High-dose infusional ifosfamide, etoposide plus methylprednisolone followed by dexamethasone, high-dose ara-C and cisplatinum and autologous stem cell transplantation for refractory or relapsed aggressive non-Hodgkin's lymphoma

Haematologica. 2002 Oct;87(10):1028-35.

Abstract

Background and objectives: A salvage program including infusional high-dose ifosfamide plus etoposide (IFOVM) was evaluated in patients with refractory or relapsed aggressive non-Hodgkin's lymphoma.

Design and methods: Forty-six patients were included. IFOVM consisted of ifosfamide (10 g/m2 as a 72-hour continuous infusion), etoposide (900 mg/m2) and methylprednisolone; responding patients underwent two cycles of DHAP and subsequently an autologous peripheral blood stem cell transplantation (APBSCT) with BEAM as the conditioning regimen.

Results: All but one patient showed tumor regression following IFOVM. Myelosuppression was brief but 26 patients developed neutropenic fever. All but two patients proceeded to DHAP. Overall response rate to IFOVM/DHAP was 59% (29% CR and 30% PR). Refractory patients had a significantly lower response rate than relapsed patients (39% vs. 85% p=0.002). All refractory patients with intermediate-high or high IPI progressed during IFOVM/DHAP. Twenty-seven patients proceeded to APBSCT. Two-year overall survival of patients with low or low-intermediate IPI was 47% [95% CI 25-69%], which was significantly better than that obtained in patients with intermediate-high or high IPI (11% [95% CI 0-22%] p=0.0001).

Interpretation and conclusions: This sequential regimen of IFOVM, followed by DHAP and consolidated with BEAM is active in relapsed or refractory patients with low or low-intermediate IPI aggressive lymphoma. However, it has little activity in those patients with intermediate or high IPI, especially in refractory lymphomas.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage*
  • Combined Modality Therapy
  • Cytarabine / administration & dosage*
  • Dexamethasone / administration & dosage*
  • Disease-Free Survival
  • Etoposide / administration & dosage*
  • Female
  • Humans
  • Ifosfamide / administration & dosage*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Male
  • Methylprednisolone / administration & dosage*
  • Middle Aged
  • Recurrence
  • Salvage Therapy
  • Stem Cell Transplantation*
  • Time Factors

Substances

  • Cytarabine
  • Etoposide
  • Dexamethasone
  • Cisplatin
  • Ifosfamide
  • Methylprednisolone

Supplementary concepts

  • DHAP protocol