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Cited by 1,215Acute Lymphoblastic Leukemia researchCNS Lymphoma Diagnosis and TreatmentChronic Lymphocytic Leukemia Research

Treating Childhood Acute Lymphoblastic Leukemia without Cranial Irradiation

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Pui, Ching-Hon, Campana, Dario, Pei, Deqing, Bowman, W. Paul, Sandlund, John T., Kaste, Sue C., Ribeiro, Raul C., Rubnitz, Jeffrey E. +16 more·2009·New England Journal of Medicine
DOI 10.1056/nejmoa0900386PMC PMC2754320
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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 (> or = 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.)

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  • ALL patients are treated with a combination of ~10 different chemotherapy agents through several phases lasting 2-3 years.

    “ALL patients are treated with a combination of ~10 different chemotherapy agents through several phases lasting 2–3 years (Inaba et al., 2013; Pui, Robison, & Look, 2008; Pui et al., 2009).”

    From Brain structure, working memory and response inhibition in childhood leukemia survivors (2017) · cites this paper as Pui et al., 2009

    The Methods > Treatment passages describe multiple chemotherapy agents given across induction, consolidation, and continuation; continuation lasted 120 weeks for girls and 146 weeks for boys. But this is a study of children with ALL, with treatment varying by risk group, so it does not establish that all ALL patients receive approximately ten agents over 2–3 years. (LLM, conf=0.83)

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Authors
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., Leung, W., Handgretinger, R., Downing, J. R., Evans, W. E., & Relling, M. V.
Affiliations
  • St. Jude Children's Research Hospital (US)
  • University of Tennessee Health Science Center (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2009-06-25
Volume
360
Issue
26
Pages
2730-2741
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa0900386
PMC
PMC2754320
OpenAlex
W2059999488
Cited by
1,215
References
0
Citations by year
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FWCI
89.75
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (U01CA060419, CA 36401, R01CA036401, R01CA060419, CA 78224, CA-51001, CA60419, CA21765, R01CA078224, R37CA036401, P30CA021765, R01CA051001)
  • National Institute of General Medical Sciences (GM61393, U01GM061393)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
  • Health Sciences › Medicine › Neurology › CNS Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
Keywords
childhood acute lymphoblastic leukemia, prophylactic cranial irradiation, central nervous system relapse, CNS leukemia, minimal residual disease, continuous complete remission, event-free survival, overall survival, risk factors, T-cell immunophenotype, avascular necrosis, fungal infection
MeSH terms
Adolescent, Antineoplastic Combined Chemotherapy Protocols, Asparaginase, Child, Child, Preschool, Combined Modality Therapy, Cyclophosphamide, Daunorubicin, Dexamethasone, Humans, Infant, Methotrexate, Remission Induction, Risk Factors, Vincristine, Mercaptopurine, Survival Analysis, Cranial Irradiation, Central Nervous System Neoplasms, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Secondary Prevention

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