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COO is determined by immunohistochemical stains, while molecular features such as double\u2010hit or triple\u2010hit disease are determined by fluorescent in situ hybridization analysis. Commercial tests for frequently recurring mutations are currently not routinely used to inform treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Risk Stratification<\/jats:title>\n                    <jats:p>Clinical prognostic systems for DLBCL, including the rituximab International Prognostic Index, age\u2010adjusted IPI, and NCCN\u2010IPI, use clinical factors for the risk stratification of patients, although this does not affect the treatment approach. Furthermore, DLBCL patients with non\u2010germinal center B\u2010cell (GCB)\u2010like DLBCL (activated B\u2010cell like and unclassifiable) have a poorer response to up\u2010front chemoimmunotherapy (CI) compared to patients with GCB\u2010like DLBCL. Those with c\u2010MYC\u2010altered disease alone and in combination with translocations in BCL2 and\/or BCL6 (particularly when the MYC translocation partner is immunoglobulin) respond poorly to up\u2010front CI and salvage autologous stem cell transplant at relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Risk\u2010Adapted Therapy<\/jats:title>\n                    <jats:p>This review will focus on differential treatment of DLBCL up\u2010front and at the time of relapse by COO and molecular features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajh.25460","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T02:44:59Z","timestamp":1552358699000},"page":"604-616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":413,"title":["Diffuse large B\u2010cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6606-9201","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Fox Chase Cancer Center, Department of Hematology and Oncology Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-5271","authenticated-orcid":false,"given":"Stefan Klaus","family":"Barta","sequence":"additional","affiliation":[{"name":"Perelman Center for Advanced Medicine, University of Pennsylvania, Division Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"SEER.SEER Database: All Lymphoid Neoplasms with Detailed Non\u2010Hodgkin Lymphoma Subtypes; SEERb Incidence Rates and Annual Percent Change by Age at Diagnosis. 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