{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:09:54Z","timestamp":1790525394576,"version":"4.1.0"},"reference-count":40,"publisher":"Walter de Gruyter GmbH","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,24]]},"abstract":"Abstract<\/jats:title>\n\nBackground<\/jats:title>\nMinimal residual disease (MRD) and hematopoietic chimerism testing influences clinical decision and therapeutic intervention in patients after allogeneic stem cell transplantation (HSCT). However, treatment approaches to induce complete donor chimerism and MRD negativity can lead to complications such as graft-versus-host disease (GvHD) and marrow aplasia. Therefore, there is a need for comprehensive characterization of the molecular remission status after transplantation.<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nWe analyzed 764 samples from 70 patients after HSCT for the simultaneous measurement of chimerism and molecular targets used for MRD testing with a digital PCR (dPCR) platform.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nMixed chimerism (MC) was detected in 219 samples from 37 patients. The mean percentage of host derived DNA in these clinical samples was 4.3%. Molecular relapse with a positive MRD marker and\/or increased WT1 expression was observed in 15 patients. In addition to WT1 overexpression, other MRD positive markers were: NPM1 (Type A, B, K), DNMT3A (R882H), MLL-PTD, IDH1 (R132H) and KRAS (G12S). Increasing MC was observed in 15 patients. This group of patients showed either a positive MRD marker, increased WT1 expression or both. Next, we analyzed whether MC or the molecular target for MRD was first detected. MC and MRD marker positivity in this group was first detected in six and two patients, respectively. In the remaining seven patients MC and MRD positivity was detected simultaneously.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nThe combination of MRD and chimerism markers in a dPCR platform represents a practical, sensitive and accurate diagnostic tool for the comprehensive assessment of the molecular remission status of patients undergoing HSCT.<\/jats:p><\/jats:sec>","DOI":"10.1515\/cclm-2018-0827","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T09:02:34Z","timestamp":1542704554000},"page":"641-647","source":"Crossref","is-referenced-by-count":36,"title":["Droplet digital PCR for the simultaneous analysis of minimal residual disease and hematopoietic chimerism after allogeneic cell transplantation"],"prefix":"10.1515","volume":"57","author":[{"given":"Miguel","family":"Waterhouse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Pfeifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Duque-Afonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Follo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Duyster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Depner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Bertz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Finke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref291","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/j.bbmt.2015.07.005","article-title":"Mixed T lymphocyte chimerism after allogeneic hematopoietic transplantation is predictive for relapse of acute myeloid leukemia and myelodysplastic syndromes","volume":"21","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1182\/blood-2007-08-104745","article-title":"Reduced-toxicity conditioning with fludarabine, BCNU and melphalan in allogeneic cell transplantation: particular activity against advanced hematologic malignancies","volume":"112","year":"2008","journal-title":"Blood"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/bjh.12792","article-title":"Relapse kinetics in acute myeloid leukemias with MLL translocations or partial tandem duplications within the MLL gene","volume":"165","year":"2014","journal-title":"Br J Haematol"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.1182\/blood.V99.12.4618","article-title":"Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction","volume":"99","year":"2002","journal-title":"Blood"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1200\/JCO.2015.63.3826","article-title":"Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission?","volume":"34","year":"2016","journal-title":"J Clin Oncol"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/sj.bmt.1702504","article-title":"Pronogstic value of hematopoietic chimerism in patients with acute leukemia after allogeneic bone marrow transplantation: a prospective study","volume":"26","year":"2000","journal-title":"Bone Marrow Transplant"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/sj.leu.2403719","article-title":"Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation","volume":"19","year":"2005","journal-title":"Leukemia"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/sj.leu.2402761","article-title":"Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Tuebingen experience","volume":"17","year":"2003","journal-title":"Leukemia"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4161\/chim.25400","article-title":"Detection and quantification of chimerism by droplet digital PCR","volume":"4","year":"2013","journal-title":"Chimerism"},{"key":"ref221","first-page":"S1083-8791(18)30322-7","article-title":"Outcomes of measurable residual disease in pediatric acute myeloid leukemia pre- and post-hematopoietic stem cell transplant: validation of difference from normal flow cytometry with chimerism studies and Wilms tumor 1 gene expression","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.exphem.2015.02.006","article-title":"Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation","volume":"43","year":"2015","journal-title":"Exp Hematol"},{"key":"ref171","first-page":"399","article-title":"Graft-versus-host disease after donor leukocyte infusions: presentation and management","volume":"38","year":"2008","journal-title":"Best Pract Res Clin Haematol"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.bbmt.2014.05.026","article-title":"Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for acute lymphoblastic leukemia","volume":"20","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1016\/j.bbmt.2015.07.005","article-title":"Mixed T lymphocyte chimerism after allogeneic hematopoietic transplantation is predictive for relapse of acute myeloid leukemia and myelodysplastic syndromes","volume":"21","year":"2015","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref121","article-title":"Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation","year":"2018","journal-title":"Bone Marrow Transplant"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.bbmt.2014.05.026","article-title":"Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for acute lymphoblastic leukemia","volume":"20","year":"2014","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1515\/cclm-2016-0900","article-title":"Early mixed