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Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated robust RT-qPCR methods for these patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>BCR-ABL1<\/jats:italic>\n                      transcripts were amplified and sequenced to characterize the underlying fusion. Residual disease monitoring was carried out by RT-qPCR with specific primers and probes using serial dilutions of appropriate\n                      <jats:italic>BCR-ABL1<\/jats:italic>\n                      and\n                      <jats:italic>GUSB<\/jats:italic>\n                      plasmid DNA calibrators. Results were expressed as log reduction of the\n                      <jats:italic>BCR-ABL1\/GUSB<\/jats:italic>\n                      ratio relative to the patient-specific baseline value and evaluated as an individual molecular response (IMR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 330 blood samples (2\u201334 per patient, median 8) from 33 CML patients (19 male, median age 62\u00a0years) were analyzed. Patients expressed seven different atypical\n                      <jats:italic>BCR-ABL1<\/jats:italic>\n                      transcripts (e1a2,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096; e6a2,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091; e8a2,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092; e13a3,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094; e14a3,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096; e13a3\/e14a3,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20092; e19a2,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912). Most patients (61%) responded well to TKI therapy and achieved an IMR of at least one log reduction 3 months after diagnosis. Four patients relapsed with a significant increase of\n                      <jats:italic>BCR-ABL1\/GUSB<\/jats:italic>\n                      ratios.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Characterization of atypical\n                      <jats:italic>BCR-ABL1<\/jats:italic>\n                      transcripts is essential for adequate patient monitoring and to avoid false-negative results. The results cannot be expressed on the International Scale (IS) and thus the common molecular milestones and guidelines for treatment are difficult to apply. We, therefore, suggest reporting IMR levels in these cases as a time-dependent log reduction of\n                      <jats:italic>BCR-ABL1<\/jats:italic>\n                      transcript levels compared to baseline prior to therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-021-03569-8","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:38:17Z","timestamp":1615077497000},"page":"3081-3089","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Assessment of individual molecular response in chronic myeloid leukemia patients with atypical BCR-ABL1 fusion transcripts: recommendations by the EUTOS cooperative network"],"prefix":"10.1007","volume":"147","author":[{"given":"Vivien","family":"Sch\u00e4fer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen E.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth","family":"Gerrard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"M\u00f6bius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Saussele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg-Nikolaus","family":"Franke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois-X.","family":"Mahon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodica","family":"Talmaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Soverini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Machova Polakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C. 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