Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation View Full Text


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Article Info

DATE

2017-11-15

AUTHORS

Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe

ABSTRACT

Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT. Furthermore, they have also been incorporated into prophylactic and pre-emptive approaches to avoid haematological relapse. In this review, we summarize the evidence from retrospective studies but also from a few prospective trials regarding the use of HMA after transplant. To aid clinicians in their daily clinical practice, we also comment on some practical aspects such as dosing and schedule, the choice of HMA and the use of complementary cellular therapies. Finally, this review also gives an overview on potential mechanisms mediating the efficacy of HMA after transplant as well as ongoing preclinical research and clinical activities aiming to further improve this treatment approach. More... »

PAGES

138-150

References to SciGraph publications

  • 2017-04-03. Low-dose 5-azacytidine as preventive therapy for relapse of AML and MDS following allogeneic HCT in BONE MARROW TRANSPLANTATION
  • 2013-03-29. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells in LEUKEMIA
  • 2009-12-21. Azacytidine treatment after discontinuation of immunosuppressants in patients with myelodysplastic syndrome and relapse after allo-SCT at a single center in BONE MARROW TRANSPLANTATION
  • 2015-11-25. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia in LEUKEMIA
  • 2013-03-01. Salvage therapy with azacitidine increases regulatory T cells in peripheral blood of patients with AML or MDS and early relapse after allogeneic blood stem cell transplantation in LEUKEMIA
  • 2015-03-23. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015 in BONE MARROW TRANSPLANTATION
  • 2012-10-31. Decitabine in patients with relapsed acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) in ANNALS OF HEMATOLOGY
  • 2017-11-18. Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI—a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group in ANNALS OF HEMATOLOGY
  • 2015-03-16. 5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft in BONE MARROW TRANSPLANTATION
  • 2009-08-31. Efficacy of a 3-day, low-dose treatment with 5-azacytidine followed by donor lymphocyte infusions in older patients with acute myeloid leukemia or chronic myelomonocytic leukemia relapsed after allografting in BONE MARROW TRANSPLANTATION
  • 2013-01-07. Azacitidine in the treatment of extramedullary relapse of AML after allogeneic hematopoietic cell transplantation in BONE MARROW TRANSPLANTATION
  • 2011-09-02. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial in LEUKEMIA
  • 2011-11-14. Durable complete remission after single agent decitabine in AML relapsing in extramedullary sites after allo-SCT in BONE MARROW TRANSPLANTATION
  • 2014-02-03. Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT in BONE MARROW TRANSPLANTATION
  • 2009-10-12. 5-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: a retrospective analysis in BONE MARROW TRANSPLANTATION
  • 2013-01-14. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation in LEUKEMIA
  • 2016-11-28. PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation in BONE MARROW TRANSPLANTATION
  • 2013-11-25. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents in LEUKEMIA
  • 2013-11-13. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes in LEUKEMIA
  • 2012-04-16. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses in LEUKEMIA
  • 2015-10-23. Model-based adaptive phase I trial design of post-transplant decitabine maintenance in myelodysplastic syndrome in JOURNAL OF HEMATOLOGY & ONCOLOGY
  • 2011-04-15. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias in LEUKEMIA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s12185-017-2364-4

    DOI

    http://dx.doi.org/10.1007/s12185-017-2364-4

    DIMENSIONS

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    PUBMED

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    41 schema:description Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT. Furthermore, they have also been incorporated into prophylactic and pre-emptive approaches to avoid haematological relapse. In this review, we summarize the evidence from retrospective studies but also from a few prospective trials regarding the use of HMA after transplant. To aid clinicians in their daily clinical practice, we also comment on some practical aspects such as dosing and schedule, the choice of HMA and the use of complementary cellular therapies. Finally, this review also gives an overview on potential mechanisms mediating the efficacy of HMA after transplant as well as ongoing preclinical research and clinical activities aiming to further improve this treatment approach.
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