OUTCOME AND TOXICITY PATTERNS IN CHILDREN AND ADOLESCENTS WITH NON-HODGKIN LYMPHOMA: A SINGLE INSTITUTION EXPERIENCE
Main Article Content
Keywords
lymphoma, age, adolescents, toxicity, outcomes
Abstract
Background: The incidence and biology of non-Hodgkin lymphoma (NHL) vary according to age. Some data suggest that the impact of age in pediatric and adolescent NHL patients depends on the histological subtype. Objectives: We aimed to analyze the impact of age at diagnosis on clinical characteristics and treatment-related toxicity in children and adolescents with NHL.
Methods: Retrospective review of medical records of children and adolescents diagnosed with NHL at the Hospital for Sick children, Toronto, between January 1995 and December 2008.
Results: 164 children were diagnosed with NHL during the study period, with a median age at diagnosis of 10 years. With a median follow-up of 6.2 years, 5-year OS in patients aged <15 and 15-18 years was 89± 2% vs 82% ± 6%, respectively (P = 0.30), and 5-year EFS was 84% ± 3% vs. 77% ± 7% (P= 0.37). In Burkitts lymphoma (BL) and lymphoblastic lymphoma (LL) there was a trend towards better outcomes in children compared to adolescents, with EFS of 91% ± 4% vs. 75% ± 15%, respectively in BL (P= 0.17), and 82% ± 7% vs. 51.4% ± 2% respectively in LL (P= 0.16). Late effects occurred in 21 patients (12.8%).
Conclusions: Children with NHL aged < 15 years tend to have better survival rates and less long-term toxicity than adolescents aged 15-18 years.
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REFERENCES
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2. Mann G, Attarbaschi A, Burkhardt B, et al. Clinical characteristics and treatment outcome of infants with non-Hodgkin lymphoma. British journal of haematology. Nov 2007;139(3):443-449.
3. Patte C, Auperin A, Gerrard M, et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. Apr 1 2007;109(7):2773-2780.
4. Burkhardt B, Mueller S, Khanam T, Perkins SL. Current status and future directions of T-lymphoblastic lymphoma in children and adolescents. British journal of haematology. May 2016;173(4):545-559.
5. Han JY, Suh JK, Lee SW, Koh KN, Im HJ, Seo JJ. Clinical characteristics and treatment outcomes of children with anaplastic large cell lymphoma: a single center experience. Blood research. Dec 2014;49(4):246-252.
6. Burkhardt B, Oschlies I, Klapper W, et al. Non-Hodgkin's lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia. Jan 2011;25(1):153-160.
7. Burkhardt B, Zimmermann M, Oschlies I, et al. The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. British journal of haematology. Oct 2005;131(1):39-49.
8. Chan JK. The new World Health Organization classification of lymphomas: the past, the present and the future. Hematol Oncol. Dec 2001; 19(4):129-150.
9. Murphy SB, Fairclough DL, Hutchison RE, Berard CW. Non-Hodgkin's lymphomas of childhood: an analysis of the histology, staging, and response to treatment of 338 cases at a single institution. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Feb 1989;7(2):186-193.
10. Cairo MS, Gerrard M, Sposto R, et al. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood. Apr 1 2007;109(7):2736-2743.
11. Brignole C, Marimpietri D, Pagnan G, et al. Neuroblastoma targeting by c-myb-selective antisense oligonucleotides entrapped in anti-GD2 immunoliposome: immune cell-mediated anti-tumor activities. Cancer letters. Oct 18 2005;228(1-2):181-186.
12. Cairo M, Pinkerton R. Childhood, adolescent and young adult non-Hodgkin lymphoma: state of the science. British Journal of Haematology. May 2016; 173(4):507-530
13. Manipadam MT, Nair S, Viswabandya A, Mathew L, Srivastava A, Chandy M. Non-Hodgkin lymphoma in childhood and adolescence: frequency and distribution of immunomorphological types from a tertiary care center in South India. World journal of pediatrics : WJP. Nov 2011;7(4):318-325.
14. Wright D, McKeever P, Carter R. Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK Children's Cancer Study Group. Journal of clinical pathology. Feb 1997;50(2):128-134.
15. Hochberg J, Waxman IM, Kelly KM, Morris E, Cairo MS. Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma: state of the science. British journal of haematology. Jan 2009;144(1):24-40.
16. Hwang IG, Yoo KH, Lee SH, et al. Clinicopathologic features and treatment outcomes in malignant lymphoma of pediatric and young adult patients in Korea: comparison of korean all-ages group and Western younger age group. Clinical lymphoma & myeloma. Nov 2007;7(9):580-586.
17. Patte C, Auperin A, Michon J, et al. The Societe Francaise d'Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood. Jun 1 2001;97(11):3370-3379.
18. Cairo MS, Sposto R, Perkins SL, et al. Burkitt's and Burkitt-like lymphoma in children and adolescents: a review of the Children's Cancer Group experience. British journal of haematology. Feb 2003;120(4):660-670.
19. Cairo MS, Sposto R, Gerrard M, et al. Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (>/= 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Feb 1 2012;30(4):387-393.
20. Mbulaiteye SM, Anderson WF, Ferlay J, et al. Pediatric, elderly, and emerging adult-onset peaks in Burkitt's lymphoma incidence diagnosed in four continents, excluding Africa. American journal of hematology. Jun 2012;87(6):573-578.
21. Trautman H, Hadzidimitriou A, Darzentas N et al. Evidence for antigen-driven development of molecularly classified Burkitt lymphomas. Blood. Nov 2009; 114(22):317.
22. Klapper W, Szczepanowski M, Burkhardt B, et al. Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials. Blood. Aug 15 2008;112(4):1374-1381.
23. Pillon M, Piglione M, Garaventa A, et al. Long-term results of AIEOP LNH-92 protocol for the treatment of pediatric lymphoblastic lymphoma: a report of the Italian Association of Pediatric Hematology and Oncology. Pediatric blood & cancer. Dec 2009;53(6):953-959.
24. Uyttebroeck A, Suciu S, Laureys G, et al. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial. European journal of cancer. Apr 2008;44(6):840-846.
25. Abromowitch M, Sposto R, Perkins S, et al. Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology Group. British journal of haematology. Oct 2008;143(2):261-267.
26. Termuhlen AM, Smith LM, Perkins SL, et al. Disseminated lymphoblastic lymphoma in children and adolescents: results of the COG A5971 trial: a report from the Children's Oncology Group. British journal of haematology. Sep 2013;162(6):792-801.
27. Tubergen DG, Krailo MD, Meadows AT, et al. Comparison of treatment regimens for pediatric lymphoblastic non-Hodgkin's lymphoma: a Childrens Cancer Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Jun 1995;13(6):1368-1376.
28. Le Deley MC, Reiter A, Williams D, et al. Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study. Blood. Feb 1 2008;111(3):1560-1566.
29. Williams DM, Hobson R, Imeson J, et al. Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on The United Kingdom Children's Cancer Study Group chemotherapy regimens. British journal of haematology. Jun 2002;117(4):812-820.
30. Brugieres L, Deley MC, Pacquement H, et al. CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood. Nov 15 1998;92(10):3591-3598.
31. Falini B, Pileri S, Zinzani PL, et al. ALK+ lymphoma: clinico-pathological findings and outcome. Blood. Apr 15 1999;93(8):2697-2706.
32. Shiota M, Nakamura S, Ichinohasama R, et al. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Blood. Sep 1 1995;86(5):1954-1960.
33. Stein H, Foss HD, Durkop H, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. Dec 1 2000;96(12):3681-3695.
34. von der Weid NX. Adult life after surviving lymphoma in childhood. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. Apr 2008;16(4):339-345.
35. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. May 12 2011;117(19):5019-5032.
36. Pillon M, Di Tullio MT, Garaventa A, et al. Long-term results of the first Italian Association of Pediatric Hematology and Oncology protocol for the treatment of pediatric B-cell non-Hodgkin lymphoma (AIEOP LNH92). Cancer. Jul 15 2004;101(2):385-394.
37. Woessmann W, Seidemann K, Mann G, et al. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Blood. Feb 1 2005;105(3):948-958.
38. Fujita N, Kobayashi R, Takimoto T, Nakagawa A, Ueda K, Horibe K. Results of the Japan Association of Childhood Leukemia Study (JACLS) NHL-98 protocol for the treatment of B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia in childhood. Leukemia & lymphoma. Feb 2011;52(2):223-229.
39. Sandlund JT, Pui CH, Zhou Y, et al. Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: results of St Jude NHL13 study. Leukemia. Jun 2009;23(6):1127-1130.
40. Ducassou S, Ferlay C, Bergeron C, et al. Clinical presentation, evolution, and prognosis of precursor B-cell lymphoblastic lymphoma in trials LMT96, EORTC 58881, and EORTC 58951. British journal of haematology. Feb 2011;152(4):441-451.
41. Kobayashi R, Yamato K, Tanaka F, et al. Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan. Pediatric blood & cancer. Feb 2010;54(2):212-215.
