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.

Abstract

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.

• Authors: Gustaaf W van Imhoff, Bronno van der Holt, Marius A Mackenzie, Mars B Van't Veer, Pierre W Wijermans, Gerrit J Ossenkoppele, Harry C Schouten, Pieter Sonneveld, Monique M C Steijaert, Philip M Kluin, Hanneke C Kluin-Nelemans, Leo F Verdonck, Dutch-Belgian Hemato-Oncology Cooperative Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 23 Issue 16 Pg. 3793-801 (Jun 01 2005) ISSN: 0732-183X [Print] United States
• PMID: 15809447 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Mitoxantrone
• Prednisone

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Combined Modality Therapy
• Cyclophosphamide (administration & dosage)
• Doxorubicin (administration & dosage)
• Etoposide (administration & dosage)
• Female
• Humans
• Lymphoma, Non-Hodgkin (therapy)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage)
• Prednisone (administration & dosage)
• Prognosis
• Remission Induction
• Risk Factors
• Stem Cell Transplantation
• Survival Rate
• Transplantation, Autologous
• Treatment Outcome
• Vincristine (administration & dosage)