NEW YORK (Reuters Health) – Even without conventional conditioning and cytoxic chemotherapy, an allogeneic hematopoietic cell transplant (HCT) can have a substantial benefit in patients with advanced hematologic malignancies.

That finding comes from a multicenter study of patients who were unable to tolerate high-intensity regimens for various reasons and who received an allogeneic HTC with minimal conditioning. “Allogeneic HCT relying on GVT (graft-versus-tumor) effects is feasible and results in cures of an appreciable number of malignancies,” the researchers found.

Dr. Rainer Storb, at the Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues explain in the Journal of Clinical Oncology online March 11 that graft-versus-tumor effects of allogeneic transplantation have been known for several years. The minimal-intensity conditioning regimen they developed allowed them to examine the inherent GVT effects of allogeneic HCT, as well as graft-versus-host disease (GVHD) uncomplicated by regimen-related toxicities.

For their study, the team analyzed outcomes in 1092 patients, median age 52 years, with advanced hematologic malignancies who received an HCT from an HLA-matched related or unrelated donor. The patients received only low-dose whole-body irradiation with or without fludarabine before the transplant, and immunosuppression post-transplant with mycophenolate mofetil plus a calcineurin inhibitor.

The regimen “avoids serious toxicities and lacks profound cytotoxic antitumor activities,” the authors point out. “Its main role is to enable sustained allogeneic engraftment, which was accomplished in 96% of patients, thereby setting in motion immunologic GVT effects.”

Depending on disease risk group, 5-year survival ranged from 25% to 60%, according to the report. Overall, at 5 years, the relapse-related mortality rate was 34.5% while the non-relapse mortality rate was 24%.

Nearly all instances of progression or relapse occurred within the first 2 years after transplantation. The investigators attribute this to a blunting of GVT effects by post-transplant immunosuppression. Later tapering of immunosuppressive drugs allowed the donor immune cells control tumor progression.

The majority of non-relapse deaths were the results of GVHD, which was associated with grafts from unrelated donors and the presence of serious comorbidities. On the other hand, chronic GVHD was associated with lower risk of relapse or progression, the researchers report, but this potential benefit was offset by increased non-relapse mortality.

Given these findings, Dr. Storb and colleagues conclude: “Major efforts should be directed toward methods that control progression of malignant disease early after HCT and more effectively prevent clinically significant GVHD.”

SOURCE: Graft-Versus-Host Disease and Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation
J Clin Oncol 2013;31.