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Current Approaches to the Management of Pediatric Hodgkin Lymphoma

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Abstract

Hodgkin lymphoma is one of the few cancers that affect both adults and children. Cure rates for Hodgkin lymphoma remain among the best for pediatric cancers. However, cure is often associated with significant delayed effects of therapy, including an elevated risk for second malignancies, cardiotoxicity, pulmonary toxicity, and gonadal and non-gonadal endocrine dysfunction. Therefore, the aim of current treatment strategies is to further improve outcomes while minimizing therapy-related complications.

At diagnosis, patients are classified into risk groups based on disease stage, and the presence of clinical, biologic, and serologic risk factors. In general, the most recent trials have intensified therapy in those patients with high-risk disease to improve disease control, and have limited therapy in those patients with low-risk disease to avoid secondary effects. In low-risk patients, multiple studies have been conducted to investigate limiting either radiation therapy or chemotherapy to prevent long-term side effects without affecting the excellent cure rate. In intermediate- and high-risk patients, many studies have examined intensifying therapy to improve event-free survival rates. In addition, response assessment by fluorine-18-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) may be particularly important in pediatric Hodgkin lymphoma; it may allow modification of treatment to maximize treatment efficacy and minimize late effects of chemotherapy and radiation therapy. Despite the improvements in treatment for all stages of Hodgkin lymphoma, there is still a subgroup of patients who do not enter remission with initial therapy or relapse after initial response to therapy. Unfortunately, standard-dose salvage chemotherapy for relapsed disease has disappointing results in terms of overall survival since patients have typically already received intensive therapy. While there is no standard of care in terms of salvage chemotherapy, high-dose chemotherapy with autologous stem cell transplant (ASCT) rescue has become the standard of care for the majority of children with relapsed Hodgkin lymphoma. The use of allogeneic transplantation is controversial in relapsed or refractory Hodgkin lymphoma; because of the high transplant-related mortality, allogeneic transplant has not been associated with improved overall survival over ASCT.

As more has been learned about the biologic mechanisms involved in Hodgkin lymphoma, biologically-based therapies are being investigated for use in this disease, both at initial diagnosis and relapse. Both immunotherapy and small molecules are being studied as possible therapeutic agents in Hodgkin lymphoma. Unfortunately, the vast majority of investigations of novel agents have occurred exclusively in adult patients. However, since pediatric Hodgkin lymphoma and adult Hodgkin lymphoma are similar, these results may potentially be extrapolated to pediatric Hodgkin lymphoma.

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References

  1. National Cancer Institute. Cancer stat fact sheets: Hodgkin lymphoma. Surveillance Epidemiology and End Results (SEER) [online]. Available from URL: http://seer.cancer.gov/statfacts/html/hodg.html [Accessed 2008 Apr 9]

  2. 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(11): 1630–6

    PubMed  CAS  Google Scholar 

  3. Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med 1998; 339: 1506–14

    Article  PubMed  CAS  Google Scholar 

  4. Smith RS, Chen Q, Hudson MM, et al. Prognostic factors for children with Hodgkin’s disease treated with combined-modality therapy. J Clin Oncol 2003 May; 21(10): 2026–33

    Article  PubMed  Google Scholar 

  5. Hodgson D, Hudson M, Constine L. Pediatric Hodgkin lymphoma: maximizing efficacy and minimizing toxicity. Semin Radiat Oncol 2007; 17: 230–42

    Article  PubMed  Google Scholar 

  6. ClinicalTrials.gov, a service of the US National Institutes of Health. Combination chemotherapy followed by radiation therapy in treating young patients with newly diagnosed Hodgkin’s lymphoma (NCT00302003) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00302003?term=NCT00302003&rank=1 [Accessed 2008 May 24]

  7. Clinical Trials.gov, a service of the US National Institutes of Health. Chemotherapy with or without additional chemotherapy and/or radiation therapy in treating children with newly diagnosed Hodgkin’s disease (NCT00025259) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00025259?term=NCT00025259&rank=1 [Accessed 2008 May 24]

