High-Stage Childhood Lymphoblastic Lymphoma Treatment

Patients with high-stage (stage III or IV) lymphoblastic lymphoma have long-term survival rates higher than 80%.[1] Unlike other pediatric non-Hodgkin lymphoma (NHL), it has been shown that lymphoblastic lymphoma responds much better to leukemia therapy with 2 years of therapy than with shorter, intensive, pulsed chemotherapy regimens.[1,2,3]

Involvement of the bone marrow may lead to confusion as to whether the patient has lymphoma or leukemia. Traditionally, patients with more than 25% marrow blasts are classified as having leukemia, and those with fewer than 25% marrow blasts are classified as having lymphoma. It is not yet clear whether these arbitrary definitions are biologically distinct or relevant for treatment design. All current therapies for advanced-stage lymphoblastic lymphoma have been derived from regimens designed for the treatment of acute lymphoblastic leukemia (ALL).

Mediastinal radiation is not necessary for patients with mediastinal masses, except in the emergency treatment of symptomatic superior vena caval obstruction or airway obstruction, where either corticosteroid therapy or low-dose radiation is usually employed. (Refer to the Treatment Option Overview section of this summary for more information on such complications.) Because of the complexities of optimal therapeutic regimens and the possibility of toxic side effects, patients should be offered the opportunity to enter into a clinical trial. Information about ongoing clinical trials is available from the NCI Web site.

The best results to date come from the Berlin-Frankfurt-Munster (BFM) group. In the GER-GPOH-NHL-BFM-90 study, the 5-year disease-free survival was 90%, and there was no difference in outcome between stage III and stage IV patients.[1] Precursor B-cell lymphoblastic lymphoma appears to have similar results using the same therapy.[4] In the GER-GPOH-NHL-BFM-95 study, the prophylactic cranial radiation was omitted, and the intensity of induction therapy was decreased slightly. There were no significant increases in central nervous system (CNS) relapses, suggesting cranial radiation may be reserved for patients with CNS disease at diagnosis.[3] Of interest, the probability of 5-year event-free survival (EFS) rates was worse in NHL-BFM-95 than in NHL-BFM-90 (82% vs. 90%, respectively). Although this difference was not statistically different, NHL-BFM-95 had a reduction of asparaginase and doxorubicin in induction, which may have affected outcome. It was proposed that the major difference in EFS between NHL-BFM-90 and NHL-BFM-95 resulted from the increased number of secondary malignancies observed in NHL-BFM-95.[3] A single-center study suggests that patients treated for lymphoblastic lymphoma have a higher incidence of secondary malignancy than do patients treated for other pediatric NHL; however, studies from the Children's Oncology Group and the Childhood Cancer Survivor Study Group do not support this finding.[5,6,7]

The Pediatric Oncology Group conducted a trial to test the effectiveness of the addition of high-dose methotrexate in T-cell ALL and T-cell lymphoblastic lymphoma. In the lymphoma patients, high-dose methotrexate did not demonstrate benefit. However, in the small cohort (n = 66) of lymphoma patients who did not receive high-dose methotrexate, the 5-year EFS was 88%.[8][Level of evidence: 1iiA] Of note, all of these patients received prophylactic craniospinal radiation therapy, which has been demonstrated not to be required in T-cell lymphoblastic lymphoma patients.[3]

Standard Treatment Options

Current data do not suggest superiority for the following standard treatment options.

• GER-GPOH-NHL-BFM-95: prednisone, dexamethasone, vincristine, daunorubicin, doxorubicin, L-asparaginase, cyclophosphamide, cytarabine, methotrexate, 6-mercaptopurine, 6-thioguanine, and CNS radiation therapy for CNS-positive patients only.[1]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III childhood lymphoblastic lymphoma and stage IV childhood lymphoblastic 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. 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.
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. 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.
4. Burkhardt B, Zimmermann M, Oschlies I, et al.: The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. Br J Haematol 131 (1): 39-49, 2005.
5. Leung W, Sandlund JT, Hudson MM, et al.: Second malignancy after treatment of childhood non-Hodgkin lymphoma. Cancer 92 (7): 1959-66, 2001.
6. Abromowitch M, Sposto R, Perkins S, et al.: Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology Group. Br J Haematol 143 (2): 261-7, 2008.
7. Bluhm EC, Ronckers C, Hayashi RJ, et al.: Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 111 (8): 4014-21, 2008.
8. Asselin BL, Devidas M, Wang C, et al.: Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404). Blood 118 (4): 874-83, 2011.