High-Stage Childhood Anaplastic Large Cell Lymphoma Treatment
Children and adolescents with high-stage (stage III or IV) anaplastic large cell lymphoma have a disease-free survival of approximately 60% to 75%.[1-6] It is unclear which strategy is best for the treatment of high-stage anaplastic large cell lymphoma. The German Berlin-Frankfurt-Munster (BFM) group used six cycles of intensive pulsed therapy, similar to their B-cell non-Hodgkin lymphoma (NHL) therapy (GER-GPOH-NHL-BFM-90 [NHL-BFM-90]).; [Level of evidence: 1iiA] Building on these results, the European Intergroup for Childhood NHL (EICNHL) group conducted the FRE-IGR-ALCL99 study (based on the GER-GPOH-NHL-BFM-90 regimen). First, this randomized study demonstrated that methotrexate 1 g/m2 infused over 24 hours plus intrathecal methotrexate and methotrexate 3 g/m2 infused over 3 hours without intrathecal methotrexate yielded similar outcomes.[Level of evidence: 1iiC] However, methotrexate 3 g/m2 over 3 hours had less toxicity than methotrexate 1 g/m2 over 24 hours.; [Level of evidence: 1iiDi] Secondly, FRE-IGR-ALCL99 randomly assigned patients to limited vinblastine versus prolonged (1 year) vinblastine exposure. Patients receiving the vinblastine plus chemotherapy regimen had a better event-free survival (EFS) in the first year after therapy (91%) than those not receiving vinblastine (74%); however, after 2 years of follow-up, the EFS was 73% for both groups.[Level of evidence: 1iiDi] Of note, the Pediatric Oncology Group (POG) trial (POG-9317) demonstrated no benefit of adding methotrexate and high-dose cytarabine to 52 weeks of the APO (doxorubicin, prednisone, and vincristine) regimen. The Italian Association of Pediatric Hematology/Oncology group has used a leukemia-like regimen for 24 months in LNH-92, with similar results as other regimens. The CCG-5941 study tested an approach similar to LNH-92, with more intensive induction and consolidation with maintenance for 1 year total duration of therapy, with similar outcome, but significant hematologic toxicity was observed.[Level of evidence: 2A]
Central nervous system (CNS) involvement in anaplastic large cell lymphoma is rare at diagnosis. In an international study of systemic childhood anaplastic large cell lymphoma, 12 of 463 (2.6%) patients had CNS involvement, three of whom had isolated CNS disease. With multiagent chemotherapy, including high-dose methotrexate, cytarabine, and intrathecal treatment, the event-free survival and overall survival of the CNS-positive group at 5 years were 50% (95% CI, 25%–75%) and 74% (45%–91%), respectively, with a median follow up of 4.1 years. The role of cranial radiation therapy is difficult to assess.Standard Treatment Options
[Note: Current data do not suggest superiority for the following standard treatment options.]
- APO: doxorubicin, prednisone, and vincristine. This regimen can be administered in the outpatient setting. The duration of therapy is 52 weeks and the cumulative dose of doxorubicin in 300 mg/m2.
- FRE-IGR-ALCL99: dexamethasone, cyclophosphamide, ifosfamide, etoposide, doxorubicin, IV methotrexate (3 g/m2 arm), cytarabine, prednisolone, and vinblastine. This regimen usually requires hospitalization for administration. The total duration of therapy is 5 months and the cumulative dose of doxorubicin is 150 mg/m2.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III childhood anaplastic large cell lymphoma and stage IV childhood anaplastic large cell lymphoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
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- Seidemann K, Tiemann M, Schrappe M, et al.: Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 97 (12): 3699-706, 2001. [PUBMED Abstract]
- Laver JH, Kraveka JM, Hutchison RE, et al.: Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol 23 (3): 541-7, 2005. [PUBMED Abstract]
- Rosolen A, Pillon M, Garaventa A, et al.: Anaplastic large cell lymphoma treated with a leukemia-like therapy: report of the Italian Association of Pediatric Hematology and Oncology (AIEOP) LNH-92 protocol. Cancer 104 (10): 2133-40, 2005. [PUBMED Abstract]
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- Brugières L, Le Deley MC, Rosolen A, et al.: Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group. J Clin Oncol 27 (6): 897-903, 2009. [PUBMED Abstract]
- Wrobel G, Mauguen A, Rosolen A, et al.: Safety assessment of intensive induction therapy in childhood anaplastic large cell lymphoma: report of the ALCL99 randomised trial. Pediatr Blood Cancer 56 (7): 1071-7, 2011. [PUBMED Abstract]
- 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. J Clin Oncol 28 (25): 3987-93, 2010. [PUBMED Abstract]
- Williams D, Mori T, Reiter A, et al.: Central nervous system involvement in anaplastic large cell lymphoma in childhood: results from a multicentre European and Japanese study. Pediatr Blood Cancer 60 (10): E118-21, 2013. [PUBMED Abstract]