Clinical trial NCT00025259: Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease
Official title: A Phase III Groupwide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Childhood Lymphocyte-Depleted Classical Hodgkin Lymphoma
Childhood Mixed Cellularity Classical Hodgkin Lymphoma
Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma
Childhood Nodular Sclerosis Classical Hodgkin Lymphoma
Stage I Childhood Hodgkin Lymphoma
Stage II Childhood Hodgkin Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage IV Childhood Hodgkin Lymphoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 1734
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase III trial is studying different chemotherapy regimens given with or without radiation therapy to compare how well they work in treating children with newly diagnosed Hodgkin's disease. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chemotherapy is more effective with or without additional chemotherapy and/or radiation therapy in treating Hodgkin's disease.

Detailed description: OBJECTIVES:

I. To compare response-based therapy to standard therapy for intermediate risk Hodgkin disease.

II. To determine whether involved field radiation therapy (IFRT) can be eliminated based upon early and complete response to multiagent chemotherapy.

III. To determine whether the addition of an additional two cycles of chemotherapy (DECA) can improve outcome in those with a slow early response to standard chemotherapy.

IV. To prospectively collect information on the individual prognostic significance of the following presenting factors: erythrocyte sedimentation rate, circulating levels of IL-10, each of the "B" symptoms - fever, night sweats, weight loss, nodal aggregate \> 6 cm, large mediastinal mass \> 1/3 thoracic diameter and number of involved nodal sites, histology, albumin, blood counts, sex and age.

V. To study the reliability and utility of \[18F\] -Fluorodeoxyglucose (FDG) Imaging (PET scans) as an imaging modality in Hodgkin disease.

VI. To determine the frequency and severity of late effects of therapy including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity and second malignant neoplasms.

VII. To serve as the therapeutic companion to biology studies in Hodgkin disease and correlate those results with response to therapy, event free-survival and overall survival.

OUTLINE: This is a randomized, multicenter study.

ARM I (ALL PATIENTS-OFF THERAPY BEFORE CALLBACK-INDUCTION CHEMOTHERAPY \[ABVE-PC\]): Patients receive doxorubicin intravenously (IV) over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. At the end of initial chemotherapy, patients undergo evaluation for response. Patients with less than 60% disease reduction are considered to have slow early response (SER). Patients with 60% or more disease reduction are considered to have rapid early response (RER).

RER: Patients receive 2 additional courses of ABVE-PC chemotherapy. After completion of treatment, patients are randomized to 1 of 4 treatment arms.

ARM II: Patients with sustained complete response (CR) undergo involved field radiation therapy (IFRT) approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.

ARM III: Patients with sustained CR receive no further treatment.

ARM IV: Patients with very good partial response (VGPR), partial response (PR) or stable disease (SD) undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.

ARM V: Patients with progressive disease are taken off therapy and treated their physician's discretion.

SER: Patients are randomized to 1 of 2 treatment arms.

ARM VI: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, cytarabine IV over 3 hours on days 1-2, and receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of ABVE-PC chemotherapy.

ARM VII: Patients receive 2 courses of ABVE-PC chemotherapy.

In both SER arms, patients with sustained CR or PR undergo IFRT approximately 3 weeks after the last course of chemotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed, pathologically confirmed Hodgkin disease (all histologies) are eligible for this protocol if they meet the following clinical stage guidelines:

  * All Stage IB regardless of bulk disease
  * All Stage IIB regardless of bulk disease
  * Stage IA only with bulk disease
  * Stage IIA only with bulk disease
  * All Stage IAE, IIAE regardless of bulk disease
  * All Stage IIIA, IIIAE, IIIAS, IIIAE+S regardless of bulk disease
  * All Stage IVA, IVAE regardless of bulk disease
* May not be staged by laparotomy alone

