Questions About Cancer? 1-800-4-CANCER

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)

Health Professional Version
Last Modified: 04/03/2014

Low-Stage Childhood NHL Treatment

Standard Treatment Options
Current Clinical Trials

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 low-stage (stage I or II) nonlymphoblastic non-Hodgkin lymphoma (NHL) was equivalent to 18 months of therapy with radiation to sites of disease, resulting in more than 85% disease-free survival (DFS) and more than 90% overall survival (OS). However, patients with lymphoblastic lymphoma had a much inferior outcome.[1,2] 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 low-stage mature B-cell NHL (Burkitt lymphoma or diffuse large B-cell lymphoma), DFS is about 95%. The Berlin-Frankfurt-Munster (BFM) group has treated risk group R1 (completely resected disease) with two cycles of multiagent chemotherapy (GER-GPOH-NHL-BFM-90 and GER-GPOH-NHL-BFM-95).[4,5] For unresected stage I/II disease (R2), patients received a cytoreductive phase followed by five cycles of chemotherapy.[4,5] In the NHL-BFM-90 study, it was shown that reducing the dose of methotrexate did not affect the results for low-stage disease.[4] In NHL-BFM-95, it was demonstrated for low-stage disease that prolonging the 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, without intrathecal chemotherapy (COG-C5961 [FAB/LMB-96]).[6][Level of evidence: 2A] For unresected stage I/II disease (group B), the above-mentioned FAB study demonstrated that reducing the 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 low-stage lymphoblastic lymphoma (stage I/II disease), about 60% of patients can achieve long-term DFS with short, pulsed chemotherapy.[2,3] However, with the use of an acute lymphoblastic leukemia approach with induction, consolidation, and maintenance therapy for a total of 24 months, DFS rates higher than 90% have been reported for children with low-stage lymphoblastic lymphoma.[8-10]

For low-stage anaplastic large cell lymphoma, the best results have come from using pulsed chemotherapy similar to mature B-cell NHL therapy. In the POG study for low-stage lymphoma using three cycles of CHOP, a 5-year event-free survival (EFS) of 88% for large cell lymphoma (anaplastic large cell lymphoma and diffuse large B-cell lymphoma) patients was reported.[3] The BFM group has used three cycles of chemotherapy following a cytoreductive prophase for completely resected stage I/II disease.[11] The FRE-IGR-ALCL99 trial used three cycles of chemotherapy following cytoreductive prophase for patients with stage I completely resected disease. The minority of stage I patients had complete resections (6 out of 36) but there were no treatment failures for these six patients. The therapy for patients without complete resection was the same as the therapy for patients with disseminated disease and the 3-year EFS (81%) and OS (97%) were not statistically different from the outcomes for patients with higher stage disease.[12][Level of evidence: 2A]

Primary cutaneous anaplastic large cell lymphoma presents a particular problem. The diagnosis can be difficult to distinguish from more benign diseases such as lymphoid papulosis.[13] Primary cutaneous anaplastic large cell lymphoma usually does not express ALK and may be treated successfully with surgical resection and/or local radiation therapy without systemic chemotherapy.[14] There are reports of surgery alone being curative for ALK-positive cutaneous anaplastic large cell lymphoma, but extensive staging and vigilant follow-up is required.

Follicular lymphoma is rare in children, with only case reports and case series to guide therapy. Although outcome is generally very good, treatments range from surgery only to multiagent chemotherapy and even autologous blood or marrow transplant.[15-20] It appears that for pediatric patients without the BCL2 rearrangement and a high proliferative index, surgical resection with no further treatment is sufficient for completely resected, localized disease. For those with tumors that have the BCL2 rearrangement, treatment like that of adult patients with follicular lymphoma is preferred (refer to the PDQ summary on Adult Non-Hodgkin Lympoma Treatment for more information).

