Current Oncology Reports

, Volume 5, Issue 6, pp 498–504

Prognostic factors in pediatric Hodgkin disease

  • Cindy L. Schwartz
Article

Abstract

The sensitivity of pediatric Hodgkin disease to radiation and chemotherapy has resulted in cure for most children and adolescents who have been diagnosed in the past three decades. Identification of prognostic factors in clinical trials has allowed for tailoring of therapeutic approaches to improve outcome in sequential trials. Tumor burden, symptoms, clinical features, pathology, response to therapy, biology, and host factors are reviewed in this context. New developments should be directed toward identification of factors associated with biologic mechanisms of disease to facilitate the development of biologically targeted therapies that will be more efficacious and less toxic.

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References and Recommended Reading

  1. 1.
    Carbone PP, Kaplan HS, Musshoff K, et al.: Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res 1971, 31:1860–1861.PubMedGoogle Scholar
  2. 2.
    Schwartz CL, Tebbi C, Constine LS, et al.: Response-based therapy for pediatric Hodgkin’s disease: Pediatric Oncology Group (POG) Protocols 9425/9426 [abstract]. Med Pediatr Oncol 2001, 37:263.Google Scholar
  3. 3.
    Landman-Parker J, Pacquement H, Leblanc T, et al.: Localized childhood Hodgkin’s disease: response adopted chemotherapy with etoposide, bleomycin, vinblastin, and prednisone before low-dose raditaion therapy: results of the French Society of Pediatric Oncology Study MDH90. J Clin Oncol 2000, 18:1500–1507. This study provides an important proposal for a prognostic system for children and offers a view of the use of response-directed therapy.PubMedGoogle Scholar
  4. 4.
    Zander T, Wiedenmann S, Wolf J: Prognostic factors in Hodgkin’s lymphoma. Ann Oncol 2002, 13(Suppl 1):67–74.PubMedGoogle Scholar
  5. 5.
    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 2002, 20:3765–3771. Report from a large randomized trial in pediatric Hodgkin disease assessing the possibility of reducing therapy (eliminating radiation) in those in complete response at the end of therapy. Relapse rates were higher in those who were not irradiated, suggesting that complete response at the end of therapy may not be a sufficiently good prognostic indicator to limit radiotherapy.PubMedCrossRefGoogle Scholar
  6. 6.
    Lister TA, Crowther D, Sutcliffe SB, et al.: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. J Clin Oncol 1989, 7:1630–1636.PubMedGoogle Scholar
  7. 7.
    Gobbi PG, Cavalli C, Gendarini A, et al.: Reevaluaton of prognostic significance of symptoms in Hodgkin’s disease. Cancer 1985, 56:2874–2880.PubMedCrossRefGoogle Scholar
  8. 8.
    Teruya-Feldstein J, Tosato Gk Jaffe ES: The role of chemokines in Hodgkin’s disease. Leuk Lymphoma 2000, 38:363–371.PubMedGoogle Scholar
  9. 9.
    Gause A, Pohl C, Tschiersch A, et al.: Clinical significance of soluble CD30 antigen in the sera of patients with untreated Hodgkin’s disease. Blood 1991, 77:1983–1988.PubMedGoogle Scholar
  10. 10.
    Bohlen H, Kessler M, Sextro M, et al.: Poor clinical outcome of patients with Hodgkin’s disease and elevated IL-10 serum levels: clinical significance of interleukin-10 serum levels for Hodgkin’s disease. Ann Hematol 2000, 79:110–113.PubMedCrossRefGoogle Scholar
  11. 11.
    Viviani S, Notti P, Bonfante V, et al.: Elevated pretreatment serum levels of IL-10 are associated with a poor prognosis in Hodgkin’s disease. The Milan Cancer Institute experience. Med Oncol 2000, 17:59–63.PubMedGoogle Scholar
  12. 12.
    Sarris AH, Kliche KO, Pethambaram P, et al.: Interleukin-10 levels are often elevated in serum of adults with Hodgkin’s disease and are associated with inferior failure free survival. Ann Oncol 1999, 10:433–440.PubMedCrossRefGoogle Scholar
  13. 13.
    Berard CW, Hutchison RE: The problem of classifying lymphomas: an orderly prescription for progress. Ann Oncol 1997, 8(Suppl 2):3–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Lukes RJ, Butler JJ: The pathology and nomenclature of Hodgkin’s disease. Cancer Res 1966, 26:1063–1083.PubMedGoogle Scholar
