Outcome and Toxicity Patterns in Children and Adolescents with Non-Hodgkin Lymphoma: A Single Institution Experience

Paola Angelini1*, Laura Rodriguez2*, Mohammed Zolaly3, Ahmed Naqvi4, Sheila Weitzman4, Oussama Abla4 and Angela Punnett4.

1 Paediatric Oncology Unit, The Royal Marsden NHS Foundation Trust, Sutton, UK.
2 Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada.
3 Department of Pediatrics, Faculty of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia
4 Department of Pediatrics, Division of Haematology and Oncology, The Hospital for Sick Children, Toronto, Canada.

Corresponding author: Paola Angelini, Children and Young People Unit, The Royal Marsden NHS Foundation Trust. Address: Downs Road, Sutton SM2 5PT, United Kingdom. Tel: +44 (0)7982960354. Email:

Published: March 1, 2018
Received: December 13, 2017
Accepted: February 2, 2018
Mediterr J Hematol Infect Dis 2018, 10(1): e2018020 DOI 10.4084/MJHID.2018.020
This article is available on PDF format at: 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 Burkitt's 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 similar long-term toxicity than adolescents aged 15-18 years.


Non-Hodgkin lymphoma (NHL) represents approximately 7% of all malignancies in children. The overall incidence of NHL increases with age, and the outcome differs amongst children being marginally less favourable in infants and adolescents.[1,2] Over the last three decades, significant improvements have been achieved in the outcome of pediatric NHL with current survival rates ranging between 80 to over 90% in mature B-cell lymphomas,[3] and only slightly lower in lymphoblastic lymphomas (LL)[4] and anaplastic large cell lymphomas (ALCL).[5] This is mostly due to treatment assignment on the basis of the histological subtype, cytogenetic abnormalities, and disease stage.[6] Adolescents have been reported to have a poorer outcome compared to children,[6] particularly in some histological subtypes such as Burkitt's lymphoma (BL).[7] This survival difference remains only partially explained and the age cut-off itself, between children and adolescents, has been set at either 14 or 15 years in different studies.[7] The aim of this retrospective study was to analyze the clinical characteristics and outcome of children with NHL treated at the Hospital for Sick Children in Toronto, Canada, and to determine whether children < 15 years of age have different clinical features, and/or outcomes than adolescents (age 15-18 years). The Hospital for Sick Children is a pediatric tertiary care center, therefore we provided all patients, including the teenagers, consistent care with pediatric protocols, and maximum enrollment into clinical trials when available, thus eliminating some of the issues which have been associated with poor outcomes in adolescents (treatment in adult centers, poor compliance, poor enrolment into clinical trials).

