Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the netherlands, 1989–2012

ABSTRACT Large, comprehensive population-based studies in acute myeloid leukemia (AML) are scarce. We conducted a nationwide population-based study on treatment, trial participation and

survival among all adult patients diagnosed with AML (_n_=12 032) and acute promyelocytic leukemia (APL; _n_=585) in the Netherlands between 1989–2012. Patients were categorized into four

periods and four age groups (18–40, 41–60, 61–70 and >70 years). The application of allogeneic stem cell transplantation increased over time among AML patients up to age 70 years. For APL

patients, the use of chemotherapy increased across all age groups. When a clinical trial was open for accrual in the Netherlands, the inclusion rates were 68%, 57%, 30% and 12% for AML

patients in the four age groups, respectively (data for APL unavailable). Relative survival improved over time among AML (up to age 70 years) and APL patients. In the period 2007–2012,

5-year relative survival rates were 54%, 38%, 14% and 2% for AML patients and 84%, 75%, 54% and 37% for APL patients in the four age groups, respectively. As survival remained poor for older

AML patients over the last two decades, clinical trials and active participation in those trials, are warranted that explore innovative treatment strategies for this elderly population.

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Article Open access 24 February 2023 REFERENCES * Estey E, Dohner H . Acute myeloid leukaemia. _Lancet_ 2006; 368: 1894–1907. Article  PubMed  Google Scholar  * Visser O, Trama A, Maynadie

M, Stiller C, Marcos-Gragera R, De Angelis R _et al_. Incidence, survival and prevalence of myeloid malignancies in Europe. _Eur J Cancer_ 2012; 48: 3257–3266. Article  CAS  PubMed  Google

Scholar  * Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM . Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. _Blood_ 2012; 119:

34–43. Article  CAS  PubMed  PubMed Central  Google Scholar  * Ostgard LS, Norgaard JM, Sengelov H, Holm MS, Jensen MK, Kallenbach M _et al_. Impact of chemotherapy delay on short- and

long-term survival in younger and older AML patients: a Danish population-based cohort study. _Leukemia_ 2014; 28: 1926–1929. Article  CAS  PubMed  Google Scholar  * Dohner H, Estey EH,

Amadori S, Appelbaum FR, Buchner T, Burnett AK _et al_. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the

European LeukemiaNet. _Blood_ 2010; 115: 453–474. Article  PubMed  Google Scholar  * Ossenkoppele G, Lowenberg B . How I treat the older patient with acute myeloid leukemia. _Blood_ 2015;

125: 767–774. Article  CAS  PubMed  Google Scholar  * Burnett A, Wetzler M, Lowenberg B . Therapeutic advances in acute myeloid leukemia. _J Clin Oncol_ 2011; 29: 487–494. Article  PubMed 

Google Scholar  * Wang ZY, Chen Z . Acute promyelocytic leukemia: from highly fatal to highly curable. _Blood_ 2008; 111: 2505–2515. Article  CAS  PubMed  Google Scholar  * Sanz MA, Grimwade

D, Tallman MS, Lowenberg B, Fenaux P, Estey EH _et al_. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. _Blood_ 2009;

113: 1875–1891. Article  CAS  PubMed  Google Scholar  * Gafter-Gvili A, Fraser A, Paul M, Leibovici L . Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. _Ann

Intern Med_ 2005; 142: 979–995. Article  PubMed  Google Scholar  * Horan JT, Logan BR, Agovi-Johnson MA, Lazarus HM, Bacigalupo AA, Ballen KK _et al_. Reducing the risk for

transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? _J Clin Oncol_ 2011; 29: 805–813. Article  PubMed  PubMed Central 

Google Scholar  * Lowenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A _et al_. High-dose daunorubicin in older patients with acute myeloid leukemia. _N Engl J Med_

2009; 361: 1235–1248. Article  PubMed  Google Scholar  * Lowenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C _et al_. Cytarabine dose for acute myeloid leukemia. _N Engl J

