Do We Need an Early Unfavorable (Intermediate) Stage of Hodgkin’s Lymphoma? Lena Specht, MD, PhD a, * , John Raemaekers, MD, PhD b a Departments of Oncology and Haematology, The Finsen Centre, Rigshospitalet, Copenhagen University Hospital, 9 Blegdamsvej, 2100 Copenhagen, Denmark b Department of Medicine, Division of Hematology, University Hospital of Nijmegen, P.O. Box 9101, Nijmegen HB 6500, The Netherlands T he Ann Arbor staging system for lymphomas remains the universally ac- cepted system for categorizing patients who have Hodgkin’s lymphoma [1]. Patients who have stage I/II disease are generally considered early stage, whereas patients who have stage III/IV are considered to have ad- vanced-stage disease. There is not complete consensus on this issue, however, as some consider stage IIB advanced and some consider stage IIIA early. Prediction of outcome by prognostic factors is important because patients may be separated accordingly into risk groups determining treatment selection. The Ann Arbor staging system cannot be relied on as the only prognostic tool in Hodgkin’s lymphoma, however. Many other features of prognostic impor- tance have become recognized, many of them related to the extent and volume of disease. The extent of disease may vary considerably in stages other than stage I, and the volume of disease in individual regions is not taken into ac- count at all in the Ann Arbor classification. The Cotswold modification of the staging system incorporates a designation for number of sites and bulk [2], but this modification has not been universally adopted. Numerous other prognostic factors for different Ann Arbor stages, presentations, treatments, and outcomes have been examined, and varying combinations of some of these factors are presently being used by different centers and groups worldwide [3,4]. DEFINITION OF INTERMEDIATE (EARLY UNFAVORABLE) STAGE In early-stage disease a separation into favorable and unfavorable (intermedi- ate-stage) disease based on the absence or presence of certain risk factors has been used by various groups for patient stratification in clinical trials. The clas- sification systems used by the German Hodgkin’s Study Group (GHSG), the *Corresponding author. E-mail address: lena.specht@rh.regionh.dk (L. Specht). 0889-8588/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.hoc.2007.07.002 hemonc.theclinics.com Hematol Oncol Clin N Am 21 (2007) 881–896 HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA