{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:10:14Z","timestamp":1779253814164,"version":"3.51.4"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Myelofibrosis (MF) is a Philadelphia chromosome\u2013negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, constitutional symptoms, cytopenias, and splenomegaly. Splenic enlargement, driven primarily by extramedullary hematopoiesis, represents a hallmark of MF and contributes substantially to symptom burden, portal hypertension, and worsening cytopenias through splenic sequestration. The identification of constitutive Janus kinase\u2013signal transducer and activator of transcription (JAK\u2013STAT) pathway activation as the central pathogenic mechanism in myeloproliferative neoplasms led to the development of JAK inhibitors, which have become the cornerstone of therapy for spleen volume reduction and symptom amelioration. Four JAK inhibitors\u2014ruxolitinib, fedratinib, pacritinib, and momelotinib\u2014are currently approved by regulatory agencies, each exhibiting distinct pharmacological profiles suited to different clinical phenotypes. Ruxolitinib remains the first-line standard for patients with adequate platelet counts, pacritinib is preferred in severe thrombocytopenia, and momelotinib is the agent of choice in anemia-dominant disease. Fedratinib serves as an effective second-line option following ruxolitinib failure. Emerging combination strategies, including pelabresib plus ruxolitinib and navitoclax plus ruxolitinib, have demonstrated superior spleen volume reduction in phase III trials and represent a promising therapeutic frontier. Conventional agents such as hydroxyurea and immunomodulatory drugs retain a role in select patients. Non-pharmacologic interventions\u2014including splenectomy, splenic irradiation, partial splenic artery embolization, and radiofrequency ablation\u2014remain valuable for patients refractory to or ineligible for medical therapy. This review provides a comprehensive and updated overview of the management of splenomegaly in MF, integrating all four approved JAK inhibitors, emerging combination therapies, peri-transplant considerations, and procedural approaches, and proposes a practical phenotype-driven treatment framework.<\/jats:p>","DOI":"10.3389\/fonc.2026.1851781","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:47:40Z","timestamp":1779252460000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Management of splenomegaly in patients with myelofibrosis in the era of JAK inhibitors: a comprehensive review"],"prefix":"10.3389","volume":"16","author":[{"given":"Yousef","family":"Al-Asa\u2019d","sequence":"first","affiliation":[{"name":"Department of Hematology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation","place":["Doha, Qatar"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nabeel","family":"Qasem","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation","place":["Doha, Qatar"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Awni","family":"Alshurafa","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation","place":["Doha, Qatar"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khalil","family":"Al-Farsi","sequence":"additional","affiliation":[{"name":"Hematology Department, National Hematology and Bone Marrow Transplant Center, University Medical City","place":["Muscat, Oman"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A.","family":"Yassin","sequence":"additional","affiliation":[{"name":"Department of Hematology, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation","place":["Doha, Qatar"]},{"name":"College of Medicine, Qatar University","place":["Doha, Qatar"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-04069-4","article-title":"Modern management of splenomegaly in patients with myelofibrosis","volume":"99","author":"Tremblay","year":"2020","journal-title":"Ann Hematol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.163","article-title":"Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study","volume":"27","author":"Tefferi","year":"2013","journal-title":"Leukemia"},{"key":"B3","volume-title":"NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms. 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