{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:12:58Z","timestamp":1790583178359,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012353","name":"Deutschen Konsortium f\u00fcr Translationale Krebsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012353","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>The treatment of elderly, nonfit acute myeloid leukemia (AML)\/MDS patients with relapsed\/refractory (R\/R) disease remains challenging. As histone demethylase LSD1 (KDM1A) is a rational therapeutic target in AML, we conducted a phase I trial (\u201crolling\u2010six design\u201d) with the LSD1 inhibitor tranylcypromine (TCP, dose levels [DL] 20, 40, 60, 80\u2009mg p.o. d1\u201028) combined with fixed\u2010dose ATRA (45\u2009mg\/m<jats:sup>2<\/jats:sup> p.o. d10\u201028) and low\u2010dose cytarabine (LDAC, 40\u2009mg\u2009s.c. d1\u201010). The primary endpoint was dose\u2010limiting toxicity (DLT) in the first 28\u2009days of treatment. The aim was the determination of the maximum tolerated TCP dose (MTD). Twenty\u2010three patients with AML and 2 with MDS were accrued. TCP was administered for a median of 39.5\u2009days (range: 11\u2013228). No DLTs were observed at any DL; MTD could not be established. No differentiation syndrome occurred. Two patients attained a PR; SD was achieved in 10 of 22 evaluable patients. Median OS was 62\u2009days (range: 14\u2013325). Accompanying studies included pharmacokinetics, serial determinations of fetal hemoglobin (HbF), detection of CD38 upregulation with treatment, as well as transcriptome changes in purified blood blasts over time. In conclusion, the combination of TCP with ATRA and LDAC was well feasible, even at the highest DL. Hence, studies with more potent LSD1 inhibitors appear warranted.<\/jats:p><jats:p>\n<jats:bold>Trial Registration:<\/jats:bold> German Clinical Trials Register (DRKS): DRKS00006055. For further Information see <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/drks.de\/search\/en\/trial\/DRKS00006055\">https:\/\/drks.de\/search\/en\/trial\/DRKS00006055<\/jats:ext-link>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14426","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T06:41:21Z","timestamp":1748932881000},"page":"266-277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sensitization of Non\u2010<scp>M3<\/scp> Acute Myeloid Leukemia Blasts to All\u2010<i>Trans<\/i> Retinoic Acid by the <scp>LSD1<\/scp> Inhibitor Tranylcypromine: <scp>TRANSATRA<\/scp> Phase I Study"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6785-5747","authenticated-orcid":false,"given":"Michael","family":"Kruszewski","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schmoor","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit Medical Center\u2014University of Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Berg","sequence":"additional","affiliation":[{"name":"Centre for Discovery in Cancer Research, Department of Oncology McMaster University  Hamilton Ontario Canada"},{"name":"Escarpment Cancer Research Institute, Hamilton Health Sciences McMaster University  Hamilton Ontario Canada"},{"name":"Department of Medicine II Hematology\/Oncology Goethe University Frankfurt\/Main  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama\u2010Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Stem Cell Transplantation Medical 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