Das Medizinportal




Aktuelle Therapiekonzepte in der Behandlung der Akuten Myeloischen Leukämie (AML) (S. 39–46)

Maximilian A. Röhnert, Christoph Röllig

  1. Röllig C, Beelen D, Braess J et al. Onkopedia Leitlinien – Akute Myeloische Leukämien (AML). Onkopedia 2018; www.onkopedia.com/de/onkopedia/guidelines/akute-myeloische-leukaemie-aml
  2. Juliusson G, Antunovic P, Derolf A 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 – 4187
  3. Hellenbrecht A, Messerer D, Gökbuget N. Häufigkeit von Leukämien bei Erwachsenen in Deutschland. Kompetenznetzwerk Leukämien 2008; 29-7-2011
  4. Southam C, Craver, L, Dargeon H, Burchenal J. A study of the natural history of acute leukemia with special reference to the duration of the disease and the occurrence of remissions. Cancer 1951; 4: 39–59
  5. Cornelissen J, Gratwohl A, Schlenk R et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 2012; 9: 579–590
  6. Grimwade D, Walker H, Harrison G et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001; 98: 1312–1320
  7. Papaemmanuil E, Gerstung M, Bullinger L et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. New Engl J Med 2016; 374: 2209–2221
  8. Dohner H, Estey E, Grimwalde D et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017; 129: 424–447
  9. Terwijn M, van Putten W, Kelder A et al. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol 2013; 31: 3889–3897
  10. Freeman S, Hills R, Virgo P et al. Measurable Residual Disease at Induction Redifines Partial Response in Acute Myeloid Leukemia and Stratifies Outcomes in Patients at Standard Risk without NPM1 Mutations. J Clin Oncol 2018; 36: 1486–1497
  11. Atallah E, Cortes J, O’Brien S et al. Establishment of baseline toxicity expectations with standard frontline chemotherapy in acute myelogenous leukemia. Blood 2007; 110: 3547–3551
  12. Rollig C, Thiede C, Gramatzki M et al. A novel prognostic model in elderly patients with acute myeloid leukemia – results of 909 patients entered into the prospective AML96 trial. Blood 2010; 116: 971–978
  13. Juliusson G, Lazarevic V, Horstedt A et al. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood 2012; 119: 3890–3899
  14. Juliusson G, Antunovic P, Derolf A 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: 4179–4187
  15. Stone R, Mandrekar S, Sanford B et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. New Engl J Med 2017; 377: 454–464
  16. Castaigne S, Pautas C, Terré C 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: 1508–1516
  17. Mandelli F, Vignetti M, Suciu S et al. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: The EORTC and GIMEMA groups study AML-10. J Clin Oncol 2009; 27: 5397–5403
  18. Burnett A, Russel N, Hill r et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol 2013; 31: 3360–3368
  19. Cornelissen J, Gratwohl A, Schlenk R et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 2012; 9: 579–590
  20. Mayer R, Davis R, Schiffer C et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. New Engl J Med 1994; 331: 896–903
  21. Schlenk R, Kayser S, Bullinger L et al. Differential impact of allelic ratio and insertion site in FLT3-ITD – positive AML with respect to allogeneic transplantation. Blood 2014; 124: 3441–3450
  22. Gale R, Green C, Allen C 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: 2776–2784
  23. Shayegi N, Kramer M, Bornhäuser M et al. The level of residual disease based on mutant NPM1 is an indepent prognostic factor for relapse and survival in AML. Blood 2013; 122: 83–92
  24. Krönke J, Schlenk R, Jensen K et al. Monitoring of minimal residual disease in NPM1-mutated acute myeloid leukemia: a study from the German-Austrian acute myeloid leukemia study group. J Clin Oncol 2011; 29: 2709–2716
  25. Krug U, Rollig C, Koschmieder A 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: 2000–2008
  26. Burnett A, Milligan D, Prentice A et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not consideres fit for intensive treatment. Cancer 2007; 109:1114–1124
  27. Kantarjian H, Thomas X, Dmoszynska A et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012; 30: 2670–2677
  28. Dombret H, Seymour J, Butrym A 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: 291–299
  29. Pleyer L, Burgstaller S, Girschikofsky M et al. Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group. Ann Hematol 2014; 93: 1825–1838
  30. Megías-Vericat J, Martínez-Cuadrón D, Sanz M, Montesinos P. Salvage regimens using conventional chemotherapy agents for relapsed/refractory adult AML patients: a systematic literature review. Ann Hematol 2018; 97: 1115–1153
  31. Schmid C, Labopin M, Nagler A et al. Treatment , risk factors , and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood 2012; 119: 1599–1606
  32. Hills R, Castaigne S, Appelbaum F 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: 986–996
  33. Lancet J, Uy G, Cortes J et al. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia. J Clin Oncol 2018; 26: 2684–2692
  34. XOSPATA® (gilteritinib) tablets, Highlights of prescription information, FDA 2018; www.accessdata.fda.gov/drugsatfda_docs/label/2018/211349s000lbl.pdf
  35. Levis M, Perl A, Altman J et al. Impact of Minimal Residual Disease and Achievement of Complete Remission/Complete Remission with Partial Hematologic Recovery (CR/CRh) on Overall Survival Following Treatment with Gilteritinib in Patients with Relapsesd/Refractory (R/R) Acute Myeloid Leukemia (AML) with FLT3 Mutations. Blood 2018; 132: 1458
  36. Cortes J, Khaled S, Martinelli G et al. Quizartinib significantly prolongs overall survival in patients with FLT3-internal tandem duplication-mutated (MUT) relapsed/refractory AML in the phase 3, randomized, controlled Quantum-R trial. EHA 2018; 218882
  37. Stein E, DiNardo C, Pollyea D et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017; 130: 722–731
  38. DiNardo C, Stein E, de Botton S et al. Durable Remissions with Ivosidenib in IDH1 -Mutated Relapsed or Refractory AML. New Engl J Med 2018; 378: 2386–2398
  39. DiNardo C, Pratz K, Pullarkat V et al. Venetoclax combined with decitabine or azacitidine in treatment-native, elderly patients with acute myeloid leukemia. Blood 2018; [Epub ahead of print]
  40. Wei A, Strickland S, Hou J et al. Venetoclax with Low-Dose Cytarabine Induces Rapid, Deep, and Durable Responses in Prevousily Untreated Older Adults with AML Ineligible for Intensive Chemotherapy. ASH 2018; Posterabstract
  41. Cortes J, Heidel F, Heuser M et al. A Phase 2 Randomized Study of Low Dose Ara-C with or without Glasdegib (PF-04449913) in Untreated Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome. Blood 2016; 128: 99
  42. Baumeister S, Murad J, Werner L et al. Phase 1 Trial auf Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma. Cancer Immunol Res. 2018; [Epub ahead of print]
  43. Stahl M, Lu B, Kim T, Zeidan A. Novel Therapies for Acute Myeloid Leukemia: Are We Finally Breaking the Deadlock? Targeted Oncology 2017; 12: 413–447



