploid and low-hypodiploid acute lymphoblastic leukemia: two distinct subtypes with consistently poor prognosis. Blood 2017;129:420(“Near-haploid” = about 27 chromosomes, “low-hypodiploid” = about 36 chromosomes)
  25. Good et al. Single-cell developmental classification of B cell precursor acute lymphoblastic leukemia at diagnosis reveals predictors of relapse. Nat Med 2018;24:474(With editorial)
  26. Kourtis et al. Oncogenic hijacking of the stress response machinery in T cell acute lymphoblastic leukemia. Nat Med 2018;24:1157(Upregulation of heat shock proteins promotes leukemic cell survival)
  27. Benshang et al. Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia. Blood 2020;135:41(Early relapse driven by retained subclones, late relapse by chemo-induced mutations in pediatric ALL)

ALL: Treatment

  1. Basssan et al. New Approaches to the Management of Adult Acute Lymphoblastic Leukemia. J Clin Oncol 2018;33:3504
  2. Lim et al. How I treat newly diagnosed and refractory T-cell acute lymphoblastic lymphoma in children and young adults. Blood 2023;141:3019
  3. Marks and Rowntree. Management of adults with T-cell lymphoblastic leukemia. Blood 2017;129:1134
  4. Kopmar and Cassaday. How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia. Blood 2023;141:1379
  5. Biossel and Baruchel. Acute lymphoblastic leukemia in adolescent and young adults: treat as adults or as children? Blood 2018;132:351 (Pediatric regimens improve outcomes)
  6. O’Dwyer et aL. Treatment strategies for adolescent and young adult patients with acute myeloid leukemia. Blood 2018;132:362
  7. Stock et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood 2019;133:1548
  8. Wolach and Stone. How I treat mixed-phenotype acute leukemia. Blood 2015;125:2477
  9. Gökbuget and Steffen. How I treat older patients with Ph/BCR-ABL–negative acute lymphoblastic leukemia. Blood 2025;145:53
  10. Curran and Stock. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood 2015;125:3702
  11. Ribera et al. Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome–negative adult lymphoblastic leukemia. Blood 2021;137:1879(MRD status after induction & early consolidation predicts need for allotransplant)
  12. Harrison CJ. Targeting signaling pathways in acute lymphoblastic leukemia: new insights. Hematology 2013:118
  13. Advani A.New immune strategies for the treatment of acute lymphoblastic leukemia: antibodies and chimeric antigen receptors. Hematology 2013:131
  14. Pikman and Stegmaier. Targeted therapy for fusion-driven high-risk acute leukemia. Blood 2018;132:1241
  15. Hunault et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 2004;104:3028
  16. Rowe et al.  Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 2005;106:3760(Overall survival 45% for patients who achieved CR with induction chemotherapy)
  17. Larson et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 1995;85:2025
  18. Thomas et al. Chemoimmunotherapy With a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome in De Novo Philadelphia Chromosome–Negative Precursor B-Lineage Acute Lymphoblastic Leukemia. J Clin Oncol 2010;28:3880(95% CR, 3 year OS 50%)
  19. Thomas et al. Outcome of Treatment in Adults With Acute Lymphoblastic Leukemia: Analysis of the LALA-94 Trial. J Clin Oncol 2004;22:4075(Allo-BMT superior in high-risk patients; auto-BMT no better than standard chemotherapy)
  20. O’Brien et al. High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia. J Clin Oncol 2013;31:676(20% CR, potential bridge to transplant, 5/65 pts long-term survivors)
  21. Fielding et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood 2007;109:944
  22. Möricke et al. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood 2008;111:4477
  23. Frey and Luger. How I treat adults with relapsed or refractory Philadelphia chromosome–negative acute lymphoblastic leukemia. Blood 2014;126:589
  24. Gökbuget et al. High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood 2011;118:3504
  25. Maury et al. Rutuximab in B-lineage adult acute lymphoblastic leukemia. NEJM 2016;375:1044(Rituximab significantly improved event-free survival)
  26. Chevallier et al. Trastuzumab for treatment of refractory/relapsed HER2-positive adult B-ALL: results of a phase 2 GRAALL study. Blood 2012;119:2474
  27. Kantarjian et al. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. NEJM 2016;375:740(Higher CR rate, modest improvement in OS with inotuzumab in RR ALL; drug caused VOD in 11%)
  28. Jabbour et al. Phase 2 study of inotuzumab ozogamicin for measurable residual disease in acute lymphoblastic leukemia in remission. Blood 2024;143:417
  29. Topp et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 2012;120:5185
  30. Advani et al. SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome–Negative B-Cell Acute Lymphoblastic Leukemia. J Clin Oncol 2022;40:1574
  31. Topp et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 2015;16:57(43% CR; 22% grade 3 or 4 neurotoxicity)
  32. Zugmaier et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood 2015;126:2578
  33. Topp et al. Phase II Trial of the Anti-CD19 Bispecific T Cell–Engager Blinatumomab Shows Hematologic and Molecular Remissions in Patients With Relapsed or Refractory B-Precursor Acute Lymphoblastic Leukemia. J Clin Oncol 2014;32:4134
  34. Kantarjian et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. NEJM 2017;376:836(Median OS 7.7 mo with blinatumomab vs 4 mo with chemo)
  35. Martinelli et al. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome–Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J Clin Oncol 2017;35;1795
  36. Topp et al. Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. Blood 2018;131:2906(“Blinatumomab delays deterioration in adults with R/R ALL”)
  37. Gökbuget et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood 2018;131:1522
  38. Litzow et al. Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults. NEJM 2024;391:320 (Risk of relapse or death reduced by 50% with adding blina to chemo)
  39. Maude et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. NEJM 2014;371:1507(27/30 patients had CR; 6-mo EFS 67%)

CAR-T therapy in ALL

  1. Badar et al. Incorporation of immunotherapy into frontline treatment for adults with B-cell precursor acute lymphoblastic leukemia. Blood 2025;145:1475
  2. Maude et al. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood 2015;125:4017
  3. Orlando et al. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med 2018;24:1504
  4. Maude et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. NEJM 2018;378:439
  5. Gardner et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 2017;129:3322(Over 90% CR rate)
  6. Park et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. NEJM 2018;378:449
  7. Gardner et al. Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood 2016;127:2406
  8. Fry et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med 2018;24:20
  9. Ghorashian et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med 2019;25:1408
  10. Xu et al. CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. NEJM 2019;381:1240(Using CCR5-negative cells; with editorial)
  11. Chiesa et al. Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia. NEJM 2023;389:899
  12. Jabbour et al. Monoclonal antibodies in acute lymphoblastic leukemia. Blood 2015;125:4010
  13. Shah et al. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results. Blood 2021;138:11
  14. Qi et al. Efficacy and safety of CD19-specific CAR T cell–based therapy in B-cell acute lymphoblastic leukemia patients with CNSL. Blood 2022;139:3376
  15. Frey NV. Approval of brexucabtagene autoleucel for adults with relapsed and refractory acute lymphocytic leukemia. Blood 2022;140:11
  16. Roddie et al. Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia. NEJM 2024;391:2219
  17. Srinagesh et al. A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia. Blood 2024;144:1689
  18. Tran and Tasian. How I treat Philadelphia chromosome–like acute lymphoblastic leukemia in children, adolescents, and young adults. Blood 2025;145:20