Materials and Methods

Research ethics approval was obtained from our institutional board. Medical records of children ≤ 18 years of age with newly diagnosed NHL admitted to the Hospital for Sick Children from January 1995 to December 2008 were retrospectively reviewed. Patients with human immunodeficiency virus infection, congenital immunodeficiency, previous organ transplantation, previous malignancy, previous chemotherapy or radiotherapy and those with a diagnosis of mycosis fungoides were excluded. NHL subtypes were classified according to 2001 WHO Classification of Haematological Malignancies.[8] Disease staging was performed according to the St. Jude staging system including a physical examination, peripheral blood and bone marrow smears, cerebrospinal fluid (CSF) analyses, serum lactate dehydrogenase (LDH) levels and adequate imaging techniques.[9] Patients with LL and ≥ 25% bone marrow (BM) blasts were diagnosed as acute lymphoblastic leukemia (ALL) and were excluded. Central nervous system (CNS) was considered positive at diagnosis if there were ≥5 lymphoma cells/µl in the CSF and/or cranial nerve palsy and/or cerebral lesions on neuroimaging. Lactate dehydrogenase (LDH) level was considered elevated if it was greater than twice the upper normal limit. B symptoms were defined as fever, drenching night sweats during the last six months, and weight loss at > 10% of baseline weight. Toxicity was graded as per CTCAE v4.
Therapy. Patients with T and B-cell LL received an ALL-type protocol consisting of a 4-drug induction (prednisone, vincristine, daunorubicin, asparaginase plus intrathecal methotrexate) therapy and consolidation (6-mercaptopurine, cyclophosphamide, cytarabine, prednisone and intrathecal methotrexate) therapy, followed by interim maintenance (high-dose methotrexate and intrathecal methotrexate), delayed intensification (dexamethasone, vincristine, doxorubicin, asparaginase, cyclophosphamide, cytarabine, thioguanine and intrathecal methotrexate) and maintenance therapy (oral 6-mercaptopurine and methotrexate plus monthly pulses of prednisone and vincristine) for a total therapy duration of 24 months. Patients with early-stage NHL including BL, diffuse large B-cell lymphoma (DLBCL), and ALCL were treated with the old POG9219 protocol consisting of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) therapy plus intrathecal methotrexate for two months. When the studies were open to accrual, patients with advanced stage LL, mature B-NHL and ALCL were recruited to the COG protocols A5971, ANHL01P1 and ANHL 0131 respectively. Off study patients received the standard arm of the protocols.
Patients with advanced-stage BL and DLBCL received LMB-96[10] type regimens consisting of a reductive phase (cyclophosphamide, vincristine, prednisone and intrathecal methotrexate and hydrocortisone) followed by induction (vincristine, prednisone, cyclophosphamide, high-dose methotrexate with folinic acid rescue and intrathecal methotrexate and hydrocortisone) therapy and consolidation (high-dose methotrexate with folinic acid, intrathecal methotrexate, hydrocortisone and cytarabine for stage III patients); stage IV patients received a higher dose of methotrexate (8 grams/m2) in induction, high-dose cytarabine and etoposide in consolidation and four cycles of maintenance therapy. Patients with advanced ALCL received the APO regimen consisting of induction (doxorubicin, vincristine, prednisone and intrathecal methotrexate) therapy followed by consolidation (6-mercaptopurine, prednisone, vincristine, doxorubicin until a cumulative dose of 300 mg/m2 which was later substituted by intravenous methotrexate) therapy for 15 cycles. In addition, cranial radiotherapy (CRT) was given to LL and ALCL patients with initial CNS involvement.
Follow up for toxicity monitoring, and disease surveillance was performed according to protocol specific or local standard of care guidelines.
Statistical analyses. Descriptive statistics were reported as absolute frequencies and percentages for qualitative data, while means, standard deviations (SD) and medians were used to describe quantitative variables. Continuous variables were stratified into categorical variables using appropriate criteria. Differences in the frequencies of each variable were evaluated by the chi-squared test and 95% confidence intervals (95% CI) for categorical variables. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan–Meier method and the differences were tested using the Log-rank test. EFS was calculated from the date of diagnosis until the first event (death from any cause, disease progression, relapse, or second malignancy) or until the date of the last follow-up. OS was calculated as the percentage of patients who were still alive at last follow-up date. Time was censored at last follow-up date if no failure occurred or if patient was lost to follow-up after completing therapy. Follow-up was updated until June 2013. A formal cumulative incidence analysis was performed regarding toxic deaths versus death related to relapse or progression. Statistical calculations were performed using SPSS software version 20.0 for Windows operating system (SPSS, Cary, NC, USA).


Patients’ characteristics. From January 1995 to December 2008, a total of 164 immunocompetent children ≤ 18 years of age were diagnosed with NHL in our Institution. The median age at diagnosis was ten years (range, 1-17) (Table 1). Patients were stratified according to their age at diagnosis into two groups: < 15 (children) and 15-18 years of age (adolescents). The male to female ratio was 1.5:1, with no significant difference between the age groups. The most frequent site of involvement was head and neck in the <15 year-group and abdomen in the 15-18 year-group. Among all NHL patients, 76% presented with advanced-stage disease (stage III or IV), 15% with elevated LDH, 38% with B symptoms, 11% with BM involvement and 9% with CNS involvement, with no significant differences between the two age groups. BL was diagnosed in 52 patients (33%), ALCL in 48 patients (29%) (including 1 primary CNS lymphoma), LL in 43 patients (26%) and DLBCL in 15 patients (8%) (including 1 primary CNS lymphoma, and 2 primary mediastinal B-cell lymphomas) and peripheral T-cell lymphoma (PTCL) in 6 patients (4%). BL was the most frequent histological subtype among children, while ALCL was the commonest among adolescents. Among 48 patients with ALCL and available Alk-1 reactivity data, 87%, and 77% of children and adolescents were positive, respectively (Not Significant, NS). As expected, 88% of LL patients had a T- and 12% had B-precursor immunophenotype.