Lokal fortgeschrittenes oder metastasiertes NSCLC: Signifikanter und anhaltender Überlebensvorteil mit Checkpoint-Inhibitor Tecentriq (S. 50–51)

  1. S3-Leitlinie Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms. Langversion 1.0 – Februar 2018. AWMF-Registernummer: 020/007OL
  2. Fachinformation Tecentriq, Stand Juli 2018
  3. Rittmeyer A et al. Lancet 2017; 389: 255−265
  4. Satouchi M et al. IASLC 18th WCLC, Yokohama/Japan, Abstract OA17.07
  5. Fachinformation Keytruda®, Stand: September 2018
  6. Borghaei H et al. N Engl J Med 2015; 373 (Suppl Appendix): 1627−1639
  7. Gadgeel SM et al. J Thorac Oncol 2017; 12 (Suppl 1); WCLC 2016: Abstract PL04a.02
  8. Barlesi F et al. ESMO 2016; Abstract LBA44
  9. Chen DS et al. Immunity 2013; 39(1): 1−10
  10. Chen DS et al. Cancer J 2018; 24(4): 193−204
  11. Hedge PS et al. Clin Cancer Res 2016; 22(8): 1865−1874
  12. Kim JM et al. Ann Oncol 2016; 27(8): 1492−1504
  13. Atkins MB et al. ASCO 2017; (Oral Abstract Session): Abstract 4505
  14. McDermott DF et al. J Clin Oncol 2016; 34(8): 833−842