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@ARTICLE{Sendker:301924,
      author       = {S. Sendker$^*$ and M. Schneider$^*$ and E. Antoniou$^*$ and
                      D. Neumann and N. Niktoreh$^*$ and U. Dirksen$^*$ and N. von
                      Neuhoff$^*$ and U. Creutzig and D. Reinhardt and K. Waack},
      title        = {{I}mproved outcomes and treatment guidance in pediatric
                      therapy-related {AML}: {AML}-{BFM} study group
                      recommendations.},
      journal      = {Blood advances},
      volume       = {9},
      number       = {11},
      issn         = {2473-9529},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2025-01194},
      pages        = {2831 - 2841},
      year         = {2025},
      abstract     = {Therapy-related acute myeloid leukemia (AML; tAML) is one
                      of the most feared therapy-emergent complications. This
                      study aims to determine the clinical and pathological
                      significance and define therapeutic implications and poor
                      prognosticators in pediatric tAML. We analyzed a total of
                      119 pediatric patients (aged 2-20 years) who were centrally
                      diagnosed with tAML within the Acute Myeloid Leukemia
                      Berlin-Frankfurt-Münster (AML-BFM) study group between 1993
                      and 2019. Compared with de novo AML, tAML was associated
                      with decreased white blood count and involvement of the
                      central nervous system. Latency to tAML was inversely
                      correlated with age at primary malignancy. Patients with
                      tAML were more likely to have abnormal karyotypes,
                      overrepresenting KMT2A rearrangements, the unfavorable
                      cytogenetics -7/del(7q), as well as complex and monosomal
                      karyotypes, whereas core-binding AML was underrepresented.
                      The occurrence of stratification-relevant molecular genetics
                      was comparable with de novo AML, whereas CEBPAdm was absent
                      in tAML. Survival rates in tAML improved from $10\%$ ±
                      $6\%$ in AML-BFM 1993/1998 to $50\%$ ± $10\%$ in the
                      registries 2012/2017; however, this is still worse than de
                      novo AML. Hematopoietic stem cell transplantation (HSCT) in
                      no evidence of leukemia (NEL; $<5\%$ blasts) after 2
                      induction cycles greatly improved survival. Adverse
                      cytogenetics, previous ionizing radiation (>35 Gy), and
                      latency ≤1 year were identified as the strongest poor
                      prognosticators. Over the past 26 years, outcome and
                      survival significantly improved in pediatric tAML. Our
                      results suggest that HSCT in NEL after 2 induction cycles is
                      the most promising therapeutic approach for achieving
                      improved survival. Radiation, adverse cytogenetics, and
                      latency ≤1 year should be considered as poor
                      prognosticators in pediatric tAML.},
      keywords     = {Humans / Child / Leukemia, Myeloid, Acute: therapy /
                      Leukemia, Myeloid, Acute: etiology / Leukemia, Myeloid,
                      Acute: mortality / Leukemia, Myeloid, Acute: diagnosis /
                      Adolescent / Child, Preschool / Female / Male / Young Adult
                      / Treatment Outcome / Prognosis / Neoplasms, Second Primary:
                      therapy / Neoplasms, Second Primary: mortality / Neoplasms,
                      Second Primary: diagnosis / Neoplasms, Second Primary:
                      etiology / Disease Management},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39969195},
      doi          = {10.1182/bloodadvances.2024014728},
      url          = {https://inrepo02.dkfz.de/record/301924},
}