Skip to main content

Hematopoietic Stem Cell Transplantation in APL

  • Chapter
  • First Online:
Acute Promyelocytic Leukemia

Abstract

The indication for hematopoietic stem cell transplant (HSCT) in APL has evolved historically from a widespread use in frontline therapy during the pre-ATRA era to a virtual rejection of this indication when patients are treated with modern treatments containing all-trans retinoic acid (ATRA), either in combination with chemotherapy, arsenic trioxide (ATO), or both. This indication has gradually been abandoned and explicitly rejected by the European LeukemiaNet recommendations. The high cure rate obtained using ATRA plus chemotherapy or ATRA plus ATO indicates that there is no role for HSCT for patients who achieve molecular remission at the end of consolidation. The HSCT in first complete remission has been relegated only for the very small fraction of patients with persistent MRD at the end of consolidation or for those who relapse. In the pre-ATO era, relapsed patients were usually treated with readministration of ATRA and chemotherapy as salvage therapy, generally containing high-dose cytarabine and an anthracycline, followed by further post-remission chemotherapy and/or HSCT. ATO-based regimens are presently regarded as the first option for treatment of relapsed APL. The selection of the most appropriate post-remission treatment option for patients in second CR, as well as the modality of HSCT when it is indicated, depends on a variety of prognostic and logistic variables, such as pretransplant molecular status, duration of first remission, age, and donor availability. There are no strict guidelines as regards the choice of autologous or allogeneic HSCT for relapsed patients in second CR. Autologous HSCT is associated with a lower transplantation-related mortality and is a reasonable option in patients without detectable MRD and prolonged duration of first CR (more than 1 year). In contrast, allogeneic HSCT involves a greater risk of nonrelapse mortality, but offers a potentially greater antileukemic activity due to the graft-versus-leukemia effect. Allogeneic HSCT could be, therefore, recommended in patients failing to achieve a second molecular remission and for those with short first CR duration.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  1. Esteve J, Escoda L, Martin G, et al. Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention. Leukemia. 2007;21(3):446–52.

    Article  CAS  Google Scholar 

  2. Coco Lo F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111–21.

    Article  Google Scholar 

  3. Sanz MA, Montesinos P, Rayon C, 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(25):5137–46.

    Article  CAS  Google Scholar 

  4. Ades L, Guerci A, Raffoux E, 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(9):1690–6.

    Article  CAS  Google Scholar 

  5. Sanz MA, Grimwade D, Tallman MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2009;113(9):1875–91.

    Article  CAS  Google Scholar 

  6. Lengfelder E, Lengfelder E, Lo-Coco F, et al. Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet. Leukemia. 2015;29(5):1084–91.

    Article  CAS  Google Scholar 

  7. de Botton S, Fawaz A, Chevret S, et al. Autologous and allogeneic stem-cell transplantation as salvage treatment of acute promyelocytic leukemia initially treated with all-trans-retinoic acid: a retrospective analysis of the European acute promyelocytic leukemia group. J Clin Oncol. 2005;23(1):120–6.

    Article  Google Scholar 

  8. Thomas X, Dombret H, Cordonnier C, et al. Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. APL Study Group. Acute promyelocytic leukemia. Leukemia. 2000;14(6):1006–13.

    Article  CAS  Google Scholar 

  9. Mandelli F, Labopin M, Granena A, et al. European survey of bone marrow transplantation in acute promyelocytic leukemia (M3). Working Party on Acute Leukemia of the European Cooperative Group for Bone Marrow Transplantation (EMBT). Bone Marrow Transplant. 1994;14(2):293–8.

    CAS  Google Scholar 

  10. Sanz MA, Labopin M, Gorin NC, et al. Hematopoietic stem cell transplantation for adults with acute promyelocytic leukemia in the ATRA era: a survey of the European Cooperative Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2007;39(8):461–9.

    Article  CAS  Google Scholar 

  11. Ganzel C, Mathews V, Alimoghaddam K, et al. Autologous transplant remains the preferred therapy for relapsed APL in CR2. Bone Marrow Transplant. 2016;51(9):1180–3.