Med_ 2011; 364: 1027–1036. Article  PubMed  Google Scholar  * Copelan EA . Hematopoietic stem-cell transplantation. _N Engl J Med_ 2006; 354: 1813–1826. Article  CAS  PubMed  Google Scholar

  * Schlenk RF, Dohner H . Genomic applications in the clinic: use in treatment paradigm of acute myeloid leukemia. _Hematology Am Soc Hematol Educ Program_ 2013; 2013: 324–330. Article 

PubMed  Google Scholar  * Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM _et al_. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative

HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? _Blood_ 2007; 109: 3658–3666. Article  CAS 

PubMed  Google Scholar  * Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J _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. Article  CAS  PubMed  Google Scholar  * Willemze R, Suciu S, Meloni G, Labar B, Marie JP, Halkes CJ _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: 219–228. Article  CAS  PubMed  Google Scholar  * Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE _et al_. Attempts to improve treatment outcomes in

acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. _Blood_ 2001; 98: 1302–1311. Article  CAS  PubMed  Google Scholar  *

Buchner T, Berdel WE, Haferlach C, Haferlach T, Schnittger S, Muller-Tidow C _et al_. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German

Acute Myeloid Leukemia Cooperative Group. _J Clin Oncol_ 2009; 27: 61–69. Article  PubMed  Google Scholar  * Derolf AR, Kristinsson SY, Andersson TM, Landgren O, Dickman PW, Bjorkholm M .

Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between 1973 and 2005. _Blood_ 2009; 113: 3666–3672. Article  CAS  PubMed

  Google Scholar  * Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D _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. Article  CAS  PubMed  Google Scholar  * Mengis C, Aebi S, Tobler A, Dahler W, Fey MF . Assessment of differences in patient

populations selected for excluded from participation in clinical phase III acute myelogenous leukemia trials. _J Clin Oncol_ 2003; 21: 3933–3939. Article  PubMed  Google Scholar  * Stevens

JM, Macdougall F, Jenner M, Oakervee H, Cavenagh J, Lister AT . Patterns of recruitment into acute myeloid leukaemia (AML) 15 and outcome for young patients with AML at a single referral

centre. _Br J Haematol_ 2009; 145: 40–44. Article  PubMed  Google Scholar  * Dechartres A, Chevret S, Lambert J, Calvo F, Levy V . Inclusion of patients with acute leukemia in clinical

trials: a prospective multicenter survey of 1066 cases. _Ann Oncol_ 2011; 22: 224–233. Article  CAS  PubMed  Google Scholar  * Lazarevic V, Horstedt AS, Johansson B, Antunovic P, Billstrom

R, Derolf A _et al_. Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience. _Blood Cancer J_

2014; 4: e188. Article  CAS  PubMed  PubMed Central  Google Scholar  * Juliusson G, Lazarevic V, Horstedt AS, Hagberg O, Hoglund M . Swedish Acute Leukemia Registry Group. Acute myeloid

leukemia in the real world: why population-based registries are needed. _Blood_ 2012; 119: 3890–3899. Article  CAS  PubMed  PubMed Central  Google Scholar  * Schouten LJ, Hoppener P, van den

Brandt PA, Knottnerus JA, Jager JJ . Completeness of cancer registration in Limburg, The Netherlands. _Int J Epidemiol_ 1993; 22: 369–376. Article  CAS  PubMed  Google Scholar  * Bennett

JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR _et al_. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British

Cooperative Group. _Ann Intern Med_ 1985; 103: 620–625. Article  CAS  PubMed  Google Scholar  * Jaffe ES, Harris NL, Stein H, Vardiman JW . (eds). _Pathology and Genetics of Tumours of

Haematopoietic and Lymphoid Tissues_. IARC: Lyon, 2001. Google Scholar  * Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H _et al_. (eds). _WHO Classification of Tumours of

Haematopoietic and Lymphoid Tissues_. IARC: Lyon, 2008. Google Scholar  * Fritz AG, Percy C, Jack A, Sobin LH, Parkin DM . (eds). _International Classification of Diseases for Oncology_, 3rd

edn. World Health Organization: Geneva, 2000. Google Scholar  * Dickman PW, Adami HO . Interpreting trends in cancer patient survival. _J Intern Med_ 2006; 260: 103–117. Article  CAS 

