Standard Treatment Options
Current Clinical Trials

Stage I and II patients with grossly resected (>90%) disease regardless of histology have an excellent prognosis, with 90% or better disease-free survival (DFS). 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 and that it produced more than 85% DFS and more than 90% overall survival.[1,2] Patients with lymphoblastic lymphoma had a much inferior outcome. A Pediatric Oncology Group 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 B-cell NHL, defined as risk group R1 (completely resected disease), the Berlin-Frankfurt-Munster (BFM) group has used a 5-day cytoreduction phase followed by two cycles of multiagent chemotherapy (BFM-90).[4] In the most recent BFM study (BFM-95), it was shown that reducing the dose of methotrexate did not affect the results for localized disease.[5] The French Society of Pediatric Oncology (SFOP) has treated all completely resected stage I and abdominal stage II (group A) with two cycles of multiagent chemotherapy (LMB-89).[6]

For localized lymphoblastic lymphoma (grossly resected, i.e., >90% stage I/II disease), about 60% of patients can achieve long-term DFS with short, pulsed chemotherapy.[2,3] However, using a 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.[7,8]

For localized anaplastic large cell lymphoma (ALCL) (grossly resected, i.e., >90% stage I/II disease), the best results have come from using pulsed chemotherapy similar to B-cell NHL therapy. The SFOP group added methotrexate to the first two cycles following cytoreduction and added four more cycles of pulsed multiagent chemotherapy (HM-89/91).[9] With an additional cycle of chemotherapy, the BFM group had shown results similar to those obtained with the BFM-90 regimen for B-cell NHL.[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

• NHL-BFM-90 (B-cell NHL): dexamethasone, cyclophosphamide, methotrexate, cytarabine, prednisolone (intrathecal [IT]), ifosfamide, etoposide, doxorubicin.[5]



• LMB-89: cyclophosphamide, vincristine, doxorubicin, prednisone.[6]

Lymphoblastic lymphoma

• NHL-BFM-90/95 (lymphoblastic): prednisone, vincristine, daunorubicin, L-asparaginase, cyclophosphamide, cytarabine, mercaptopurine, methotrexate (intravenous and IT).[7,8]

Anaplastic large cell lymphoma

• HM89/91: vincristine, cyclophosphamide, prednisone, methotrexate, doxorubicin, etoposide (vinblastine and bleomycin HM91).[9]



• NHL-BFM-90 (ALCL): dexamethasone, cyclophosphamide, methotrexate, cytarabine, prednisolone (IT), ifosfamide, etoposide, doxorubicin.[10]

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, stage I childhood small noncleaved cell lymphoma, stage I childhood lymphoblastic lymphoma, stage I childhood anaplastic large cell lymphoma, stage II childhood large cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage II childhood lymphoblastic lymphoma and stage II 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

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. Patte C, Auperin A, Michon J, et al.: 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. Blood 97 (11): 3370-9, 2001.  [PUBMED Abstract]
   
   
7. 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]
   
   
8. 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]
   
   
9. Brugières L, Deley MC, Pacquement H, et al.: CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood 92 (10): 3591-8, 1998.  [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]
    
    

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