Table 1 Table 1. Characteristics of the Patients.

Treatment outcome. At a median follow-up of 6.2 years (range 0.1–15.7 years), the 5-year EFS for all patients was 82% ± 3% and the 5-year OS 88% ± 2%. EFS was comparable in children < 15 years of age and adolescents (84% ± 3% vs. 77% ± 7%, P = 0.37), as well as 5-year OS (89± 2% % vs 82% ± 6%, P = 0.30) (Figure 1A).  When the patients were stratified by histological subtype, some trends became evident. Among BL patients, the 5-year EFS tended to be superior in children compared to adolescents (91% ± 4% vs 75% ± 15%, respectively; P= 0.17). Similarly, children with LL had better EFS then adolescents (82% ±7% vs 51.4% ± 2%, P= 0.16) (Figure 1A).
Among ALCL patients 5-year EFS was comparable in children and adolescents (81.4 ± 7.6% and 87 ± 7% respectively, P= 0.68) (Figure 1B), irrespective of skin, mediastinum, lung, liver and spleen involvement. Among 6 PTCL patients, 5 children aged < 15 years are currently alive and disease free and the only adolescent died from treatment-related toxicity.

Figure 1  Figure 1A. OS and EFS by age. Figure  1B. EFS by age and histological subtype.

Overall, twenty patients (12.2%) relapsed, 7 in the primary site only (35%), 4 in CNS alone (20%), 3 in the bone marrow alone (15%), 1 in each of liver only, neck only and testicular only (5% each site), and 3 (15%) in multiple sites. Five patients with BL (9.6%) relapsed (median time since diagnosis 4 months), as well as 2 (13%) with DLBCL (median time since diagnosis 13.6 months), 8 (19 %) with LL (median time since diagnosis 18.4 months), 3 (6%) with ALCL (median time since diagnosis 6.5 months) and two (33%) with PTCL (median time since diagnosis 5 months). Due to the low number of events, no comparison was possible between children and adolescents. Two patients underwent allogeneic hematopoietic stem cell transplant (HSCT) after one and two salvage chemotherapy regimen(s), and 3 underwent autologous HSCT after one salvage chemotherapy regimen. Twelve patients died from disease progression (7.3%). The cumulative incidence (CI) of death due to disease progression was 7.3% and 9.3% in the patients <15 and 15–18 years, respectively. Six patients (3.7%) died from treatment-related toxicity. The CI of toxic death was 3.6% and 5.7% in the patients aged < 15 and 15–18 years respectively.
Late effects
. Twenty-one patients (12.8%) developed late effects related to disease and/or treatment, with no significant differences between children and adolescents (Table 2). Patients who had undergone radiotherapy or HSCT (either autologous or allogeneic) were more likely to develop late effects. Six of 17 patients (35.3%) who had  received  radiotherapy developed  late effects, versus 15 of 147 who did not (P < 0.05).

Table 1 Table 2

One had total body irradiation as part of HSCT conditioning regimen; five had cranial irradiation (4 as upfront treatment due to CNS involvement at diagnosis, one patient due to CNS relapse).  Five of 11 patients (45.5%) who underwent HSCT developed late sequelae, versus 16 of 153 who did not (P < 0.05). Two BL survivors developed a second malignancy, a papillary thyroid carcinoma and a myelodysplastic syndrome, both among children <15 years of age, at 6 and 7 years since the end of treatment, respectively.


Non-Hodgkin lymphoma is one of the most common cancers diagnosed among adolescents.[11] Age has been shown to be of prognostic value in some histology subtypes, but the age threshold is not defined and varies in different histology subtypes. We chose to use 15 years of age as limit between children and adolescents, in line with SEER and ASH definition.[12]
Overall, the demographic characteristics of our patients do not deviate from the literature. Of note, ALCL was the second most common lymphoma and constitutes 29% of the cases in our series, higher than most of the literature data.[7,13-15] A possible explanation of these differences could be the racial diversity of our Canadian population. Further epidemiological studies on the incidence of lymphoma subtypes in populations of different ethnic background and on the pathogenesis of ALCL could improve our understanding.
We observed a significantly worse outcome among adolescents with BL, as previously reported by other authors.[17,18] In the NHL-BFM group, 5-year EFS was 88% in children compared to 82% in adolescents (P= 0.06).[6] However, in a more recent study on pediatric patients with mature B lineage NHL, the 3-year EFS was 89% and 84%, for patients <15 years versus > 15 years of age, respectively.[19] Differences in biology and genetics have been hypothesized to be responsible for this different outcome, but this question is still unanswered. Mbulaiteye et al. found that BL incidence may have trimodal incidence peaks, and concluded that BL peaking at different ages might have different etiology and/or biology.[20] Trautmann et al. reported age biased differences, with two gene rearrangements occurring almost exclusively in patients <14 years of age, and hypothesized that an antigen-driven selection might differ between pediatric and adult Burkitt’s lymphoma cases.[21] Other authors did not find significant differences between pediatric and adult BL with respect to immunophenotype, genomic aberrations or gene expression profiles.[22]
The addition of rituximab to the therapy of all mature B-NHL, based on the results of the recently closed international study, has proven beneficial both in children and adolescents.[23] Our paper focuses on patients treated before the introduction of rituximab, to have a homogenous population, and therefore does not contribute information in this respect.
We observed a trend towards an inferior outcome for adolescents with LL. This has also been reported previously.[24-26] Termuhlen et al., reported that among patients with advanced stage LL, age <10 years was associated with improved outcomes (P < 0·001).[27] The CCG502 trial reported an increased relative risk of treatment failure of 2.7 for the 38 patients >14 years of age compared with 156 patients <10 years of age at diagnosis (P= 0.008).[28] Similar results were reported by the BFM.[6]
In this report, there was no difference in outcome related to age in ALCL, which is similar to the literature data.[29-31,6] Although not significant, the finding of an increased incidence of ALK1-negative ALCL in the adolescent group is in keeping with other reports.[32-34]
Regarding outcomes, patients <15 years experienced more treatment-related complications but had slightly lower treatment-related mortality. The long-term toxicities including second malignancies were lower than expected,[35] explained by the combination of short follow up time in some patients and the use of newer treatment regimens designed to maintain survival while reducing long-term morbidity.
Our series presents some limitations. While the advantage of a single institutional series lies in the homogeneous radiological and pathological assessment, the limitation is in the small size of the study population. We decided to use the WHO 2001 classification, as using the 2008 revised version[36] would have led to further dividing into subgroups too small to allow any statistical analysis. As well, being a pediatric tertiary care center, we provided all patients, including the teenagers, consistent care with pediatric protocols, maximum enrollment into clinical trials when available, thus eliminating some of the issues which have been associated with poor outcomes in adolescents (treatment in adult centers, poor compliance, poor enrolment into clinical trials). Thus the differences that we observed in outcome and toxicity are more likely to be related to real differences in the biology of the disease between children and adolescents.
Our results are similar to those reported by the large groups.[3,6,23,24,28,37-46] The optimal treatment for adolescent NHL patients has not yet been established, and the reasons for the inferior outcomes in adolescents are not completely clear. Potential explanations include patient-related factors, disease-related factors and therapeutic strategies. Patient-related factors include psychosocial aspects unique to this age group, like the transition from the dependence of childhood to the autonomy of adulthood, including disagreements with authority figures, confusion about responsibilities, lack of communication, and failure to accurately perceive the severity of their cancer and the risk it poses. All of these factors will negatively affect the quality of cancer care they receive and their chances of survival.[47]
In summary, we confirm the differences reported in the literature between children and adolescents (> 15 years at diagnosis), in particular with respect to better survival and reduced risk of long-term toxicity in children. While our population was homogeneously assessed and treated, differences were often non-statistically significant due to the low numbers. More collaborative research is needed to better define disease-specific age ranges, by analyzing disease-specific biology and patient characteristics.


