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Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)     
Last Modified: 02/12/2008
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Localized Non-Hodgkin Lymphoma in Children and Adolescents

Standard Treatment Options

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 (CCG) 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 (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 B-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-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-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.

Standard Treatment Options

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

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


DLBCL and Burkitt Lymphoma

  • NHL-BFM-90 (B-NHL): dexamethasone, cyclophosphamide, methotrexate, cytarabine, prednisolone (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 (IV 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]


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]