Originally published as JCO Early Release 10.1200/JCO.2005.07.039 on April 4 2005

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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

From the Department of Hematology, University Medical Center Groningen; Department of Pathology, Groningen University Hospital; Groningen; Data Center and Department of Internal Medicine, Erasmus MC, Rotterdam; Department of Internal Medicine, University Medical Center Nijmegen St Radboud, Nijmegen; Department of Internal Medicine, Leyenburg Hospital, The Hague; Department of Hematology, VU Medical Center, Amsterdam; Department of Internal Medicine, University Hospital Maastricht, Maastricht; and Department of Hematology, University Medical Center Utrecht, Utrecht, the Netherlands

Address reprint requests to Gustaaf W. van Imhoff, MD, Department of Hematology, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands; e-mail: g.w.van.imhoff{at}int.umcg.nl

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 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.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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