Subcutaneous mature T-cell lymphomas are very rare in children. An oral retinoid (bexarotene) has been reported to be active against subcutaneous T-cell lymphomas in children.[21]

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

Table 4. Standard Treatment Options for Low-Stage Non-Hodgkin Lymphoma
Disease Treatment Options 
ALL = acute lymphoblastic leukemia; BFM = Berlin-Frankfurt-Munster; CCG = Children's Cancer Group.
Burkitt lymphoma or diffuse large B-cell lymphoma (DLBCL) (completely resected) GER-GPOH-NHL-BFM-95 (R1): Two cycles of chemotherapy.[5]
COG-C5961 (FAB/LMB-96) (Group A): Two cycles of chemotherapy.[6]
Burkitt lymphoma or DLBCL (nonresected stage I/II) GER-GPOH-NHL-BFM-95 (R2): Prephase + four cycles of chemotherapy (4-hour methotrexate infusion).[5]
COG-C5961 (FAB/LMB-96) (Group B): Prephase + four cycles of chemotherapy (reduced-intensity arm).[7]
POG-8314/POG-8719: Three cycles of chemotherapy (no radiation or maintenance therapy).[3]
Lymphoblastic lymphoma GER-GPOH-NHL-BFM-95: Induction, consolidation, intensification, and maintenance therapy (2 years of total therapy); ALL-type induction and consolidation, high-dose methotrexate courses × 4, and ALL-type maintenance therapy (2 years of total therapy).[8,9]
COG-A5971 (NCT00004228): Modified CCG-BFM ALL therapy; 2 years of total therapy.[10]
Anaplastic large cell lymphoma POG-8314/POG-8719: Three cycles of chemotherapy (no radiation or maintenance therapy).[3]
GER-GPOH-NHL-BFM-90: Prephase + three cycles of chemotherapy (only for completely resected disease).[11]
FRE-IGR-ALCL99: Prephase + six cycles of chemotherapy (for disease not completely resected).[12]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials 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. 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. Termuhlen AM, Smith LM, Perkins SL, et al.: Outcome of newly diagnosed children and adolescents with localized lymphoblastic lymphoma treated on Children's Oncology Group trial A5971: a report from the Children's Oncology Group. Pediatr Blood Cancer 59 (7): 1229-33, 2012.  [PUBMED Abstract]

  11. 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]

  12. Attarbaschi A, Mann G, Rosolen A, et al.: Limited stage I disease is not necessarily indicative of an excellent prognosis in childhood anaplastic large cell lymphoma. Blood 117 (21): 5616-9, 2011.  [PUBMED Abstract]

  13. 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]

  14. 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]

  15. Kumar R, Galardy PJ, Dogan A, et al.: Rituximab in combination with multiagent chemotherapy for pediatric follicular lymphoma. Pediatr Blood Cancer 57 (2): 317-20, 2011.  [PUBMED Abstract]

  16. Oschlies I, Salaverria I, Mahn F, et al.: Pediatric follicular lymphoma--a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin's Lymphoma--Berlin-Frankfurt-Munster (NHL-BFM) multicenter trials. Haematologica 95 (2): 253-9, 2010.  [PUBMED Abstract]

  17. Lorsbach RB, Shay-Seymore D, Moore J, et al.: Clinicopathologic analysis of follicular lymphoma occurring in children. Blood 99 (6): 1959-64, 2002.  [PUBMED Abstract]

  18. Agrawal R, Wang J: Pediatric follicular lymphoma: a rare clinicopathologic entity. Arch Pathol Lab Med 133 (1): 142-6, 2009.  [PUBMED Abstract]

  19. Louissaint A Jr, Ackerman AM, Dias-Santagata D, et al.: Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement. Blood 120 (12): 2395-404, 2012.  [PUBMED Abstract]

  20. Attarbaschi A, Beishuizen A, Mann G, et al.: Children and adolescents with follicular lymphoma have an excellent prognosis with either limited chemotherapy or with a "Watch and wait" strategy after complete resection. Ann Hematol 92 (11): 1537-41, 2013.  [PUBMED Abstract]

  21. Mehta N, Wayne AS, Kim YH, et al.: Bexarotene is active against subcutaneous panniculitis-like T-cell lymphoma in adult and pediatric populations. Clin Lymphoma Myeloma Leuk 12 (1): 20-5, 2012.  [PUBMED Abstract]