Annals of Oncology Advance Access originally published online on June 6, 2005
Annals of Oncology 2005 16(8):1359-1365; doi:10.1093/annonc/mdi248
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© 2005 European Society for Medical Oncology
High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study
1 University Hospital Cologne, First Department of Internal Medicine, Germany 2 Carl-Thiem-Hospital Cottbus, Second Medical Hospital, Germany 3 University Hospital Charitè Berlin, Section for Hematology/Oncology, Germany4 University Hospital Bonn, Department of Internal Medicine, Germany 5 Klinikum Oldenburg, Department II of Internal Medicine, Germany 6 University Hospital Lübeck, Section for Hematology/Oncology, Germany
* Correspondence to: Dr A. Josting, First Department of Internal Medicine, University Hospital Cologne, Joseph-Stelzmann-Str 9, 50924 Cologne, Germany. Email: andreas.josting{at}uni-koeln.de
Background: Combination chemotherapy can cure patients with non-Hodgkin's lymphoma (NHL), but those who suffer treatment failure or relapse still have a poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) can improve the outcome of these patients. We evaluated an intensified high-dose sequential chemotherapy program with a final myeloablative course.
Patients and methods: Inclusion criteria were age 18–65 years, histologically proven primary progressive or relapsed aggressive NHL and eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40 mg (day 1–4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day 51); patients with partial (PR) or complete remission (CR) received cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and etoposide 500 mg/m2 (day 58–62). The final myeloblative course was BEAM: cytarabine 200 mg/m2 12q (day 81–84), etoposide 150 mg/m2 12q (day 81–84), melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT.
Results: Fifty-seven patients (median age 43 years, range 24–65) were enrolled: 23 (40%) patients were refractory to primary therapy and 34 (60%) patients had relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63% PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11% PR). Toxicity was tolerable. Median follow-up was 25 months (range 1–76 months). Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25% and 47% for all patients, respectively. FF2F at 2 years for patients with relapse and for patients refractory to primary therapy were 35% and 9% (P=0.0006), respectively. OS at 2 years for patients with relapse and for patients refractory to primary therapy were 58% and 24% (P=0.0044), respectively.
Conclusions: We conclude that this regimen is feasible, tolerable and effective in patients with relapsed NHL. In contrast, the results in patients with progressive disease are unsatisfactory. This program is currently being modified by addition of rituximab for patients with relapsed aggressive NHL.
Key words: high-dose chemotherapy, non-Hodgkin's lymphoma, relapse
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