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  • Juul-Dam, KL (author)

Deep Sequencing of Leukemia-specific Mutations in Peripheral Blood Identifies Children with Imminent Relapse of Acute Myeloid Leukemia

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/287684
  • https://gup.ub.gu.se/publication/287684URI

Supplementary language notes

  • Language:English

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  • Subject category:vet swepub-contenttype
  • Subject category:kon swepub-publicationtype

Notes

  • Relapse remains the major problem in childhood acute myeloid leukemia (AML). The outcome in children with imminent relapse may improve if preemptive therapy is initiated at first evidence of leukemia regrowth. This requires measurable residual disease (MRD) monitoring after therapy completion, but only 40% of children with AML harbor genetic abnormalities applicable for quantification using standardized qPCR assays. To enable disease surveillance for all patients, we investigated the potential of early relapse detection in peripheral blood (PB) using patient-tailored deep sequencing (DS) MRD analysis. PB samples were collected at monthly intervals during follow-up from 45 children diagnosed with AML and treated according to the NOPHO-DBH AML 2012 protocol between January 2013 and May 2016 in Denmark, Norway, Sweden and Finland (508 samples, median 11 samples/patient, range 3–27). In relapsed patients, MRD-suitable leukemia-specific single nucleotide variants (SNVs) were identified with exome sequencing (ES) in diagnostic samples and verified at relapse. SNVs were analyzed in PB samples obtained during the months before overt relapse using DS with a sensitivity of 0.02% variant allele frequency (VAF). Until October 1st 2017, 14 patients experienced relapse within 18 months from therapy completion, and in 6 patients analysis has been completed. ES identified 37 leukemia-specific SNVs at diagnosis (median 4 SNVs/patient, range 2–12) of which 23 were also present at relapse (median 3 SNVs/patient, range 1–9). Fourteen MRD-suitable SNVs (1–3/patient) were quantified with DS. In all patients, at least one SNV was detected in PB before overt relapse occurred. The first PB sample showing MRD positivity (median error corrected VAF 0.15%, range 0.03–0.85) preceded hematological relapse at a median interval of 2.3 months (range 0.6–4.7). In conclusion, high-sensitivity quantification of leukemia-specific SNVs can facilitate early detection of imminent relapse and provide a chance for initiation of preemptive treatment.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Delsing Malmberg, ErikGothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xmaerg (author)
  • Rehammar, Anna,1978Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences(Swepub:gu)xlanns (author)
  • Kristiansson, Erik,1978Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper,Department of Mathematical Sciences(Swepub:gu)xkrier (author)
  • Abrahamsson, Jonas,1954Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics(Swepub:gu)xabrjo (author)
  • Aggerholm, A (author)
  • Dirdal, MM (author)
  • Jahnukainen, Kirsi (author)
  • Lausen, Birgitte (author)
  • Ommen, HB (author)
  • Hasle, Henrik (author)
  • Fogelstrand, Linda,1974Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xsvlin (author)
  • Göteborgs universitetInstitutionen för biomedicin (creator_code:org_t)

Related titles

  • In:NOPHO Annual Meeting 2019

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