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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
2001-7-18
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pubmed:abstractText |
Conventional allografting produces considerable regimen-related toxicities that generally limit this treatment to patients younger than 55 years and in otherwise good medical condition. T cell-mediated graft-versus-tumor (GVT) effects are known to play an important role in the elimination of malignant disease after allotransplants. A minimally myelosuppressive regimen that relies on immunosuppression for allogeneic engraftment was developed to reduce toxicities while optimizing GVT effects. Pre-transplant total-body irradiation (200 cGy) followed by post-transplant immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) permitted human leukocyte antigen (HLA)-matched sibling donor hematopoietic cell engraftment in 82% of patients (n = 55) without prior high-dose therapy. The addition of fludarabine (90 mg/m2) facilitated engraftment in all 28 subsequent patients. Overall, fatal progression of underlying disease occurred in 20% of patients after transplant. Non-relapse mortality occurred in 11% of patients. Toxicities were low. Grade 2-4 acute graft-versus-host disease (GVHD) associated with primary engraftment developed in 47% of patients, and was readily controlled in all but two patients. Donor lymphocyte infusions (DLI) were not very effective at converting a low degree of mixed donor/host chimerism to full donor chimerism; however, the addition of fludarabine reduced the need for DLI. With a median follow-up of 244 days, 68% of patients were alive, with 42% of patients in complete remission, including molecular remissions. Remissions occurred gradually over periods of weeks to a year. If long-term efficacy is demonstrated, such a strategy would expand treatment options for patients who would otherwise be excluded from conventional allografting.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0077-8923
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pubmed:author |
pubmed-author:BlumeK GKG,
pubmed-author:ChaunceyTT,
pubmed-author:FeinsteinLL,
pubmed-author:FlowersCC,
pubmed-author:GeorgesGG,
pubmed-author:KingJ WJWJr,
pubmed-author:LittleM TMT,
pubmed-author:MaloneyDD,
pubmed-author:MarinFF,
pubmed-author:McSweeneyP APA,
pubmed-author:NashR ARA,
pubmed-author:NiederwieserDD,
pubmed-author:RadicaAA,
pubmed-author:SandmaierBB,
pubmed-author:ShizuruJJ,
pubmed-author:StorbRR,
pubmed-author:WoolfreyAA,
pubmed-author:ZauchaJ MJM
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pubmed:issnType |
Print
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pubmed:volume |
938
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
328-37; discussion 337-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11458521-Adult,
pubmed-meshheading:11458521-Animals,
pubmed-meshheading:11458521-Clinical Trials, Phase I as Topic,
pubmed-meshheading:11458521-Clinical Trials, Phase II as Topic,
pubmed-meshheading:11458521-Cyclosporine,
pubmed-meshheading:11458521-Disease Progression,
pubmed-meshheading:11458521-Dogs,
pubmed-meshheading:11458521-Forecasting,
pubmed-meshheading:11458521-Graft Enhancement, Immunologic,
pubmed-meshheading:11458521-Graft Survival,
pubmed-meshheading:11458521-Graft vs Host Disease,
pubmed-meshheading:11458521-Graft vs Tumor Effect,
pubmed-meshheading:11458521-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:11458521-Histocompatibility,
pubmed-meshheading:11458521-Humans,
pubmed-meshheading:11458521-Immunosuppressive Agents,
pubmed-meshheading:11458521-Lymphocyte Transfusion,
pubmed-meshheading:11458521-Methotrexate,
pubmed-meshheading:11458521-Middle Aged,
pubmed-meshheading:11458521-Mycophenolic Acid,
pubmed-meshheading:11458521-Neoplasms,
pubmed-meshheading:11458521-Prednisone,
pubmed-meshheading:11458521-Radiation Chimera,
pubmed-meshheading:11458521-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:11458521-Tissue Donors,
pubmed-meshheading:11458521-Transplantation, Homologous,
pubmed-meshheading:11458521-Transplantation Conditioning,
pubmed-meshheading:11458521-Treatment Outcome,
pubmed-meshheading:11458521-Vidarabine,
pubmed-meshheading:11458521-Whole-Body Irradiation
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pubmed:year |
2001
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pubmed:articleTitle |
Nonmyeloablative hematopoietic cell transplantation. Replacing high-dose cytotoxic therapy by the graft-versus-tumor effect.
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pubmed:affiliation |
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., D1-100, P.O. Box 19024, Seattle, Washington 98109-1024, USA. lfeinste@fhcrc.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Review
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