42. Windsor R, Stiller C, Webb D. Peripheral T-cell lymphoma in childhood: population-based experience in the United Kingdom over 20 years. Pediatric blood & cancer. Apr 2008;50(4):784-787.
43. Le Deley MC, Rosolen A, Williams DM, et al. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Sep 1 2010;28(25):3987-3993.
44. Lowe EJ, Sposto R, Perkins SL, et al. Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: final results of Children's Cancer Group Study 5941. Pediatric blood & cancer. Mar 2009;52(3):335-339.
45. Wood WA, Lee SJ. Malignant hematologic diseases in adolescents and young adults. Blood. Jun 2 2011;117(22):5803-5815.
1. Bollard CM, Lim MS, Gross TG, Committee COGN-HL. Children's Oncology Group's 2013 blueprint for research: non-Hodgkin lymphoma. Pediatric blood & cancer. Jun 2013;60(6):979-984.
2. Mann G, Attarbaschi A, Burkhardt B, et al. Clinical characteristics and treatment outcome of infants with non-Hodgkin lymphoma. British journal of haematology. Nov 2007;139(3):443-449.
3. Patte C, Auperin A, Gerrard M, et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood. Apr 1 2007;109(7):2773-2780.
4. Burkhardt B, Mueller S, Khanam T, Perkins SL. Current status and future directions of T-lymphoblastic lymphoma in children and adolescents. British journal of haematology. May 2016;173(4):545-559.
5. Han JY, Suh JK, Lee SW, Koh KN, Im HJ, Seo JJ. Clinical characteristics and treatment outcomes of children with anaplastic large cell lymphoma: a single center experience. Blood research. Dec 2014;49(4):246-252.
6. Burkhardt B, Oschlies I, Klapper W, et al. Non-Hodgkin's lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia. Jan 2011;25(1):153-160.
7. Burkhardt B, Zimmermann M, Oschlies I, et al. The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. British journal of haematology. Oct 2005;131(1):39-49.
8. Chan JK. The new World Health Organization classification of lymphomas: the past, the present and the future. Hematol Oncol. Dec 2001; 19(4):129-150.
9. Murphy SB, Fairclough DL, Hutchison RE, Berard CW. Non-Hodgkin's lymphomas of childhood: an analysis of the histology, staging, and response to treatment of 338 cases at a single institution. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Feb 1989;7(2):186-193.
10. Cairo MS, Gerrard M, Sposto R, et al. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood. Apr 1 2007;109(7):2736-2743.
11. Brignole C, Marimpietri D, Pagnan G, et al. Neuroblastoma targeting by c-myb-selective antisense oligonucleotides entrapped in anti-GD2 immunoliposome: immune cell-mediated anti-tumor activities. Cancer letters. Oct 18 2005;228(1-2):181-186.
12. Cairo M, Pinkerton R. Childhood, adolescent and young adult non-Hodgkin lymphoma: state of the science. British Journal of Haematology. May 2016; 173(4):507-530
13. Manipadam MT, Nair S, Viswabandya A, Mathew L, Srivastava A, Chandy M. Non-Hodgkin lymphoma in childhood and adolescence: frequency and distribution of immunomorphological types from a tertiary care center in South India. World journal of pediatrics : WJP. Nov 2011;7(4):318-325.
14. Wright D, McKeever P, Carter R. Childhood non-Hodgkin lymphomas in the United Kingdom: findings from the UK Children's Cancer Study Group. Journal of clinical pathology. Feb 1997;50(2):128-134.
15. Hochberg J, Waxman IM, Kelly KM, Morris E, Cairo MS. Adolescent non-Hodgkin lymphoma and Hodgkin lymphoma: state of the science. British journal of haematology. Jan 2009;144(1):24-40.
16. Hwang IG, Yoo KH, Lee SH, et al. Clinicopathologic features and treatment outcomes in malignant lymphoma of pediatric and young adult patients in Korea: comparison of korean all-ages group and Western younger age group. Clinical lymphoma & myeloma. Nov 2007;7(9):580-586.
17. Patte C, Auperin A, Michon J, et al. The Societe Francaise d'Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood. Jun 1 2001;97(11):3370-3379.
18. Cairo MS, Sposto R, Perkins SL, et al. Burkitt's and Burkitt-like lymphoma in children and adolescents: a review of the Children's Cancer Group experience. British journal of haematology. Feb 2003;120(4):660-670.
19. Cairo MS, Sposto R, Gerrard M, et al. Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (>/= 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Feb 1 2012;30(4):387-393.
20. Mbulaiteye SM, Anderson WF, Ferlay J, et al. Pediatric, elderly, and emerging adult-onset peaks in Burkitt's lymphoma incidence diagnosed in four continents, excluding Africa. American journal of hematology. Jun 2012;87(6):573-578.
