Intensified preparative regimens and autologous transplantation in refractory or relapsed intermediate grade non-Hodgkin's lymphoma

Abstract

patients with relapsed or refractory IGL received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used: cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (n = 66) and cyclophosphamide, BCNU, etoposide (CBV) (n = 33). As clinical features and results were not different for the two preparative regimens, results were combined. For all patients undergoing autologous transplantation, 5-year actuarial overall survival (OS) was 34% ± 6%; 5-year event-free survival (EFS) was 26% ± 5%. For patients who responded to primary therapy, salvage therapy, or both, OS was 42% ± 7%; for nonresponders to prior therapy, OS was 14% ± 7%, P Ͻ 0.025. OS was better among patients responding to salvage therapy (50% ± 9%), than among patients who had a complete response to initial therapy, but failed to respond or were untested/unevaluable with respect to salvage therapy (26% ± 10%; P Ͻ 0.025). On multivariate analysis, response to salvage therapy was associated with survival following autologous transplantation (P Ͻ 0.005). Treatment related mortality was 9% overall and only 6% after G-CSF and GM-CSF were introduced into routine clinical practice. High-intensity preparative therapy is highly effective, with acceptable treatmentrelated mortality, in patients with IGL who have responded to induction therapy, salvage therapy, or both. The best responses are observed in patients responding to salvage therapy. Randomized prospective studies will be needed to further define the role of intensified preparative regimens. Bone Marrow Transplantation (2000) preparative regimens, long-term disease-free survival (DFS) has been associated with disease chemoresponsiveness. 3-7 However, even among patients with sensitive disease, long-term DFS has generally been seen in only 30-50% of patients. 2,5-8 Among patients with resistant disease, less than 10% survive long-term. 3,6 Intensification of the preparative regimen is one potential means of improving these clinical results. [9][10][11][12] Since 1986, we have studied two intensified preparative regimens in patients with relapsed or refractory IGL. One regimen added etoposide to the standard cyclophosphamide-TBI regimen, the other used augmented dose BCNU in combination with etoposide and cyclophosphamide. This report summarizes our experience with augmented preparative therapy in patients with relapsed or refractory IGL undergoing autologous transplantation. Patients and methods Patients and eligibilityRecords of all patients who received autologous stem cell transplantation (ASCT) at Vanderbilt University Medical Center or the affiliated Nashville Veteran's Affairs Hospital between September 1986 and June 1998 were reviewed. Patients were included in the study if both the initial and the most recent pathological material prior to transplantation were interpreted as IGL. Following review by two of the authors (WRM, TLM) at the time this report was prepared, patients with low-grade NHL evolving...

Intensification of salvage treatment with high‐dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non‐Hodgkin's lymphoma

“…In this relatively large patient group, 81% of evaluable cases responded to HDS. This rate compared very favourably with the results hitherto reported in both retrospective or prospective treatment series using a variety of different regimens (51–69%) (Bosly et al , 1992; Mills et al , 1995; Rapoport et al , 1997; Stiff et al , 1998; Guglielmi et al , 1999; Stein et al , 2000). The vast majority of HDS‐treated patients achieved a minimum disease state before ASCT and 90% of them were in CR at completion of the salvage programme.…”

“…Patients with aggressive non‐Hodgkin's lymphoma (NHL) who fail initial treatment or subsequently relapse have a very poor outcome, as less than 10% obtain a prolonged disease‐free interval using conventional salvage regimens (Armitage, 1993; Gisselbrecht et al , 1993; Vose et al , 1993). To improve these results, high‐dose chemotherapy (HDCT) programmes with autologous haematopoietic stem cell transplantation (ASCT) have been introduced (Philip et al , 1987; Gribben et al , 1989; Bosly et al , 1992; Mills et al , 1995; Rapoport et al , 1997; Stiff et al , 1998; Guglielmi et al , 1999; Stein et al , 2000). In the single phase III study to date (Philip et al , 1995), the survival advantage from ASCT was confirmed in patients with late relapse (> 12 months) (Guglielmi et al , 1998, 1999) or with at least one risk factor according to the International Prognostic Index (IPI) (The International non‐Hodgkin's Lymphoma Prognostic Factors Project, 1993; Blay et al , 1998).…”

Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road?

“…Pulmonary toxicity (interstitial pneumonia) has also been described. Carmustine (BCNU)-containing regimens such as BEAM 5 and CBV 10,11 are also associated with a higher incidence of pulmonary toxicity (pulmonary fibrosis) due to metabolites of the drug. Etoposide-containing regimens 5,10-13 have higher rates of mucositis and the late development of myelodysplasia and acute leukemia.…”

Autologous Stem Cell Transplantation using a Modified TAM Conditioning Regimen for Clinically Aggressive Non-Hodgkin's Lymphoma

“…TRM has decreased in recent years due to improvements in supportive care and the use of PBSC, although the TRM rate has been shown to be ＜10% in a recent report (8). Gutierrez-Delgado et al reported a 13% TRM rate for the TBI-containing group of patients and 21% for the chemotherapy-alone group of patients.…”