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@ARTICLE{Platzbecker:141767,
      author       = {U. Platzbecker$^*$ and J. M. Middeke$^*$ and K. Sockel$^*$
                      and R. Herbst and D. Wolf and C. D. Baldus and U.
                      Oelschlägel and A. Mütherig and L. Fransecky and R.
                      Noppeney and G. Bug$^*$ and K. S. Götze and A. Krämer$^*$
                      and T. Bochtler$^*$ and M. Stelljes and C. Groth and A.
                      Schubert$^*$ and M. Mende$^*$ and F. Stölzel$^*$ and C.
                      Borkmann$^*$ and A. S. Kubasch$^*$ and M. von Bonin$^*$ and
                      H. Serve$^*$ and M. Hänel and U. Dührsen and J.
                      Schetelig$^*$ and C. Röllig$^*$ and M. Kramer$^*$ and G.
                      Ehninger$^*$ and M. Bornhäuser$^*$ and C. Thiede$^*$},
      title        = {{M}easurable residual disease-guided treatment with
                      azacitidine to prevent haematological relapse in patients
                      with myelodysplastic syndrome and acute myeloid leukaemia
                      ({RELAZA}2): an open-label, multicentre, phase 2 trial.},
      journal      = {The lancet / Oncology Oncology},
      volume       = {19},
      number       = {12},
      issn         = {1470-2045},
      address      = {London},
      publisher    = {The Lancet Publ. Group},
      reportid     = {DKFZ-2018-02036},
      pages        = {1668-1679},
      year         = {2018},
      abstract     = {Monitoring of measurable residual disease (MRD) in patients
                      with advanced myelodysplastic syndromes (MDS) or acute
                      myeloid leukaemia (AML) who achieve a morphological complete
                      remission can predict haematological relapse. In this
                      prospective study, we aimed to determine whether MRD-guided
                      pre-emptive treatment with azacitidine could prevent relapse
                      in these patients.The relapse prevention with azacitidine
                      (RELAZA2) study is an open-label, multicentre, phase 2 trial
                      done at nine university health centres in Germany. Patients
                      aged 18 years or older with advanced MDS or AML, who had
                      achieved a complete remission after conventional
                      chemotherapy or allogeneic haemopoietic stem-cell
                      transplantation, were prospectively screened for MRD during
                      24 months from baseline by either quantitative PCR for
                      mutant NPM1, leukaemia-specific fusion genes (DEK-NUP214,
                      RUNX1-RUNX1T1, CBFb-MYH11), or analysis of donor-chimaerism
                      in flow cytometry-sorted CD34-positive cells in patients who
                      received allogeneic haemopoietic stem-cell transplantation.
                      MRD-positive patients in confirmed complete remission
                      received azacitidine 75 mg/m2 per day subcutaneously on days
                      1-7 of a 29-day cycle for 24 cycles. After six cycles, MRD
                      status was reassessed and patients with major responses (MRD
                      negativity) were eligible for a treatment de-escalation. The
                      primary endpoint was the proportion of patients who were
                      relapse-free and alive 6 months after the start of
                      pre-emptive treatment. Analyses were done per protocol. This
                      trial is registered with ClincialTrials.gov, number
                      NCT01462578, and finished recruitment on Aug 21,
                      2018.Between Oct 10, 2011, and Aug 20, 2015, we screened 198
                      patients with advanced MDS (n=26) or AML (n=172), of whom 60
                      $(30\%)$ developed MRD during the 24-month screening period
                      and 53 $(88\%)$ were eligible to start study treatment. 6
                      months after initiation of azacitidine, 31 $(58\%,$ $95\%$
                      CI 44-72) of 53 patients were relapse-free and alive
                      (p<0·0001; one-sided binomial test for null hypothesis
                      pexp≤0·3). With a median follow-up of 13 months (IQR
                      8·5-22·8) after the start of MRD-guided treatment,
                      relapse-free survival at 12 months was $46\%$ $(95\%$ CI
                      32-59) in the 53 patients who were MRD-positive and received
                      azacitidine. In MRD-negative patients, 12-month relapse-free
                      survival was $88\%$ $(95\%$ CI 82-94; hazard ratio 6·6
                      $[95\%$ CI 3·7-11·8], p<0·0001). The most common (grade
                      3-4) adverse event was neutropenia, occurring in 45 $(85\%)$
                      of 53 patients. One patient with neutropenia died because of
                      an infection considered possibly related to study
                      treatment.Pre-emptive therapy with azacitidine can prevent
                      or substantially delay haematological relapse in
                      MRD-positive patients with MDS or AML who are at high risk
                      of relapse. Our study also suggests that continuous MRD
                      negativity during regular MRD monitoring might be prognostic
                      for patient outcomes.Celgene Pharma, José Carreras
                      Leukaemia Foundation, National Center for Tumor Diseases
                      (NCT), and German Cancer Consortium (DKTK) Foundation.},
      cin          = {L301 / L501 / G330 / L101 / L201 / L701},
      ddc          = {610},
      cid          = {I:(DE-He78)L301-20160331 / I:(DE-He78)L501-20160331 /
                      I:(DE-He78)G330-20160331 / I:(DE-He78)L101-20160331 /
                      I:(DE-He78)L201-20160331 / I:(DE-He78)L701-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30442503},
      doi          = {10.1016/S1470-2045(18)30580-1},
      url          = {https://inrepo02.dkfz.de/record/141767},
}