Hagenbeek, A.

High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients (Article)

2009-02-01T00:00:00Z

Mantle cell lymphoma (MCL) has a dismal outcome when treated with conventional chemotherapy. This single arm phase 2 study evaluated intensive consolidation treatment of patients with newly diagnosed MCL up to the age of 65 years, responsive to R-CHOP (rituximab, cyclophosphamide, oncovin, adriamycin, prednisolone). Endpoints for evaluation were toxicity, failure-free survival (FFS) and overall survival (OS). Eighty-seven patients were treated with three cycles of R-CHOP. Sixty-six patients responded to R-CHOP with at least a partial response, 62 continued protocol treatment with high-dose cytarabine (Ara-C; 2000 mg/m2, bid. over 4 d) and 61 patients received rituximab and stem cell harvest, followed by BEAM (carmustine, etoposide, Ara-C, melphalan) and autologous stem cell rescue. Non-haematological toxicity, grades III and IV, was seen in 8% of the patients after R-CHOP, in 22% after high-dose Ara-C and in 55% after BEAM. The overall response rate was 70% (complete response rate 64%, partial response rate 6%), FFS and OS at 4 years were 36 ± 7% and 66 ± 6%, respectively. The FFS and OS at 4 years from the evaluation after BEAM in the 61 R-CHOP responsive patients was 46 ± 9% and 79 ± 7%, respectively. In conclusion, high-dose Ara-C and BEAM with stem cell rescue in newly diagnosed MCL patients responsive to R-CHOP is a manageable treatment with respect to toxicity. This regimen leads to long-term, but probably not durable, remissions.

First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: Results of a phase 1/2 trial (Article)

2008-06-15T00:00:00Z

Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/ responders was 8.8/ 32.6 months, and median duration of response was 29.9 months at a median/ maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274.

Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease (Article)

2007-11-08T00:00:00Z

BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year eventfree survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P = 0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041.) Copyright

Machten van tien (Inaugural Lecture)

1994-03-18T00:00:00Z

Cost-effectiveness of autologous bone marrow transplantation in comparison to conventional chemotherapy in patients with non-Hodgkin's lymphoma (Research Paper)

1994-01-01T00:00:00Z

A prospective randomized clinical trial with simultaneous data collection for an economic appraisal was carried out to assess the effectiveness, quality of life and cost implications of ABMT vs standard chemotherapy in slowly responding patients with intermediate- and high-grade malignant non-Hodgkin's lymphoma (NHL). The patients had a partial response after three cycles of chemotherapy and had no evidence of BM involvement of NHL. The overall and disease-free survival at 3 years were 61% and 60%, respectively, in the ABMT group and 85% and 77% in the CHOP group (P = NS). Moreover, there were more (severe) complications and symptoms in the ABMT than in the CHOP group. The average costs of CHOP chemotherapy were significantly lower than the average costs in the ABMT group (CHOP: US$ 3118 vs ABMT: US$ 34,447). Considering long-term consequences the ABMT group was more expensive (US$ 34,580) and patients experienced 0.14 life years and 0.22 quality adjusted life years less than the CHOP group (discount rate 5%). As a result, changing therapy from CHOP to ABMT, as primary treatment in slow responders to CHOP, can not be recommended as the required additional investment does not produce health gains in terms of survival or quality of life.