The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight- year study of 155 patients

Abstract

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.

Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin’s disease: retrospective analysis of 158 cases from the French registry

“…Even if the number of cases with refractory disease is relatively small, our data (5-year EFS, 26.1 Ϯ 9.26%) confirm the poor prognosis of this subset of patients. Similar results have been reported by the London group, 4 with a 33% PFS rate at 6 years (95%, confidence interval 21-50%) in a population of 46 patients with primary refractory HD treated with the BEAM regimen. The team from Stanford University recently reported results with high-dose therapy and autografting that appeared to be better than ours in patients with refractory HD, with 5year EFS rate from 48 to 53%.…”

“…With the same median time interval from diagnosis to ASCT of 28 months, the risk appears to be lower in Chopra's series, who reported only two cases of MDS out of 155 transplantations after the BEAM conditioning regimen in a single center 8-year study. 4 Darrington et al 25 reported an estimated cumulative incidence of MDS and secondary leukemia of 4% at 5 years in a one-center study of 511 ASCT for lymphoid malignancies, and they estimated that the probability of MDS or leukemia among patients with HD alive at 5 years was 11%. Post-autologous Table 3 Results of prospective and randomized trials testing chemotherapy or CMT in advanced HD Research group (Ref.…”

“…1 In this group of patients, autologous stem cell transplantation (ASCT) has been widely investigated and progression-free survival (PFS) rates of 25 to 60% have been reported. [2][3][4][5][6][7][8] In this setting, the British National Lymphoma Investigation group has demonstrated in a randomized trial that high-dose therapy followed by ASCT improved both event-free survival (EFS) and PFS as compared with conventional-dose treatment. 9 Thus, many authors recommend transplant to patients after relapse from any front-line chemotherapy regimen regardless of the duration of initial remission.…”

Poor outcome in adolescents with high-risk Hodgkin lymphoma

“…Josting et al found the 5-year OS of patients with primary progressive disease was 26% for all patients compared to 43% of those treated with HDT (32). HDT with autologous stem cell transplantation has shown promising results in a number of studies, with better reported disease free survival rates of 31-42% (33,34), and this approach is now often adopted for those who are chemo-responsive, although further confirmatory trials are needed. It is clear that the adolescents had more early deaths, most of which were secondary to refractory or primary progressive disease.…”

Early relapse and refractory disease remain risk factors in the anthracycline and autologous transplant era for patients with relapsed/refractory classical Hodgkin lymphoma: a single centre intention‐to‐treat analysis

“…However some groups report similar outcomes comparing these groups (Smith et al , 2011). Of note, most of these analyses are performed once patients have reached HDT/ASCR (Chopra et al , 1993; Nademanee et al , 1995; Horning et al , 1997; Sweetenham et al , 1999; Majhail et al , 2006) rather than by intention‐to‐treat (ITT) (Ferme et al , 2002), which limits the true extent of conclusions that can be drawn on the relative risk of ER/FTF compared to the LR patients, by selecting the good‐risk group of patients who have responded to salvage treatment and reached HDT/ASCR.…”