Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Epidemiology

Evolution of relative survival for acute promyelocytic leukemia patients alive at landmark time-points: a population-based study

Leukemia volume 32, pages 2263–2303 (2018)Cite this article

Subjects

Access through your institution
Buy or subscribe

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML) accounting for ~5% of all new cases [1]. Through a variety of mechanisms, accumulation of APL cells leads to coagulopathy which in turn gives rise to severe bleeding diathesis, a distinct presenting feature of APL, and the reason for the high incidence of early hemorrhagic deaths [2, 3]. Therefore, prompt initiation of all-trans retinoic acid (ATRA)-treatment and supportive care upon first suspicion of APL is critical to restore normal coagulation and reduce risk of early deaths [3]. Contrasting to the life-threatening initial phase of APL, patients surviving this critical period have excellent outcomes characterized by low relapse risk and survival rates surpassing those of other AML subtypes [4]. The objective of this study was to investigate when the survival of APL patients normalizes to that of a gender, age, and calendar-year-matched general population.

The study was approved by the Danish Data Protection Agency (2014-41-3204) and was based on the Danish National Acute Leukemia Registry (DNLR) [5]. We included newly diagnosed patients with de novo APL (dnAPL), secondary APL (sAPL), or therapy-related APL (tAPL) between 2000 and 2014. The diagnosis of APL required fulfillment of one or more of following diagnostic criteria: (i) presence of the chromosomal translocation of t(15;17)(q22;q12) by classical G-banding, (ii) fluorescence in-situ hybridization (FISH) analysis positive for PML-RARA fusion gene product, and/or (iii) a polymerase chain reaction (PCR) confirming presence of the PML-RARA fusion gene product. One case of variant APL with the variant translocation t(5;17)(q35;q21) was included [6]. sAPL was defined as APL diagnosed in the setting of an existing myeloid disease [7]. tAPL was defined as APL occurring after chemotherapy and/or radiotherapy for other hematological cancers, solid tumors, or non-malignant diseases [7]. For simplicity and due to the limited number of cases, the sAPL and tAPL cases were grouped together as non-dnAPL.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Dinmohamed AG, Visser O, van Norden Y, Blijlevens NMA, Cornelissen JJ, Huls GA, et al. Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the Netherlands, 1989–2012. Leukemia. 2016;30:24–31.

    Article  CAS  Google Scholar 

  2. Lehmann S, Ravn A, Carlsson L, Antunovic P, Deneberg S, Möllgård 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;25:1128–34.

    Article  CAS  Google Scholar 

  3. Tallman MS, Altman JK. How I treat acute promyelocytic leukemia. Blood 2009;114:5126–35.

    Article  CAS  Google Scholar 

  4. 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;118:1248–54.

    Article  CAS  Google Scholar 

  5. Ostgard L, Nørgaard JM, Raaschou-Jensen K, Pedersen RS, Rønnov-Jessen D, Trøllund Pedersen P, et al. The Danish National Acute Leukemia Registry. Clin Epidemiol. 2016;8:553–60.

    Article  Google Scholar 

  6. Grimwade D, Biondi A, Mozziconacci MJ, Hagemeijer A, Berger R, Neat M, et al. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Français de Cytogénétique Hématologique, Groupe de Français d’Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOME. Blood. 2000;96:1297–308.

    CAS  Google Scholar 

  7. Granfeldt Østgård LS, Medeiros BC, Sengeløv H, Nørgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a national population-based cohort study. J Clin Oncol. 2015;33:3641–9.

    Article  Google Scholar 

  8. 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;94:1192–200.

    CAS  Google Scholar 

  9. Perme MP, Henderson R, Stare J. An approach to estimation in relative survival regression. Biostatistics. 2008;10:136–46.

    Article  Google Scholar 

  10. Mantha S, Goldman DA, Devlin SM, Lee J-W, Zannino D, Collins M, et al. Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era. Blood. 2017;129:1763–7.

    Article  CAS  Google Scholar 

  11. Sanz MA, Lo Coco F, Martín G, Avvisati G, Rayón C, Barbui T, et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96:1247–53.

    CAS  Google Scholar 

  12. Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood. 2012;119:3890–9.

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Tarec Christoffer El-Galaly, Jan Maxwell Nørgaard.

Authors and Affiliations

  1. Department of Haematology, Aalborg University Hospital, Aalborg, Denmark

    Jorne Lionel Biccler, Marianne Tang Severinsen, Martin Bøgsted, Lasse Hjort Jakobsen & Tarec Christoffer El-Galaly

  2. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

    Jorne Lionel Biccler, Marianne Tang Severinsen, Martin Bøgsted, Lasse Hjort Jakobsen & Tarec Christoffer El-Galaly

  3. Department of Haematology, Aarhus University Hospital, Aarhus, Denmark

    Lene Sofie Granfeldt Østgård & Jan Maxwell Nørgaard

  4. Department of Haematology, Odense University Hospital, Odense, Denmark

    Claus Werenberg Marcher

  5. Department of Haematology, Roskilde Hospital, Roskilde, Denmark

    Peter Møller

  6. Department of Haematology, Herlev Hospital, Herlev, Denmark

    Claudia Schöllkopf

  7. Department of Haematology, Rigshospitalet, Copenhagen, Denmark

    Lone Smidstrup Friis

Authors
  1. Jorne Lionel Biccler
    View author publications

    Search author on:PubMed Google Scholar

  2. Lene Sofie Granfeldt Østgård
    View author publications

    Search author on:PubMed Google Scholar

  3. Marianne Tang Severinsen
    View author publications

    Search author on:PubMed Google Scholar

  4. Claus Werenberg Marcher
    View author publications

    Search author on:PubMed Google Scholar

  5. Peter Møller
    View author publications

    Search author on:PubMed Google Scholar

  6. Claudia Schöllkopf
    View author publications

    Search author on:PubMed Google Scholar

  7. Lone Smidstrup Friis
    View author publications

    Search author on:PubMed Google Scholar

  8. Martin Bøgsted
    View author publications

    Search author on:PubMed Google Scholar

  9. Lasse Hjort Jakobsen
    View author publications

    Search author on:PubMed Google Scholar

  10. Tarec Christoffer El-Galaly
    View author publications

    Search author on:PubMed Google Scholar

  11. Jan Maxwell Nørgaard
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Jorne Lionel Biccler.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Biccler, J.L., Østgård, L.S.G., Severinsen, M.T. et al. Evolution of relative survival for acute promyelocytic leukemia patients alive at landmark time-points: a population-based study. Leukemia 32, 2263–2303 (2018). https://doi.org/10.1038/s41375-018-0054-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41375-018-0054-8

Search

Advanced search

Quick links