title: High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging.
abstract: We previously reported that three risk factors (RF): initial remission duration <1 year, active B symptoms, and extranodal disease predict outcome in relapsed or refractory Hodgkin lymphoma (HL). Our goal was to improve event-free survival (EFS) for patients with multiple RF and to determine if response to salvage therapy impacted outcome. We conducted a phase II intent-to-treat study of tailored salvage treatment: patients with zero or one RF received standard-dose ifosfamide, carboplatin, and etoposide (ICE); patients with two RF received augmented ICE; patients with three RF received high-dose ICE with stem cell support. This was followed by evaluation with both computed tomography and functional imaging (FI); those with chemosensitive disease underwent high-dose chemoradiotherapy and autologous stem cell transplantation (ASCT). There was no treatment-related mortality. Compared to historical controls this therapy eliminated the difference in EFS between the three prognostic groups. Pre-ASCT FI predicted outcome; 4-year EFS rates was 33% vs. 77% for patients transplanted with positive versus negative FI respectively, P = 0.00004, hazard ratio 4.61. Risk-adapted augmentation of salvage treatment in patients with HL is feasible and improves EFS in poorer-risk patients. Our data suggest that normalisation of FI pre-ASCT predicts outcome, and should be the goal of salvage treatment.
authors.affiliation: Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. moskowic@mskcc.org
authors.forename: Craig H
authors.initials: CH
authors.lastname: Moskowitz
authors.forename: Joachim
authors.initials: J
authors.lastname: Yahalom
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Daniel
authors.initials: D
authors.lastname: Filippa
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Tarun
authors.initials: T
authors.lastname: Kewalramani
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Moskowitz
authors.forename: Robert David
authors.initials: RD
authors.lastname: Rice
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Maragulia
authors.forename: Jill
authors.initials: J
authors.lastname: Vanak
authors.forename: Tanya
authors.initials: T
authors.lastname: Trippett
authors.forename: Paul
authors.initials: P
authors.lastname: Hamlin
authors.forename: Steven
authors.initials: S
authors.lastname: Horowitz
authors.forename: Ariela
authors.initials: A
authors.lastname: Noy
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
authors.forename: Carol
authors.initials: C
authors.lastname: Portlock
authors.forename: David
authors.initials: D
authors.lastname: Straus
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004812:Epidemiologic Methods; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D016879:Salvage Therapy / Q000379:methods; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide