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Adult life after surviving lymphoma in childhood

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Abstract

Introduction

Almost all pediatric lymphomas are malignant, high-grade tumors. The combined incidence of Hodgkin’s disease (HD) and non-Hodgkin lymphoma (NHL) reaches 10 to 12 new cases a year per million children under the age of 16 years, representing about 10% of all pediatric cancers. HD makes up to 40% and NHL 60% of pediatric lymphomas. During the last 20 years, cure rates raised dramatically so that currently over 90% of children and adolescents with HD and about 80% of those with NHL can be cured. As cure can be achieved in a large majority of patients, long-term effects and quality of life of the survivors are nowadays the principal challenges to pediatric oncologists.

Discussion

Like survivors from acute lymphoblastic leukemia, young adults cured from NHL may present with neurocognitive deficits, especially if treated at a young age and with cranial irradiation. Intrathecal or high-dose intravenous chemotherapy with methotrexate may induce the same problems, although in a lesser extent and severity. Large enough prospective cohort studies like the CCSS in the USA were able to show an increased risk of second malignant neoplasms, especially brain tumors in patients formerly treated with cranial irradiation. Reduced fertility can follow exposure to cyclophosphamide, especially in the male. Cardiac function must be serially evaluated over the long to very long-term because of potential cardiomyopathy after high anthracycline doses and/or mediastinal irradiation.

Survivors from HD are at high risk of late complications. Radiation therapy to the neck and mediastinum (mantle field) induces a 50% risk of developing hypothyroidism and a 20% risk of developing thyroid nodules at 20 years. The risk of thyroid cancer is 18 times higher the expected rate for the general population. Secondary aggressive breast cancer shows a cumulative risk of 30% at 30 years after radiotherapy. Other structures affected by mediastinal irradiation are the heart (pericardial, myocardial and endocardial structures), the great arteries (fibrosis, stenosis, aneurysms) and the central portion of the lungs (diffusion troubles, restrictive pneumopathy). Cardiac toxicity can be enhanced by the concomitant therapy with adriamycin and lung toxicity by bleomycin. Radiotherapy to the paraaortic and iliacal lymph nodes can affect gonadal function both in males and females; concomitant chemotherapy with alkylating agents like cyclophosphamide and especially procarbazine have a synergistic action and can lead to premature menopause as well as infertility.

Although the vast majority of survivors from pediatric lymphomas fare well, a minority present with extreme symptoms of depression and psychosomatic distress; female sex, low socio-economic status and treatment with intensive chemotherapy are important risk factors for a poor psychosocial outcome.

Conclusion

It is therefore crucial, but not always easy, to inform patients and families about potential late effects and organize follow-up after the pediatric age. A well functioning network of pediatric oncologists, GP’s, adult oncologists and other specialists of adult medicine must be developed in order to prevent, early detect and treat expected long-term toxicities.

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References

  1. Bhatia S, Robison LL, Meadows AT, LESG Investigators (2001) 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. Blood 98:768a

    Google Scholar 

  2. Blanco JG, Edick MJ, Hancock ML, Winick NJ, Dervieux T, Amylon MD, Bash RO, Behm FG, Camitta BM, Pui CH, Raimondi SC, Relling MV (2002) Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies. Pharmacogenetics 12:605–611

    Article  PubMed  CAS  Google Scholar 

  3. Byrne J, Fears TR, Gail MH (1992) Early menopause in long-term survivors of cancer during adolescence. Am J Obstetr Gynecol 166:788–793

    CAS  Google Scholar 

  4. Chapman RM, Sutcliffe SB, Malpas JS (1979) Cytotoxic-induced ovarian failure in women with Hodgkin’s disease. I. Hormone function.. J Am Med Assoc 242:1877–1881

    Article  CAS  Google Scholar 

  5. Chow LML, Nathan PC, Hodgson DC, Jenkin D, Weitzman S, Grant RM, Manson D, Bross A, Doyle JJ, Danjoux C, Greenberg ML (2006) Survival and late effects in children with Hodgkin’s lymphoma treated with MOP/ABV and low-dose, extended-field irradiation. J Clin Oncol 24:5735–5741

    Article  PubMed  CAS  Google Scholar 

  6. de Cunha MF, Meistrich ML, Fuller LM (1984) Recovery of spermatogenesis after treatment for Hodgkin’s disease: limiting dose of MOPP chemotherapy. J Clin Oncol 2:571–578

    PubMed  Google Scholar 

  7. Donaldson SS, Kaplan HS (1982) Complications of treatment of Hodgkin’s disease in children. Cancer Treat Rep 66:977–983

    PubMed  CAS  Google Scholar 

  8. Dreyer ZE, Blatt J, Bleyer A (2002) Late effects of childhood cancer and its treatment. In: Pizzo PA, Poplack DG (eds) Principles and Practice of Pediatric Oncology. vol. 4. Lippincott and Wilkins, Philadelphia, pp 1431–1461

