High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors

Abstract

Eight-five consecutive patients with relapsed or refractory Hodgkin's disease (HD) underwent high-dose chemotherapy or chemo/radiotherapy followed by autologous bone marrow (ABMT) and/or peripheral blood stem cell (PBSC) transplantation. Two preparative regimens were used. Twenty- two patients (26%) without prior radiation received fractionated total body irradiation (FTBI) 1,200 Gy in combination with high-dose etoposide (VP-16) 60 mg/kg and cyclophosphamide (CTX) 100 mg/kg. Sixty- three patients (74%) with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. The median age was 32 years (range, 16 to 56). The median number of prior chemotherapy regimens was three (range, 1 to 7). Forty-three patients (51%) received transplants in first relapse or second complete remission (CR), whereas 33 (39%) received transplants after second or subsequent relapse. All relapsed patients, except one, received conventional salvage chemotherapy and/or radiotherapy in an attempt to reduce tumor bulk before transplant. At the time of analysis in April 1994, fifty-seven patients (67%) are alive, including 44 (52%) in continuous CR, with a median follow-up for the surviving patients of 28 months (range, 7 to 66). Thirty patients (35%) relapsed at a median of 9 months (range, 1 to 43). Eleven patients (13%) died of transplant-related complications including veno- occlusive disease of the liver (VOD) in five, acute and late interstitial pneumonitis in three, graft failure in one, cerebral hemorrhage in one, and therapy-induced myelodysplasia (MDS)/acute leukemia in one patient. At a median follow-up of 25 months (range, 0.6 to 66), the cumulative probability of 2-year overall and disease-free survival (DFS) of all 85 patients is 75% (95% confidence interval [CI] 64% to 84%) and 58% (95% CI 47% to 69%), respectively. Three independent prognostic variables were identified by univariate analysis: number of prior chemotherapy regimens, prior radiotherapy, and extranodal disease at ABMT. Multivariate stepwise Cox regression identified the number of prior chemotherapy regimens as the only significant prognostic factor predicting for both relapse and DFS. There were no significant differences in the outcome of the treatment between the two preparative regimens. Our results confirm that high- dose therapy and ABMT is an effective therapy for patients with relapsed or refractory HD. Earlier transplantation is recommended before the development of drug resistance and end organ damage that results from repeated attempts of salvage therapy.

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

“…In light of the favourable prognosis for this subgroup, clinical trials evaluating intensified strategies or maintenance therapy may not be appropriate. Interestingly, EN involvement of lung and bone marrow were adversely prognostic on univariate analysis -similar to a report of patients with relapsed/refractory HL patients undergoing ASCT between 1987and 1995(Horning et al, 1997. Detailed investigation of clinical and pathological features of patients with EN lung or marrow involvement seems warranted, in light of their particularly poor prognosis.…”

“…Most patients had received ABVD alone as induction therapy. These outcomes are comparable to historical series of unselected patients undergoing ASCT for HL Reece et al, 1994;Nademanee et al, 1995;Brice et al, 1997;Horning et al, 1997;Ferme et al, 2002;Majhail et al, 2006;Sirohi et al, 2008). One large, registrybased study, which was restricted to refractory HL patients, reported a 32% 5-year PFS and 36% OS after ASCT (Sweetenham et al, 1999).…”

Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine‐based high‐dose chemotherapy regimen

“…A favourable trend for FEAM, as compared to other regimens, can be also envisaged by the very low occurrence of severe nausea and vomiting (6Á6%) and diarrhoea (5Á7%) along with the lack of any kidney and liver toxicity, including veno-occlusive liver disease. This latter complication was reported to occur in up to 2-4% of patients receiving carmustine-/melphalan-based conditionings (Nademanee et al, 1995;Puig et al, 2006;Blijlevens et al, 2008).…”

RB but not R‐HCVAD is a feasible induction regimen prior to auto‐HCT in frontline MCL: results of SWOG Study S1106

“…For patients between 61 and 65 years old, each site had to select either CBV (carmustine [BCNU]/cyclophosphamide/etoposide) or BEAM (BCNU/ etoposide/cytarabine/melphalan) as the sole preparative regimen (Chopra et al, 1993;Reece et al, 1994) for that site. For patients aged less than 61 years, the sites had to select either CBV, BEAM, or total body irradiation/cyclophosphamide/etoposide (Nademanee et al, 1995) as the sole preparative regimen.…”