Fractionated cyclophosphamide and back to back high dose methotrexate and cytosine arabinoside improves outcome in patients with stage III high grade small non-cleaved cell lymphomas (Snccl): A randomized trial of the pediatric oncology group

M. L. Brecher, M. R. Schwenn, M. J. Coppes, W. P. Bowman, M. P. Link, C. W. Berard, J. J. Shuster, S. B. Murphy

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27 Scopus citations


Background. The Pediatric Oncology Group (POG) conducted a two-arm, randomized study for the treatment of children and adolescents with stage III small, non-cleaved cell lymphoma (SNCCL). Regimen A, based on the group's previous best treatment for this group of patients, included cyclophosphamide (CTX) and high-dose methotrexate (MTX), as well as vincristine (VCR), prednisone (PRED), and intrathecal (IT) chemoprophylaxis. Regimen B, based on a single institution pilot study (Total B therapy), consisted of two rapidly alternating chemotherapy combinations (CTX, VCR, doxorubicin; MTX, and cytarabine (Ara-C) plus coordinated IT chemotherapy. Procedure. One hundred thirty-four consecutive patients were entered on this study. Seventy patients were randomized to Regimen A, and 64 patients to Regimen B. One hundred and twenty-two patients are eligible for response. Results. Complete remission (CR) was achieved by 81% (52/64) of patients on Regimen A, and 95% (55/58) of patients on Regimen B (p = 0.014 one-sided). The two-year event-free survival (EFS) is 64% (SE = 6%) on Regimen A, and 79% (SE = 6%) on Regimen B (p = 0.027 by one-sided logrank test). No patient has relapsed on either regimen after a year from diagnosis, although one patient had a second malignancy at day 371. Severe, but manageable, hematologic toxicity was seen in the majority of patients on both regimens, but was more frequent on Regimen B. Conclusions. We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short, six-month chemotherapy regimen of fractionated CTX alternated with coordinated MTX and Ara-C. Results suggest that drug schedule, not simple drug selection, influences outcome.

Original languageEnglish
Pages (from-to)526-533
Number of pages8
JournalMedical and Pediatric Oncology
Issue number6
StatePublished - 13 Oct 1997



  • Dose intensification
  • Fractionated cyclophosphamide
  • High-dose methotrexate
  • Small non-cleaved cell lymphoma

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