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, with more than 85% disease-free survival (DFS) and more than 90% overall survival. 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. 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 receive 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. In NHL-BFM-95, it was demonstrated for low-stage disease that prolonging the duration of methotrexate infusion did not improve outcome. 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]).[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.
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 of 88% for large cell lymphoma (ALCL and DLBCL) patients was reported. The BFM group has used three cycles of chemotherapy following a cytoreductive prophase for completely resected stage I/II disease.