    Article  CAS  PubMed  Google Scholar 

  12. Holter Chakrabarty JL, Rubinger M, Le Rademacher J, et al. Autologous is superior to allogeneic hematopoietic cell transplantation for acute promyelocytic leukemia in second complete remission. Biol Blood Marrow Transplant. 2014;20(7):1021–5.

    Article  Google Scholar 

  13. Sanz MA, Lo-Coco F, Martin G, 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(4):1247–53.

    CAS  Google Scholar 

  14. Breccia M, Diverio D, Noguera NI, et al. Clinico-biological features and outcome of acute promyelocytic leukemia patients with persistent polymerase chain reaction-detectable disease after the AIDA front-line induction and consolidation therapy. Haematologica. 2004;89(1):29–33.

    Google Scholar 

  15. Sanz MA, Martín G, Gonzalez M, 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(4):1237–43.

    Article  CAS  Google Scholar 

  16. Platzbecker U, Avvisati G, Cicconi L, 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(6):605–12.

    Article  CAS  Google Scholar 

  17. Estey EH. Treatment options for relapsed acute promyelocytic leukaemia. Best Pract Res Clin Haematol. 2003;16(3):521–34.

    Article  CAS  Google Scholar 

  18. Castagnola C, Lunghi M, Corso A, et al. Management of acute promyelocytic leukemia relapse in the ATRA era. Haematologica. 1998;83(8):714–7.

    CAS  Google Scholar 

  19. Thirugnanam R, George B, Chendamarai E, et al. Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen. Biol Blood Marrow Transplant. 2009;15(11):1479–84.

    Article  CAS  Google Scholar 

  20. Yanada M, Tsuzuki M, Fujita H, et al. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013;121(16):3095–102.

    Article  CAS  Google Scholar 

  21. Sanz MA, La Rubia de J, Bonanad S, et al. Prolonged molecular remission after PML/RAR alpha-positive autologous peripheral blood stem cell transplantation in acute promyelocytic leukemia: is relevant pretransplant minimal residual disease in the graft? Leukemia. 1998;12(6):992–5.

    Article  CAS  Google Scholar 

  22. Ruiz-Arguelles GJ, Garces-Eisele J, Ruiz-Arguelles A. Continued complete remission after a PML/RAR-alpha+ autograft in acute promyelocytic leukaemia. Eur J Haematol. 1996;56(3):186–7.

    Article  CAS  Google Scholar 

  23. Montesinos P, Diaz-Mediavilla J, Deben G, et al. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis. Haematologica. 2009;94(9):1242–9.

    Article  CAS  PubMed  Google Scholar 

  24. de Botton S, Sanz MA, Chevret S, et al. Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy. Leukemia. 2006;20(1):35–41.

    Article  Google Scholar 

  25. Tallman MS, Tallman MS. Treatment of relapsed or refractory acute promyelocytic leukemia. Best Pract Res Clin Haematol. 2007;20(1):57–65.

    Article  Google Scholar 

  26. Yanada M, Yanada M, Yano S, et al. Autologous hematopoietic cell transplantation for acute promyelocytic leukemia in second complete remission: outcomes before and after the introduction of arsenic trioxide. Leuk Lymphoma. 2017;58(5):1061–7.

    Article  Google Scholar 

  27. Lo-Coco F, Romano A, Mengarelli A, et al. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia: results in patients treated in second molecular remission or with molecularly persistent disease. Leukemia. 2003;17(10):1930–3.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Miguel A. Sanz M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Sanz, J., Sanz, M.A. (2018). Hematopoietic Stem Cell Transplantation in APL. In: Abla, O., Lo Coco, F., Sanz, M. (eds) Acute Promyelocytic Leukemia . Springer, Cham. https://doi.org/10.1007/978-3-319-64257-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-64257-4_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-64256-7

  • Online ISBN: 978-3-319-64257-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics