Outcome and Toxicity Patterns in Children and Adolescents with Non-Hodgkin Lymphoma: A Single Institution Experience
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.
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
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Materials and Methods
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 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).
|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 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).
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.
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). 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. 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. 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. Other authors did not find significant differences between pediatric and adult BL with respect to immunophenotype, genomic aberrations or gene expression profiles.
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. 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). 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). Similar results were reported by the BFM.
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, 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 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.
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.
- 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. https://doi.org/10.1002/pbc.24416 PMid:23255391 PMCid:PMC4327936
- 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. https://doi.org/10.1111/j.1365-2141.2007.06796.x
- 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
- 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. https://doi.org/10.1111/bjh.14017 PMid:26991119
- 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. https://doi.org/10.5045/br.2014.49.4.246 PMid:25548758 PMCid:PMC4278006
- 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. https://doi.org/10.1038/leu.2010.245 PMid:21030984
- 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. https://doi.org/10.1111/j.1365-2141.2005.05735.x PMid:16173961
- 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. https://doi.org/10.1002/hon.660 PMid:11754390
- 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. https://doi.org/10.1200/JCO.19126.96.36.199 PMid:2915234
- 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
- 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. https://doi.org/10.1016/j.canlet.2004.11.065 PMid:15936140
- 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 https://doi.org/10.1111/bjh.14035 PMid:27133800
- 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. https://doi.org/10.1007/s12519-011-0303-7
- 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. https://doi.org/10.1136/jcp.50.2.128 PMid:9155693 PMCid:PMC499737
- 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. https://doi.org/10.1111/j.1365-2141.2008.07393.x PMid:19087093
- 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. https://doi.org/10.3816/CLM.2007.n.044 PMid:18186966
- 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. https://doi.org/10.1182/blood.V97.11.3370 PMid:11369626
- 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. https://doi.org/10.1046/j.1365-2141.2003.04134.x PMid:12588354
- 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. https://doi.org/10.1200/JCO.2010.33.3369 PMid:22215753 PMCid:PMC3269965
- 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. https://doi.org/10.1002/ajh.23187 PMid:22488262 PMCid:PMC3358448
- Trautman H, Hadzidimitriou A, Darzentas N et al. Evidence for antigen-driven development of molecularly classified Burkitt lymphomas. Blood. Nov 2009; 114(22):317.
- 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. https://doi.org/10.1182/blood-2008-01-136465 PMid:18509088
- 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
- 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. https://doi.org/10.1002/pbc.22162 PMid:19621432
- 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. https://doi.org/10.1016/j.ejca.2008.02.011 PMid:18342502
- 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. https://doi.org/10.1111/j.1365-2141.2008.07320.x PMid:18759768 PMCid:PMC3057023
- 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. https://doi.org/10.1111/bjh.12460 PMid:23889312
- 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. https://doi.org/10.1200/JCO.19188.8.131.528 PMid:7751881
- 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. https://doi.org/10.1182/blood-2007-07-100958 PMid:17957029
- 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. https://doi.org/10.1046/j.1365-2141.2002.03482.x PMid:12060115
- 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
- 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
- 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
- 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
- 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.
- 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. https://doi.org/10.1182/blood-2011-01-293050 PMid:21300984 PMCid:PMC3109529
- 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. https://doi.org/10.1002/cncr.20382 PMid:15241838
- 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. https://doi.org/10.1182/blood-2004-03-0973 PMid:15486066
- 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. https://doi.org/10.3109/10428194.2010.537794 PMid:21261497
- 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. https://doi.org/10.1038/leu.2008.400 PMid:19194463 PMCid:PMC2843413
- 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. https://doi.org/10.1111/j.1365-2141.2010.08541.x PMid:21210776
- 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
- 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. https://doi.org/10.1002/pbc.21293 PMid:18022899
- 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. https://doi.org/10.1200/JCO.2010.28.5999 PMid:20679620
- 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. https://doi.org/10.1002/pbc.21817 PMid:18985718 PMCid:PMC2769495
- 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. https://doi.org/10.1111/bjh.14240 PMid:27392319
- Wood WA, Lee SJ. Malignant hematologic diseases in adolescents and young adults. Blood. Jun 2 2011;117(22):5803-5815. https://doi.org/10.1182/blood-2010-12-283093 PMid:21398581