PubMed  Google Scholar  * Hakulinen T . Cancer survival corrected for heterogeneity in patient withdrawal. _Biometrics_ 1982; 38: 933–942. Article  CAS  PubMed  Google Scholar  * Pulte D,

Gondos A, Brenner H . Improvements in survival of adults diagnosed with acute myeloblastic leukemia in the early 21st century. _Haematologica_ 2008; 93: 594–600. Article  PubMed  Google

Scholar  * Thein MS, Ershler WB, Jemal A, Yates JW, Baer MR . Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. _Cancer_ 2013; 119: 2720–2727.

Article  PubMed  Google Scholar  * Sant M, Minicozzi P, Mounier M, Anderson LA, Brenner H, Holleczek B _et al_. Survival for haematological malignancies in Europe between 1997 and 2008 by

region and age: results of EUROCARE-5, a population-based study. _Lancet Oncol_ 2014; 15: 931–942. Article  PubMed  Google Scholar  * Lang K, Earle CC, Foster T, Dixon D, Van Gool R, Menzin

J . Trends in the treatment of acute myeloid leukaemia in the elderly. _Drugs Aging_ 2005; 22: 943–955. Article  PubMed  Google Scholar  * Oran B, Weisdorf DJ . Survival for older patients

with acute myeloid leukemia: a population-based study. _Haematologica_ 2012; 97: 1916–1924. Article  PubMed  PubMed Central  Google Scholar  * Lehmann S, Ravn A, Carlsson L, Antunovic P,

Deneberg S, Mollgard L _et al_. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. _Leukemia_ 2011;

25: 1128–1134. Article  CAS  PubMed  Google Scholar  * Tomas JF, Fernandez-Ranada JM . About the increased frequency of acute promyelocytic leukemia among Latinos: the experience from a

center in Spain. _Blood_ 1996; 88: 2357–2358. CAS  PubMed  Google Scholar  * Douer D, Preston-Martin S, Chang E, Nichols PW, Watkins KJ, Levine AM . High frequency of acute promyelocytic

leukemia among Latinos with acute myeloid leukemia. _Blood_ 1996; 87: 308–313. CAS  PubMed  Google Scholar  * Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL _et al_.

Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. _Blood_ 2011; 118: 1248–1254. Article  CAS  PubMed  PubMed Central  Google Scholar  * Juliusson

G, Karlsson K, Lazarevic V, Wahlin A, Brune M, Antunovic P _et al_. Hematopoietic stem cell transplantation rates and long-term survival in acute myeloid and lymphoblastic leukemia:

real-world population-based data from the Swedish Acute Leukemia Registry 1997-2006. _Cancer_ 2011; 117: 4238–4246. Article  PubMed  Google Scholar  * Hahn T, McCarthy PL Jr, Hassebroek A,

Bredeson C, Gajewski JL, Hale GA _et al_. Significant improvement in survival after allogeneic hematopoietic cell transplantation during a period of significantly increased use, older

recipient age, and use of unrelated donors. _J Clin Oncol_ 2013; 31: 2437–2449. Article  PubMed  PubMed Central  Google Scholar  * Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S,

Dreger P _et al_. Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. _Bone Marrow

Transplant_ 2015; 50: 476–482. Article  CAS  PubMed  PubMed Central  Google Scholar  * Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A _et al_. Karyotypic analysis

predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. _Blood_ 2000; 96: 4075–4083.