  15. 15.
    Karayalcin G, Behm FG, Geiser PW, et al.: Lymphocyte predominant Hodgkin’s disease: clinico-pathologic features and results of treatment. The Pediatric Oncology Group experience. Med Pediatr Oncol 1997, 29:519–525.PubMedCrossRefGoogle Scholar
  16. 16.
    Ambinder RF, Browning PJ, Lorenzana I, et al.: Epstein-Barr virus and childhood Hodgkin’s disease in Honduras and the United States. Blood 1993, 81:462–467.PubMedGoogle Scholar
  17. 17.
    MacLennan KA, Bennett MH, Tu A, et al.: Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin’s disease: a study of 1659 patients. Cancer 1989, 64:1686–1693.PubMedCrossRefGoogle Scholar
  18. 18.
    Von Wasielewski R, Seth S, Franklin J, et al.: Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin’s disease, allowing for known prognostic factors. Blood 2000, 95:1207–1213.Google Scholar
  19. 19.
    Von Wasielewski S, Franklin J, Fischer R, et al.: Nodular sclerosing Hodgkin disease: new grading predicts prognosis in intermediate and advanced stages. Blood 2003, 101:4063–4069.CrossRefGoogle Scholar
  20. 20.
    Mauch E, Tarbell NJ, Weinstein H, et al.: Stage IA-IIA supradiaphragmatic Hodgkin’s disease: prognostic factors in surgically staged patients. J Clin Oncol 1988, 6:1576–1583.PubMedGoogle Scholar
  21. 21.
    Shankar AG, Ashley S, Radford M, et al.: Does histology influence outcome n childhood Hodgkin’s disease: results from the United Kingdom Children’s Cancer Study Group. J Clin Oncol 1997, 15:2622–2630.PubMedGoogle Scholar
  22. 22.
    Gehan EA, Sullivan MP, Fuller LM, et al.: The Intergroup Hodgkin’s disease in children: a study of stages I and II. Cancer 1990, 65:1429–1437.PubMedCrossRefGoogle Scholar
  23. 23.
    Von Wasielewski R, Mengel M, Fischer R, et al.: Classical Hodgkin’s disease: clinical impact of the immunophenotype. Am J Pathol 1997, 151:1123–1130.Google Scholar
  24. 24.
    Hasenclever D, Deihl V: A prognostic score for advanced Hodgkin’s disease: International Prognostic Factors Project on advanced Hodgkin’s disease. N Engl J Med 1998, 339:1506–1514.PubMedCrossRefGoogle Scholar
  25. 25.
    Hutchinson RJ, Fryer CJ, Davis PC, et al.: MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin’s disease in children: results of the Children’s Cancer Group Phase III Trial. J Clin Oncol 1998, 16:897–906.PubMedGoogle Scholar
  26. 26.
    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 1997, 15:1769–1779.Google Scholar
  27. 27.
    Smith RS, Chen Q, Hudson MM: Prognostic factors for children with Hodgkin’s disease treated with combinedmodality therapy. J Clin Oncol 2003, 21:2026–2033.PubMedCrossRefGoogle Scholar
  28. 28.
    Dieckmann K, Potter 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 Radiat Oncol Biol Phys 2003, 56:644–652. This is a critically important analysis of the important prognostic factors in pediatric Hodgkin disease. It shows that NSII histology and “B” symptoms, both related to the biology of Hodgkin disease, are more significant prognostic factors than traditional measures of disease burden.CrossRefGoogle Scholar
  29. 29.
    Gobbi PG, Zinzani PL, Broglia C, et al.: Comparison of prognostic models in patients with advanced Hodgkin disease: promising results from integration of the best three systems. Cancer 2001, 91:1467–1478.PubMedCrossRefGoogle Scholar
  30. 30.
    Zanotti R, Trolese A, Ambrosetti A, et al.: Serum levels of soluble CD30 improve International Prognostic Score in predicting the outcome of advanced Hodgkin’s lymphoma. Ann Oncol 2002, 13:1908–1914.PubMedCrossRefGoogle Scholar
  31. 31.
    Axdorph U, Sjoberg J, Grimfors G, et al.: Biological markers may add to prediction of outcome achieved by the International Prognostic Score in Hodgkin’s disease. Ann Oncol 2000, 11:1405–1411.PubMedCrossRefGoogle Scholar
  32. 32.
    Canellos GP, Anderson JR, Propert KJ, et al.: Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992, 327:1478–1484.PubMedCrossRefGoogle Scholar
  33. 33.
    Donaldson SS, Hudson MM, Lamborn KR, et al.: VAMP and lowdose, involved-field radiation for children and adolescents with favorable, early-stage Hodgkin’s disease: results of a prospective clinical trial. J Clin Oncol 2002, 20:3081–3087.PubMedCrossRefGoogle Scholar
