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PMID: 15774790 Published · ppublish English Journal Article Multicenter Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.

Baron F, Maris MB, Sandmaier BM, Storer BE, Sorror M, Diaconescu R, Woolfrey AE, Chauncey TR, Flowers ME, Mielcarek M, Maloney DG, Storb R

Abstract

We have used a nonmyeloablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy. We analyzed GVT effects in 322 patients given grafts from HLA-matched related (n = 192) or unrelated donors (n = 130). Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD; P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003). New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning.

MeSH Terms
Adolescent Adult Aged Child Child, Preschool Comorbidity Female Graft Rejection Graft vs Tumor Effect/drug effects,radiation effects Hematopoietic Stem Cell Transplantation/methods Humans Immunosuppressive Agents/therapeutic use Leukemia/mortality,therapy Male Middle Aged Probability Transplantation Conditioning/methods Treatment Outcome Vidarabine/analogs & derivatives,therapeutic use
Chemicals
Immunosuppressive Agents Vidarabine fludarabine
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Baron Frédéric
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
Maris Michael B
Sandmaier Brenda M
Storer Barry E
Sorror Mohamed
Diaconescu Razvan
Woolfrey Ann E
Chauncey Thomas R
Flowers Mary E D
Mielcarek Marco
Maloney David G
Storb Rainer
Article Info
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Abbr.
J Clin Oncol
ISSN
0732-183X
Published
2005-03-20
Pages
1993-2003
Language
English
Region
United States
NLM ID
8309333
Subset
IM
Grants
NCI NIH HHS · CA18029 · United States
NHLBI NIH HHS · HL36444 · United States
NCI NIH HHS · CA78902 · United States
NCI NIH HHS · CA92058 · United States
NIDDK NIH HHS · DK064715 · United States
NCI NIH HHS · CA15704 · United States
NCI NIH HHS · P01 CA078902 · United States
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