BCR-ABL positive ALL

  1. Chiaretti and Foà. How I treat adult Ph+ ALL. Blood 2025;145:11
  2. Foà R. Ph-Positive Acute Lymphoblastic Leukemia — 25 Years of Progress. NEJM 2025; 391:1941
  3. Towatari et al. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood 2004;104:3507
  4. Ottmann and Wassmann. Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Hematology 2005:118-122
  5. Yanada et al. High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group. J Clin Oncol 2006;24:460
  6. Short et al. Impact of complete molecular response on survival in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood 2016;128:504(Patients who have CMR @ 3 mo have excellent long term outcomes without transplant)
  7. Wassmann et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood 2006;108:1469
  8. de Labarthe et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 2007;109:1408
  9. Vignetti et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome–positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol. Blood 2007;109:3676
  10. Ottman et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood 2007;110:2309
  11. Ravandi et al. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia. Blood 2010;116:2070(2 yr OS 64%)
  12. Porkka et al. Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome–positive leukemia. Blood 2008;112:1005(imatinib does not cross BBB well, less effective)
  13. Foà et al. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood 2011;118:6521(Dasatinib plus steroids causes complete hematologic remission in over 90% of patients)
  14. Rousselot et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome–positive ALL. Blood 2016;128:774(36% 5 year OS)
  15. Fielding et al. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood 2014;123:843(4 year OS improved from 22% to 38% with addition of imatinib)
  16. Chalandon et al. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood 2015;125:3711(Less intense induction plus TKI as effective, less toxic than hyperCVAD plus TKI)
  17. Kim et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood 2015;126:746(2 year OS 72%; MRD status early in remission predicted outcome)
  18. Chalandon et al. Nilotinib with or without cytarabine for Philadelphia-positive acute lymphoblastic leukemia. Blood 2024;143:2363
  19. Comoli et al. BCR-ABL–specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors. Blood 2017;129:582(Report of 3 patients, all obtained CR)
  20. Foà et al. Dasatinib–Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. NEJM 2020;383:1613(88% DFS at 18 mo)

ALL: Stem Cell Transplantation

AML and ALL: complications

  1. Zuckerman et al. How I treat hematologic emergencies in adults with acute leukemia. Blood 2012;120:1993
  2. Wang et al. Management of hemostatic complications in acute leukemia: Guidance from the SSC of the ISTH. J Thromb Haemost 2020;18:3174
  3. Pui C. Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and Treatment. Hematology 2006;142-6
  4. Rollig and Ehninger. How I treat hyperleukocytosis in acute myeloid leukemia. Blood 2015;125:3246
  5. Lichtman and Rowe. Hyperleukocytic leukemias: rheological, clinical, and therapeutic considerations. Blood 1982; 60:279
  6. Azoulay et al. How I manage acute respiratory failure in patients with hematological malignancies. Blood 2024:143:971
  7. Byrd et al. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review. J Clin Oncol 1995;13:1800
  8. Rank et al. Thromboembolism in acute lymphoblastic leukemia: results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years. Blood 2018;131:2475(8% cumulative incidence; highest risk with asparaginase treatment)
  9. Zwicker et al.The prevention and management of asparaginase‐related venous thromboembolism in adults: Guidance from the SSC on Hemostasis and Malignancy of the ISTH. J Thromb Haemost 2020;18:278
  10. Aldoss and Douerl. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood 2020;135:987
  11. Ku et al. Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival. Blood 2009;113:3911
  12. Mitchell et al. Validation of a predictive model for identifying an increased risk for thromboembolism in children with acute lymphoblastic leukemia: results of a multicenter cohort study. Blood 2010;115: 4999(Asparaginase use, central catheters, steroid use, and thrombophilia risk factors for VTE)
  13. Orvain et al. Thromboembolism prophylaxis in adult patients with acute lymphoblastic leukemia treated in the GRAALL-2005 study. Blood 2020;136:328(Antithrombin/heparin prophylaxis partially effective; fibrinogen concentrates increase clotting risk)
  14. Libourel et al. Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia. Blood 2016;128:1854
  15. Kwaan H. Double hazard of thrombophilia and bleeding in leukemia. Hematology 2007:151
  16. Gernsheimer et al. Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo-controlled, randomized clinical trial. Blood 2022;140:1254 (No apparent benefit)
  17. Hijiya et al. Cumulative Incidence of Secondary Neoplasms as a First Event After Childhood Acute Lymphoblastic Leukemia. JAMA 2007;297:1207(6% incidence of 2nd neoplasm after 30 yrs)
  18. Nielsen et al. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia: a nationwide study. Blood 2011;118:4062