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18-03-2013 | Immunology | Article

Allogeneic HCT feasible in patients with advanced hematologic malignancies

Abstract

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medwireNews: Allogeneic hematopoietic cell transplantation (HCT) relying on graft-versus-tumor (GVT) effects is a feasible treatment regimen for patients with advanced hematologic malignancies who cannot tolerate high-intensity regimens, report researchers.

However, the investigators note that the beneficial GVT effects associated with graft-versus-host disease (GVHD) were offset by increased non-relapse mortality (NRM).

"Major efforts should be directed toward methods that control progression of malignant disease early after HCT and more effectively prevent clinically significant GVHD," they write.

Rainer Storb (Fred Hutchinson Cancer Research Center, Seattle, Washington) and team investigated the GVT effects of a minimal-intensity conditioning regimen for allogeneic HCT. The study included 1092 patients (median age 56 years) with advanced hematologic malignancies who were unable to tolerate high-intensity regimens because of their age, serious comorbidities, or previous high-dose HCT.

The patients received low-dose total body irradiation with (n=840) or without (n=222) fludarabine 30 mg/m2 per day on days 4, 3, and 2 before HCT from HLA-matched related (n=611) or unrelated (n=481) donors.

As reported in the Journal of Clinical Oncology, sustained engraftment was observed in 96% of the patients.

Lasting remissions were observed in between 45% and 75% of the patients, and 5-year survival ranged from 25% to 60%. These differences were largely influenced by comorbid conditions, disease risk, and GVHD, the researchers say.

The 5-year NRM rate was 24% and the relapse mortality rate was 34.5%. Most relapses occurred early while the immune system was compromised.

The researchers note that most NRM was the result of GVHD, and that the most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors.

It was observed that heightened GVT effects among the patients were associated with chronic, but not acute GVHD. "Reducing or eliminating clinically significant acute GVHD would, therefore, not be expected to increase the risk of relapse," say Storb et al.

"Effective prevention of chronic GVHD would decrease NRM but increase mortality related to relapse or progression," they add. "Although the resultant trading of one cause of death for another would not change overall mortality, effective prevention would avert the considerable morbidity associated with chronic GCHD and its treatment."

They suggest that improved cure rates could emerge from approaches that delay disease progression until the grafted immune system has recovered sufficiently to generate GVT effects.

By Nikki Withers, medwireNews Reporter

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