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Revista Brasileira de Hematologia e Hemoterapia

Print version ISSN 1516-8484

Rev. Bras. Hematol. Hemoter. vol.34 no.5 São Paulo  2012

http://dx.doi.org/10.5581/1516-8484.20120087 

SCIENTIFIC COMMENTS

 

A step towards the cure of Burkitt's lymphoma in developing countries

 

 

Claudete Esteves Klumb

Instituto Nacional de Câncer - INCA, Rio de Janeiro, RJ, Brazil

Corresponding author

 

 

The outcome of sporadic Burkitt's lymphoma (BL) in high-income countries may be considered excellent due to its overall cure rate of roughly 90%(1-4). Three major US and European childhood cancer groups [Lymphoma malignancy B-cell (LMB), BerlinFrankfurt-Munster (BFM), Children's Cancer Group/Children Oncology Group (CCG/COG)] contributed to the most effective treatment strategies to date. Nevertheless, the treatment has pronounced toxic effects such as long periods of mucositis, hematological toxic effects as well as the potential risk of severe infection. Assuredly, the improvement of supportive care has contributed to these better outcomes(1-4). On the other hand, in low-income countries, therapeutic schemes need to be modified in accordance with local conditions in order to avoid unacceptable treatment-related mortality(5).

In this issue Cunha et al.(6) present a retrospective study of 50 cases of BL in children and adolescents who were treated with chemotherapy regimens containing intermediate methotrexate doses (500 mg/m2). The probability of overall survival was 73% (median follow-up of35 months). The data show a favorable step with improvement in the results of BL treatment in Brazil even considering the high mortality rate (23.8%) observed in the study. Reinforcing the predicted tumor burden value in the prognosis of BL patients, survival was significantly lower for patients with uric acid levels > 7 mg/dL. In addition, these results may also show that the impact of methotrexate on the overall success may be of less importance in patients with lower tumor load compared with those with larger tumor masses(7). Thus, the efficacy of treatment may depend as much on the number of drugs used (at least 4-6 drugs systemically) as on their doses and so lower dose multidrug regimens may improve outcome without comparable increases in toxicity(8).

Although the study by Cunha et al.(6) provides important information on the approach to BL care in Brazil, there are still several areas to be addressed. Differences among survival rates in a large country such as Brazil are worthy of comment. The mean tumor burden at diagnosis has an important impact on the outcome(9). Even though the Brazilian Government Healthcare System (SUS - Sistema Único de Saúde) covers most chemotherapy drug costs, primary healthcare should be improved for earlier diagnosis. Moreover, supportive care facilities remain inadequate in some Brazilian regions where resources are limited. Enhancement of laboratory monitoring, aggressive hydratation and the use of urate oxidase in patients with high risk of tumor lysis syndrome will result in fewer toxic events and better treatment outcomes(10).

The availability of rituximab in the SUS to treat B-cell lymphomas in adult patients has ledto the possibility of obtaining excellent results in children with less toxicity by combining thisdrug with chemotherapy. However, there is a question as to whether rituximab is an effectivedrug in pediatric B-cell non-Hodgkin lymphoma (B-NHL). This drug was tested in a phaseII short-window study showing that it can be safely added to a pediatric chemotherapeuticregimen(11). Even so, only controlled clinical trials will allow an evaluation of the role of thisdrug in the treatment of pediatric B-NHL.

Taking these considerations into account, results like those of high-income countries may be achieved by directing research towards designing protocol regimens in formal clinical trials with chemotherapy tailored by tumor burden. The primary goal of therapy studies in developing countries today is to define risk groups as accurately as possible, so that the patients receive therapy consistent with the best possible outcome while further reduction of acute and chronic toxicity may be achieved.

 

References

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2. Gerrard M, Cairo MS, Weston C, Auperin A, Pinkerton R, Lambilliote A, Sposto R, McCarthy K, Lacombe MJ, Perkins SL, Patte C; FAB LMB96 International Study Committee. Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Br J Haematol. 2008;141(6):840-7.         [ Links ]

3. Reiter A, Schrappe M, Tiemann M, Ludwig WD, Yakisan E, Zimmermann M, et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood. 1999;94(10):3294-306.         [ Links ]

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6. KC Cunha, MC Oliveira, AC Gomes, LP de Castro, MB Viana. Clinical course and prognostic factors of children with Burkitt's lymphoma in a developing country: the experience of a single centre in Brazil. Rev Bras Hematol Hemoter. 2012;34(5):361-6.         [ Links ]

7. Woessmann W, Seidemann K, Mann G, Zimmermann M, Burkhardt B, Oschlies I, Ludwig WD, Klingebiel T, Graf N, Gruhn B, Juergens H, Niggli F, Parwaresch R, Gadner H, Riehm H, Schrappe M, Reiter A; BFM Group. 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. 2005;105(3):948-58.         [ Links ]

8. Cairo MS, Krailo MD, Morse M, Hutchinson RJ, Harris RE, Kjeldsberg CR, et al. Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a children's cancer group report. Leukemia. 2002;16(4):594-600.         [ Links ]

9. Miles RR, Arnold S, Cairo MS. Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia. Br J Haematol. 2012;156(6):730-43.         [ Links ]

10. Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-86.         [ Links ]

11. Meinhardt A, Burkhardt B, Zimmermann M, Borkhardt A, Kontny U, Klingebiel T, Berthold F, Janka-Schaub G, Klein C, Kabickova E, Klapper W, Attarbaschi A, Schrappe M, Reiter A; Berlin-Frankfurt-Münster group. Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia. J Clin Oncol. 2010(19):3115-21.         [ Links ] Comment in: J Clin Oncol. 2010;28(19):3104-6.         [ Links ]

 

 

Corresponding author:
Claudete Esteves Klumb
Instituto Nacional de Câncer- INCA Programa de Hemato-Oncologia Molecular, Laboratório de Hemato-Oncologia Celular e Molecular
Praça da Cruz Vermelha Nº 23 - Centro
20230130 Rio de Janeiro, RJ, Brazil
Phone: 55 21 32071198
cklumb@inca.gov.br

Submitted: 8/17/2012
Accepted: 8/26/2012
Conflict-of-interest disclosure: The author declares no competing financial interest