{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:36:37Z","timestamp":1761597397029},"reference-count":17,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Programmed cell death\u20101 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101) is involved in one of the inhibitory pathways of the B7\u2010cluster of differentiation (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>) 28 family; this pathway is known to be involved in the attenuation of T\u2010cell responses and promotion of T\u2010cell tolerance. <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 is known to negatively regulate T\u2010cell receptor\u2010mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\u2010positive cells in follicular lymphoma (<jats:styled-content style=\"fixed-case\">FL<\/jats:styled-content>) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 positivity in the rituximab era (R\u2010era) has not yet been elucidated. We retrospectively studied 82 patients with <jats:styled-content style=\"fixed-case\">FL<\/jats:styled-content> uniformly treated with standard <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content> therapy at six institutions between 2001 and 2009 (median follow\u2010up for survivors: 55\u00a0months). We also collected and examined biopsy specimens for diagnosis with respect to <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 positivity. The <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 positivity was significantly higher in male patients and patients with high beta\u20102 microglobulin (B2M\u00a0\u2265\u00a03.0) (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.03 and 0.003, respectively). Three\u2010year progression free survival (<jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>) and overall survival (<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>) were 60% and 86%, respectively. By univariate analysis, elevated <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.07) worsened <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>. Male gender (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.03), high <jats:styled-content style=\"fixed-case\">FLIPI<\/jats:styled-content> score (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.05), and high B2M levels (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.08) worsened <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>. Multivariate analysis detected no significant prognostic factors, including <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 positivity. However, in male subgroup, high levels of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\u2010positive cells were found to be a prognostic factor for <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>. Addition of rituximab might have altered the prognostic impact of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101\u2010positive cells.<\/jats:p>","DOI":"10.1111\/ejh.12075","type":"journal-article","created":{"date-parts":[[2013,1,19]],"date-time":"2013-01-19T07:22:36Z","timestamp":1358580156000},"page":"286-290","source":"Crossref","is-referenced-by-count":22,"title":["Prognostic significance of programmed cell death\u20101\u2010positive cells in follicular lymphoma patients may alter in the rituximab era"],"prefix":"10.1111","volume":"90","author":[{"given":"Hiroyuki","family":"Takahashi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Tomita","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Yokohama City 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