Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.

Waits, Tom; Greco, F. Anthony; Jp, Greer; Johnson, David H.; Wolff, S. N.; Stein, RS; McMaster, Mary L.; Hainsworth, John D.

doi:10.1200/jco.1993.11.5.943

Cited by 37 publications

(12 citation statements)

References 35 publications

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“…A number of studies have addressed this question by escalating the dose of one or more of the drugs used in the CHOP regimen. 11,[16][17][18][19] In general, this strategy has been met with limited success because early toxicity was substantial and time intervals between therapies had to be extended, a high incidence of early secondary MDS/AML was reported, and superior outcome could not be demonstrated. 20 This latter finding is also supported by the results of a recent study of the DSHNHL that compared 6 courses of standard CHOEP-21 with a dose-escalated version of this regimen (cumulative doses of cyclophosphamide and etoposide were 750 versus 1600 and 300 versus 600 mg/m 2 per cycle, respectively).…”

Section: Discussionmentioning

confidence: 99%

Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

Glaß

Kloess

Bentz

et al. 2006

Blood

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Section: Discussionmentioning

confidence: 99%

Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

Glaß

Kloess

Bentz

et al. 2006

Blood

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“…Median survival for the entire group was 22 months, with a 5-year actuarial survival of 34% ± 6%. Age, gender, stage at presentation, the use of prior radiation therapy, the prior use of high intensity-brief duration chemotherapy, 16 the use of CBV as compared to CY-VP-TBI, and the use of 1200 cGy as compared to 1000 cGy as the TBI dose were not significantly associated with survival following transplantation. There was a trend for patients with T cell lymphoma to have better survival following transplantation than patients with B cell lymphoma; 5-year OS 56% ± 18% vs 31% ± 6% (P = 0.06).…”

Section: Survivalmentioning

confidence: 95%

Intensified preparative regimens and autologous transplantation in refractory or relapsed intermediate grade non-Hodgkin's lymphoma

Stein

Goodman

et al. 2000

Bone Marrow Transplant

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patients with relapsed or refractory IGL received intensified preparative therapy and underwent autologous transplantation at a single institution. Two intensified preparative regimens were used: cyclophosphamide, etoposide, total body irradiation (CY-VP-TBI) (n = 66) and cyclophosphamide, BCNU, etoposide (CBV) (n = 33). As clinical features and results were not different for the two preparative regimens, results were combined. For all patients undergoing autologous transplantation, 5-year actuarial overall survival (OS) was 34% ± 6%; 5-year event-free survival (EFS) was 26% ± 5%. For patients who responded to primary therapy, salvage therapy, or both, OS was 42% ± 7%; for nonresponders to prior therapy, OS was 14% ± 7%, P Ͻ 0.025. OS was better among patients responding to salvage therapy (50% ± 9%), than among patients who had a complete response to initial therapy, but failed to respond or were untested/unevaluable with respect to salvage therapy (26% ± 10%; P Ͻ 0.025). On multivariate analysis, response to salvage therapy was associated with survival following autologous transplantation (P Ͻ 0.005). Treatment related mortality was 9% overall and only 6% after G-CSF and GM-CSF were introduced into routine clinical practice. High-intensity preparative therapy is highly effective, with acceptable treatmentrelated mortality, in patients with IGL who have responded to induction therapy, salvage therapy, or both. The best responses are observed in patients responding to salvage therapy. Randomized prospective studies will be needed to further define the role of intensified preparative regimens. Bone Marrow Transplantation (2000) preparative regimens, long-term disease-free survival (DFS) has been associated with disease chemoresponsiveness. 3-7 However, even among patients with sensitive disease, long-term DFS has generally been seen in only 30-50% of patients. 2,5-8 Among patients with resistant disease, less than 10% survive long-term. 3,6 Intensification of the preparative regimen is one potential means of improving these clinical results. [9][10][11][12] Since 1986, we have studied two intensified preparative regimens in patients with relapsed or refractory IGL. One regimen added etoposide to the standard cyclophosphamide-TBI regimen, the other used augmented dose BCNU in combination with etoposide and cyclophosphamide. This report summarizes our experience with augmented preparative therapy in patients with relapsed or refractory IGL undergoing autologous transplantation. Patients and methods Patients and eligibilityRecords of all patients who received autologous stem cell transplantation (ASCT) at Vanderbilt University Medical Center or the affiliated Nashville Veteran's Affairs Hospital between September 1986 and June 1998 were reviewed. Patients were included in the study if both the initial and the most recent pathological material prior to transplantation were interpreted as IGL. Following review by two of the authors (WRM, TLM) at the time this report was prepared, patients with low-grade NHL evolving...

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“…[8][9][10] Various studies suggest that high-dose therapy, with or without stem cell support, of chemosensitive poor prognosis patients improves the percentage of patients achieving complete response as well as long-term survival. 4,[11][12][13][14][15][16] However there are currently no prospective randomized trials which have confirmed the benefit of high-dose therapy as firstline treatment of poor risk NHL patients. 2 Our primary aim was to determine the feasibility of an intensified induction therapy yielding a high response rate in young poor risk NHL patients, followed by high-dose consolidation in chemosensitive patients.…”

Section: Discussionmentioning

confidence: 99%

“…Various induction regimens derived from the original CHOP regimen have been evaluated in such patients, although alternate approaches incorporating etoposide have been used. 12,17 In this trial we chose to increase the doses of the two most active compounds, doxorubicin and cyclophosphamide, in combination with etoposide, which has shown its efficacy both as first-line therapy and in relapsing NHL patients. 17,18 Doxorubicin dose was limited to The only toxic death observed in the trial occurred on the first day of the first course in a patient who developed fatal tumor lysis syndrome, at the first dose level.…”

Section: Discussionmentioning

confidence: 99%

“…17 The response rate to BEAM therapy in the 16 evaluable patients was 69% as compared to 30% in 34 evaluable patients treated with high-dose busulfan/cyclophosphamide reported by Lee et al 20 On an intent-to-treat basis, 24 patients (73%) had achieved CR at the end of treatment, which is comparable to rates observed by other investigators. 12,19 The data suggest that intensification with BEAM contributed significantly to the favorable outcome of these high-risk patients, since half of the patients were in PR after induction therapy and all patients who had not reached CR after intensification underwent disease progression. It is however not possible to draw any conclusions on the benefit of the second intensification by ICE therapy in this limited series of patients.…”

Section: Discussionmentioning

confidence: 99%

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A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors

et al. 2000

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Patients with NHL and two or three factors of the International Prognostic Index (IPI) have a poor prognosis. We performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. Untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum LDH, ECOG performance status Ͼ1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1-2; etoposide days 1-3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3-4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76-99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64-78%) and the event-free survival 58% (95% CI 50-66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates. Leukemia (2000) 14, 2159-2165.

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Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.

Cited by 37 publications

References 35 publications

Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

Intensified preparative regimens and autologous transplantation in refractory or relapsed intermediate grade non-Hodgkin's lymphoma

A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors

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