Parma international protocol: pilot study of DHAP followed by involved- field radiotherapy and BEAC with autologous bone marrow transplantation

Abstract

Fifty patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) who had relapsed after a complete remission induced by an Adriamycin-containing chemotherapy regimen participated in this prospective pilot study. The patients ranged in age from 16 to 60 years (median 42 years). All patients received dexamethasone, high-dose cytarabine, and cisplatin (DHAP) for two courses at 3- to 4-week intervals. Patients achieving a partial or complete response were scheduled to receive involved-field radiotherapy and high-dose carmustine, etoposide, cytarabine, and cyclophosphamide (BEAC), followed by autologous bone marrow transplantation (ABMT). Among 48 evaluable patients (ie, 1 was lost to follow-up and 1 had no measurable disease) 7 patients obtained a complete response (CR) and another 21 patients achieved partial response (PR), whereas the remaining 20 patients failed. One responder died of treatment-related toxicity, and six others declined ABMT. The patient with no measurable disease did not progress on DHAP and was submitted to ABMT. Twenty-two patients underwent ABMT [20 with BEAC and 2 with cyclophosphamide plus total body irradiation (TBI)] of whom 2 (9%) died of toxicity and 10 relapsed. One patient was a suicide at 28 months post-ABMT in CCR and 9 are alive disease-free 24 months to 32 months (median 30 months) post- ABMT. The actuarial 2-year event-free survival for patients undergoing transplantation is 40%. This prospective multicenter trial documents the ability of DHAP followed by ABMT to produce durable complete remission in a significant proportion of patients with relapsed aggressive NHL. Forty-four percent of all patients with relapsed lymphoma who entered the study actually underwent ABMT and 20% of the total group are projected to be long-term disease-free survivors.

The Role of Intensive Therapy and Autologous Blood and Marrow Transplantation for Chemotherapy‐Sensitive Relapsed and Primary Refractory Non‐Hodgkin’s Lymphoma: Identification of Major Prognostic Groups

“…Indeed, it could be argued that multidrug resistance was induced with the repetitive cycles of salvage chemotherapy. However, these possibilities are highly unlikely, because (1) patients transplanted in PR had a high CR rate (87%); (2) the PFS of 48% for the entire cohort is similar to the results of other ABMT studies with other intensive-therapy regimens, some of which use minimal salvage therapy prior to transplant (Mills et al, 1995;Petersen et al, 1990;Freedman et al, 1990;Colombat et al, 1990;Philip et al, 1991;Vose et al, 1993), (3) subjects in PR and CR at transplant had similar patient-and disease-related characteristics; (4) the PR group received a median of one additional cycle of conventional dose salvage chemotherapy; and (5) the number of cycles of prior salvage chemotherapy was not independently predictive of outcome.…”

“…Outcome after conventional-dose salvage chemotherapy is also dependent on remission status. The predicted survival of patients achieving CR with conventional dose salvage therapy alone is 5-42% at 3 years and < 5% for those with only a PR (Bosly et al, 1992;Philip et al, 1991;Velasquez et al, 1988Velasquez et al, , 1994Tura et al, 1993;Cabanillas et al, 1987Cabanillas et al, , 1982Cabanillas et al, , 1988Philip & Fisher, 1985;Chao et al, 1990;Goss et al, 1991;Herbrecht et al, 1991;Salles et al, 1994;Haq et al, 1994). Although a direct comparison with conventional-dose therapy was not the purpose of our study, it provides a preliminary analysis of outcome after ABMT versus conventional-dose salvage therapy according to remission status.…”

Autologous Transplant in Lymphoma: Experience in a Limited Resource Mexican Reference Center

“…The efficacy of HDC-AHSCT was demonstrated in the PARMA study, reporting a DFS of 46% and an OS of 53% in refractory or relapsing DLBC NHL in the era prior to the use of Rituximab [16] when compared with patients treated with conventional chemotherapy. Recently, the SWOG S9704 study [18] compared management with CT (CHOP/R-CHOP) vs. HDC-AHSCT in patients with intermediate-high and high IPI DLBC NHL, and reported benefits in transplanted patients in terms of DFS (56% vs. 69%, HR 1.7 (95% CI 1.18-2.51) p=0.005). Also, the European Mantle Cell Lymphoma Network compared treatment with autologous transplant versus standard chemotherapy and maintenance with Interferon alpha; they found a greater progression-free survival in the transplanted group versus the maintenance group (39 versus 17 months, p=0.0108, 95% CI 39-69) [19,20].…”

Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant‐eligible patients with non‐Hodgkin lymphoma and Hodgkin disease

“…High‐dose therapy and autologous haemopoietic stem cell transplantation (SCT) has a clearly established role in the management of both Hodgkin disease (HD) and non‐Hodgkin lymphoma (NHL) (Philip et al , 1991; Linch et al , 1993; Freedman et al , 1996; Yuen et al , 1997; Goldman et al , 1998; Shipp et al , 1999). Peripheral blood stem cells (PBSC) are preferred for rescue after high‐dose therapy as they give more rapid haemopoietic engraftment with associated reductions in both antibiotic and blood product usage, together with reduced length of in‐patient stay (Russell & Pacey, 1992; To et al , 1992; Ager et al , 1995; Schmitz et al , 1996).…”