  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. PMid:23255391 PMCid:PMC4327936 
  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. PMid:17132719 PMCid:PMC1852229 
  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. PMid:26991119     
  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.  PMid:25548758 PMCid:PMC4278006 
  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. PMid:21030984     
  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.  PMid:16173961     
  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. PMid:11754390     
  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. PMid:2915234     
  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. PMid:17138821 PMCid:PMC1852225 
  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. PMid:15936140     
  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 PMid:27133800     
  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. PMid:9155693 PMCid:PMC499737 
  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. PMid:19087093   
  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.  PMid:18186966     
  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. PMid:11369626     
  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. PMid:12588354     
  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. PMid:22215753 PMCid:PMC3269965  
  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. PMid:22488262 PMCid:PMC3358448  
  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. PMid:18509088   
  23. Veronique Minard-Colin, Anne Auperin, Marta Pillon, Amos Burke, James Robert Anderson, Donald A. Barkauskas, et al. Results of the randomized Intergroup trial Inter-B-NHL Ritux 2010 for children and adolescents with high-risk B-cell non-Hodgkin lymphoma (B-NHL) and mature acute leukemia (B-AL): Evaluation of rituximab (R) efficacy in addition to standard LMB chemotherapy (CT) regimen. Journal of Clinical Oncology 34, no. 15_suppl (May 2016) 10507-10507 
  24. 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. PMid:19621432     
  25. 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. PMid:18342502     
  26. 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.  PMid:18759768 PMCid:PMC3057023  
  27. 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. PMid:23889312     
  28. 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. PMid:7751881     
  29. 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. PMid:17957029     
  30. 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. PMid:12060115    
  31. 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. PMid:9808552     
  32. Falini B, Pileri S, Zinzani PL, et al. ALK+ lymphoma: clinico-pathological findings and outcome. Blood. Apr 15 1999;93(8):2697-2706. PMid:10194450     
  33. 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. PMid:7655022  
  34. 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. PMid:11090048     
  35. 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. 
  36. 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. PMid:21300984 PMCid:PMC3109529  
  37. 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. PMid:15241838     
  38. 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. PMid:15486066     
  39. 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. PMid:21261497     
  40. 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. PMid:19194463 PMCid:PMC2843413   
  41. 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. PMid:21210776     
  42. 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. PMid:19856396     
  43. 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.  PMid:18022899     
  44. 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. PMid:20679620    
  45. 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. PMid:18985718 PMCid:PMC2769495   
  46. Pillon M, Mussolin L, Carraro E, Conter V, Aricò M, Vinti L, Garaventa A, Piglione M, Buffardi S, Sala A, Santoro N, Lo Nigro L, Mura R, Tondo A, Casale F, Farruggia P, Pierani P, Cesaro S, d'Amore ES, Basso G. Detection of prognostic factors in children and adolescents with Burkitt and Diffuse Large B-Cell Lymphoma treated with the AIEOP LNH-97 protocol. Br J Haematol. 2016 Nov;175(3):467-47547. PMid:27392319     
  47. Wood WA, Lee SJ. Malignant hematologic diseases in adolescents and young adults. Blood. Jun 2 2011;117(22):5803-5815. PMid:21398581         


Abstract views:


Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Copyright (c) 2018 Mediterranean Journal of Hematology and Infectious Diseases

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
© PAGEPress 2008-2018     -     PAGEPress is a registered trademark property of PAGEPress srl, Italy.     -     VAT: IT02125780185