Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy
We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter t...
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| Veröffentlicht in: | Leukemia 2006-01, Vol.20 (1), p.35-41 |
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| creator | de Botton, S Sanz, M A Chevret, S Dombret, H Martin, G Thomas, X Mediavilla, J D Recher, C Ades, L Quesnel, B Brault, P Fey, M Wandt, H Machover, D Guerci, A Maloisel, F Stoppa, A M Rayon, C Ribera, J M Chomienne, C Degos, L Fenaux, P |
| description | We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age or = 10,000/ mm3) (P or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established. |
| doi_str_mv | 10.1038/sj.leu.2404006 |
| format | Article |
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In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARalpha isoform (P= 0.0003) and high WBC counts (> or = 10,000/ mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P= 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (> or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2404006</identifier><identifier>PMID: 16307026</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Acids ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Chemotherapy ; Combined Modality Therapy ; Disease prevention ; Follow-Up Studies ; Humans ; Leukemia ; Leukemia, Promyelocytic, Acute - diagnosis ; Leukemia, Promyelocytic, Acute - drug therapy ; Medical prognosis ; Nervous system ; Prognosis ; Recurrence ; Risk Factors ; Survival Rate ; Treatment Outcome ; Tretinoin - therapeutic use</subject><ispartof>Leukemia, 2006-01, Vol.20 (1), p.35-41</ispartof><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-e66e84d376f09f07d4e7965790ec110b73210d31524c5c0293d1553f2381c5bb3</citedby><cites>FETCH-LOGICAL-c418t-e66e84d376f09f07d4e7965790ec110b73210d31524c5c0293d1553f2381c5bb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16307026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Botton, S</creatorcontrib><creatorcontrib>Sanz, M A</creatorcontrib><creatorcontrib>Chevret, S</creatorcontrib><creatorcontrib>Dombret, H</creatorcontrib><creatorcontrib>Martin, G</creatorcontrib><creatorcontrib>Thomas, X</creatorcontrib><creatorcontrib>Mediavilla, J D</creatorcontrib><creatorcontrib>Recher, C</creatorcontrib><creatorcontrib>Ades, L</creatorcontrib><creatorcontrib>Quesnel, B</creatorcontrib><creatorcontrib>Brault, P</creatorcontrib><creatorcontrib>Fey, M</creatorcontrib><creatorcontrib>Wandt, H</creatorcontrib><creatorcontrib>Machover, D</creatorcontrib><creatorcontrib>Guerci, A</creatorcontrib><creatorcontrib>Maloisel, F</creatorcontrib><creatorcontrib>Stoppa, A M</creatorcontrib><creatorcontrib>Rayon, C</creatorcontrib><creatorcontrib>Ribera, J M</creatorcontrib><creatorcontrib>Chomienne, C</creatorcontrib><creatorcontrib>Degos, L</creatorcontrib><creatorcontrib>Fenaux, P</creatorcontrib><creatorcontrib>PETHEMA Group</creatorcontrib><creatorcontrib>European APL Group</creatorcontrib><title>Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARalpha isoform (P= 0.0003) and high WBC counts (> or = 10,000/ mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P= 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (> or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.</description><subject>Acids</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Chemotherapy</subject><subject>Combined Modality Therapy</subject><subject>Disease prevention</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Promyelocytic, Acute - diagnosis</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Medical prognosis</subject><subject>Nervous system</subject><subject>Prognosis</subject><subject>Recurrence</subject><subject>Risk Factors</subject><subject>Survival Rate</subject><subject>Treatment Outcome</subject><subject>Tretinoin - therapeutic use</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptks2PFCEQxYnRuOPq1aMhmuytxwIamj5uNutHsokXPROGrrYZ6WYEOuv89zLZSfzIhgMJ_N6jileEvGawZSD0-7zfBly3vIUWQD0hG9Z2qpFSsqdkA1p3jep5e0Fe5LwHOF2q5-SCKQEdcLUh4fZXSXbGYQ3BpiNNGOwhI_ULtW4tSA8pzkcM0R2Ld7S-9QNnb2lJaAsO9N6XidoQmuqy5CovfokVtM4P1C4DdRPOsUyY7OH4kjwbbcj46rxfkm8fbr_efGruvnz8fHN917iW6dKgUqjbQXRqhH6Ebmix65XsekDHGOw6wRkMgkneOumA92JgUoqRC82c3O3EJbl68K3F_1wxFzP77LB2uGBcs1Gd1pz1rIJv_wP3cU1Lrc1wDlIIAF2hdw_QdxvQ-GWMtVd3cjTXTGspGG9FpbaPUHUN9b9cXHD09fwfwdVfggltKFOOYS0-LvlRZ5dizglHc0h-rmEZBuY0BCbvTQ3GnIegCt6cu1p3Ndk_-Dl18RuV4KwB</recordid><startdate>200601</startdate><enddate>200601</enddate><creator>de