Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium
dc.contributor.author | Messinger, Yoav | en_US |
dc.contributor.author | Gaynon, Paul S. | en_US |
dc.contributor.author | Raetz, Elizabeth | en_US |
dc.contributor.author | Hutchinson, Raymond J. | en_US |
dc.contributor.author | DuBois, Steven | en_US |
dc.contributor.author | Glade-Bender, Julia | en_US |
dc.contributor.author | Sposto, Richard | en_US |
dc.contributor.author | van der Giessen, Jeannette | en_US |
dc.contributor.author | Eckroth, Elena | en_US |
dc.contributor.author | Bostrom, Bruce C. | en_US |
dc.date.accessioned | 2010-07-06T14:28:26Z | |
dc.date.available | 2011-03-01T16:26:45Z | en_US |
dc.date.issued | 2010-08 | en_US |
dc.identifier.citation | Messinger, Yoav; Gaynon, Paul; Raetz, Elizabeth; Hutchinson, Raymond; DuBois, Steven; Glade-Bender, Julia; Sposto, Richard; van der Giessen, Jeannette; Eckroth, Elena; Bostrom, Bruce C. (2010). "Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium." Pediatric Blood & Cancer 55(2): 254-259. <http://hdl.handle.net/2027.42/77437> | en_US |
dc.identifier.issn | 1545-5009 | en_US |
dc.identifier.issn | 1545-5017 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/77437 | |
dc.description.abstract | Background Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies. Procedure This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4-drug induction chemotherapy with vincristine, dexamethasone, pegylated L -asparaginase, and doxorubicin (VXLD) in children with relapsed ALL. Results Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1 mg/m 2 ). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose-limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3 mg/m 2 ). One patient had dose-limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia. Conclusions The combination of bortezomib (1.3 mg/m 2 ) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3 mg/m 2 cohort for a phase II estimate of response. Study registered at ClinicalTrials.gov ( http://clinicaltrials.gov/ct2/show/NCT00440726 ). Pediatr Blood Cancer 2010;55:254–259. © 2010 Wiley-Liss, Inc. | en_US |
dc.format.extent | 100410 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Pediatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan Medical School, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationother | Pediatric Hematology and Oncology, Children's Hospitals and Clinics of Minnesota, St. Paul, Minnesota ; Pediatric Hematology and Oncology, Children's Hospitals and Clinics of Minnesota, 345 N. Smith Avenue, St. Paul, MN 55102. | en_US |
dc.contributor.affiliationother | Division of Hematology/Oncology, University of Southern California, Los Angeles, California | en_US |
dc.contributor.affiliationother | Department of Pediatrics, New York University School of Medicine, New York, New York | en_US |
dc.contributor.affiliationother | Department of Pediatrics, UCSF School of Medicine, San Francisco, California | en_US |
dc.contributor.affiliationother | Pediatric Oncology, Columbia University, New York, New York | en_US |
dc.contributor.affiliationother | Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California | en_US |
dc.contributor.affiliationother | Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California | en_US |
dc.contributor.affiliationother | Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, California | en_US |
dc.contributor.affiliationother | Pediatric Hematology and Oncology, Children's Hospitals and Clinics of Minnesota, Minneapolis, Minnesota | en_US |
dc.identifier.pmid | 20582937 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/77437/1/22456_ftp.pdf | |
dc.identifier.doi | 10.1002/pbc.22456 | en_US |
dc.identifier.source | Pediatric Blood & Cancer | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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