Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

As the treatment of Hodgkin lymphoma has improved, factors that influence outcome have diminished in importance. Several factors, however, continue to influence the success and choice of therapy. These factors are interrelated in the sense that disease stage, bulk, and biologic aggressiveness are frequently codependent. Further complicating the identification of prognostic factors are their use in determining the aggressiveness of therapy. For example, in a report from the German-Austrian Pediatric multicenter trial DAL-HD-90, bulk disease was not a prognostic factor for outcome on multivariate analysis. However, in this study boost irradiation doses were given to patients who had post-chemotherapy residual disease, which could have obfuscated the relevance of bulky disease at presentation.[1] This underscores the complexity in determining prognostic factors.

Pretreatment factors associated with an adverse outcome in one or more studies include advanced stage of disease, the presence of B symptoms, the presence of bulk disease, extranodal extension, male sex, and elevated erythrocyte sedimentation rate. Examples from selected multi-institutional studies are discussed here. In the German Pediatric Oncology and Hematology Group (GPOH) GPOH-95 study, B symptoms, histology, and male sex were adverse prognostic factors for event-free survival on multivariate analysis.[2] In 320 children with clinically staged Hodgkin lymphoma treated in the Stanford-St. Jude-Dana Farber Cancer Institute consortium, male gender; stage IIB, IIIB, or IV disease; white blood cell count 11,500/mm³ or higher; and hemoglobin lower than 11.0g/dL were significant prognostic factors for inferior disease-free survival and overall survival. Prognosis was also associated with the number of adverse factors.[3] In the CCG-5942 study, the combination of B symptoms and bulky disease was associated with an inferior outcome.[4]

There is some controversy as to whether histology is an important prognostic factor.[5] Serum markers that have been associated with an adverse outcome include soluble vascular cell adhesion molecule-1,[6] tumor necrosis factor,[7] soluble CD30,[8] beta-2 microglobulin,[9] transferrin, and serum IL-10 level.[10] High levels of caspase 3 in Reed-Sternberg (R-S) cells have been associated with a favorable outcome.[11]

The rapidity of response to initial cycles of chemotherapy also appears to be prognostically important and is being used in the research setting to determine subsequent therapy.[12-14] Positron emission tomography (PET) scanning is being evaluated as a method to assess early response in pediatric Hodgkin lymphoma. Fluorodeoxyglucose (FDG)-PET avidity after two cycles of chemotherapy for Hodgkin lymphoma in adults has been shown to predict treatment failure and progression-free survival.[15,16][Level of evidence: 2Diii][17] Further studies are required to assess the magnitude of the prognostic effect with different chemotherapy regimens and to determine whether improved outcome can be achieved by altering the therapeutic strategy based on early PET response.

Although prognostic factors will continue to change because of risk stratification and choice of therapy, parameters such as disease stage, bulk, systemic symptomatology, and early response to chemotherapy are likely to remain relevant to outcome. Nonetheless, as therapy becomes increasingly tailored to prognostic factors and therapeutic response, overall outcome should become less affected by these parameters.

References

1. Dieckmann K, Pötter R, Hofmann J, et al.: Does bulky disease at diagnosis influence outcome in childhood Hodgkin's disease and require higher radiation doses? Results from the German-Austrian Pediatric Multicenter Trial DAL-HD-90. Int J Radiat Oncol Biol Phys 56 (3): 644-52, 2003.  [PUBMED Abstract]
   
   
2. Rühl U, Albrecht M, Dieckmann K, et al.: Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial. Int J Radiat Oncol Biol Phys 51 (5): 1209-18, 2001.  [PUBMED Abstract]
   
   
3. Smith RS, Chen Q, Hudson M, et al.: Prognostic factors in pediatric Hodgkin's disease. [Abstract] Int J Radiat Oncol Biol Phys 51 (3 Suppl 1): 119, 2001. 
   
   
4. Nachman JB, Sposto R, Herzog P, et al.: Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol 20 (18): 3765-71, 2002.  [PUBMED Abstract]
   
   
5. Shankar AG, Ashley S, Radford M, et al.: Does histology influence outcome in childhood Hodgkin's disease? Results from the United Kingdom Children's Cancer Study Group. J Clin Oncol 15 (7): 2622-30, 1997.  [PUBMED Abstract]
   
   
6. Christiansen I, Sundström C, Enblad G, et al.: Soluble vascular cell adhesion molecule-1 (sVCAM-1) is an independent prognostic marker in Hodgkin's disease. Br J Haematol 102 (3): 701-9, 1998.  [PUBMED Abstract]
   
   
7. Warzocha K, Bienvenu J, Ribeiro P, et al.: Plasma levels of tumour necrosis factor and its soluble receptors correlate with clinical features and outcome of Hodgkin's disease patients. Br J Cancer 77 (12): 2357-62, 1998.  [PUBMED Abstract]
   
   
8. Nadali G, Tavecchia L, Zanolin E, et al.: Serum level of the soluble form of the CD30 molecule identifies patients with Hodgkin's disease at high risk of unfavorable outcome. Blood 91 (8): 3011-6, 1998.  [PUBMED Abstract]
   
   
9. Chronowski GM, Wilder RB, Tucker SL, et al.: An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease. Cancer 95 (12): 2534-8, 2002.  [PUBMED Abstract]
   
   
10. Bohlen H, Kessler M, Sextro M, et al.: Poor clinical outcome of patients with Hodgkin's disease and elevated interleukin-10 serum levels. Clinical significance of interleukin-10 serum levels for Hodgkin's disease. Ann Hematol 79 (3): 110-3, 2000.  [PUBMED Abstract]
    
    
11. Dukers DF, Meijer CJ, ten Berge RL, et al.: High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome. Blood 100 (1): 36-42, 2002.  [PUBMED Abstract]
    
    
12. Carde P, Koscielny S, Franklin J, et al.: Early response to chemotherapy: a surrogate for final outcome of Hodgkin's disease patients that should influence initial treatment length and intensity? Ann Oncol 13 (Suppl 1): 86-91, 2002.  [PUBMED Abstract]
    
    
13. Weiner MA, Leventhal B, Brecher ML, et al.: Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study. J Clin Oncol 15 (8): 2769-79, 1997.  [PUBMED Abstract]
    
    
14. Landman-Parker J, Pacquement H, Leblanc T, et al.: Localized childhood Hodgkin's disease: response-adapted chemotherapy with etoposide, bleomycin, vinblastine, and prednisone before low-dose radiation therapy-results of the French Society of Pediatric Oncology Study MDH90. J Clin Oncol 18 (7): 1500-7, 2000.  [PUBMED Abstract]
    
    
15. Hutchings M, Loft A, Hansen M, et al.: FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 107 (1): 52-9, 2006.  [PUBMED Abstract]
    
    
16. Gallamini A, Hutchings M, Rigacci L, et al.: Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study. J Clin Oncol 25 (24): 3746-52, 2007.  [PUBMED Abstract]
    
    
17. Dann EJ, Bar-Shalom R, Tamir A, et al.: Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome. Blood 109 (3): 905-9, 2007.  [PUBMED Abstract]
    
    

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