title: Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a children's cancer group report.
abstract: Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol ('Orange') to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOP-based induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass > or = one-third thoracic diameter at T5 and/or LDH > or =2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard- vs. high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 +/- 7% and 80 +/- 7%, respectively. The 5-year EFS and OS were significantly better in the standard- vs. high-risk subgroups (100% vs. 61 +/- 11%) (P < 0.003) and (100% vs. 65 +/- 11%) (P < 0.01), respectively. Lactate dehydrogenase (LDH) > or =2 x normal (NL) was associated with significantly poorer outcomes (LDH > or =2 x NL vs. <2 x NL) (5-year EFS: 55 +/- 12% vs. 100%) (P < 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH <2 x NL) and Murphy stage III disease.
authors.affiliation: Children's Hospital of New York, Columbia University, New York, NY, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Cairo
authors.forename: M D
authors.initials: MD
authors.lastname: Krailo
authors.forename: M
authors.initials: M
authors.lastname: Morse
authors.forename: R J
authors.initials: RJ
authors.lastname: Hutchinson
authors.forename: R E
authors.initials: RE
authors.lastname: Harris
authors.forename: C R
authors.initials: CR
authors.lastname: Kjeldsberg
authors.forename: M E
authors.initials: ME
authors.lastname: Kadin
authors.forename: E
authors.initials: E
authors.lastname: Radel
authors.forename: L J
authors.initials: LJ
authors.lastname: Steinherz
authors.forename: E
authors.initials: E
authors.lastname: Morris
authors.forename: J L
authors.initials: JL
authors.lastname: Finlay
authors.forename: A T
authors.initials: AT
authors.lastname: Meadows
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D010865:Pilot Projects; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D007770:L-Lactate Dehydrogenase; D008727:Methotrexate