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

Br J Haematol. 2019 Oct;187(1):39-48. doi: 10.1111/bjh.16014. Epub 2019 Jun 10.

Abstract

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.

Keywords: Hodgkin lymphoma; paediatric; positron emission tomography; radiation; response adapted.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bleomycin / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Drug Monitoring / methods
  • Etoposide / administration & dosage
  • Female
  • Hodgkin Disease / diagnostic imaging
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / radiotherapy
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Neoplasm Staging
  • Positron-Emission Tomography / methods
  • Prednisone / administration & dosage
  • Prospective Studies
  • Radiotherapy, Adjuvant
  • Recurrence
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vinorelbine / administration & dosage
  • Young Adult

Substances

  • Bleomycin
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Vinorelbine
  • Ifosfamide
  • Prednisone