Current Clinical Trials

The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.

Cancer in children and adolescents is rare. Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. (Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.)

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[1] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up since cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Childhood Hodgkin lymphoma is one of the few pediatric malignancies that shares aspects of its biology and natural history with an adult cancer. When treatment approaches for children were modeled after those used for adults, substantial morbidities (primarily musculoskeletal growth inhibition) resulted from the unacceptably high radiation doses.[2,3] Thus, new strategies utilizing chemotherapy and lower-dose radiation were developed.[4] Approximately 90% to 95% of children with Hodgkin lymphoma can be cured, prompting increased attention to devising nonmorbid therapy for these patients. Contemporary treatment programs use a risk-adapted approach in which patients receive multiagent chemotherapy (with intensity varying by stage) and low-dose involved-field irradiation.

Hodgkin lymphoma comprises 6% of childhood cancers. A striking male:female predominance is found among young children, with a ratio of 4:1 for 3- to 7-year-olds, and 3:1 for 7- to 9-year-olds. For patients older than 10 years, the ratio is 1.3:1 (a ratio more similar to that of adults).[5] In the United States, Hodgkin lymphoma is uncommon in children younger than 10 years. Younger children have a higher incidence of lymphocyte-predominant and mixed cellularity histology and a lower incidence of nodular-sclerosing histology than adolescents and adults. The incidence of Hodgkin lymphoma continues to increase during the early teen and adolescent years. In one clinical trial for children and adolescents with Hodgkin lymphoma, 3% of patients were aged between 0 and 4 years, 12% of patients were aged between 5 and 9 years, 44% of patients were aged between 10 and 14 years, and 41% were older than 15 years.[6] In non-European Union countries, there is a similar rate in young adults but a much higher incidence in childhood.[7,8] For children and adolescents in the United States, there is an increased risk of Hodgkin lymphoma in families with higher parental incomes and higher education level. There is a lower incidence of Hodgkin lymphoma in families with large numbers of children.[8]

Hodgkin lymphoma is characterized by a variable number of characteristic multinucleated giant cells (Reed-Sternberg [R-S] cells) or large mononuclear cell variants (Hodgkin cells) in an inflammatory milieu. This inflammatory milieu consists of small lymphocytes, histiocytes, epithelioid histiocytes, neutrophils, eosinophils, plasma cells, and fibroblasts in different proportions depending on the histologic subtype.[9] It has been conclusively shown that R-S cells and/or Hodgkin cells represent a clonal population. Almost all cases of Hodgkin lymphoma arise from preapoptotic germinal center B cells that cannot synthesize immunoglobulin.[10,11] The R-S cell appears to be resistant to apoptotic stimuli. Deregulation of the nuclear transcription factor NFkB in the R-S cells may explain the resistance to apoptosis.

Epstein-Barr virus (EBV) genetic material can be detected in R-S or Hodgkin cells from some patients with Hodgkin lymphoma. EBV positivity is most commonly observed in tumors with mixed-cellularity histology and is uncommon in patients with lymphocyte-predominant histology.[12-16] EBV positivity is more common in children younger than 10 years [12,16] and in most cases of childhood Hodgkin lymphoma in developing countries.[13,14,17] The incidence of EBV tumor cell positivity for Hodgkin lymphoma in developed countries is 15% to 25% in adolescents and young adults.[15,16,18] EBV serologic status is not a prognostic factor for failure-free survival in pediatric and young adult Hodgkin lymphoma patients.[12,15,16,18,19] Patients with a prior history of serologically confirmed infectious mononucleosis have a fourfold increased risk of developing EBV-positive Hodgkin lymphoma; these patients are not at increased risk for EBV-negative Hodgkin lymphoma.[20] Although rare, Hodgkin lymphoma can be familial.

