Abstract
This nationwide population-based study assessed trends in treatment, trial participation and survival among 1833 adult patients diagnosed with acute lymphoblastic leukemia (ALL) in the Netherlands between 1989 and 2012 reported to the Netherlands Cancer Registry. Patients were categorized into four periods and five age groups (18–24, 25–39, 40–59, 60–69 and ⩾70 years). The application of allogeneic stem cell transplantation (alloSCT), particularly reduced-intensity conditioning (RIC) alloSCT, increased over time up to age 70 years. The inclusion rate in the trials was 67, 66, 55, 58 and 0% for the five age groups. Survival improved over time for patients below 70 years. Five-year relative survival in the period 2007–2012 was 75, 57, 37, 22 and 5% for the five age groups. In that same period, 5-year overall survival among patients aged 18–39 years was 68% for the chemotherapy-alone group and 66% for the alloSCT group. For patients aged 40–69 years, the corresponding estimates were 24 and 41%. Pronounced survival improvement observed among patients aged 18–39 years might mainly be explained by implementation of pediatric-based regimens since 2005, whereas among patients aged 40–69 years, increased application of RIC-alloSCT has contributed significantly to the observed improvement. Outcome of patients aged ⩾70 remains unsatisfactory, indicating a need for specific trials for the elderly.
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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.
Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 2001; 97: 1211–1218.
Arico M, Valsecchi MG, Rizzari C, Barisone E, Biondi A, Casale F et al. Long-term results of the AIEOP-ALL-95 trial for childhood acute lymphoblastic leukemia: insight on the prognostic value of DNA index in the framework of Berlin–Frankfurt–Muenster-based chemotherapy. J Clin Oncol 2008; 26: 283–289.
Kamps WA, van der Pal-de Bruin KM, Veerman AJ, Fiocco M, Bierings M, Pieters R . Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004. Leukemia 2010; 24: 309–319.
Stanulla M, Schrappe M . Treatment of childhood acute lymphoblastic leukemia. Semin Hematol 2009; 46: 52–63.
Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol 2012; 30: 1663–1669.
Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM 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: 3760–3767.
Dombret H, Cluzeau T, Huguet F, Boissel N . Pediatric-like therapy for adults with ALL. Curr Hematol Malig Rep 2014; 9: 158–164.
Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T et al. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol 2003; 21: 774–780.
de Bont JM, Holt B, Dekker AW, van der Does-van den Berg A, Sonneveld P, Pieters R . Significant difference in outcome for adolescents with acute lymphoblastic leukemia treated on pediatric vs adult protocols in the Netherlands. Leukemia 2004; 18: 2032–2035.
Hallbook H, Gustafsson G, Smedmyr B, Soderhall S, Heyman M, Swedish Adult Acute Lymphocytic Leukemia G. Treatment outcome in young adults and children >10 years of age with acute lymphoblastic leukemia in Sweden: a comparison between a pediatric protocol and an adult protocol. Cancer 2006; 107: 1551–1561.
Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer 2007; 48: 254–261.
Stock W, La M, Sanford B, Bloomfield CD, Vardiman JW, Gaynon P et al. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children's Cancer Group and Cancer and Leukemia Group B studies. Blood 2008; 112: 1646–1654.
Ribera JM, Oriol A, Sanz MA, Tormo M, Fernandez-Abellan P, del Potro E et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol 2008; 26: 1843–1849.
Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: The GRAALL-2003 Study. J Clin Oncol 2009; 27: 911–918.
Haiat S, Marjanovic Z, Lapusan S, Vekhoff A, Rio B, Corre E et al. Outcome of 40 adults aged from 18 to 55 years with acute lymphoblastic leukemia treated with double-delayed intensification pediatric protocol. Leuk Res 2011; 35: 66–72.
Rijneveld AW, van der Holt B, Daenen SM, Biemond BJ, de Weerdt O, Muus P et al. Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40. Leukemia 2011; 25: 1697–1703.
Daenen S, van der Holt B, Dekker AW, Willemze R, Rijneveld AW, Biemond BJ et al. Intensive chemotherapy to improve outcome in patients with acute lymphoblastic leukemia over the age of 40: a phase II study for efficacy and feasibility by HOVON. Leukemia 2012; 26: 1726–1729.
Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008; 111: 1827–1833.
Cornelissen JJ, van der Holt B, Verhoef GE, van't Veer MB, van Oers MH, Schouten HC et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 2009; 113: 1375–1382.
