Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial.

Guglielmi, Cesare; Gómez, Francisca; Philip, Thierry; Hagenbeek, Anton; Martelli, Maurizio; Sebban, Catherine; Milpied, Noël; Bron, Dominique; Cahn, Jean‐Yves; Somers, R.; Sonneveld, Pieter; Gisselbrecht, Christian; Lelie, Hans van der; Chauvin, Franck

doi:10.1200/jco.1998.16.10.3264

Cited by 135 publications

(92 citation statements)

References 22 publications

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“…Several groups have recently reported on prognostic features in patients with recurrent aggressive NHL. 4,[26][27][28] We confirmed that serum LDH provided strong independent prognostic information in patients with recurrent NHL. The association of disease stage with survival was less significant (P = 0.02) and there was a strong interaction of this parameter with phenotype (Table 4).…”

Section: Bone Marrow Transplantationsupporting

confidence: 65%

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

Besien

Rodriguez²,

Tomany

et al. 2001

Bone Marrow Transplant

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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

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Section: Bone Marrow Transplantationsupporting

confidence: 65%

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

Besien

Rodriguez²,

Tomany

et al. 2001

Bone Marrow Transplant

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“…Of particular importance, these responses are seen in a heavily pretreated population with several poor prognostic features such as chemo-resistant disease (Josting et al, 2000), relapse within a year (Brice et al, 1997;Guglielmi et al, 1998), advanced disease stage (Blay et al, 1998) and previous ASCT. Response to salvage chemotherapy is important prior to ASCT, as it is correlated with survival post-transplant (Philip et al, 1987;Brice et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

Waters

Cunningham

et al. 2005

Br J Cancer

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There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64 -91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation.

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“…Thus, for the relapse group, inclusion criteria were: refractory disease or end-of-treatment to relapse interval Ͻ1 year. 13,14,31 In addition, nine patients with aggressive lymphoma with at least two adverse prognostic factors according to the IPI, received this tandem protocol as first-line therapy after debulking chemotherapy with ACVBP induction. 7 In this group of patients, the remission rate is only 65% and tandem high-dose procedures may have a role in treatment strategies to improve the response rate and consolidation.…”

Section: Discussionmentioning

confidence: 99%

Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins’s disease or non-Hodgkin’s lymphoma

Fitoussi

Simon

Brice

et al. 1999

Bone Marrow Transplant

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Summary:To improve the results of high-dose therapy with autologous stem cell transplantation, new conditioning regimens with acceptable toxicity must be developed. The aim of this study was to evaluate the feasibility and toxicity of two myeloablative regimens performed at a 2-month interval. After salvage chemotherapy and collection of peripheral stem cell progenitors (median CD34 ؉ cells/kg: 11 ؋ 10 6 /kg), (n ‫؍‬ 15) patients with aggressive non-Hodgkin's lymphoma with poor prognostic factors or refractory Hodgkin's disease (n ‫؍‬ 9) received intensified regimens. The first conditioning regimen, consisting of BCNU-cyclophosphamide-VP16-mitoxantrone was followed by transplantation of a median number of 4 ؋ 10 6 CD34 ؉ cells/kg; then, after a median interval of 56 days, a second preparative regimen, combining busulfan-aracytine-melphalan or TBI ؉ aracytine-melphalan, was followed by transplantation of a median of 4 ؋ 10 6 CD34 ؉ cells/kg. After regimens 1 and 2, respectively: median time to neutrophil recovery Ͼ500/ l was 11 days (both times); median time to platelet counts Ͼ50 000/ l was 14 and 36 days, but values Ͼ20 000/ l were reached by days 13 and 16 (P ‫؍‬ 0.9); mucositis grade III-IV was observed in 11 and 15 cases. The median number of days with fever Ͼ38؇C was significantly higher (7.8 days) after the second transplant (P Ͻ0.05). Three cases of veno-occlusive disease (VOD) were observed after the second transplant. At a median follow-up of 18 months, 14/24 (58%) patients remained in CR, seven patients had died (two of VOD and five after relapse) and two were alive in relapse. These results indicate that tandem transplants performed at a 2-month interval in poor risk lymphoma can be used with acceptable hematotoxicity. VOD remains the major drawback and hepatotoxic drugs, such as busulfan, should be used with caution. Longer term followup of a larger cohort of patients is needed to ascertain the overall efficacy. Keywords: tandem transplants; Hodgkin's disease; nonHodgkin's lymphoma; veno-occlusive disease Conventional-dose anthracycline-containing chemotherapy associated with radiotherapy has now been well documented to result in long-term disease-free survival in 60-70% of the patients with advanced Hodgkin's disease (HD) 1 and 45-50% of those with unselected aggressive non-Hodgkin's lymphoma (NHL). 2 For NHL patients, prognosis is determined based on the clinical characteristics defined by the International Prognostic Index (IPI), 3 with the survival rate for patients with 0-2 adverse factors ranging from 80 to 60%. However, for patients with Ͼ2 adverse prognostic factors actuarial survival is inferior to 40% and for those with primary refractory disease who fail to achieve complete remission (CR) after standard chemotherapy, the prognosis is poor with conventional salvage chemotherapy. 4 The most promising approach for these very poorrisk patients is the use of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT). Prospective trials have shown HDT ϩ ASCT to be superior to che...

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Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial.

Abstract: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.

Cited by 135 publications

References 22 publications

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

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

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins’s disease or non-Hodgkin’s lymphoma

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