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      Clinical course and prognostic factors of children with Burkitt's lymphoma in a developing country: the experience of a single centre in Brazil

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          Abstract

          Objective:

          Burkitt's lymphoma is the most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course and prognostic factors of children and adolescents with Burkitt's lymphoma treated in the Hematology Unit of Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG).

          Methods:

          A retrospective cohort study was made of 50 consecutive cases of children and adolescents aged 16 years or less with Burkitt's lymphoma admitted between January 1981 and December 2007. Prognostic factors associated with death were evaluated using the Kaplan-Meier method and compared by the two-tailed log-rank test.

          Results:

          The median age at diagnosis was 4.7 years. Most patients had abdominal tumors (66.7%) and advanced disease (68.9%) at diagnosis. Thirty-eight patients (84.4%) achieved complete clinical remission and 33 (73.3%) were alive at the first remission. Twelve children (26.7%) died. The median follow-up was 35 months with the probability of overall survival being 73% (89.2% and 35.7% for patients with uric acid < 7 mg/dL and ≥ 7.0 mg/dL, respectively - p-value < 0.001). Uric acid was the only significant prognostic factor at diagnosis.

          Conclusion:

          Our findings confirm the favorable prognosis of children with Burkitt's lymphoma even when treated with intermediate doses of methotrexate (500 mg/m2). Survival was significantly lower for individuals with concentrations of uric acid > 7 mg/dL.

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          Most cited references81

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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.

          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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            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.

            A previous study (LMB89) of the French Society of Pediatric Oncology for childhood mature B-cell lymphoma (B-NHL) demonstrated a 92% 3-year event-free survival (EFS) for intermediate-risk group B defined as "non-resected" stage II/I and CNS-negative advanced-stage IIV/IV (70% of cases). We performed the FAB/LMB96 trial to assess the possibility of reducing treatment in children/adolescents with intermediate-risk B-NHL without jeopardizing survival. "Early responding" patients (tumor response > 20% at day 7) were randomized in a factorial design between 4 arms, 2 receiving half-dose of cyclophosphamide in the second induction course with cyclophosphamide, Oncovin (vincristine), prednisone, Adriamycin (doxorubicin), methotrexate (COPADM) and 2 not receiving the maintenance course M1. A total of 657 patients were randomized (May 1996 to June 2001) and 637 were analyzed. The analysis showed no significant effect of any of the treatment reductions on EFS and survival. The 4-year EFS was 93.4% and 90.9% in the groups with full-dose and half-dose of cyclophosphamide (RR = 1.3, P = .40) and 91.9% and 92.5% in the groups with and without M1 (RR = 1.01, P = .98). There was no interaction between the 2 treatment reductions or between each treatment reduction and LDH level or histologic subtypes (Burkitt/Burkitt-like or large B-cell). Children/adolescents with intermediate-risk B-NHL who have an early response and achieve a complete remission after the first consolidation course can be cured with a 4-course treatment with a total dose of only 3.3 g/m2 cyclophosphamide and 120 mg/m2 doxorubicin.
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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.

              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
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Revista Brasileira de Hematologia e Hemoterapia
                Associação Brasileira de Hematologia e Hemoterapia
                1516-8484
                1806-0870
                2012
                : 34
                : 5
                : 361-366
                Affiliations
                Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, MG, Brazil
                Author notes
                Corresponding author: Maria Christina Lopes Araujo Oliveira Departamento de Pediatria - Unidade de Hematologia Pediátrica. Hospital das Clínicas, Universidade Federal de Minas Gerais - UFMG Av. Prof. Alfredo Balena, 190 30130-100 Belo Horizonte, MG, Brazil chrismariana@ 123456gmail.com
                Article
                10.5581/1516-8484.20120093
                3486827
                23125545
                0726b38b-4b79-4d82-a05a-76ed07ba7e90

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

                History
                : 17 April 2012
                : 25 June 2012
                Categories
                Original Article

                Hematology
                uric acid,prognosis,survival,lymphoma, non-hodgkin,child,burkitt's lymphoma
                Hematology
                uric acid, prognosis, survival, lymphoma, non-hodgkin, child, burkitt's lymphoma

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