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

K. Van Besien, A. Rodriguez, S. Tomany, A. Younes, M. Donato, A. Sarris, S. Giralt, R. Mehra, B. Andersson, J. Gajewski, R. Champlin, F. Cabanillas

    Research output: Contribution to journalArticle

    11 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)397-404
    Number of pages8
    JournalBone marrow transplantation
    Volume27
    Issue number4
    DOIs
    StatePublished - Mar 20 2001

      Fingerprint

    Keywords

    • Lymphoma
    • Prognostic factors
    • Transplantation

    ASJC Scopus subject areas

    • Hematology
    • Transplantation

    Cite this

    Van Besien, K., Rodriguez, A., Tomany, S., Younes, A., Donato, M., Sarris, A., Giralt, S., Mehra, R., Andersson, B., Gajewski, J., Champlin, R., & Cabanillas, F. (2001). 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, 27(4), 397-404. https://doi.org/10.1038/sj.bmt.1702793