  8. ClinicalTrials.gov, a service of the US National Institutes of Health. Combination chemotherapy and radiation therapy in treating young patients with newly diagnosed Hodgkin lymphoma (NCT01026220) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT01026220?term=AHOD0831&rank=1 [Accessed 2010 Jan 2]

  9. Schellong G, Potter R, Bramswig J, et al. High cure rates and reduced long-term toxicity in pediatric Hodgkin’s disease: the German-Austrian Multicenter Trial DAL-HD-90. The German-Austrian Pediatric Hodgkin’s Disease Study Group. J Clin Oncol 1999 Dec; 17(12): 3736–44

    PubMed  CAS  Google Scholar 

  10. Ruhl 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 Radiation Oncology Biol Phys 2001; 51(5); 1209–18

    Article  CAS  Google Scholar 

  11. Donaldson S, Link M, Weinstein H, et al. Final results of a prospective clinical trial with VAMP and low-dose involved-field radiation for children with low-risk Hodgkin’s disease. J Clin Oncol 2007; 25: 332–7

    Article  PubMed  CAS  Google Scholar 

  12. Hudson M, Krasin M, Link M, et al. Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin’s disease. J Clin Oncol 2004; 22: 4541–50

    Article  PubMed  CAS  Google Scholar 

  13. 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 2007 Aug; 25(24): 3746–52

    Article  PubMed  CAS  Google Scholar 

  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 2000; 18(7): 1500–7

    PubMed  CAS  Google Scholar 

  15. Nachman J, 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(18): 3765–71

    Article  PubMed  Google Scholar 

  16. Tebbi CK, Mendenhall N, London WB, et al. Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine, and etoposide (DBVE) and radiation: a Pediatric Oncology Group (POG) study. Pediatr Blood Cancer 2006; 46: 198–202

    Article  PubMed  CAS  Google Scholar 

  17. Laskar S, Gupta T, Vimal S, et al. Consolidation radiation after complete remission in Hodgkin’s disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need? J Clin Oncol 2004; 22: 62–8

    Article  PubMed  CAS  Google Scholar 

  18. Arya L, Dinand V, Thavaraj V, et al. Hodgkin’s disease in Indian children: outcome with chemotherapy alone. Pediatr Blood Cancer 2006; 46: 26–34

    Article  PubMed  Google Scholar 

  19. Hakvoort-Cammel F, Buitendijk S, van den Heuvel-Eibrink M, et al. Treatment of Pediatric dodgkin disease avoiding radiotherapy: excellent outcome with the Rotterdam-HD-84-Protocol. Pediatr Blood Cancer 2004; 43: 8–16

    Article  PubMed  Google Scholar 

  20. Schwartz CL, Constine LS, Villaluna D, et al. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood 2009; 114: 2051–9

    Article  PubMed  CAS  Google Scholar 

  21. Tebbi CK, London WB, Freidmann D, et al. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin’s disease. J Clin Oncol 2007; 25: 493–500

    Article  PubMed  CAS  Google Scholar 

  22. Karayalcin G, Behm FG, Gieser PW, et al. Lymphocyte predominant Hodgkin disease: clinico-pathologic features and results of treatment. The Pediatric Oncology Group experience. Med Pediatr Oncol 1997; 29: 519–25

    Article  PubMed  CAS  Google Scholar 

  23. Sandoval C, Venkateswaran L, Billups C, et al. Lymphocyte-predominant Hodgkin disease in children. J Ped Heme/Onc 2002; 24: 269–73

    Google Scholar 

  24. Pellegrino B, Terrier-Lacombe MJ, Oberlin O, et al. Lymphocyte-predominant Hodgkin’s lymphoma in children: therapeutic abstention after initial lymph node resection. A study of the French Society of Pediatric Oncology. J Clin Oncol 2003; 21: 2948–52

    Article  PubMed  CAS  Google Scholar 

  25. Murphy SB, Morgan ER, Katzenstein HM, et al. Results of little or no treatment for lymphocyte-predominant Hodgkin disease in children and adolescents. J Pediatr Hematol Oncol 2003; 25: 684–7

