Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy [see comments]

Abstract

The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16–213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post- BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: “B” symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors.

Managing relapsed and refractory Hodgkin lymphoma

“…induction failure) had the worst outcomes when compared with those who relapsed but the HDT regimen and ASCT were associated with 45% EFS (Moskowitz et al, 2004). For all refractory and relapsed HL, chemosensitivity to the pretransplant regimen was always a major prognostic factor for outcome after HDT Reece et al, 1994).…”

Intensive therapy and autotransplantation in hodgkin's disease

“…While selected studies of further conventional therapy have reported prolonged progression-free survival in at least 50% of such patients [ l l , 121, there is little published data regarding the results of autotransplantation in a comparable group of patients. However, our own group has transplanted 23 such patients [19]; at present, with an updated minimum follow-up of two years, the actuarial five-year progression-free survival in this group is 72% (95% CI 43-88%). Although it may be argued that some of these patients were "overtreated" with autologous transplantation, it is noteworthy that the early transplant-related mortality in this group was quite low (5%) and that progressive HD remained the primary problem, occurring in about 25%.…”

“…In this setting, then, most investigators would accept the superiority of high-dose regimens and autologous transplantation without a Phase I11 trial. Likewise, patients whose initial CR lasts < I 2 months generally have a progression-free survival well under 25% with further conventional therapy [ l , 10.63, 641 versus 30-75% at four to five years with autologous transplantation; thus, autografting appears superior in this subgroup as well [6,19,251.…”

Autologous transplantation in relapsed and refractory Hodgkin's disease

“…Treating recurrence after primary chemotherapy is a difficult issue. The choice is between salvage radiotherapy in patients with isolated nodal relapse (4), conventional salvage chemotherapy (5) or HDCT followed by ASCT (6)(7)(8)(9).…”

“…High-dose chemotherapy followed by autologous SCT HDCT followed by ASCT has been shown to produce 30-65% long-term DFS in selected patients with refractory and relapsed HD (6)(7)(8)(9). In addition, the reduction of early transplantrelated mortality from 10% to 25% reported in earlier studies to less than 5% in more recent studies has led to the widespread acceptance of HDCT and ASCT.…”