title: A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors.
abstract: Patients with NHL and two or three factors of the International Prognostic Index (IPI) have a poor prognosis. We performed a prospective trial of intensive induction therapy followed with high-dose consolidation in such patients to determine the feasibility of this approach, as well as the response rate and survival. Untreated patients with aggressive lymphoma under the age of 60 with two or three adverse prognostic factors (disseminated stage, increased serum LDH, ECOG performance status >1) were prospectively included between June 1995 and April 1998 in a trial evaluating intensive induction chemotherapy with the ACE regimen (adriamycin day 1; cyclophosphamide days 1-2; etoposide days 1-3), with G-CSF support. Patients in complete remission after induction received one course of intensification with stem cell support (BEAM regimen), whereas patients in partial response received two intensifications (BEAM, then ICE regimens). Thirty-three patients (median age 38 years) were included. All patients presented WHO grade 4 leukopenia and 84% grade 3-4 thrombocytopenia during induction. There was one toxic death during induction. Twenty-nine patients proceeded to high-dose consolidation, including 12 patients who received a second high-dose treatment. The overall response rate was 88% (95% CI 76-99%), both after induction therapy and treatment completion. Thirty-nine percent of the patients had achieved complete remission after induction, and 73% after treatment completion. With a median follow-up after treatment onset of 29 months, the projected 3-year overall survival was 71% (95% CI 64-78%) and the event-free survival 58% (95% CI 50-66%). Event-free survival was significantly shorter in patients who did not achieve CR after induction therapy or after treatment completion. Early therapeutic intensification after intensive induction chemotherapy is feasible in patients with poor prognosis aggressive NHL and shows promising response and survival rates.
authors.affiliation: Service d'Hématologie, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
authors.forename: C
authors.initials: C
authors.lastname: Dumontet
authors.forename: C
authors.initials: C
authors.lastname: Thieblemont
authors.forename: D
authors.initials: D
authors.lastname: Espinouse
authors.forename: F
authors.initials: F
authors.lastname: Bouafia
authors.forename: O
authors.initials: O
authors.lastname: Hequet
authors.forename: G
authors.initials: G
authors.lastname: Salles
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008558:Melphalan; D002330:Carmustine