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Late isolated central nervous system relapse in childhood B-cell acute lymphoblastic leukemia treated with intensified systemic therapy and delayed reduced-dose cranial radiation: A report from the Children’s Oncology Group study AALL02P2
  • +7
  • Caroline Hastings,
  • Yichen Chen,
  • Meenakshi Devidas,
  • A. Ritchey,
  • Naomi Winick,
  • William Carroll,
  • Stephen Hunger,
  • Brent Wood,
  • Robert Marcus,
  • Julio Barredo
Caroline Hastings
UCSF Benioff Children's Hospital Oakland

Corresponding Author:caroline.hastings@ucsf.edu

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Yichen Chen
St Jude Children's Research Hospital
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Meenakshi Devidas
Saint Jude Children's Research Hospital
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A. Ritchey
Children’s Hospital of Pittsburgh of UPMC
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Naomi Winick
UT Southwestern
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William Carroll
New York University Medical Center
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Stephen Hunger
Children's Hospital of Philadelphia
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Brent Wood
Children's Hospital of Los Angeles
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Robert Marcus
Ascension Sacred Heart Hospital Pensacola
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Julio Barredo
University of Miami
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Abstract

Background: Patients with late, occurring ≥18 months post-diagnosis, isolated central nervous relapse (iCNS-R) of B-acute lymphoblastic leukemia (ALL) have excellent outcomes with chemotherapy plus cranial radiotherapy, with 5-yr overall survival (OS) approaching 80% in POG 9412. Subsequent relapse and radiation-related morbidity remain the causes of treatment failure and long-term sequelae. COG AALL02P2 aimed to maintain outcomes in patients with late iCNS-R using intensified chemotherapy and a decrease in cranial irradiation from 1800 to 1200 cGy. Procedures: COG AALL02P2 enrolled 118 eligible patients with B-ALL and early iCNS-R who received intensified systemic therapy, triple intrathecal chemotherapy and 1200 cGy cranial irradiation delivered at 12 months, with maintenance chemotherapy continuing until104 weeks post-diagnosis. Results: The 3-yr event-free and overall survival (EFS) and OS were 64.3±4.5% and 79.6±3.8%, with 46.1% (18/39) of relapses including the CNS. Of the 112 patients who completed therapy, 78 received protocol-specified radiation. Study enrollment was closed after interim monitoring analysis showed inferior EFS compared to POG 9412. Patients with initial NCI standard risk classification fared better than high risk patients. Conclusions: COG AALL02P2 showed inferior EFS but similar OS compared to POG 9412. Limitations included a small sample size, more intensive prior therapies, and a significant number of patients (34/118, 29%) who did not receive protocol-directed radiation due to early relapse prior to 1 year or did not otherwise follow the treatment plan. New approaches are needed to improve outcome for these patients and determine the optimal timing and dose of cranial radiation in the treatment of iCNS-R.
10 Feb 2021Submission Checks Completed
10 Feb 2021Assigned to Editor
10 Feb 2021Submitted to Pediatric Blood & Cancer
16 Feb 2021Reviewer(s) Assigned
10 Mar 2021Review(s) Completed, Editorial Evaluation Pending
02 Apr 2021Editorial Decision: Revise Major
16 Jun 20211st Revision Received
16 Jun 2021Submission Checks Completed
16 Jun 2021Assigned to Editor
18 Jun 2021Reviewer(s) Assigned
13 Jul 2021Review(s) Completed, Editorial Evaluation Pending
13 Jul 2021Editorial Decision: Accept