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Non-Hodgkin's Lymphoma

Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival

Bone Marrow Transplantation volume 27, pages 397–404 (2001)Cite this article

Abstract

The purpose of the study was to evaluate in patients with recurrent intermediate-grade NHL, the tolerance to and efficacy of an intensive salvage regimen consisting of high doses of ifosfamide, etoposide and mitoxantrone with G-CSF support, followed by autologous stem cell transplantation and to identify prognostic factors for survival in patients with recurrent aggressive lymphoma. Patients with recurrent intermediate-grade NHL under the age of 60 years were eligible. Induction consisted of ifosfamide 10 g/m2 and etoposide 900 mg/m2 with G-CSF 5 μg/kg twice a day. Upon recovery, patients underwent stem cell apheresis. Patients achieving complete remission (CR) underwent autologous stem cell transplantation using BEAM conditioning. Those with partial remission (PR) received treatment with ifosfamide 10 g/m2, mitoxantrone 20 mg/m2 and G-CSF 5 μg/kg. Those with CR received BEAM, those with PR received cyclophosphamide 4.5 g/m2, etoposide 1200 mg/m2 and cisplatin 135 mg/m2 with stem cell rescue followed by BEAM. Antibiotic prophylaxis was given with all treatment cycles. The results were compared with those obtained in a prior study that used MINE-ESHAP salvage. Forty-four patients with recurrent intermediate-grade NHL were enrolled between March 1994 and September 1996. Median age was 50 years (24–61). Eleven patients had transformed lymphoma and seven had a T cell phenotype. Response rate to the high-dose ifosfamide regimen was 77% ± 12% after two cycles and the complete response rate was 41% ± 14%. Myelosuppression was profound but short. Median nadir ANC was 0 and the median duration of ANC <0.5 × 109/l was 6 days (range 3–12). No severe infections occurred; 55% of the patients required blood transfusion and 42% required platelet transfusions. Myelosuppression and transfusion requirements were similar after the first and second cycles. Thirty-five of the 44 patients proceeded to autologous stem cell transplantation and one transplant-related death occurred. With a median follow-up of 52 months, progression-free survival at 2 years is 38% ± 14% and survival is 52% ± 15%. Data from these 44 patients were pooled with data on 53 patients who had received salvage treatment with MINE-ESHAP, for a multivariate analysis of prognostic factors. In multivariate analysis, serum LDH was strongly associated with survival. The use of a more intensive salvage regimen, did not result in a significant increase in long-term outcome, despite a high response rate. In conclusion, duration of treatment, response rates, treatment-related mortality and survival compare favorably with previous salvage regimens, but recurrence remains a major problem. Long-term survival in recurrent large cell lymphoma is influenced more by disease characteristics than by the type of salvage regimen used. Bone Marrow Transplantation (2001) 27, 397–404.

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Authors and Affiliations

  1. Division of Medicine, Departments of Stem Cell Transplantation, MD Anderson Cancer Center, Houston, TX, USA

    K van Besien, M Donato, S Giralt, R Mehra, B Andersson, J Gajewski & R Champlin

  2. Lymphoma MD Anderson Cancer Center, Houston, TX, USA

    A Rodriguez, A Younes, A Sarris & F Cabanillas

  3. American Medical Association, Chicago, IL, USA

    S Tomany

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  1. K van Besien
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van Besien, K., Rodriguez, A., Tomany, S. et al. Phase II study of a high-dose ifosfamide-based chemotherapy regimen with growth factor rescue in recurrent aggressive NHL. High response rates and limited toxicity, but limited impact on long-term survival. Bone Marrow Transplant 27, 397–404 (2001). https://doi.org/10.1038/sj.bmt.1702793

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