Low-Stage Childhood NHL Treatment

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 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 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 [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 (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, using an acute lymphoblastic leukemia approach with induction, consolidation, and maintenance for a total of 24 months, the BFM group (NHL-BFM-90/95) has shown more than 90% DFS for low-stage lymphoblastic lymphoma.[8,9]

For low-stage anaplastic large cell lymphoma (ALCL), 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 (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] 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.[11][Level of evidence: 2A]

Primary cutaneous ALCL presents a particular problem. The diagnosis can be difficult to distinguish from more benign diseases such as lymphoid papulosis.[12] Primary cutaneous ALCL usually does not express ALK and may be treated successfully with surgical resection and/or local radiation therapy without systemic chemotherapy.[13] There are reports of surgery alone being curative for ALK-positive cutaneous ALCL, 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. Case series reporting a variety of chemotherapy approaches have resulted in good outcomes.[14]

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

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
11. 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.
12. 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.
13. 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.
14. 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.