Treating childhood acute lymphoblastic leukemia without cranial irradiation

Ching Hon Pui, Dario Campana, Deqing Pei, W. Paul Bowman, John T. Sandlund, Sue C. Kaste, Raul C. Ribeiro, Jeffrey E. Rubnitz, Susana C. Raimondi, Mihaela Onciu, Elaine Coustan-Smith, Larry E. Kun, Sima Jeha, Cheng Cheng, Scott C. Howard, Vickey Simmons, Amy Bayles, Monika L. Metzger, James M. Boyett, Wing LeungRupert Handgretinger, James R. Downing, William E. Evans, Mary V. Relling

Research output: Contribution to journalArticle

718 Scopus citations

Abstract

BACKGROUND: Prophylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse. METHODS: We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted from treatment in all children with newly diagnosed ALL. A total of 498 patients who could be evaluated were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission-induction treatment. The duration of continuous complete remission in the 71 patients who previously would have received prophylactic cranial irradiation was compared with that of 56 historical controls who received it. RESULTS: The 5-year event-free and overall survival probabilities for all 498 patients were 85.6% (95% confidence interval [CI], 79.9 to 91.3) and 93.5% (95% CI, 89.8 to 97.2), respectively. The 5-year cumulative risk of isolated CNS relapse was 2.7% (95% CI, 1.1 to 4.3), and that of any CNS relapse (including isolated relapse and combined relapse) was 3.9% (95% CI, 1.9 to 5.9). The 71 patients had significantly longer continuous complete remission than the 56 historical controls (P = 0.04). All 11 patients with isolated CNS relapse remained in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blast cells at diagnosis and a high level of minimal residual disease (≥1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the genetic abnormality t(1;19)(TCF3-PBX1), any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. CONCLUSIONS: With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted from the treatment of childhood ALL. (ClinicalTrials.gov number, NCT00137111.)

Original languageEnglish (US)
Pages (from-to)2730-2741
Number of pages12
JournalNew England Journal of Medicine
Volume360
Issue number26
DOIs
StatePublished - Jun 25 2009

ASJC Scopus subject areas

  • Medicine(all)

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    Pui, C. H., Campana, D., Pei, D., Bowman, W. P., Sandlund, J. T., Kaste, S. C., Ribeiro, R. C., Rubnitz, J. E., Raimondi, S. C., Onciu, M., Coustan-Smith, E., Kun, L. E., Jeha, S., Cheng, C., Howard, S. C., Simmons, V., Bayles, A., Metzger, M. L., Boyett, J. M., ... Relling, M. V. (2009). Treating childhood acute lymphoblastic leukemia without cranial irradiation. New England Journal of Medicine, 360(26), 2730-2741. https://doi.org/10.1056/NEJMoa0900386