Approximately 80% of patients present with painless adenopathy, commonly in the supraclavicular or cervical area. Enlarged nodes are generally firm and have a rubbery texture. Many patients have some degree of mediastinal involvement at presentation. Approximately 25% of patients may have systemic symptoms such as fever, night sweats, and weight loss that are secondary to release of lymphokines and cytokines by R-S or Hodgkin cells. Approximately 20% of patients will have a mediastinal mass whose maximum diameter is greater than one-third of the chest diameter and/or a node or nodal aggregate larger than 10 cm. Approximately 80% to 85% of children and adolescents with Hodgkin lymphoma have involvement of lymph nodes and/or the spleen only (stages I–III). The remaining 15% to 20% of patients will have noncontiguous extranodal involvement (stage IV). The most common sites of extranodal involvement are the lung, liver, bones, and bone marrow.[6,21]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood Hodgkin lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.  [PUBMED Abstract]
   
   
2. Donaldson SS, Kaplan HS: Complications of treatment of Hodgkin's disease in children. Cancer Treat Rep 66 (4): 977-89, 1982.  [PUBMED Abstract]
   
   
3. Mauch PM, Weinstein H, Botnick L, et al.: An evaluation of long-term survival and treatment complications in children with Hodgkin's disease. Cancer 51 (5): 925-32, 1983.  [PUBMED Abstract]
   
   
4. Donaldson SS, Link MP: Hodgkin's disease. Treatment of the young child. Pediatr Clin North Am 38 (2): 457-73, 1991.  [PUBMED Abstract]
   
   
5. Spitz MR, Sider JG, Johnson CC, et al.: Ethnic patterns of Hodgkin's disease incidence among children and adolescents in the United States, 1973-82. J Natl Cancer Inst 76 (2): 235-9, 1986.  [PUBMED Abstract]
   
   
6. 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]
   
   
7. Macfarlane GJ, Evstifeeva T, Boyle P, et al.: International patterns in the occurrence of Hodgkin's disease in children and young adult males. Int J Cancer 61 (2): 165-9, 1995.  [PUBMED Abstract]
   
   
8. Grufferman S, Gilchrist GS, Pollock BH, et al.: Socioeconomic status, the Epstein-Barr virus and risk of Hodgkin's disease in children. [Abstract] Leuk Lymphoma 42 (Suppl 1): P-054, 40, 2001. 
   
   
9. Pileri SA, Ascani S, Leoncini L, et al.: Hodgkin's lymphoma: the pathologist's viewpoint. J Clin Pathol 55 (3): 162-76, 2002.  [PUBMED Abstract]
   
   
10. Kanzler H, Küppers R, Hansmann ML, et al.: Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 184 (4): 1495-505, 1996.  [PUBMED Abstract]
    
    
11. Diehl V, von Kalle C, Fonatsch C, et al.: The cell of origin in Hodgkin's disease. Semin Oncol 17 (6): 660-72, 1990.  [PUBMED Abstract]
    
    
12. Armstrong AA, Alexander FE, Cartwright R, et al.: Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis. Leukemia 12 (8): 1272-6, 1998.  [PUBMED Abstract]
    
    
13. Araujo I, Bittencourt AL, Barbosa HS, et al.: The high frequency of EBV infection in pediatric Hodgkin lymphoma is related to the classical type in Bahia, Brazil. Virchows Arch 449 (3): 315-9, 2006.  [PUBMED Abstract]
    
    
14. Makar RR, Saji T, Junaid TA: Epstein-Barr virus expression in Hodgkin's lymphoma in Kuwait. Pathol Oncol Res 9 (3): 159-65, 2003.  [PUBMED Abstract]
    
    
15. Herling M, Rassidakis GZ, Medeiros LJ, et al.: Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome. Clin Cancer Res 9 (6): 2114-20, 2003.  [PUBMED Abstract]
    
    
16. Claviez A, Tiemann M, Lüders H, et al.: Impact of latent Epstein-Barr virus infection on outcome in children and adolescents with Hodgkin's lymphoma. J Clin Oncol 23 (18): 4048-56, 2005.  [PUBMED Abstract]
    
    
17. Weinreb M, Day PJ, Niggli F, et al.: The consistent association between Epstein-Barr virus and Hodgkin's disease in children in Kenya. Blood 87 (9): 3828-36, 1996.  [PUBMED Abstract]
    
    
18. Jarrett RF, Stark GL, White J, et al.: Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study. Blood 106 (7): 2444-51, 2005.  [PUBMED Abstract]
    
    
19. Herling M, Rassidakis GZ, Vassilakopoulos TP, et al.: Impact of LMP-1 expression on clinical outcome in age-defined subgroups of patients with classical Hodgkin lymphoma. Blood 107 (3): 1240; author reply 1241, 2006.  [PUBMED Abstract]
    
    
20. Hjalgrim H, Askling J, Rostgaard K, et al.: Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med 349 (14): 1324-32, 2003.  [PUBMED Abstract]
    
    
21. 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]
    
    

Back to Top

< Previous Section  |  Next Section >