    Google Scholar 

  9. Felix CA (1998) Secondary leukemias induced by topoisomerase-targeted drugs. Biochim Biophys Acta 1400:233–255

    PubMed  CAS  Google Scholar 

  10. Felix CA, Walker AH, Lange BJ, Williams TM, Winick NJ, Cheung NK, Lovett BD, Nowell PC, Blair LA, Rebbeck TR (1998) Association of CYP3A4 genotype with treatment-related leukemia. Proc Natl Acad Sci USA 95:13176–13181

    Article  PubMed  CAS  Google Scholar 

  11. Green DM, Zevon MA, Rock KM, Chavez F (2002) Fatigue after treatment for Hodgkin’s disease during childhood or adolescence. Proc Am Soc Clin Oncol 21:396a

    Google Scholar 

  12. Hancock SL, Donaldson SS, Hoppe RT (1993) Cardiac disease following treatment of Hodgkin’s disease in children and adolescents. J Clin Oncol 11:1199–1203

    Google Scholar 

  13. Hertzberg H, Huk WJ, Ueberall MA, Langer T, Meier W, Dopfer R, Skalej M, Lackner H, Bode U, Janssen G Zintl F, Beck JD (1997) CNS late effects after ALL therapy in childhood. Part I: neuroradiological findings in long-term survivors of childhood ALL. An evaluation of the interferences between morphology and neuropsychological performance. The German Late Effects Working Group. Med Ped Oncol 28:387–400

    Article  CAS  Google Scholar 

  14. Horning SJ, Hoppe RT, Kaplan HS (1981) Female reproductive potential after treatment for Hodgkin’s disease. N Engl J Med 304:1377–1381

    Article  PubMed  CAS  Google Scholar 

  15. Kaldor JM, Day NE, Clarke EA, van Leeuwen FE, Henry-Amar M, Fiorentino MV, Bell J, Pedersen D, Band P, Assouline D, Koch M, Choi W, Prior P, Blair V, Langmark F, Pompe Kern V, Neal F, Peters D, Pfeiffer R, Karjalainen S, Cuzick J, Sutcliffe SB, Somers R, Pellac-Cosset B, Papagallo GL, Fraser P, Storm H, Stovall M (1990) Leukemia following Hodgkin’s disease. New Engl J Med 322:7–13

    Article  PubMed  CAS  Google Scholar 

  16. Katz JA, Pollock BH, Jacaruso D, Morad A (1993) Final attained height in patients successfully treated for childhood acute lymphoblastic leukemia. J Pediatr 123:546–552

    Article  PubMed  CAS  Google Scholar 

  17. Kremer LCM, van Dalen EC, Offringa M, Otenkamp J, Voute PA (2001) Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study. J Clin Oncol 19:191–196

    PubMed  CAS  Google Scholar 

  18. Kremer LCM, van der Pal HJH, Offringa M, van Dalen EC, Voute PA (2002) Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 13:819–829

    Article  PubMed  CAS  Google Scholar 

  19. Le Floch O, Donaldson SS, Kaplan HS (1976) Pregnancy following oophoropexy in total node irradiation in women with Hodgkin’s disease. Cancer 38:2263–2265

    Article  PubMed  Google Scholar 

  20. Lin HMJ, Teitell MA (2005) Second malignancy after treatment of pediatric Hodgkin’s disease. J Pediatr Hematol Oncol 27:28–36

    Article  PubMed  Google Scholar 

  21. Mackie EJ, Radford M, Shalet SM (1996) Gonadal function following chemotherapy for childhood Hodgkin’s disease. Med Pediatr Oncol 7:74–78

    Article  Google Scholar 

  22. Metayer C, Lynch CF, Clarke EA, Glimelius B, Storm H, Pukkala E, Joensuu T, van Leeuwen FE, van’t Veer MB, Curtis RE, Holowaty EJ, Andersson M, Wiklund T, Gospodarowicz M, Travis LB (2000) Second cancers among long-term survivors of Hodgkin’s disease diagnosed in childhood and adolescence. J Clin Oncol 18:2435–2443

    PubMed  CAS  Google Scholar 

  23. Mulhern RK, Reddick WE, Palmer SL, Glass JO, Elkin TD, Kun LE, Taylor J, Langston J, Gajjar A (1999) Neurocognitive deficits in medulloblastoma survivors and white matter loss. Ann Neurol 46:834–841

    Article  PubMed  CAS  Google Scholar 

  24. Naoe T, Takeyama K, Yogozawa T, Kiyoi H, Seto M, Uike N, Ino T, Utsunomiya A, Maruta A, Jin-Nai L, Kamada N, Kubota Y, Nakamura H, Shimazaki C, Horiike S, Kodera Y, Saito H, Ueda R, Wiemels J, Ohno R (2000) Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1and CYP3A4 in 469 Japanese patients with therapy-related leukemia/myelodysplastic syndrome and de novo acute myeloid leukemia. Clin Cancer Res 6:4091–4095