21. Trautman H, Hadzidimitriou A, Darzentas N et al. Evidence for antigen-driven development of molecularly classified Burkitt lymphomas. Blood. Nov 2009; 114(22):317.
22. Klapper W, Szczepanowski M, Burkhardt B, et al. Molecular profiling of pediatric mature B-cell lymphoma treated in population-based prospective clinical trials. Blood. Aug 15 2008;112(4):1374-1381.
23. Pillon M, Piglione M, Garaventa A, et al. Long-term results of AIEOP LNH-92 protocol for the treatment of pediatric lymphoblastic lymphoma: a report of the Italian Association of Pediatric Hematology and Oncology. Pediatric blood & cancer. Dec 2009;53(6):953-959.
24. Uyttebroeck A, Suciu S, Laureys G, et al. Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial. European journal of cancer. Apr 2008;44(6):840-846.
25. Abromowitch M, Sposto R, Perkins S, et al. Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology Group. British journal of haematology. Oct 2008;143(2):261-267.
26. Termuhlen AM, Smith LM, Perkins SL, et al. Disseminated lymphoblastic lymphoma in children and adolescents: results of the COG A5971 trial: a report from the Children's Oncology Group. British journal of haematology. Sep 2013;162(6):792-801.
27. Tubergen DG, Krailo MD, Meadows AT, et al. Comparison of treatment regimens for pediatric lymphoblastic non-Hodgkin's lymphoma: a Childrens Cancer Group study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Jun 1995;13(6):1368-1376.
28. Le Deley MC, Reiter A, Williams D, et al. Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study. Blood. Feb 1 2008;111(3):1560-1566.
29. Williams DM, Hobson R, Imeson J, et al. Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on The United Kingdom Children's Cancer Study Group chemotherapy regimens. British journal of haematology. Jun 2002;117(4):812-820.
30. Brugieres L, Deley MC, Pacquement H, et al. CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood. Nov 15 1998;92(10):3591-3598.
31. Falini B, Pileri S, Zinzani PL, et al. ALK+ lymphoma: clinico-pathological findings and outcome. Blood. Apr 15 1999;93(8):2697-2706.
32. Shiota M, Nakamura S, Ichinohasama R, et al. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Blood. Sep 1 1995;86(5):1954-1960.
33. Stein H, Foss HD, Durkop H, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. Dec 1 2000;96(12):3681-3695.
34. von der Weid NX. Adult life after surviving lymphoma in childhood. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. Apr 2008;16(4):339-345.
35. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood. May 12 2011;117(19):5019-5032.
36. Pillon M, Di Tullio MT, Garaventa A, et al. Long-term results of the first Italian Association of Pediatric Hematology and Oncology protocol for the treatment of pediatric B-cell non-Hodgkin lymphoma (AIEOP LNH92). Cancer. Jul 15 2004;101(2):385-394.
37. Woessmann W, Seidemann K, Mann G, et al. The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Blood. Feb 1 2005;105(3):948-958.
38. Fujita N, Kobayashi R, Takimoto T, Nakagawa A, Ueda K, Horibe K. Results of the Japan Association of Childhood Leukemia Study (JACLS) NHL-98 protocol for the treatment of B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia in childhood. Leukemia & lymphoma. Feb 2011;52(2):223-229.
39. Sandlund JT, Pui CH, Zhou Y, et al. Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: results of St Jude NHL13 study. Leukemia. Jun 2009;23(6):1127-1130.
40. Ducassou S, Ferlay C, Bergeron C, et al. Clinical presentation, evolution, and prognosis of precursor B-cell lymphoblastic lymphoma in trials LMT96, EORTC 58881, and EORTC 58951. British journal of haematology. Feb 2011;152(4):441-451.
41. Kobayashi R, Yamato K, Tanaka F, et al. Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan. Pediatric blood & cancer. Feb 2010;54(2):212-215.
42. Windsor R, Stiller C, Webb D. Peripheral T-cell lymphoma in childhood: population-based experience in the United Kingdom over 20 years. Pediatric blood & cancer. Apr 2008;50(4):784-787.
43. Le Deley MC, Rosolen A, Williams DM, et al. Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Sep 1 2010;28(25):3987-3993.
44. Lowe EJ, Sposto R, Perkins SL, et al. Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: final results of Children's Cancer Group Study 5941. Pediatric blood & cancer. Mar 2009;52(3):335-339.
45. Wood WA, Lee SJ. Malignant hematologic diseases in adolescents and young adults. Blood. Jun 2 2011;117(22):5803-5815.