hematopoietic chimerism detection by digital droplet PCR in patients undergoing gender-mismatched hematopoietic stem cell transplantation","volume":"55","year":"2017","journal-title":"Clin Chem Lab Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.1182\/blood.V99.12.4618","article-title":"Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction","volume":"99","year":"2002","journal-title":"Blood"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.3892\/mmr.2016.5593","article-title":"A technical application of quantitative next generation sequencing for chimerism evaluation","volume":"14","year":"2016","journal-title":"Mol Med Rep"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.exphem.2015.02.006","article-title":"Digital PCR to assess hematopoietic chimerism after allogeneic stem cell transplantation","volume":"43","year":"2015","journal-title":"Exp Hematol"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1365-2141.1994.tb05039.x","article-title":"Aplasia after donor lymphocyte infusion (DLI) for CML in relapse after sex-mismatched BMT: recovery of donor-type haemopoiesis predicted by non-isotopic in situ hybridization (ISH)","volume":"88","year":"1994","journal-title":"Br J Haematol"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1200\/JCO.2009.22.4865","article-title":"Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study","volume":"27","year":"2009","journal-title":"J Clin Oncol"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/bjh.12792","article-title":"Relapse kinetics in acute myeloid leukemias with MLL translocations or partial tandem duplications within the MLL gene","volume":"165","year":"2014","journal-title":"Br J Haematol"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4161\/chim.25400","article-title":"Detection and quantification of chimerism by droplet digital PCR","volume":"4","year":"2013","journal-title":"Chimerism"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1365-2141.1994.tb05039.x","article-title":"Aplasia after donor lymphocyte infusion (DLI) for CML in relapse after sex-mismatched BMT: recovery of donor-type haemopoiesis predicted by non-isotopic in situ hybridization (ISH)","volume":"88","year":"1994","journal-title":"Br J Haematol"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1182\/blood-2007-08-104745","article-title":"Reduced-toxicity conditioning with fludarabine, BCNU and melphalan in allogeneic cell transplantation: particular activity against advanced hematologic malignancies","volume":"112","year":"2008","journal-title":"Blood"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1365-2141.2008.07488.x","article-title":"Monitoring minimal residual disease in acute myeloid leukaemia with NPM1 mutations by quantitative PCR: clonal evolution is a limiting factor","volume":"144","year":"2009","journal-title":"Br J Haematol"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/sj.leu.2402761","article-title":"Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Tuebingen experience","volume":"17","year":"2003","journal-title":"Leukemia"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s00277-016-2623-0","article-title":"Sensitive and accurate quantification of JAK2 V617F mutation in chronic myeloproliferative neoplasms by droplet digital PCR","volume":"95","year":"2016","journal-title":"Ann Hematol"},{"key":"ref391","first-page":"399","article-title":"Graft-versus-host disease after donor leukocyte infusions: presentation and management","volume":"38","year":"2008","journal-title":"Best Pract Res Clin Haematol"},{"key":"ref341","article-title":"Diagnostic value of highly-sensitive chimerism analysis after allogeneic stem cell transplantation","year":"2018","journal-title":"Bone Marrow Transplant"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/sj.bmt.1702504","article-title":"Pronogstic value of hematopoietic chimerism in patients with acute leukemia after allogeneic bone marrow transplantation: a prospective study","volume":"26","year":"2000","journal-title":"Bone Marrow Transplant"},{"key":"ref01","first-page":"S1083-8791(18)30322-7","article-title":"Outcomes of measurable residual disease in pediatric acute myeloid leukemia pre- and post-hematopoietic stem cell transplant: validation of difference from normal flow cytometry with chimerism studies and Wilms tumor 1 gene expression","year":"2018","journal-title":"Biol Blood Marrow Transplant"},{"key":"ref311","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/sj.leu.2403719","article-title":"Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation","volume":"19","year":"2005","journal-title":"Leukemia"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1515\/cclm-2016-0900","article-title":"Early mixed hematopoietic chimerism detection by digital droplet PCR in patients undergoing gender-mismatched hematopoietic stem cell transplantation","volume":"55","year":"2017","journal-title":"Clin Chem Lab Med"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1200\/JCO.2009.22.4865","article-title":"Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study","volume":"27","year":"2009","journal-title":"J Clin Oncol"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1365-2141.2008.07488.x","article-title":"Monitoring minimal residual disease in acute myeloid leukaemia with NPM1 mutations by quantitative PCR: clonal evolution is a limiting factor","volume":"144","year":"2009","journal-title":"Br J Haematol"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.3892\/mmr.2016.5593","article-title":"A technical application of quantitative next generation sequencing for chimerism evaluation","volume":"14","year":"2016","journal-title":"Mol Med Rep"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1200\/JCO.2015.63.3826","article-title":"Allogeneic hematopoietic cell transplantation for acute myeloid leukemia: time to move toward a minimal residual disease-based definition of complete remission?","volume":"34","year":"2016","journal-title":"J Clin Oncol"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s00277-016-2623-0","article-title":"Sensitive and accurate quantification of JAK2 V617F mutation in chronic myeloproliferative neoplasms by droplet digital PCR","volume":"95","year":"2016","journal-title":"Ann Hematol"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/cclm.2019.57.issue-5\/cclm-2018-0827\/cclm-2018-0827.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2018-0827\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T22:41:34Z","timestamp":1619044894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2018-0827\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,24]]},"references-count":40,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1515\/cclm-2018-0827","relation":{},"ISSN":["1437-4331","1434-6621"],"issn-type":[{"value":"1437-4331","type":"electronic"},{"value":"1434-6621","type":"print"}],"subject":[],"published":{"date-parts":[[2019,4,24]]}}}