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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0005953,
umls-concept:C0006142,
umls-concept:C0015020,
umls-concept:C0025344,
umls-concept:C0183683,
umls-concept:C0301944,
umls-concept:C0344211,
umls-concept:C0439859,
umls-concept:C0729078,
umls-concept:C1171411,
umls-concept:C1317973,
umls-concept:C1328050,
umls-concept:C1516213,
umls-concept:C1521721,
umls-concept:C1561960,
umls-concept:C1948053,
umls-concept:C2347804
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pubmed:issue |
11
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pubmed:dateCreated |
1994-6-27
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pubmed:abstractText |
4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty-three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high-dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
83
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
3132-7
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:8193351-Adult,
pubmed-meshheading:8193351-Amifostine,
pubmed-meshheading:8193351-Bone Marrow Purging,
pubmed-meshheading:8193351-Bone Marrow Transplantation,
pubmed-meshheading:8193351-Breast Neoplasms,
pubmed-meshheading:8193351-Combined Modality Therapy,
pubmed-meshheading:8193351-Cyclophosphamide,
pubmed-meshheading:8193351-Female,
pubmed-meshheading:8193351-Hematopoietic Stem Cells,
pubmed-meshheading:8193351-Humans,
pubmed-meshheading:8193351-Transplantation, Autologous
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pubmed:year |
1994
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pubmed:articleTitle |
Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support.
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pubmed:affiliation |
Bone Marrow Transplant Program, University of Colorado, Denver, CO 80262.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Randomized Controlled Trial
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