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 (Chopra et al , 1993; Reece et al , 1994).…”

Autologous stem cell transplant for early relapsed/refractory Hodgkin lymphoma: results from two transplant centres

“…While ASCT offers durable remission to about 50% of patients, others fare poorly even with this intensive approach. B symptoms and extranodal (EN) involvement at relapse have been identified as poor prognostic factors after ASCT, as have bulky or chemoresistant disease (Chopra et al , 1993; Reece et al , 1994; Nademanee et al , 1995; Brice et al , 1997; Horning et al , 1997; Ferme et al , 2002; Majhail et al , 2006). The impact of induction failure or early relapse (<12 months remission duration) on outcomes after ASCT is less clear, with progression‐free survival (PFS) estimates ranging widely, from 20% to 50%, in this group (Chopra et al , 1993; Nademanee et al , 1995; Brice et al , 1997; Horning et al , 1997; Sweetenham et al , 1999; Ferme et al , 2002; Majhail et al , 2006).…”

Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disorders using BEAM–CAMPATH conditioning: an effective regimen with low procedure‐related toxicity

“…The use of high-dose therapy and autologous haemopoietic stem cell transplantation has a clearly established role in the treatment of Hodgkin's disease and non-Hodgkin's lymphoma (NHL) (Reece et al, 1994;Philip et al, 1995;Freedman et al, 1996). In contrast, the place of allogeneic transplantation in lymphoma is controversial as reported studies both from single centres and from registries have shown a high transplant-related mortality (TRM).…”