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

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          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 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.

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          Most cited references45

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          CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features.

          T Marafioti, K Pulford, B Falini … (2000)
          Anaplastic large cell lymphoma (ALCL) represents a generally recognized group of large cell lymphomas. Defining features consist of a proliferation of predominantly large lymphoid cells with strong expression of the cytokine receptor CD30 and a characteristic growth pattern. With the use of molecular and clinical criteria, 3 entities of ALCL have been identified: primary systemic anaplastic lymphoma kinase (ALK)(+) ALCL, primary systemic ALK(-) ALCL, and primary cutaneous ALCL. ALK expression is caused by chromosomal translocations, most commonly t(2;5). ALK(+) ALCL predominantly affects young male patients and, if treated with chemotherapy, has a favorable prognosis. It shows a broad morphologic spectrum, with the "common type," the small cell variant, and the lymphohistiocytic variant being most commonly observed. The knowledge of the existence of these variants is essential in establishing a correct diagnosis. ALK(-) ALCL occurs in older patients, affecting both genders equally and having an unfavorable prognosis. The morphology and the immunophenotype of primary cutaneous ALCL show an overlap with that of lymphomatoid papulosis. Both diseases have an excellent prognosis, and secondary systemic dissemination is only rarely observed. The described ALCL entities usually derive from cytotoxic T cells. In contrast, large B-cell lymphomas with anaplastic morphology are believed to represent not a separate entity but a morphologic variant of diffuse large B-cell lymphoma. Malignant lymphomas with morphologic features of both Hodgkin disease and ALCL have formerly been classified as Hodgkin-like ALCL. Recent immunohistologic studies, however, suggest that ALCLs Hodgkin-like represent either cases of tumor cell-rich classic Hodgkin disease or (less commonly) ALK(+) ALCL or ALK(-) ALCL. (Blood. 2000;96:3681-3695)
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            The Société Française d'Oncologie Pédiatrique 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.

            C Coze, Catherine Patte, M J Terrier … (2001)
            This study was undertaken to show that a high survival rate can be obtained in B-cell (Burkitt and large B-cell) lymphoma and L3 leukemia with multiagent chemotherapy adapted to the tumor burden (stage, resection status, percentage of blasts in bone marrow, and central nervous system [CNS] involvement) and early response to chemotherapy, to investigate actual prognostic factors, and to see if large B-cell lymphoma can be treated with the same regimen as Burkitt lymphoma. Patients were classified into 3 risk groups. Group A (resected stage I and abdominal stage II) received 2 courses of vincristine, cyclophosphamide, doxorubicin, and prednisone. Group B (patients not eligible for groups A or C) received 5 courses of chemotherapy with, in addition, high-dose methotrexate, 3 g/m(2) over 3 hours; infusional cytarabine; and intrathecal (IT) methotrexate. Group C (patients with CNS involvement and acute lymphoblastic leukemia with at least 70% of blasts in bone marrow) received 8 courses with, in addition, high-dose methotrexate, 8 g/m(2); high-dose cytarabine; etoposide; and triple IT. Except in group A, treatment started with a prephase (COP, low-dose vincristine and cyclophosphamide). It was intensified for patients who did not respond to COP in group B and any patient with residual viable cells after the consolidation phase. A total of 561 patients were enrolled in the SFOP LMB89 protocol (July 1989-June 1996). Five-year survival is 92.5% (95% confidence interval [CI], 90%-94%) and event-free survival (EFS) 91% (95% CI, 89%-93%). EFS is 98% (95% CI, 90%-100%), 92% (95% CI, 89%-95%), and 84% (95% CI, 77%-90%) for group A, B, and C, respectively. In group B, multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value, no response after COP, and age of at least 15 years were associated with a lower EFS. CNS involvement was the only prognostic factor in group C. (Blood. 2001;97:3370-3379)
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              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.

              Norbert Graf, Thomas Klingebiel, Reza Parwaresch … (2005)
              In the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster 95 (NHL-BFM95) study, we tested by randomization whether for patients with B-cell neoplasms methotrexate as intravenous infusion over 4 hours (MTX-4h) is not inferior to, but less toxic than, a 24-hour intravenous infusion (MTX-24h). Second, we investigated against the historical control of study NHL-BFM90, whether for patients with moderate tumor mass MTX can be reduced from 5 g/m(2) to 1 g/m(2). Patients received 2 5-day therapy courses in risk group R1 (resected), 4 in R2 (lactate dehydrogenase [LDH] 500 to 1000 U/L and/or central nervous system [CNS] disease). Courses contained MTX 1 g/m(2) in R1 + R2 and 5 g/m(2) in R3 + R4. Of 505 patients (April 1996 to March 2001), 364 were randomized to receive MTX-4h or MTX-24h. Failure-free survival (pFFS, 1 year) for arm MTX-4h versus MTX-24h, respectively, was 95% +/- 5% (n = 20) versus 100% (n = 19) in R1, 94% +/- 2% (n = 88) versus 96% +/- 2% (n = 95) in R2, and 77% +/- 5% (n = 62) versus 93% +/- 3% (n = 69) in R3 +/- R4 (per-protocol analysis). Incidence of mucositis grade III/IV was significantly lower with MTX-4h in all risk groups. For patients in R2, event-free survival (pEFS) was 95% +/- 2% (n = 222) in NHL-BFM95 (MTX 1 g/m(2)) and 97% +/- 1% (n = 154) in NHL-BFM90 (MTX 5 g/m(2)). In conclusion, MTX-4h was less toxic than MTX-24h. MTX-4h was noninferior to MTX-24h for limited stage B-cell non-Hodgkin lymphoma (B-NHL) but not for advanced disease. For limited disease, MTX 1 g/m(2) is noninferior to 5 g/m(2).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mediterr J Hematol Infect Dis
                Journal ID (iso-abbrev): Mediterr J Hematol Infect Dis
                Journal ID (publisher-id): Mediterranean Journal of Hematology and Infectious Diseases
                Title: Mediterranean Journal of Hematology and Infectious Diseases
                Publisher: Università Cattolica del Sacro Cuore
                ISSN (Electronic): 2035-3006
                Publication date Collection: 2018
                Publication date (Electronic): 01 March 2018
                Volume: 10
                Issue: 1
                Electronic Location Identifier: e2018020
                Affiliations
                [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
                Author notes
                Correspondence to: 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: paola_angelini@ 123456yahoo.com
                Article
                Publisher ID: mjhid-10-1-e2018020
                DOI: 10.4084/MJHID.2018.020
                PMC ID: 5841941
                SO-VID: d06950b8-bb39-414c-bacd-6f8582e101ac
                Copyright statement: Copyright @ 2018
                License:

                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.

                History
                Date received : 13 December 2017
                Date accepted : 02 February 2018
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: lymphoma,age,adolescents,toxicity,outcomes
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: lymphoma, age, adolescents, toxicity, outcomes

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