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

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

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

"In most clinical situations, the failure-free survival followinghigh-dose therapy with ABMT for Hodgkin's disease is superiorto conventional dose salvage chemotherapy," he said, "buttransplantation's ability to improve overall survival has notbeen demonstrated. However, at our institution, we recommend transplantationfor any patient who has relapsed after chemotherapy."

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

Conventional Salvage Chemo

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

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

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

Radiation Results

Good results have been achieved with radiation therapy, but inrelatively small numbers of patients, some of whom also receivedchemotherapy. In five published studies with about 100 patientstotal, complete responses rates have ranged as high as 92%. Disease-freesurvival at 5 years has ranged between 24% and 50%.

The best results have occurred in patients with initial remissionsexceeding a year and in those without extranodal disease. "Ifyou wanted to argue, you could say that the disease-free survivalresults with radiation therapy have been as good as any salvagetherapy 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 bloodstem cell support have shown encouraging results, he said. Atthe University of Nebraska, 5-year failure-free survival is 40%among 85 patients. British investigators have reported a 47% long-termfailure-free survival, including 57% in patients with long initialremissions and 41% in patients with short initial remissions.

Stanford researchers have reported a 60% progression-free survivalin patients treated with ABMT after relapse or failure to achieveremission, compared with 30% for another group treated with conventionalchemotherapy. Overall survival favored the transplant group (55%vs 46%) but did not reach statistical significance, Dr. Biermansaid.

The best results have come from a Vancouver study that showedan 80% to 85% failure-free survival in patients with long initialremissions. Overall, two thirds of the 57 patients remained failurefree at 7 years. "These results are clearly better than anythingthat has ever been reported in the literature," Dr. Biermancommented.

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

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

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

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