Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-4-9
pubmed:abstractText
Prior studies of non-T-cell-depleted (TCD) transplantation have demonstrated a reduction in relapse in patients receiving escalated doses of TBI; however, overall survival in these studies was not significantly improved due to increased treatment-related toxicity seen at the higher doses of irradiation. Toxicity was in part related to an increased incidence of GVHD. Because T-cell depletion of donor bone marrow reduces the incidence of GVHD and other treatment-related complications after allogeneic bone marrow transplantation, it was postulated that TBI dose may be safely escalated in this setting and may decrease the risk of relapse following TCD BMT. Herein, we report the results of a trial assessing the safety and impact of escalated doses of TBI after TCD BMT. Two hundred adults with hematologic malignancies were treated in consecutive cohorts defined by increasing doses of TBI (1400, 1480, and 1560 cGy) in combination with cyclophosphamide. In vitro T-cell depletion using anti-CD6 monoclonal antibody was used for GVHD prophylaxis. The incidence of grade II or greater acute GVHD in patients receiving 1560 cGy (36%) was significantly higher than in patients receiving 1400 cGy (18%) (P = .04) or 1480 cGy (13%) (P = .01). Two-year treatment-related mortality was significantly higher in patients who received 1560 cGy of TBI (33%) than in those who received 1400 cGy (20%) (P = .04) or 1480 cGy (19%) (P = .05). The increased dose of TBI did not reduce the rates of relapse, with the estimated 2-year risk of relapse being 24% (1400 cGy), 24% (1480 cGy), and 31% (1560 cGy) for the 3 cohorts of patients. Overall survival at 2 years was inferior for patients receiving 1560 cGy of TBI (36%) compared with those who received 1400 cGy (55%) or 1480 cGy (58%) (P = .01). We conclude that dose escalation of TBI is associated with increased GVHD and inferior survival following TCD BMT. Future efforts to reduce the risk of relapse after TCD BMT should focus on immunologic methods to induce the graft-versus-leukemia effect after BMT rather than intensification of the ablative regimen by escalation of irradiation dose.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:issn
1083-8791
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
139-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11939603-Adolescent, pubmed-meshheading:11939603-Adult, pubmed-meshheading:11939603-Aged, pubmed-meshheading:11939603-Bone Marrow Transplantation, pubmed-meshheading:11939603-Dose-Response Relationship, Radiation, pubmed-meshheading:11939603-Female, pubmed-meshheading:11939603-Graft vs Host Disease, pubmed-meshheading:11939603-Hematologic Diseases, pubmed-meshheading:11939603-Humans, pubmed-meshheading:11939603-Lymphocyte Depletion, pubmed-meshheading:11939603-Male, pubmed-meshheading:11939603-Middle Aged, pubmed-meshheading:11939603-Recurrence, pubmed-meshheading:11939603-Survival Analysis, pubmed-meshheading:11939603-Survival Rate, pubmed-meshheading:11939603-Transplantation, Isogeneic, pubmed-meshheading:11939603-Treatment Outcome, pubmed-meshheading:11939603-Whole-Body Irradiation
pubmed:year
2002
pubmed:articleTitle
Effect of total body irradiation dose escalation on outcome following T-cell-depleted allogeneic bone marrow transplantation.
pubmed:affiliation
Center for Hematologic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. edwin_alyea@dfci.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't