Botton, S</creator><creator>Sanz, M A</creator><creator>Chevret, S</creator><creator>Dombret, H</creator><creator>Martin, G</creator><creator>Thomas, X</creator><creator>Mediavilla, J D</creator><creator>Recher, C</creator><creator>Ades, L</creator><creator>Quesnel, B</creator><creator>Brault, P</creator><creator>Fey, M</creator><creator>Wandt, H</creator><creator>Machover, D</creator><creator>Guerci, A</creator><creator>Maloisel, F</creator><creator>Stoppa, A M</creator><creator>Rayon, C</creator><creator>Ribera, J M</creator><creator>Chomienne, C</creator><creator>Degos, L</creator><creator>Fenaux, P</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>200601</creationdate><title>Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy</title><author>de Botton, S ; Sanz, M A ; Chevret, S ; Dombret, H ; Martin, G ; Thomas, X ; Mediavilla, J D ; Recher, C ; Ades, L ; Quesnel, B ; Brault, P ; Fey, M ; Wandt, H ; Machover, D ; Guerci, A ; Maloisel, F ; Stoppa, A M ; Rayon, C ; Ribera, J M ; Chomienne, C ; Degos, L ; Fenaux, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-e66e84d376f09f07d4e7965790ec110b73210d31524c5c0293d1553f2381c5bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Acids</topic><topic>Antineoplastic Combined Chemotherapy Protocols - 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Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Botton, S</au><au>Sanz, M A</au><au>Chevret, S</au><au>Dombret, H</au><au>Martin, G</au><au>Thomas, X</au><au>Mediavilla, J D</au><au>Recher, C</au><au>Ades, L</au><au>Quesnel, B</au><au>Brault, P</au><au>Fey, M</au><au>Wandt, H</au><au>Machover, D</au><au>Guerci, A</au><au>Maloisel, F</au><au>Stoppa, A M</au><au>Rayon, C</au><au>Ribera, J M</au><au>Chomienne, C</au><au>Degos, L</au><au>Fenaux, P</au><aucorp>PETHEMA Group</aucorp><aucorp>European APL Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2006-01</date><risdate>2006</risdate><volume>20</volume><issue>1</issue><spage>35</spage><epage>41</epage><pages>35-41</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>We analyzed the incidence, presenting features, risk factors of extramedullary (EM) relapse occurring in acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy by using a competing-risk method. In total, 740/ 806 (92%) patients included in three multicenter trials (APL91, APL93 trials and PETHEMA 96) achieved CR, of whom 169 (23%) relapsed, including 10 EM relapses. Nine relapses involved the central nervous system (CNS) and one the skin, of which two were isolated EM relapse. In patients with EM disease, median WBC count was 26950/mm3 (7700-162000). The 3-year cumulative incidence of EM disease at first relapse was 5.0%. Univariate analysis identified age <45 years (P=0.05), bcr3 PML-RARalpha isoform (P= 0.0003) and high WBC counts (> or = 10,000/ mm3) (P<0.0001) as risk factors for EM relapse. In multivariate analysis, only high WBC count remained significant (P= 0.001). Patients with EM relapse had a poorer outcome since median survival from EM relapse was 6.7 months as compared to 26.3 months for isolated BM relapse (P=0.04). In conclusion, EM relapse in APL occurs more frequently in patients with increased WBC counts (> or = 10,000/mm3) and carries a poor prognosis. Whether CNS prophylaxis should be systematically performed in patients with WBC > or = 10,000/mm3 at diagnosis remains to be established.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>16307026</pmid><doi>10.1038/sj.leu.2404006</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Acids Antineoplastic Combined Chemotherapy Protocols - therapeutic use Chemotherapy Combined Modality Therapy Disease prevention Follow-Up Studies Humans Leukemia Leukemia, Promyelocytic, Acute - diagnosis Leukemia, Promyelocytic, Acute - drug therapy Medical prognosis Nervous system Prognosis Recurrence Risk Factors Survival Rate Treatment Outcome Tretinoin - therapeutic use |
| title | Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy |
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