CAS  PubMed  Google Scholar  * Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ _et al_. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete

remission: systematic review and meta-analysis of prospective clinical trials. _JAMA_ 2009; 301: 2349–2361. Article  CAS  PubMed  PubMed Central  Google Scholar  * Gale RP, Wiernik PH,

Lazarus HM . Should persons with acute myeloid leukemia have a transplant in first remission? _Leukemia_ 2014; 28: 1949–1952. Article  CAS  PubMed  Google Scholar  * Schlenk RF, Dohner K,

Mack S, Stoppel M, Kiraly F, Gotze K _et al_. Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults

with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. _J Clin Oncol_ 2010; 28: 4642–4648. Article  PubMed  Google Scholar  * Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra

J, Bornhauser M, Juliusson G _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. Article  CAS  PubMed  Google Scholar  * Giles FJ, Borthakur G, Ravandi F, Faderl S, Verstovsek S, Thomas D _et al_. The haematopoietic cell

transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. _Br J Haematol_

2007; 136: 624–627. Article  PubMed  Google Scholar  * Klepin HD, Geiger AM, Tooze JA, Kritchevsky SB, Williamson JD, Pardee TS _et al_. Geriatric assessment predicts survival for older

adults receiving induction chemotherapy for acute myelogenous leukemia. _Blood_ 2013; 121: 4287–4294. Article  CAS  PubMed  PubMed Central  Google Scholar  * Fenaux P, Mufti GJ,

Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U _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_ 2010; 28: 562–569. Article  CAS  PubMed  Google Scholar  * Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH _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. Article  CAS  PubMed

  PubMed Central  Google Scholar  * Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J _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. Article  CAS  PubMed  PubMed Central  Google Scholar  * Scher KS, Hurria A . Under-representation of older adults in cancer registration trials: known problem, little

progress. _J Clin Oncol_ 2012; 30: 2036–2038. Article  PubMed  Google Scholar  * Dinmohamed AG, van Norden Y, Visser O, Posthuma EF, Huijgens PC, Sonneveld P _et al_. The use of medical

claims to assess incidence, diagnostic procedures and initial treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia in the Netherlands. _Leukemia research_ 2015; 39:

177–182. Article  PubMed  Google Scholar  * Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E _et al_. A randomized comparison of all transretinoic acid (ATRA) followed by

chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group. _Blood_ 1999; 94: 1192–1200. CAS  PubMed

  Google Scholar  * Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A _et al_. All-trans-retinoic acid in acute promyelocytic leukemia. _N Engl J Med_ 1997; 337:

1021–1028. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the European

Organization for Research and Treatment of Cancer (EORTC) for permission to use data on trial participation from their clinical AML trials for this research. We also thank the Stem Cell

Transplantation (SCT) Working Party of the HOVON for permission to use data on SCTs for this study. We are grateful to Dr Mirian Brink (Netherlands Comprehensive Cancer Organisation) for

additional data analysis. The contents of this publication and methods used are solely the responsibility of the authors and do not necessarily represent the official views of the EORTC.

This work was supported by a grant from The Netherlands Organization for Health Research and Development (ZonMw; grant #152001007). AUTHOR CONTRIBUTIONS AGD, OV and MJ-L designed the study;

OV analyzed the data; OV, YvN and JJC collected the data; AGD wrote the manuscript with contributions from OV, YvN, NMNA, JJC, GAH, PCH, PS, AAvdL, GJO, BL and MJ-L; and all authors read,

commented on and approved the final version of the manuscript. AUTHOR INFORMATION Author notes * A G Dinmohamed and O Visser: These authors contributed equally to this work. AUTHORS AND

AFFILIATIONS * Department of Hematology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands A G Dinmohamed, J J Cornelissen, P Sonneveld, B Löwenberg 

& M Jongen-Lavrencic * Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands O Visser & P C Huijgens * Clinical Trial Center-HOVON Data Center, Erasmus MC Cancer

Institute, Erasmus University Medical Center, Rotterdam, The Netherlands Y van Norden * Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands N M A

Blijlevens & G A Huls * Department of Hematology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands P C Huijgens, A A van de Loosdrecht & G J

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DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies this paper on the Leukemia website SUPPLEMENTARY

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Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the Netherlands, 1989–2012. _Leukemia_ 30, 24–31 (2016).

https://doi.org/10.1038/leu.2015.188 Download citation * Received: 13 May 2015 * Revised: 29 June 2015 * Accepted: 08 July 2015 * Published: 17 July 2015 * Issue Date: January 2016 * DOI:

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