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


METHODS
We analyzed GVT effects in 322 patients given grafts from HLA-matched related (n = 192) or unrelated donors (n = 130).


RESULTS
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).


CONCLUSIONS
New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning.
Baron
Frédéric
F
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024, USA.
Maris
Michael B
MB
Sandmaier
Brenda M
BM
Storer
Barry E
BE
Sorror
Mohamed
M
Diaconescu
Razvan
R
Woolfrey
Ann E
AE
Chauncey
Thomas R
TR
Flowers
Mary E D
ME
Mielcarek
Marco
M
Maloney
David G
DG
Storb
Rainer
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006084:Graft Rejection; D020350:Graft vs Tumor Effect / Q000187:drug effects* / Q000528:radiation effects; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007938:Leukemia / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011336:Probability; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine