Standard Treatment Options
Current Clinical Trials

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ Editorial Boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence ¹ for more information.)

Patients with stage I and II disease have an excellent prognosis, regardless of histology. A Children’s Cancer Group study demonstrated that pulsed chemotherapy with cyclophosphamide, vincristine, methotrexate, and prednisone (COMP) administered for 6 months for localized nonlymphoblastic non-Hodgkin lymphoma (NHL) was equivalent to 18 months of therapy with radiation to sites of disease, with more than 85% disease-free survival (DFS) and more than 90% overall survival.[1,2] Patients with lymphoblastic lymphoma had a much inferior outcome. A Pediatric Oncology Group (POG) study tested 9 weeks of short, pulsed chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), with or without radiation to involved sites and with or without 24 weeks of maintenance chemotherapy.[3] The results showed no benefit of radiation or maintenance chemotherapy, but the DFS for nonlymphoblastic lymphoma was superior to that of lymphoblastic lymphoma (90% vs. 60%).

For localized mature B-cell NHL (Burkitt or diffuse large B-cell lymphoma [DLBCL]), DFS is about 95%. The Berlin-Frankfurt Munster (BFM) group has treated risk group R1 (completely resected disease) with two cycles of multiagent chemotherapy (BFM-90) ².[4] For unresected stage I/II disease (R2), patients receive a cytoreductive phase followed by five cycles of chemotherapy.[4] In the BFM-90 study, it was shown that reducing the dose of methotrexate did not affect the results for localized disease.[4] In BFM-95, it was demonstrated for localized disease that prolonging duration of methotrexate infusion did not improve outcome.[5] The French Society of Pediatric Oncology (SFOP) and French-American-British (FAB) studies have treated all completely resected stage I and abdominal stage II (group A) with two cycles of multiagent chemotherapy and without intrathecal chemotherapy (SFOP-LMB-96 ³).[6][Level of evidence: 2A] For unresected stage I/II disease (group B), the above-mentioned FAB study demonstrated that reducing duration of therapy to four cycles of chemotherapy following a cytoreduction phase and reducing the cumulative doses of cyclophosphamide and doxorubicin did not affect outcome.[7]

For localized lymphoblastic lymphoma (stage I/II disease), about 60% of patients can achieve long-term DFS with short, pulsed chemotherapy.[2,3] However, using an acute lymphoblastic leukemia approach with induction, consolidation, and maintenance for a total of 24 months, the BFM group (BFM-90/95) has shown more than 90% DFS for localized lymphoblastic lymphoma.[8,9]

For localized anaplastic large cell lymphoma (ALCL) (stage I/II disease), the best results have come from using pulsed chemotherapy similar to mature B-cell NHL therapy. In the POG study for localized lymphoma using three cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), a 5-year event-free survival of 88% for large cell lymphoma (ALCL and DLBCL) patients was reported.[3] The BFM group has used three cycles of chemotherapy following a cytoreductive prophase for completely resected stage I/II disease.[10] Primary cutaneous ALCL presents a particular problem. The diagnosis can be difficult to distinguish from more benign diseases such as lymphoid papulosis.[11] Many cutaneous ALCL are ALK-negative and may be treated successfully with surgical resection and/or local radiotherapy without systemic chemotherapy.[12] There are reports of surgery alone being curative for ALK-positive cutaneous ALCL, but extensive staging and vigilant follow-up is required.

Standard treatment options are based on histology; however, current data do not suggest superiority between regimens listed below for a specific histology.

Large cell lymphoma: both diffuse large B-cell lymphoma (DLBCL) and ALCL

• Vincristine, doxorubicin, cyclophosphamide, prednisone, mercaptopurine, and methotrexate.[3]

DLBCL and Burkitt lymphoma

Completely resected disease:

• NHL-BFM-95 (B-cell NHL): dexamethasone, cyclophosphamide, methotrexate (1 g/m² over 4 hours), cytarabine, prednisolone (intrathecal [IT]), ifosfamide, etoposide, doxorubicin.[5]
• FAB/LMB-96: ³FAB/LMB-96: cyclophosphamide, vincristine, doxorubicin, prednisone.[6][Level of evidence: 2A]

Incompletely resected disease:

• NHL-BFM-95 (B-cell NHL): dexamethasone, cyclophosphamide, methotrexate (1 g/m²), cytarabine, prednisolone (IT), ifosfamide, etoposide, doxorubicin.[5]
• FAB/LMB-96 ³: cyclophosphamide, vincristine, prednisone, methotrexate (IT), high-dose methotrexate (3 g/m²), doxorubicin, cytarabine, etoposide. Reduced intensity arm for group B.[7]

Lymphoblastic lymphoma

• NHL-BFM-90/95 (lymphoblastic): prednisone, vincristine, daunorubicin, L-asparaginase, cyclophosphamide, cytarabine, mercaptopurine, methotrexate (intravenous and IT).[8,9]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I childhood large cell lymphoma ⁴, stage I childhood small noncleaved cell lymphoma ⁵, stage I childhood lymphoblastic lymphoma ⁶, stage I childhood anaplastic large cell lymphoma ⁷, stage II childhood large cell lymphoma ⁸, stage II childhood small noncleaved cell lymphoma ⁹, stage II childhood lymphoblastic lymphoma ¹⁰ and stage II childhood anaplastic large cell lymphoma ¹¹. 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 ¹².

References

1. Meadows AT, Sposto R, Jenkin RD, et al.: Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin's lymphoma of children: a report from the Childrens Cancer Study Group. J Clin Oncol 7 (1): 92-9, 1989.  [PUBMED Abstract]
   
   
2. Anderson JR, Jenkin RD, Wilson JF, et al.: Long-term follow-up of patients treated with COMP or LSA2L2 therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group. J Clin Oncol 11 (6): 1024-32, 1993.  [PUBMED Abstract]
   
   
3. Link MP, Shuster JJ, Donaldson SS, et al.: Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med 337 (18): 1259-66, 1997.  [PUBMED Abstract]
   
   
4. Reiter A, Schrappe M, Tiemann 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 94 (10): 3294-306, 1999.  [PUBMED Abstract]
   
   
5. 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 105 (3): 948-58, 2005.  [PUBMED Abstract]
   
   
6. Gerrard M, Cairo MS, Weston C, et al.: 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 141 (6): 840-7, 2008.  [PUBMED Abstract]
   
   
7. 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 109 (7): 2773-80, 2007.  [PUBMED Abstract]
   
   
8. Reiter A, Schrappe M, Ludwig WD, et al.: Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood 95 (2): 416-21, 2000.  [PUBMED Abstract]
   
   
9. Burkhardt B, Woessmann W, Zimmermann M, et al.: Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol 24 (3): 491-9, 2006.  [PUBMED Abstract]
   
   
10. 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]
    
    
11. Kumar S, Pittaluga S, Raffeld M, et al.: Primary cutaneous CD30-positive anaplastic large cell lymphoma in childhood: report of 4 cases and review of the literature. Pediatr Dev Pathol 8 (1): 52-60, 2005 Jan-Feb.  [PUBMED Abstract]
    
    
12. Hinshaw M, Trowers AB, Kodish E, et al.: Three children with CD30 cutaneous anaplastic large cell lymphomas bearing the t(2;5)(p23;q35) translocation. Pediatr Dermatol 21 (3): 212-7, 2004 May-Jun.  [PUBMED Abstract]
    
    

Glossary Terms

Nonrandomized, controlled clinical trial with total mortality as an endpoint. See Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (PDQ®) for more information.