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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.
AuthorsM S Cairo, M D Krailo, M Morse, R J Hutchinson, R E Harris, C R Kjeldsberg, M E Kadin, E Radel, L J Steinherz, E Morris, J L Finlay, A T Meadows
JournalLeukemia (Leukemia) Vol. 16 Issue 4 Pg. 594-600 (Apr 2002) ISSN: 0887-6924 [Print] England
PMID11960338 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • L-Lactate Dehydrogenase
  • Methotrexate
Topics
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • L-Lactate Dehydrogenase (metabolism)
  • Lymphoma, Non-Hodgkin (drug therapy, enzymology, pathology)
  • Male
  • Methotrexate (administration & dosage)
  • Neoplasm Staging
  • Pilot Projects
  • Prognosis
  • Treatment Outcome

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