Intensive chemotherapy with cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation for relapsed Hodgkin's disease.

Abstract

Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy.

Tandem high‐dose chemotherapy and autologous stem cell transplantation in refractory/relapsed Hodgkin's lymphoma: A monocenter prospective study

“…In some studies, a prognostic score has been defined based on the selection of patient groups with a significantly different outcome after HDCT [7,[30][31][32]. Moskowitz et al [33] stratified three groups of patients treated with HDCT on the basis of three adverse prognostic factors (extranodal disease, B symptoms, and initial duration of response less than 1 year).…”

“…The treatment of refractory or relapsed disease has been investigated extensively and high-dose chemotherapy (HDCT) with autologous stem cell support has become the standard protocol in patients with chemo-sensitive disease after induction therapy. Indeed, several nonrandomized studies [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] have suggested a better outcome for patients receiving HDCT. These results have been confirmed by two randomized studies [18,19] comparing a single course of HDCT to conventional chemotherapy in chemo-sensitive patients.…”

VIP (etoposide, ifosfamide and cisplatinum) as a salvage intensification program in relapsed or refractory Hodgkin’s disease

“…31 Of the various prognostic factors identified for long-term disease-free survival in high-dose chemotherapy trials, one of the most frequently found is the chemosensitivity of HD at the time of transplantation. 16,24,[27][28][29][30] Salvage chemotherapy before BMT could therefore play an important role in the curability of patients with primary refractory or relapsed HD.We report here the results of a phase II trial of the VIP regimen for patients in whom intensification was envisaged early on in the course of therapy. This treatment was offered in unselected heavily pre-treated patients with poor prognosis Hodgkin's disease who were potentially eligible (aged less than 60 year, no prior extensive bone marrow irradiation and no medical contradiction) for intensive ther-…”

“…23 Prognostic factors allowing the identification of a subgroup of patients who would particularly benefit from highdose therapy have been extensively sought. 16,24,[27][28][29][30] Discrepancies persist regarding their legitimacy probably due to non-homogeneous patient characteristics and selection in the different cohorts studied. 31 Of the various prognostic factors identified for long-term disease-free survival in high-dose chemotherapy trials, one of the most frequently found is the chemosensitivity of HD at the time of transplantation.…”

“…31 Of the various prognostic factors identified for long-term disease-free survival in high-dose chemotherapy trials, one of the most frequently found is the chemosensitivity of HD at the time of transplantation. 16,24,[27][28][29][30] Salvage chemotherapy before BMT could therefore play an important role in the curability of patients with primary refractory or relapsed HD.…”