    PubMed  CAS  Google Scholar 

  25. Neglia JP, Friedman DL, Yasui Y, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL (2001) Second malignant neoplasms in five-year survivors of childhood cancer: Childhood Cancer Survivor Study. J Natl Cancer Inst 93:618–629

    Article  PubMed  CAS  Google Scholar 

  26. Ochs J, Mulhern R, Fairclough D, Parvey L, Whitaker J, Ch’ien L, Mauer A, Simone J (1991) Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study. J Clin Oncol 9:145–151

    PubMed  CAS  Google Scholar 

  27. Oeffinger KC, Mertens AC, Sklar CA, Yasui Y, Fears T, Stovall M, Vik TA, Inskip PD, Robison LL (2003) Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 21:1359–1365

    Article  PubMed  Google Scholar 

  28. Ortin TT, Shostak CA, Donaldson SS (1990) Gonadal status and reproductive function following treatment for Hodgkin’s disease in childhood: the Stanford experience. Int J Radiat Oncol Biol Phys 19:873–880

    PubMed  CAS  Google Scholar 

  29. Pui CH, Relling MV, Rivera GK, Hancock ML, Raimondi SC, Heslop HE, Santana VM, Ribeiro RC, Sandlung JT, Mahmoud HH, Evans WE, Crist WM, Krance RA (1995) Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases. Leukemia 9:1990–1996

    PubMed  CAS  Google Scholar 

  30. Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA, Kun LE, Walter AW, Evans WE, Pui CH (1999) High incidence of secondary brain tumors after radiotherapy and antimetabolites. Lancet 354:34–39

    Article  PubMed  CAS  Google Scholar 

  31. Robison LL, Mertens AC, Boice JD, Breslow NE, Donaldson SS, Green DM, Li FP, Meadows AT, Mulvihill JJ, Neglia JP, Nesbit ME, Packer RJ, Potter JD, Sklar CA, Smith MA, Stovall M, Strong LC, Yasui Y, Zeltzer LK (2002) Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project. Med Pediatr Oncol 38:229–239

    Article  PubMed  Google Scholar 

  32. Robison LL, Bathia S (2003) Late effects among survivors of leukemia and lymphoma during childhood and adolescence. Br J Haematol 122:345–359

    Article  PubMed  Google Scholar 

  33. Sanders JE, Hawley J, Levy W, Gooley T, Buckner CD, Deeg HJ, Doney K, Storb R, Sullivan K, Witherspoon R, Appelbaum FR (1996) Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total body irradiation and bone marrow transplantation. Blood 87:3045–3052

    PubMed  CAS  Google Scholar 

  34. Shamberger RC, Sherins RJ, Rosenberg SA (1981) The effects of post-operative adjuvant chemotherapy and radiotherapy on testicular function in men undergoing treatment for soft-tissue sarcoma. Cancer 47:2368–2374

    Article  PubMed  CAS  Google Scholar 

  35. Sklar C, Mertens A, Walter A, Mitchell D, Nesbit M, O’Leary M, Hutchinson R, Meadows AT, Robison L (1993) Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation. J Pediatr 123:59–64

    Article  PubMed  CAS  Google Scholar 

  36. Sklar C, Whitton J, Mertens A, Stovall M, Green D, Marina N, Greffe B, Wolden S, Robison L (2000) Abnormalities of the thyroid in survivors of Hodgkin’s disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 85:3227–3232

    Article  PubMed  CAS  Google Scholar 

  37. Smith MA, Rubinstein L, Anderson JR, Arthur D, Catalano PJ, Freidlin B, Heyn R, Khayat A, Krailo M, Land VJ, Miser J, Shuster J, Vena D (1999) Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol 17:569–577

    PubMed  CAS  Google Scholar 

  38. Tucker MA, Coleman CN, Cox RS, Varghese A, Rosenberg SA (1988) Risk of second cancers after treatment for Hodgkin’s disease. N Engl J Med 318:76–81

    Article  PubMed  CAS  Google Scholar 

  39. von der Weid NX (2001) Late effects in long-term survivors of ALL in childhood: experiences from the SPOG Late Effects Study. Swiss Med Wkly 131:180–187

    Google Scholar 

  40. von der Weid NX, Mosimann I, Hirt A, Wacker P, Nenadov Beck M, Imbach P, Caflisch U, Niggli F, Feldges A, Wagner HP (2003) Intellectual outcome in children and adolescents with acute lymphoblastic leukemia treated with chemotherapy alone: age- and sex-related differences. Eur J Cancer 39:359–365

    Article  Google Scholar 

  41. Zebrack BJ, Zeltzer LK, Whitton J, Mertens AC, Odom L, Berkow R, Robison LL (2002) Psychological outcomes in long-term survivors of childhood leukemia, Hodgkin’s disease and non-Hodgkin’s lymphoma: a report from the Childhood Cancer Survivor Study. Pediatrics 110:42–52

    Article  PubMed  Google Scholar 

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von der Weid, N.X. Adult life after surviving lymphoma in childhood. Support Care Cancer 16, 339–345 (2008). https://doi.org/10.1007/s00520-007-0369-x

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