    Article  PubMed  Google Scholar 

  26. ClinicalTrials.gov, a service of the US National Institutes of Health. Treating young patients with newly diagnosed, low stage, lymphocyte predominant Hodgkin’s disease (NCT0010719) [online] Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00107198?term=NCT00107198&rank=1[Accessed 2008 May 24]

  27. Kelly KM, Hutchinson RJ, Sposto R, et al. Feasibility of upfront doseintensive chemotherapy in children with advanced-stage Hodgkin’s lymphoma: preliminary results from the Children’s Cancer Group Study CCG-59704. Ann Oncol 2002; 13Suppl. 1: 107–11

    Article  PubMed  Google Scholar 

  28. 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(8): 2769–79

    PubMed  CAS  Google Scholar 

  29. ClinicalTrials.gov, a service of the US National Institutes of Health. Combination chemotherapy in treating young patients with Hodgkin’s lymphoma (NCT00433459) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00433459?term=NCT00433459&rank=1 [Accessed 2008 Jun 3]

  30. Longo DL, Duffey PL, Young RC, et al. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin disease after combination chemotherapy: the low probability of cure. J Clin Oncol 1992; 10: 210–8

    PubMed  CAS  Google Scholar 

  31. Viviani S, Santoro A, Negretti E, et al. Salvage chemotherapy in Hodgkin disease: results in patients relapsing more than twelve months after first complete remission. Ann Oncol 1990; 1: 123–7

    PubMed  CAS  Google Scholar 

  32. David K, Mauro L, Evens AM. Relapsed and refractory Hodgkin lymphoma: transplantation strategies and novel therapeutic options. Curr Treat Options Oncol 2007; 8: 352–74

    Article  PubMed  Google Scholar 

  33. Josting A, Franklin J, May M, et al. New prognostic score based on treatment outcome of patients with relapsed Hodgkin’s lymphoma registered in the database of the German Hodgkin’s Lymphoma Study Group. J Clin Oncol 2002; 20: 221–30

    Article  PubMed  Google Scholar 

  34. Bierman PJ, Lynch JC, Bociek RG, et al. The International Prognostic Factors Project Score for advanced Hodgkin’s disease is useful for predicting outcome of autologous stem cell transplantation. Ann Oncol 2002; 13: 1370–7

    Article  PubMed  CAS  Google Scholar 

  35. Schellong G, Dorffel W, Claviez A, et al. Salvage therapy of progressive and recurrent Hodgkin’s disease: results from a multicenter study of the Pediatric DAL/GPOH-HD Study Group. J Clin Oncol 2005; 23(25): 6181–9

    Article  PubMed  Google Scholar 

  36. Lieskovsky YE, Donaldson SS, Torres MA, et al. High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin’s disease: results and prognostic indices. J Clin Oncol 2004; 22: 4532–40

    Article  PubMed  Google Scholar 

  37. Kobrinsky N, Sposto R, Shah N, et al. Outcomes of treatment of children and adolescents with recurrent non-Hodgkin’s lymphoma and Hodgkin’s disease with dexamethasone, etoposide, cisplatin, cytarabine, and L-asparaginase, maintenance chemotherapy, and transplantation. Children’s Cancer Group Study CCG-5912. J Clin Oncol 2001; 19: 2390–6

    PubMed  CAS  Google Scholar 

  38. Cole PD, Schwartz CL, Drachtman RA, et al. Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin’s disease: a children’s oncology group report. J Clin Oncol 2009; 27: 1456–61

    Article  PubMed  CAS  Google Scholar 

  39. ClinicalTrials.gov, a service of the US National Institutes of Health. Gemcitabine and vinorelbine in treating young patients with recurrent or refractory Hodgkin’s lymphoma (NCT00070304) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00070304?term=NCT00070304&rank=1 [Accessed 2008 Jun 18]

  40. Linch DC, Goldstone AH, McMillan A, et al. Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin’s disease: results of a BNLI randomised trial. Lancet 1993; 341: 1051–4