  34. 34.
    Dorffel W, Luders H, Ruhl U, et al.: Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin’s disease in children and adolescents: analysis and outlook. Klin Padiatr 2003, 215:139–145.PubMedCrossRefGoogle Scholar
  35. 35.
    Wickmann L, Luders H, Dorffel W: 18-FDG-PET-findings in children and adolescents with Hodgkin’s disease: retrospective evaluation of the correlation to other imaging procedures in initial staging and to the predictive value of follow up examinations [in German]. Klin Padiatr 2003, 215:146–150. An important study for consideration as we begin to use PET scans for staging and prediction of response in pediatric Hodgkin disease.PubMedCrossRefGoogle Scholar
  36. 36.
    Kostakoglu L, Coleman M, Leonard JP, et al.: PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin’s disease. J Nucl Med 2002, 43:1018–1027.PubMedGoogle Scholar
  37. 37.
    Stein H, Mason DY, Gerdes JT: The expression of the Hodgkin’s disease associated antigen Ki-1 in reactive and malignancies are derived from activated lymphoid cells. Blood 1985, 66:848–858.PubMedGoogle Scholar
  38. 38.
    Croager E, Gout AM, Abraham LJ: Involvement of Sp1 and microsatellite repressor sequences in the transcriptional control of the human CD30 gene. Am J Pathol 2000, 156:1723–1731.PubMedGoogle Scholar
  39. 39.
    Aizawa S, Nakano H, Ishida T, et al.: TRAF5 and TRAF2 are involved in CD30-mediated NF-kappaB activation. J Biol Chem 1997, 272:2042–2045.PubMedCrossRefGoogle Scholar
  40. 40.
    Duckett CS, Gedrich RW, Gifillan MC, Thompson CB: Induction of NF-kappaB by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol Cell Biol 1997, 17:1535–1542.PubMedGoogle Scholar
  41. 41.
    Horie R, Higashihara M, Watanabe T: Hodgkin’s lymphoma and CD30 signal transduction. Int J Hematol 2003, 77:37–47.PubMedCrossRefGoogle Scholar
  42. 42.
    Foy TM, Aruffo A, Bajorath J, et al.: Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 1996, 14:591–617.PubMedCrossRefGoogle Scholar
  43. 43.
    Karin M, Delhase M: The IkappaB kinase (IKK) and NF-kappaB: key elements of proinflammatory signaling. Semin Immunol 2000, 12:85–98.PubMedCrossRefGoogle Scholar
  44. 44.
    Bargou RC, Leng C, Krappmann D, et al.: High level nuclear NF-kappaB and Oct-2 is a common feature of cultured Hodgkin/Reed-sternberg cells. Blood 1996, 87:4340–4347.PubMedGoogle Scholar
  45. 45.
    Samy SM, Richter BWM, Duckett CS: Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin’s disease cells. Blood 2000, 96:4307–4312.Google Scholar
  46. 46.
    Ravi R, Bedi GC, Engstrom LW, et al.: Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB. Nature Cell Biol 2001, 3:409–416.PubMedCrossRefGoogle Scholar
  47. 47.
    Durkop H, Foss HD, Demel G, et al.: Tumor necrosis factor receptor-associated factor 1 is overexpressed in Reed-Sternberg cells of Hodgkin’s disease and Epstein-Barr Virus-transformed lymphoid cells. Blood 1999, 93:617–623.PubMedGoogle Scholar
  48. 48.
    Wang CY, Mayo MW, Korneluk RG, et al.: NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998, 281:1680–1683.PubMedCrossRefGoogle Scholar
  49. 49.
    Christiansen I, Enblad G, Kalkner KM, et al.: Soluble ICAM-1 in Hodgkin’s disease: a promising independent predictive marker for survival. Leuk Lymphoma 1995, 19:243–251.PubMedGoogle Scholar
  50. 50.
    Hayes JD, Pulford DJ: The glutathione S-transferase supergene family: regulation of GST and the contribution to the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol 1995, 30:445–600.PubMedGoogle Scholar
  51. 51.
    Caggana M, Liber HL, Mauch PM, et al.: In vivo somatic mutation in the lymphoctyes of Hodgkin’s disease patients. Environ Mol Mutagen 1991, 18:6–13.PubMedCrossRefGoogle Scholar
  52. 52.
    Kuppers R, Rajewsky K: The origin of Hodgkin and Reed/ Sternberg cells in Hodgkin’s disease. Annu Rev Immunol 1998, 16:471–493.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2003

Authors and Affiliations

  • Cindy L. Schwartz
    • 1
  1. 1.Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimoreUSA

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