Thomas DA, O'Brien S, Cortes J, Kantarjian H . New approaches to the management of Philadelphia-chromosome-positive acute lymphocytic leukemia. Curr Hematol Malig Rep 2007; 2: 183–189.
Booth CM, Tannock IF . Evaluation of treatment benefit: randomized controlled trials and population-based observational research. J Clin Oncol 2013; 31: 3298–3299.
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.
Fritz AG, Percy C, Jack A, Sobin LH, Parkin DM (eds). International Classification of Diseases for Oncology, 3rd edn. World Health Organization: : Geneva, Switzerland, 2000.
Henson DE, Ries LA . The relative survival rate. Cancer 1995; 76: 1687–1688.
Ederer F, Heise H . Instructions to IBM 650 Programmers in Processing, Survival Computations. Methodological Note No. 10. End Results Evaluation Section. National Cancer Institute: Bethesda, MD, USA, 1959..
Dickman PW, Sloggett A, Hills M, Hakulinen T . Regression models for relative survival. Stat Med 2004; 23: 51–64.
Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S et al. Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII/ECOG2993 trial. Br J Haematol 2012; 157: 463–471.
Juliusson G, Karlsson K, Hallbook H . Population-based analyses in adult acute lymphoblastic leukemia. Blood 2010; 116: 1011; author reply 1012.
Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ . A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood 2010; 115: 206–214.
Gokbuget N . How I treat older patients with ALL. Blood 2013; 122: 1366–1375.
Bachanova V, Weisdorf D . Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant 2008; 41: 455–464.
Gupta V, Richards S, Rowe J . Acute Leukemia Stem Cell Transplantation Trialists' Collaborative G. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood 2013; 121: 339–350.
Cornelissen JJ, Carston M, Kollman C, King R, Dekker AW, Lowenberg B et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 2001; 97: 1572–1577.
Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR 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: 843–850.
Brissot E, Labopin M, Beckers MM, Socie G, Rambaldi A, Volin L et al. Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Haematologica 2014; 100: 392–399.
Hussein KK, Dahlberg S, Head D, Waddell CC, Dabich L, Weick JK et al. Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy. Blood 1989; 73: 57–63.
Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P 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: 2025–2037.
Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 2000; 18: 547–561.
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.
Pulte D, Gondos A, Brenner H . Improvement in survival in younger patients with acute lymphoblastic leukemia from the 1980s to the early 21st century. Blood 2009; 113: 1408–1411.
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.
Toft N, Schmiegelow K, Klausen TW, Birgens H . Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998–2008. Br J Haematol 2012; 157: 97–104.
Pulte D, Redaniel MT, Jansen L, Brenner H, Jeffreys M . Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups. Haematologica 2013; 98: 222–229.
Pulte D, Jansen L, Gondos A, Katalinic A, Barnes B, Ressing M et al. Survival of adults with acute lymphoblastic leukemia in Germany and the United States. PLoS One 2014; 9: e85554.
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.
Guru Murthy GS, Venkitachalam R, Mehta P . Trends in survival outcomes of B-lineage acute lymphoblastic leukemia in elderly patients: analysis of Surveillance, Epidemiology, and End Results database. Leuk Lymphoma 2015, 1–5.
Redaniel MT, Pulte D, Jeffreys M . Survival disparities by age and country of diagnosis for patients with acute leukemia. Leuk Lymphoma 2015; e-pub ahead of print 6 March 2015; doi:10.3109/10428194.2015.1014358.
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. Leuk Res 2015; 39: 177–182.
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 the data on trial participation from their clinical ALL trials for this research. We also thank the HOVON stem cell transplantation (SCT) Working Party for permission to use data on SCTs for this study. 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 grants from The Netherlands Organization for Health Research and Development (ZonMw; Grant No.152001007).
Author contributions
AGD, AS, MJ-L and AWR: designed the study; MvdM: analyzed the data; OV, AGD and JJC: collected the data; AGD and AS: wrote the manuscript with contributions from MvdM, OV, PS, JJC, MJ-L and AWR; and all authors read, commented on and approved the final version of the manuscript.
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Dinmohamed, A., Szabó, A., van der Mark, M. et al. Improved survival in adult patients with acute lymphoblastic leukemia in the Netherlands: a population-based study on treatment, trial participation and survival. Leukemia 30, 310–317 (2016). https://doi.org/10.1038/leu.2015.230
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DOI: https://doi.org/10.1038/leu.2015.230
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