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Br J Haematol. 2019 Jun 10. doi: 10.1111/bjh.16014. [Epub ahead of print]

Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children's Oncology Group.

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Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Department of Pediatrics, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
Division of Pediatric Hematology/Oncology, Robert Wood Johnson Medical School, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Department of Biostatistics, University of Florida, Children's Oncology Group, Statistics and Data Center, Gainesville, FL, USA.
Children's Oncology Group, Statistics and Data Center, Monrovia, CA, USA.
Department of Therapeutic Radiology, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT, USA.
Department of Radiation Oncology, University of Toronto, Princess Margaret Hospital, Toronto, Ontario, Canada.
Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Department of Radiology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
Division of Pediatric Hematology, Oncology and BMT, Medical College of Wisconsin, Milwaukee, WI, USA.


The AHOD0831 study for paediatric patients with high risk Hodgkin lymphoma tested a response-based approach designed to limit cumulative alkylator exposure and reduce radiation volumes. Patients (Stage IIIB/IVB) received two cycles of ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide). Rapid early responders [RER, no positron emission tomography (PET) activity above mediastinal blood pool] were consolidated with 2 cycles of ABVE-PC. Slow early responders (SER) received 2 cycles of ifosfamide/vinorelbine and 2 cycles of ABVE-PC. Radiotherapy was administered to sites of initial bulk and/or SER. By intent-to-treat analysis, 4-year second event-free survival (EFS; freedom from second relapse or malignancy) was 91·9% [95% confidence interval (CI): 86·1-95·3%], below the projected baseline of 95% (P = 0·038). Five-year first EFS and overall survival (OS) rates are 79·1% (95% CI: 71·5-84·8%) and 95% (95% CI: 88·8-97·8%). Eight of 11 SER patients with persistent PET positive lesions at the end of chemotherapy had clinical evidence of active disease (3 biopsy-proven, 5 with progressive disease or later relapses). Although this response-directed approach did not reach the ambitiously high pre-specified target for second EFS, EFS and OS rates are comparable with results of recent trials despite the reduction in radiotherapy volumes from historical involved fields. Persistent PET at end of chemotherapy identifies a cohort at an especially high risk for relapse/early progression.


Hodgkin lymphoma; paediatric; positron emission tomography; radiation; response adapted


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