Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen
Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP...
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Veröffentlicht in: | Blood 2008-08, Vol.112 (3), p.903-909 |
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creator | Laport, Ginna G. Alvarnas, Joseph C. Palmer, Joycelynne M. Snyder, David S. Slovak, Marilyn L. Cherry, Athena M. Wong, Ruby M. Negrin, Robert S. Blume, Karl G. Forman, Stephen J. |
description | Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome. |
doi_str_mv | 10.1182/blood-2008-03-143115 |
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Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2008-03-143115</identifier><identifier>PMID: 18519812</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Benzamides ; Biological and medical sciences ; Child ; Child, Preschool ; Combined Modality Therapy ; Dose Fractionation, Radiation ; Etoposide - therapeutic use ; Female ; Follow-Up Studies ; Hematologic and hematopoietic diseases ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic Stem Cell Transplantation - mortality ; Humans ; Imatinib Mesylate ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; Piperazines - therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy ; Pyrimidines - therapeutic use ; Remission Induction - methods ; Risk Factors ; Siblings ; Survival Analysis ; Transplantation ; Transplantation, Homologous ; Treatment Outcome ; Whole-Body Irradiation</subject><ispartof>Blood, 2008-08, Vol.112 (3), p.903-909</ispartof><rights>2008 American Society of Hematology</rights><rights>2008 INIST-CNRS</rights><rights>2008 by The American Society of Hematology 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-3174c2c4a05ad09c993322ac2a066fdda1d8c9411ed9d37c0a1e915fd5d47863</citedby><cites>FETCH-LOGICAL-c421t-3174c2c4a05ad09c993322ac2a066fdda1d8c9411ed9d37c0a1e915fd5d47863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20548187$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18519812$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laport, Ginna G.</creatorcontrib><creatorcontrib>Alvarnas, Joseph C.</creatorcontrib><creatorcontrib>Palmer, Joycelynne M.</creatorcontrib><creatorcontrib>Snyder, David S.</creatorcontrib><creatorcontrib>Slovak, Marilyn L.</creatorcontrib><creatorcontrib>Cherry, Athena M.</creatorcontrib><creatorcontrib>Wong, Ruby M.</creatorcontrib><creatorcontrib>Negrin, Robert S.</creatorcontrib><creatorcontrib>Blume, Karl G.</creatorcontrib><creatorcontrib>Forman, Stephen J.</creatorcontrib><title>Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen</title><title>Blood</title><addtitle>Blood</addtitle><description>Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Benzamides</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Combined Modality Therapy</subject><subject>Dose Fractionation, Radiation</subject><subject>Etoposide - therapeutic use</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic Stem Cell Transplantation - mortality</subject><subject>Humans</subject><subject>Imatinib Mesylate</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Piperazines - therapeutic use</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy</subject><subject>Pyrimidines - therapeutic use</subject><subject>Remission Induction - methods</subject><subject>Risk Factors</subject><subject>Siblings</subject><subject>Survival Analysis</subject><subject>Transplantation</subject><subject>Transplantation, Homologous</subject><subject>Treatment Outcome</subject><subject>Whole-Body Irradiation</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uk2P0zAQjRCILQv_ACFf4BawnaRNOCChFV9SJTjs3Zrak8bgeILtFnrjP_AP-R9IOG21CxdOljzvvXkz84riseDPhWjli40jMqXkvC15VYq6EqK5UyxEI_MHl_xuseCcL8u6W4mL4kGMnznPKNncLy5E24iuFXJR_F6T35YJw8gCjjZGS55Rzz4N1oFBNw0WmB4CjRRpxF8_fk4UbbJ7ZKB3CZk7jNNAGwcxWc0c7r5kGWDQZ00GztEWPebKgCMkmsjijNPoHEsBfJwc-ARpbtvnLiyj9ICGRbtx1m-ZIU8hvmTAJC8PCIHh9wmDRa-RfbNpYGnATAU9a0DK1EQJHNuQOTAbAhh7lM_WcTYQrcE869aO6B8W93pwER-d38vi-u2b66v35frjuw9Xr9elrqVIZSVWtZa6Bt6A4Z3uuqqSErQEvlz2xoAwre5qIdB0plppDgI70fSmMfWqXVaXxauT7LTbjGg0-jy6U1OwI4SDIrDq34q3g9rSXsm6FU0jssCzs0CgrzuMSeVTzTsEj7SLatlV-f7LOgPrE1AHijFgf9NEcDXHRh1jo-bYKF6pU2wy7cnfBm9J55xkwNMzAKIGl9fttY03OMmb7LRd3U6KeZt7i0FFfTyVsQF1Uobs_538ATz57cU</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Laport, Ginna G.</creator><creator>Alvarnas, Joseph C.</creator><creator>Palmer, Joycelynne M.</creator><creator>Snyder, David S.</creator><creator>Slovak, Marilyn L.</creator><creator>Cherry, Athena M.</creator><creator>Wong, Ruby M.</creator><creator>Negrin, Robert S.</creator><creator>Blume, Karl G.</creator><creator>Forman, Stephen J.