Parma Study Confirms ABMT Superiority

June 1, 1995

LOS ANGELES--The final report of the Parma study, presented at the American Society of Clinical Oncology meeting, confirms the superiority of dose intensification with autologous bone marrow transplantation (ABMT) over conventional chemotherapy in patients with relapsed diffuse non-Hodgkin's lymphoma (NHL).

LOS ANGELES--The final report of the Parma study, presented atthe American Society of Clinical Oncology meeting, confirms thesuperiority of dose intensification with autologous bone marrowtransplantation (ABMT) over conventional chemotherapy in patientswith relapsed diffuse non-Hodgkin's lymphoma (NHL).

"High-dose chemotherapy with ABMT increases both event-freesurvival and overall survival and can be considered as standardtreatment of high- and intermediate-grade NHL in sensitive relapse,"Thierry O. Philip, MD, director of the Centre Leon Berard, Lyon,France, said in his report at the plenary session.

Although ABMT has been widely used in these patients for nearlytwo decades, results of previous studies had been questioned primarilybecause of lack of uniform patient selection criteria and inabilityto prove survival benefit. At a 1985 meeting in Parma, Italy,a protocol for a definitive prospective randomized multicenterstudy was developed.

The criteria were designed to select patients most likely to becured with chemotherapy, Dr. Philip said. The protocol was opento patients with diffuse high- or intermediate-grade lymphomain first or second relapse who had a previous complete responsewith an Adriamycin-containing regimen. Patients over 60 yearsof age and those with CNS or bone marrow involvement were excludedfrom the trial.

The study began with 216 patients who received two courses ofDHAP (dexamethasone, ara-C, and cisplatin). Those in partial orcomplete response were then defined as sensitive relapses, andall others were defined as resistant relapses and were excludedfrom the study.

Those patients in sensitive relapse (109 eligible) were then randomizedto receive either conventional treatment (four additional coursesof DHAP followed by involved-field radiotherapy) or dose-intensivetherapy consisting of involved-field radiotherapy plus high-dosechemotherapy--BCNU, etoposide, ara-C, and cyclophosphamide (BEAC)--followedby ABMT. In both arms, patients received radiotherapy only ifone or more relapsed tumor sites measured more than 5 cm.

Response rates were significantly higher with ABMT (84% versus45% for conventional DHAP), as were complete responses (78% vs40%). At a median of 63 months of follow-up, disease-free survivalwas 46% for the transplant patients, compared with 12% for theDHAP group.

Overall survival at 63 months was significantly better for theABMT patients: 53% versus 32% for the DHAP arm. Dr. Philip notedthat the 32% survival rate is the "best ever reported forchemotherapy in relapsed NHL with diffuse histology."

Morbidity and treatment-related mortality were increased in thehigh-dose arm. One third (18) of these patients had episodes ofgrade 3 and 4 toxicity, compared with only three patients in theDHAP group. There were three toxic deaths in the transplant patients(6% toxic death rate) and none on the conventional arm.

Although 18 of the DHAP patients who relapsed received high-dosetherapy/ABMT as salvage, only 2 of these patients are still alive."High-dose chemotherapy with ABMT was not able to rescuethe patient after DHAP failure," he said.