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
Hauptverfasser: 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.
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container_issue 3
container_start_page 903
container_title Blood
container_volume 112
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.
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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 (&gt; 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 (&lt; 30 × 109/L vs &gt; 30 × 109/L) and disease status (CR1 vs &gt; CR1). The median time to relapse for CR1 and for beyond CR1 patients was 12 months and 9 months, respectively. 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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&amp;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 (&gt; 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 (&lt; 30 × 109/L vs &gt; 30 × 109/L) and disease status (CR1 vs &gt; 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. 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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 (&gt; 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 (&lt; 30 × 109/L vs &gt; 30 × 109/L) and disease status (CR1 vs &gt; 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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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
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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