Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation
A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a c...
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| Veröffentlicht in: | Leukemia 2003-11, Vol.17 (11), p.2178-2182 |
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| creator | VENDITTI, A MAURILLO, L PICARDI, A FRANCHI, A COCO, F. L AMADORI, S BUCCISANO, F DEL POETA, G MAZZONE, C TAMBURINI, A DEL PRINCIPE, M. I CONSALVO, Ml DE FABRITIIS, P CUDILLO, L |
| description | A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse. |
| doi_str_mv | 10.1038/sj.leu.2403138 |
| format | Article |
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L ; AMADORI, S ; BUCCISANO, F ; DEL POETA, G ; MAZZONE, C ; TAMBURINI, A ; DEL PRINCIPE, M. I ; CONSALVO, Ml ; DE FABRITIIS, P ; CUDILLO, L</creator><creatorcontrib>VENDITTI, A ; MAURILLO, L ; PICARDI, A ; FRANCHI, A ; COCO, F. L ; AMADORI, S ; BUCCISANO, F ; DEL POETA, G ; MAZZONE, C ; TAMBURINI, A ; DEL PRINCIPE, M. I ; CONSALVO, Ml ; DE FABRITIIS, P ; CUDILLO, L</creatorcontrib><description>A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2403138</identifier><identifier>PMID: 14576731</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Acute Disease ; Acute myeloid leukemia ; Adult ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Autografts ; Biological and medical sciences ; Chemotherapy ; Combined Modality Therapy ; Etoposide - administration & dosage ; Female ; Flow cytometry ; Hematologic and hematopoietic diseases ; Humans ; Idarubicin - administration & dosage ; Immunophenotyping ; Leukemia ; Leukemia, Myeloid - drug therapy ; Leukemia, Myeloid - mortality ; Leukemia, Myeloid - therapy ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Leukocyte Count ; Longitudinal Studies ; Male ; Medical sciences ; Middle Aged ; Minimal residual disease ; Mitoxantrone - administration & dosage ; Multivariate analysis ; Neoplasm, Residual - diagnosis ; Patients ; Predictive Value of Tests ; Probability ; Recurrence ; Remission ; Risk Assessment ; Risk groups ; Stem Cell Transplantation ; Stem cells ; Survival Analysis ; Time Factors ; Transplantation ; Transplantation, Autologous ; Treatment Outcome</subject><ispartof>Leukemia, 2003-11, Vol.17 (11), p.2178-2182</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Nov 2003</rights><rights>Nature Publishing Group 2003.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-db7430260bbf9828144be9392a23dba8a76916b732b178ea92f2a2f4b0b2c6c13</citedby><cites>FETCH-LOGICAL-c400t-db7430260bbf9828144be9392a23dba8a76916b732b178ea92f2a2f4b0b2c6c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2728,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15232814$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14576731$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VENDITTI, A</creatorcontrib><creatorcontrib>MAURILLO, L</creatorcontrib><creatorcontrib>PICARDI, A</creatorcontrib><creatorcontrib>FRANCHI, A</creatorcontrib><creatorcontrib>COCO, F. L</creatorcontrib><creatorcontrib>AMADORI, S</creatorcontrib><creatorcontrib>BUCCISANO, F</creatorcontrib><creatorcontrib>DEL POETA, G</creatorcontrib><creatorcontrib>MAZZONE, C</creatorcontrib><creatorcontrib>TAMBURINI, A</creatorcontrib><creatorcontrib>DEL PRINCIPE, M. I</creatorcontrib><creatorcontrib>CONSALVO, Ml</creatorcontrib><creatorcontrib>DE FABRITIIS, P</creatorcontrib><creatorcontrib>CUDILLO, L</creatorcontrib><title>Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation</title><title>Leukemia</title><addtitle>Leukemia</addtitle><description>A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse.</description><subject>Acute Disease</subject><subject>Acute myeloid leukemia</subject><subject>Adult</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Autografts</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Combined Modality Therapy</subject><subject>Etoposide - administration & dosage</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Idarubicin - administration & dosage</subject><subject>Immunophenotyping</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid - drug therapy</subject><subject>Leukemia, Myeloid - mortality</subject><subject>Leukemia, Myeloid - therapy</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Leukocyte Count</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Minimal residual disease</subject><subject>Mitoxantrone - administration & dosage</subject><subject>Multivariate analysis</subject><subject>Neoplasm, Residual - diagnosis</subject><subject>Patients</subject><subject>Predictive Value of Tests</subject><subject>Probability</subject><subject>Recurrence</subject><subject>Remission</subject><subject>Risk Assessment</subject><subject>Risk groups</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Survival Analysis</subject><subject>Time Factors</subject><subject>Transplantation</subject><subject>Transplantation, Autologous</subject><subject>Treatment Outcome</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kUuLFDEUhQtRnHZ0604Jiu6qzaOeSxl8wYAudF0kqVvdaVNJmcdI_zN_nrfp0gbBRUjgfLn3cE5RPGV0y6jo3sTD1kLe8ooKJrp7xYZVbVPWdc3uFxvadW3Z9Ly6Kh7FeKD0JDYPiytW1W3TCrYpfn0JkIJ0cbHSJTIbZ2ZpSYBoxoyP0USQEYiFO7BkCTAanSLRFkGNus9J-xmIcWSRyYBD8adJeyJ1TkDmI1hvRvyev8NsJA7WYO6M25G92e3L0eNsvYfZpz0EuRyJdCOROXnrdz5HEhPMRIO15OIS93j3uHgwSRvhyXpfF9_ev_t687G8_fzh083b21JXlKZyVG0lKG-oUlPf8Y5VlYJe9FxyMSrZybbpWaNawRVrO5A9n1CaKkUV141m4rp4fZ67BP8jQ0zDbOLJkHSABoeWCVrjQfDlP-DB5-DQ28AbzJthJx1SL_5LcVrXHXpDaHuGdPAxBpiGJWAt4TgwOpxqH-JhwEiHtXb88HydmtUM4wVfe0bg1QrIiLVNmKU28cLVXJyyQe7ZmXMy5QB_gT-LfgO4EcSQ</recordid><startdate>20031101</startdate><enddate>20031101</enddate><creator>VENDITTI, A</creator><creator>MAURILLO, L</creator><creator>PICARDI, A</creator><creator>FRANCHI, A</creator><creator>COCO, F. 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L ; AMADORI, S ; BUCCISANO, F ; DEL POETA, G ; MAZZONE, C ; TAMBURINI, A ; DEL PRINCIPE, M. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Leukocyte Count</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Minimal residual disease</topic><topic>Mitoxantrone - administration & dosage</topic><topic>Multivariate analysis</topic><topic>Neoplasm, Residual - diagnosis</topic><topic>Patients</topic><topic>Predictive Value of Tests</topic><topic>Probability</topic><topic>Recurrence</topic><topic>Remission</topic><topic>Risk Assessment</topic><topic>Risk groups</topic><topic>Stem Cell Transplantation</topic><topic>Stem cells</topic><topic>Survival Analysis</topic><topic>Time Factors</topic><topic>Transplantation</topic><topic>Transplantation, Autologous</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VENDITTI, A</creatorcontrib><creatorcontrib>MAURILLO, L</creatorcontrib><creatorcontrib>PICARDI, A</creatorcontrib><creatorcontrib>FRANCHI, A</creatorcontrib><creatorcontrib>COCO, F. 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L</au><au>AMADORI, S</au><au>BUCCISANO, F</au><au>DEL POETA, G</au><au>MAZZONE, C</au><au>TAMBURINI, A</au><au>DEL PRINCIPE, M. I</au><au>CONSALVO, Ml</au><au>DE FABRITIIS, P</au><au>CUDILLO, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation</atitle><jtitle>Leukemia</jtitle><addtitle>Leukemia</addtitle><date>2003-11-01</date><risdate>2003</risdate><volume>17</volume><issue>11</issue><spage>2178</spage><epage>2182</epage><pages>2178-2182</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>14576731</pmid><doi>10.1038/sj.leu.2403138</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acute Disease Acute myeloid leukemia Adult Antineoplastic Combined Chemotherapy Protocols - therapeutic use Autografts Biological and medical sciences Chemotherapy Combined Modality Therapy Etoposide - administration & dosage Female Flow cytometry Hematologic and hematopoietic diseases Humans Idarubicin - administration & dosage Immunophenotyping Leukemia Leukemia, Myeloid - drug therapy Leukemia, Myeloid - mortality Leukemia, Myeloid - therapy Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Leukocyte Count Longitudinal Studies Male Medical sciences Middle Aged Minimal residual disease Mitoxantrone - administration & dosage Multivariate analysis Neoplasm, Residual - diagnosis Patients Predictive Value of Tests Probability Recurrence Remission Risk Assessment Risk groups Stem Cell Transplantation Stem cells Survival Analysis Time Factors Transplantation Transplantation, Autologous Treatment Outcome |
| title | Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation |
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