{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:55Z","timestamp":1787027815178,"version":"build-2736575974"},"reference-count":86,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Pre-fibrotic myelofibrosis (pre-PMF) is a rare subentity of myeloproliferative neoplasm (MPN) with limited overall survival and the potential for progression toward overt, symptomatic myelofibrosis or blastic transformation. To date, a consensus on the treatment of pre-PMF, especially in asymptomatic cases, has yet to be reached. Interferon therapy has been employed as an effective treatment for MPN for many decades, due to its immunomodulatory properties and disease-modifying effects. Methods: The objective of this monocentric study was to evaluate hematological, molecular, and clinical responses, as well as the overall outcome, to pegylated interferon (peginterferon) in pre-PMF cases harboring a JAK2 or CALR mutation. Results: In a cohort of 55 consecutive patients with a median follow-up period of 3.89 (1.63; 6.10) years, a high rate of complete hematological response (81%) was documented after 24 months. Deep molecular responses with a &gt;50% reduction in allele burden were documented in 54.6% of the JAK2-mutated and 7.7% of CALR-mutated patients, respectively (p = 0.023). Concerning fibrosis, at least the stabilization of disease was achieved in 73% of evaluable patients. Furthermore, only one case of blastic transformation was observed, along with three cases of thromboembolic events in the JAK2-mutated cohort. Conclusions: The study confirms the substantial efficacy of interferon in pre-PMF patients with rapid hematological normalization in most patients. Molecular responses were striking, but largely confined to JAK2-mutated patients. To our knowledge, this is the largest retrospective cohort of strictly WHO-defined pre-PMF patients treated with interferon and observed for a reasonable duration of time.<\/jats:p>","DOI":"10.3390\/cancers17243940","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T14:49:01Z","timestamp":1765291741000},"page":"3940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rapid Hematological and Molecular Response to Pegylated Interferon in WHO-Defined Pre-Fibrotic Myelofibrosis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1247-7948","authenticated-orcid":false,"given":"Sigrid","family":"Machherndl-Spandl","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"},{"name":"Medical 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Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-6849","authenticated-orcid":false,"given":"Otto","family":"Zach","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular and Genetic Diagnostics, Ordensklinikum Linz, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5654-6190","authenticated-orcid":false,"given":"Gerald","family":"Webersinke","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular and Genetic Diagnostics, Ordensklinikum Linz, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gruber-Rossipal","sequence":"additional","affiliation":[{"name":"Department, Institute of Clinical and Molecular Pathology, Ordensklinikum Linz, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Beham-Schmid","sequence":"additional","affiliation":[{"name":"Department, Institute of Clinical and Molecular Pathology, Ordensklinikum Linz, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Maier","sequence":"additional","affiliation":[{"name":"Department, Institute of Clinical and Molecular Pathology, Ordensklinikum Linz, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9649-5850","authenticated-orcid":false,"given":"Irene","family":"Strassl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"},{"name":"Medical Faculty, Johannes Kepler University, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2729-9706","authenticated-orcid":false,"given":"Johannes","family":"Clausen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"},{"name":"Medical Faculty, Johannes Kepler University, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Nikoloudis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"},{"name":"Medical Faculty, Johannes Kepler University, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-066X","authenticated-orcid":false,"given":"Wolfgang","family":"Schimetta","sequence":"additional","affiliation":[{"name":"Department of Applied Systems Research and Statistics, Johannes Kepler University, 4040 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4118-0111","authenticated-orcid":false,"given":"Holger","family":"Rumpold","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"},{"name":"Medical Faculty, Johannes Kepler University, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-9700","authenticated-orcid":false,"given":"Veronika","family":"Buxhofer-Ausch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I: Hematology with Stem-Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz\u2014Elisabethinen, 4020 Linz, Austria"},{"name":"Medical Faculty, Johannes Kepler University, 4020 Linz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1182\/blood-2016-10-695940","article-title":"Genetic basis and molecular pathophysiology of classical myeloproliferative 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