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ABMT Recommended for Relapsed Hodgkin's Disease, But Better Overall Survival Not Yet Proved

ABMT Recommended for Relapsed Hodgkin's Disease, But Better Overall Survival Not Yet Proved

The bulk of available evidence has made a persuasive case for early bone marrow transplantation as the treatment of choice for patients with relapsed Hodgkin's disease, Philip J. Bierman, MD, said at a lymphoma conference sponsored by the University of Texas M.D. Anderson Cancer Center.

However, Dr. Bierman's confidence in autologous bone marrow transplantation (ABMT) hinges on an important caveat: The procedure has not been shown to improve overall survival.

"In most clinical situations, the failure-free survival following high-dose therapy with ABMT for Hodgkin's disease is superior to conventional dose salvage chemotherapy," he said, "but transplantation's ability to improve overall survival has not been demonstrated. However, at our institution, we recommend transplantation for any patient who has relapsed after chemotherapy."

To date, only a single randomized trial has compared ABMT with conventional salvage therapy for relapsed Hodg-kin's disease. This trial was conducted by the British National Lymphoma Investigation and was stopped early after accrual of only 40 patients due to improved outcome in the patients receiving high-dose therapy, said Dr. Bierman, associate professor of medicine, University of Nebraska.

Conventional Salvage Chemo

Conventional salvage chemotherapy has produced unspectacular results in a number of studies, Dr. Bierman said. National Cancer Institute investigators have reported 24% long-term survival among patients who had initial remissions of 12 months or more after MOPP therapy and were treated with MOPP-based therapy in relapse. Among patients with shorter remissions, only about 10% survived long term, Dr. Bierman said.

The best reported results have come from an Italian study showing a 46% long-term failure-free survival in patients who had long initial remissions and then were treated at relapse with MOPP, ABVD, or a combination of the two. However, Dr. Bierman noted that the study excluded patients who developed secondary leukemias or who had cardiac or pulmonary deaths.

In general, other studies of conventional salvage chemotherapy have found long-term failure-free survival in no more than 25% to 30% of patients, with much worse results in patients with short initial remissions or induction failure.

Radiation Results

Good results have been achieved with radiation therapy, but in relatively small numbers of patients, some of whom also received chemotherapy. In five published studies with about 100 patients total, complete responses rates have ranged as high as 92%. Disease-free survival at 5 years has ranged between 24% and 50%.

The best results have occurred in patients with initial remissions exceeding a year and in those without extranodal disease. "If you wanted to argue, you could say that the disease-free survival results with radiation therapy have been as good as any salvage therapy or, in fact, as good as bone marrow transplantation," Dr. Bierman said.

Survival With ABMT

Studies of high-dose salvage therapy with ABMT or peripheral blood stem cell support have shown encouraging results, he said. At the University of Nebraska, 5-year failure-free survival is 40% among 85 patients. British investigators have reported a 47% long-term failure-free survival, including 57% in patients with long initial remissions and 41% in patients with short initial remissions.

Stanford researchers have reported a 60% progression-free survival in patients treated with ABMT after relapse or failure to achieve remission, compared with 30% for another group treated with conventional chemotherapy. Overall survival favored the transplant group (55% vs 46%) but did not reach statistical significance, Dr. Bierman said.

The best results have come from a Vancouver study that showed an 80% to 85% failure-free survival in patients with long initial remissions. Overall, two thirds of the 57 patients remained failure free at 7 years. "These results are clearly better than anything that has ever been reported in the literature," Dr. Bierman commented.

ABMT in Hodgkin's Disease Patients With Induction Failure

Transplantation has shown promise in Hodgkin's disease patients who have induction failure, as well as in patients with relapsed disease, Dr. Bierman said at the M.D. Anderson lymphoma symposium (see story above).

At the University of Nebraska, about one fourth of 44 such patients have achieved long-term remission. Dr. Bierman noted that the patients "spanned the gamut from those with progressive disease to those with good partial responses initially."

Canadian investigators recently reported that about half of 30 induction failures had durable failure-free survival after bone marrow or peripheral stem cell transplantation (Blood 86:451, 1995).

"Without any prospective trials or comparative studies, I would submit that if a patient is an induction failure, the patient should proceed to high-dose therapy with autologous transplantation,Dr. Bierman said.

 
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