</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080801</creationdate><title>Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen</title><author>Laport, Ginna G. ; Alvarnas, Joseph C. ; Palmer, Joycelynne M. ; Snyder, David S. ; Slovak, Marilyn L. ; Cherry, Athena M. ; Wong, Ruby M. ; Negrin, Robert S. ; Blume, Karl G. ; Forman, Stephen J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-3174c2c4a05ad09c993322ac2a066fdda1d8c9411ed9d37c0a1e915fd5d47863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Benzamides</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Combined Modality Therapy</topic><topic>Dose Fractionation, Radiation</topic><topic>Etoposide - therapeutic use</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic Stem Cell Transplantation - mortality</topic><topic>Humans</topic><topic>Imatinib Mesylate</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Piperazines - therapeutic use</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy</topic><topic>Pyrimidines - therapeutic use</topic><topic>Remission Induction - methods</topic><topic>Risk Factors</topic><topic>Siblings</topic><topic>Survival Analysis</topic><topic>Transplantation</topic><topic>Transplantation, Homologous</topic><topic>Treatment Outcome</topic><topic>Whole-Body Irradiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laport, Ginna G.</creatorcontrib><creatorcontrib>Alvarnas, Joseph C.</creatorcontrib><creatorcontrib>Palmer, Joycelynne M.</creatorcontrib><creatorcontrib>Snyder, David S.</creatorcontrib><creatorcontrib>Slovak, Marilyn L.</creatorcontrib><creatorcontrib>Cherry, Athena M.</creatorcontrib><creatorcontrib>Wong, Ruby M.</creatorcontrib><creatorcontrib>Negrin, Robert S.</creatorcontrib><creatorcontrib>Blume, Karl G.</creatorcontrib><creatorcontrib>Forman, Stephen J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laport, Ginna G.</au><au>Alvarnas, Joseph C.</au><au>Palmer, Joycelynne M.</au><au>Snyder, David S.</au><au>Slovak, Marilyn L.</au><au>Cherry, Athena M.</au><au>Wong, Ruby M.</au><au>Negrin, Robert S.</au><au>Blume, Karl G.</au><au>Forman, Stephen J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>112</volume><issue>3</issue><spage>903</spage><epage>909</epage><pages>903-909</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Allogeneic hematopoietic cell transplantation (HCT) is the only known curative modality for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Sixty-seven patients with HLA-matched sibling donors received fractionated total body irradiation (FTBI) and high-dose VP16, whereas 11 patients received FTBI/VP16/cyclophosphamide, and 1 patient received FTBI/VP16/busulfan. The median age was 36 years. At the time of HCT, 49 patients (62%) were in first complete remission (CR1) and 30 patients (38%) were beyond CR1 (> CR1). The median follow-up was 75 months (range, 14-245 months). The 10-year overall survival for the CR1 and beyond CR1 patients was 54% and 29% (P = .01), respectively, and event-free survival was 48% and 26% (P = .02), respectively. There was no significant difference in relapse incidence (28% vs 41%, P = .28), but nonrelapse mortality was significantly higher in the beyond CR1 patients, (31% vs 54%, P = .03, respectively). By univariate analysis, factors affecting event-free and overall survival were white blood cell count at diagnosis (< 30 × 109/L vs > 30 × 109/L) and disease status (CR1 vs > CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. Our results indicate that FTBI/VP16 with or without cyclophosphamide confers long-term survival in Ph+ ALL patients and that disease status at the time of HCT is an important predictor of outcome.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>18519812</pmid><doi>10.1182/blood-2008-03-143115</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Antineoplastic Combined Chemotherapy Protocols - therapeutic use Benzamides Biological and medical sciences Child Child, Preschool Combined Modality Therapy Dose Fractionation, Radiation Etoposide - therapeutic use Female Follow-Up Studies Hematologic and hematopoietic diseases Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic Stem Cell Transplantation - methods Hematopoietic Stem Cell Transplantation - mortality Humans Imatinib Mesylate Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged Piperazines - therapeutic use Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy Pyrimidines - therapeutic use Remission Induction - methods Risk Factors Siblings Survival Analysis Transplantation Transplantation, Homologous Treatment Outcome Whole-Body Irradiation |
title | Long-term remission of Philadelphia chromosome–positive acute lymphoblastic leukemia after allogeneic hematopoietic cell transplantation from matched sibling donors: a 20-year experience with the fractionated total body irradiation–etoposide regimen |
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