{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:10:06Z","timestamp":1777417806066,"version":"3.51.4"},"reference-count":66,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2002,12,1]],"date-time":"2002-12-01T00:00:00Z","timestamp":1038700800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE:<\/jats:title>\n                    <jats:p>To review the role of all- trans retinoic acid (ATRA) and arsenic trioxide in central nervous system (CNS) relapses of acute promyelocytic leukemia (APL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CASE SUMMARY:<\/jats:title>\n                    <jats:p>A 69-year-old white man diagnosed with APL presented with bleeding diathesis. His molecular and cytogenetic studies were positive for promyelocytic leukemia\u2014retinoic acid receptor\u03b1 (PML-RAR\u03b1) and t(15;17) transformation. Complete molecular and cytogenetic remission was achieved with ATRA, daunorubicin, and cytarabine. Within 6 months, the patient was readmitted for investigation of severe global headaches and an ataxic gait. His peripheral blood and cerebral spinal fluid were positive for PML-RAR\u03b1 fusion protein. Intrathecal chemotherapy and radiation, as well as ATRA, were the main treatment modalities provided. Molecular and cytogenetic remission was again obtained. Three months later, a second relapse occurred in the CNS and the peripheral blood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION:<\/jats:title>\n                    <jats:p>APL is typically treated with anthacycline-based chemotherapy and ATRA. Approximately 85\u201395% of patients achieve complete remission (CR); however, the relapse rate has been reported to be about 30\u201340%. A thorough literature search (MEDLINE, EMBASE, CANCERLIT, 1966\u2013January 2002) revealed only 54 cases of extramedullary disease, of which 35 involved the CNS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The introduction of ATRA has improved patient survival dramatically. APL relapse, in general, has been in part attributable to repetitive or prolonged exposure to ATRA and the possibility of additional chromosomal changes, making the disease more refractory to treat. Given the evidence, one could argue that, with repeated ATRA treatment, CR duration may be shortened. However, limited data are available to guide the appropriate management of APL relapsed to the CNS with either ATRA, chemotherapy, or arsenic trioxide. In our opinion, treatment using arsenic trioxide is an unconventional option worthy of exploring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.1a471","type":"journal-article","created":{"date-parts":[[2003,6,4]],"date-time":"2003-06-04T16:10:08Z","timestamp":1054743008000},"page":"1900-1906","source":"Crossref","is-referenced-by-count":15,"title":["CNS Relapses of Acute Promyelocytic Leukemia after All-\n                    <i>Trans<\/i>\n                    Retinoic Acid"],"prefix":"10.1177","volume":"36","author":[{"given":"Lisa D","family":"Burry","sequence":"first","affiliation":[{"name":"Lisa D Burry BScPhm PharmD, Critical Care Specialist, Education Coordinator, Surgical Clinical Co-ordinator, Mt. 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