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

Research paper by Frédéric F Baron, Michael B MB Maris, Brenda M BM Sandmaier, Barry E BE Storer, Mohamed M Sorror, Razvan R Diaconescu, Ann E AE Woolfrey, Thomas R TR Chauncey, Mary E D ME Flowers, Marco M Mielcarek, David G DG Maloney, Rainer R Storb

Indexed on: 19 Mar '05Published on: 19 Mar '05Published in: Journal of clinical oncology : official journal of the American Society of Clinical Oncology



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.

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