    Article  PubMed  CAS  Google Scholar 

  41. Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 2002; 359: 2065–71

    Article  PubMed  CAS  Google Scholar 

  42. Schmitz N, Haverkamp H, Josting A, et al. Long term follow up in relapsed Hodgkin’s disease (HD): updated results of the HD-R1 study comparing conventional chemotherapy (cCT) to high-dose chemotherapy (HDCT) with autologous haemopoietic stem cell transplantation (ASCT) of the German Hodgkin Study Group (GHSG) and the Working Party Lymphoma of the European Group for Blood and Marrow Transplantation (EBMT) [abstract no. 6508]. J Clin Oncol 2005; 23 Suppl.: 562S

    Google Scholar 

  43. Peniket AJ, Elvira MCRd, Taghipour G, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant 2003; 31: 667–78

    Article  PubMed  CAS  Google Scholar 

  44. ClinicalTrials.gov, a service of the US National Institutes of Health (NCT00057954) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00057954?term=NCT00057954&rank=1. [Accessed 2008 Jun 18]

  45. ClinicalTrials.gov, a service of the US National Institutes of Health (NCT00697684) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00697684?term=NCT00697684&rank=1 [Accessed 2008 Jun 18]

  46. ClinicalTrials.gov, a service of the US National Institutes of Health (NCT00385788) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00385788?term=NCT00385788&rank=1 [Accessed 2008 Jun 18]

  47. Leonard JP, Rosenblatt JD, Bartlett NL, et al. Phase II study of SGN-30 (anti-CD30 monoclonal antibody) in patients with refractory or recurrent Hodgkin’s disease. ASH Annual Meeting Abstracts 2004; 104: 2635

    Google Scholar 

  48. Bartlett NL, Younes A, Carabasi MH, et al. A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30 + hematologic malignancies. Blood 2008; 111(4): 1848–54

    Article  PubMed  CAS  Google Scholar 

  49. Ansell SM, Horwitz SM, Engert A, et al. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin’s lymphoma and anaplastic large-cell lymphoma. J Clin Oncol 2007; 25(19): 2764–9

    Article  PubMed  CAS  Google Scholar 

  50. Younes A, Forero-Torres A, Bartlett N, et al. A novel antibody-drug conjugate, SGN-35 (anti-CD30-Auristatin), induces objective responses in patients with relapsed or refractory Hodgkin lymphoma: preliminary results of a phase I tolerability study [abstract no. P099]. Haematologica 2007; 92Suppl. 5: 64

    Google Scholar 

  51. Schnell R, Dietlein M, Staak JO, et al. Treatment of refractory Hodgkin’s lymphoma with an iodine-131-labeled murine anti-CD30 monoclonal antibody. J Clin Oncol 2005; 23(21): 4669–78

    Article  PubMed  CAS  Google Scholar 

  52. Schulz H, Rehwald U, Morschhauser F, et al. Rituximab in relapsed lymphocyte-predominant Hodgkin Lymphoma: long-term results of a phase-II trial of the German Hodgkin Lymphoma Study Group (GHSG). Blood 2008; 111(1): 109–11

    Article  PubMed  CAS  Google Scholar 

  53. O’Mahony D, Janik JE, Carrasquillo JA, et al. Yttrium-90 radiolabeled humanized anti-CD25 monoclonal antibody, daclizumab, provides effective therapy for refractory and relapsed Hodgkin’s lymphoma [abstract no. 1060]. Haematologica 2007; 92Suppl. 5: 18

    Google Scholar 

  54. Karin M, Cao Y, Greten F, et al. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002; 2: 301–10

    Article  PubMed  CAS  Google Scholar 

  55. Li X, Stark GR. NFkappaB-dependent signaling pathways. Exp Hematol 2002; 30: 285–96

    Article  PubMed  CAS  Google Scholar 

  56. Blum KA, Johnson JL, Niedzwiecki D, et al. Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: cancer and leukemia Group B protocol 50206. Leuk Lymphoma 2007; 48(7): 1313–9

    Article  PubMed  CAS  Google Scholar 

  57. ClinicalTrials.gov, a service of the US National Institutes of Health (NCT00381940) [online]. Available from URL: http://www.clinicaltrials.gov/ct2/show/NCT00381940?term=NCT00381940&rank=1 [Accessed 2008 Jun 3]

  58. Younes A, Fanale M, Pro B, et al. A phase II study of a novel oral isotype-selective histone deacetylase (HDAC) inhibitor in patients with relapsed or refractory Hodgkin lymphoma [abstract no. 8000]. J Clin Oncol 2007; 25 Suppl.: 441S

    Google Scholar 

  59. Donaldson SS, Kaplan HS. Complications of treatment of Hodgkin’s disease in children. Cancer Treat Rep 1982; 66: 977–89

    PubMed  CAS  Google Scholar 

  60. Hancock SL, Donaldson SS, Hoppe RT. Cardiac disease following treatment of Hodgkin’s disease in children and adolescents. J Clin Oncol 2007; 25 Suppl.: 441S

    Google Scholar 

  61. Chow LML, Nathan PC, Hodgson DC, et al. Survival and late effects in children with Hodgkin’s lymphoma treated with MOP/ABV and low-dose, extended-field irradiation. J Clin Oncol 2006; 24: 5735–41

    Article  PubMed  CAS  Google Scholar 

  62. Kremer LCM, van Dalen EC, Offringa M, et al. Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 2001; 19: 191–6

    PubMed  CAS  Google Scholar 

  63. Neglia JP, Friedman DL, Yasui Y, et al. Second malignant neoplasms in five-year survivors of childhood cancer: Childhood Cancer Survivor Study. J Natl Cancer Inst 2001; 93: 618–29

    Article  PubMed  CAS  Google Scholar 

  64. Bhatia S, Robison LL, Meadows AT, et al. High risk of second malignant neoplasms (SMN) continues with extended follow-up of childhood Hodgkin’s disease (HD) cohort: report from the Late Effects Study Group [abstract]. Blood 2001; 98: 768a

    Google Scholar 

  65. Sigurdson AJ, Ronckers CM, Mertens AC, et al. Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study. Lancet 2005; 365: 2014–23

    Article  PubMed  Google Scholar 

  66. Kaldor JM, Day NE, Clarke EA, et al. Leukemia following Hodgkin’s disease. N Engl J Med 1990; 322: 7–13

    Article  PubMed  CAS  Google Scholar 

  67. Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2000; 85: 3227–32

    Article  PubMed  CAS  Google Scholar 

  68. Thomson AB, Wallace WH, Sklar C. Testicular function. In: Wallace WH, Green DM, editors. Late effects of childhood cancer. London: Arnold, 2004: 239–56

    Google Scholar 

  69. Mackie EJ, Radford M, Shalet SM. Gonadal function following chemotherapy for childhood Hodgkin’s disease. Med Pediatr Oncol 1996; 7: 74–8

    Article  Google Scholar 

  70. Critchley HO, Thomson AB, Wallace WH. Ovarian and uterine function and reproductive potential. In: Wallace WH, Green DM, editors. Late effects of childhood cancer. London: Arnold, 2004: 225–38

    Google Scholar 

  71. Horning SJ, Hoppe RT, Kaplan HS. Female reproductive potential after treatment for Hodgkin’s disease. N Engl J Med 1981; 304: 1377–81

    Article  PubMed  CAS  Google Scholar 

  72. Bokemeyer C, Schmoll HJ, van Rhee J, et al. Long-term gonadal toxicity after therapy for Hodgkin’s and non-Hodgkin’s lymphoma. Ann Hematol 1994; 68: 105–10

    Article  PubMed  CAS  Google Scholar 

  73. Byrne J, Fears TR, Gail MH. Early menopause in long-term survivors of cancer during adolescence. Am J Obstetr Gynecol 1992; 166: 788–93

    CAS  Google Scholar 

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Acknowledgments

No sources of funding were used to assist in the preparation of this review. Kara Kelly has received honoraria support from Sigma Tau Pharmaceuticals for lectures on Hodgkin lymphoma. Jennifer Freed has no conflicts of interest to declare that are directly relevant to the content of this review.

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Freed, J., Kelly, K.M. Current Approaches to the Management of Pediatric Hodgkin Lymphoma. Pediatr-Drugs 12, 85–98 (2010). https://doi.org/10.2165/11316170-000000000-00000

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