Impact of three courses of intensified CHOP prior to high-dose sequential therapy followed by autologous stem-cell transplantation as first-line treatment in poor-risk, aggressive non-hodgkin's lymphoma: comparative analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40.

Autor:	van Imhoff GW; Department of Hematology, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands. g.w.van.imhoff@int.umcg.nl, van der Holt B, Mackenzie MA, Van't Veer MB, Wijermans PW, Ossenkoppele GJ, Schouten HC, Sonneveld P, Steijaert MM, Kluin PM, Kluin-Nelemans HC, Verdonck LF
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2005 Jun 01; Vol. 23 (16), pp. 3793-801. Date of Electronic Publication: 2005 Apr 04.
DOI:	10.1200/JCO.2005.07.039
Abstrakt:	Purpose: Timing, appropriate amount, and composition of treatment before high-dose therapy and autologous stem-cell transplantation (ASCT) in patients with poor-risk, aggressive non-Hodgkin's lymphoma (NHL) are still unknown. We conducted two consecutive multicenter phase II trials with up-front, high-dose, sequential chemotherapy and ASCT in poor-risk, aggressive NHL. Both trials had identical inclusion criteria and only differed in amount and duration of induction treatment before ASCT. Patients and Methods: Between 1994 and 2001, 147 newly diagnosed, poor-risk, aggressive NHL patients, age < or = 65 years with stage III to IV and lactate dehydrogenase (LDH) more than 1.5x upper limit of normal (ULN), entered the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) -27 and HOVON-40 trials. Treatment in HOVON-27 consisted of two up-front, high-dose induction courses followed by carmustine, etoposide, cytarabine, and melphalan plus ASCT in responding patients. In HOVON-40, the same treatment was preceded by three intensified courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Results: Patient characteristics in both trials were comparable: 80% had diffuse large B-cell lymphoma, 77% had stage IV disease, and median LDH levels were 3.1x ULN. Complete remission (CR) in both trials was 45% to 51%. Before ASCT, CR was 14% in HOVON-27 versus 28% in HOVON-40 (P = .03). Treatment failure was similar (27%). Four-year survival estimates in HOVON-27 compared with HOVON-40 were overall survival, 21% v 50% (P = .007); event-free survival, 15% v 49% (P = .0001); and disease-free survival, 34% v 74% (P = .008). This different outcome favoring HOVON-40 remained highly significant when correcting for competing risk factors in multivariate analysis. Conclusion: In patients with poor-risk, aggressive NHL, addition of intensified CHOP before up-front, high-dose, sequential therapy and ASCT significantly improved the duration of response and survival.
Databáze:	MEDLINE
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