  * Surgically staged patients must also have presurgical staging
* Bilirubin no greater than 1.5 times normal
* SGOT or SGPT less than 2.5 times normal
* Creatinine no greater than 1.5 times normal
* Creatinine clearance greater than 40 mL/min
* Radioisotope glomerular filtration rate greater than 70 mL/min
* Shortening fraction at least 27% by echocardiogram
* Ejection fraction at least 50% by MUGA
* No pathologic prolongation of QTc interval on 12-lead electrocardiogram
* FEV_1/FVC greater than 60% by pulmonary function test
* Pulse oximetry greater than 94%
* No evidence of dyspnea at rest
* No exercise intolerance
* Adequate venous access
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No prior chemotherapy
* At least 1 month since prior corticosteroids except prednisone for respiratory distress
* No prior radiotherapy

Primary outcomes:
measure: Event-free Survival
timeFrame: 5 years
Secondary outcomes:
measure: Disease Response Assessed by Modified RECIST Criteria
timeFrame: Protocol therapy: the overall duration of which is: (n=1527) an average of 137.1 days, median 133.0 days, interquartile range: 101.0, 164.0 days.
measure: Grade 3 or 4 Non-hematologic Toxicity
timeFrame: Protocol therapy: the overall duration of which is: (n=1684) an average of 137.3 days, median 133.0 days, interquartile range: 101.0, 164.0 days.
measure: Overall Survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center
state: Florida
city: Fort Myers
country: United States
facility: Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital/Joe DiMaggio Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Miami
country: United States
facility: Baptist Hospital of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic - Orlando
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Boise
country: United States
facility: Saint Luke's Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital New Orleans
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Clinical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Kalamazoo Center for Medical Studies
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital-Royal Oak
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: University of Missouri - Ellis Fischel
state: Missouri
city: Kansas City
country: United States
facility: The Childrens Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation CCOP
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Brooklyn
country: United States
facility: Brooklyn Hospital Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University/Herbert Irving Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Asheville
country: United States
facility: Mission Hospital-Memorial Campus
state: North Carolina
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Fargo
country: United States
facility: Sanford Medical Center-Fargo
state: North Dakota
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital/Toledo Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at Saint Francis
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Greenville
country: United States
facility: Greenville Cancer Treatment Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Chattanooga
country: United States
facility: T C Thompson Children's Hospital
state: Tennessee
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Science Center-Amarillo
state: Texas
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Childrens Hospital-King's Daughters
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center - Portsmouth
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Carilion Clinic Children's Hospital
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital and Health Center
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Center
state: Washington
city: Charleston
country: United States
facility: West Virginia University Charleston
state: West Virginia
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital-Adelaide
state: South Australia
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John's
country: Canada
facility: Janeway Child Health Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Chedoke Hospital at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: Petah Tikua
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Grafton
country: New Zealand
facility: Starship Children's Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: San Juan
country: Puerto Rico
facility: San Jorge Children's Hospital
city: Geneva
country: Switzerland
facility: Swiss Pediatric Oncology Group - Geneva
Study officials:
affiliation: Children's Oncology Group
name: Debra Friedman
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnston RL, Mottok A, Chan FC, Jiang A, Diepstra A, Visser L, Telenius A, Gascoyne RD, Friedman DL, Schwartz CL, Kelly KM, Scott DW, Horton TM, Steidl C. A gene expression-based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma. Blood. 2022 Feb 10;139(6):889-893. doi: 10.1182/blood.2021011941.
citation: Giulino-Roth L, Pei Q, Buxton A, Bush R, Wu Y, Wolden SL, Constine LS, Kelly KM, Schwartz CL, Friedman DL. Subsequent malignant neoplasms among children with Hodgkin lymphoma: a report from the Children's Oncology Group. Blood. 2021 Mar 18;137(11):1449-1456. doi: 10.1182/blood.2020007225.
citation: Welch JJG, Schwartz CL, Higman M, Chen L, Buxton A, Kanakry JA, Kahwash SB, Hutchison RE, Friedman DL, Ambinder RF. Epstein-Barr virus DNA in serum as an early prognostic marker in children and adolescents with Hodgkin lymphoma. Blood Adv. 2017 Apr 24;1(11):681-684. doi: 10.1182/bloodadvances.2016002618. eCollection 2017 Apr 25.
citation: Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. doi: 10.1200/JCO.2013.52.5410. Epub 2014 Oct 13.