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

Abstract

Summary: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 fac- 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. Keywords: lymphoma; transplantation; prognostic factors Commonly used regimens for reinduction of patients with recurrent aggressive non-Hodgkin's lymphoma (NHL) are either platinum-based (DHAP or ESAP), 1 or ifosfamidebased (most commonly MINE). 2 Both types of regimens induce responses in approximately two thirds of patients and complete remission rates of approximately 30% to 40%. 3 Autologous transplantation results in durable remissions in approximately half of the responding patients, 3 but lack of response to pre-transplant chemotherapy and recurrence after transplantation limit the clinical impact of this strategy. Overall only approximately 20% of patients with recurrent NHL targeted for auto-transplant, achieve durable remissions. 4 Dose-intensity can be optimized by increasing the dose of a particular drug, or by decreasing the treatment interval (ie increasing the dose density). 5 We studied a salvage regimen consisting of high doses of ifosfamide, etoposide alternating with high-dose ifosfamide and mitoxantrone. With G-CSF support and prophylactic antibiotics, we were able

Targeting bone marrow lymphoid niches in acute lymphoblastic leukemia

“…Salvage chemotherapy consisted of ifosfamide 10 gm/m 2 CIVI on days 4–6 with mesna, etoposide 150 mg/m 2 IV twice daily on days 4–6, dexamethasone 5 mg/m 2 PO or IV twice daily on days 4–10. 35 The study population consisted of 13 patients, 11 males and 2 females, with a median age of 46 years (range 19–69). Eleven patients had a B-precursor immunophenotype, and one patient each had a t(9;22) and 11q23 rearrangement (Table 1).…”

Phase II study of autologous transplantation with interleukin-2-incubated peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or refractory non-Hodgkin lymphoma

“…Salvage chemotherapy consisted of 1 to 3 cycles of ifosfamide and etoposide [2] (Table 1). Upon recovery from the first or second treatment cycle, stem cell apheresis was performed.…”

“…The conditioning regimen for patients with intermediate-grade, transformed, or immunoblastic lymphoma was BEAM chemotherapy. BEAM consisted of carmustine 300 mg/m 2 Each bag of cryopreserved peripheral blood progenitor cells (PBPC) was thawed rapidly in a 40°C water bath. Cell count, viability, Gram stain, culture, and assays for colony-forming units were performed on a small aliquot of the thawed product.…”

“…High-dose chemotherapy with autologous transplantation is the treatment of choice for patients with recurrent lymphoma, but it is effective in only a minority of patients because of a high incidence of disease recurrence [1][2][3]. Lymphomas are also sensitive to immunotherapy, as indicated by their responses to interferon [4][5][6] and in particular to interleukin (IL)-2 [7,8].…”

Ifosfamide in Hematological Malignancies of Adults

“…The projected 5-year overall survival (OS) was 52% and progression-free survival was 32%. In the study of Van Besien et al [14], OR after ifosfamide (10 g/m 2 ) and etoposide (900 mg/m 2 ) was 77% with 16% CRs, after ifosfamide (10 g/m 2 ) and mitoxantrone (20 mg/m 2 ) OR was 73% with 41% CRs. Comparing the results with those obtained with MINE-ESHAP regimen, previously used, the adoption of a more intensive salvage regimen did not increase the long-term outcome, despite the higher response rate.…”