The most widely used staging scheme for childhood non-Hodgkin lymphoma (NHL) is that of the St. Jude Children's Research Hospital (Murphy Staging).
Stage I Childhood NHL
In stage I childhood NHL, a single tumor or nodal area is involved, excluding the abdomen and mediastinum.
Stage II Childhood NHL
In stage II childhood NHL, disease extent is limited to a single tumor with regional node involvement, two or more tumors or nodal areas involved on one side of the diaphragm, or a primary gastrointestinal tract tumor (completely resected) with or without regional node involvement.
Stage III Childhood NHL
In stage III childhood NHL, tumors or involved lymph node areas occur on both sides of the diaphragm. Stage III NHL also includes any primary intrathoracic (mediastinal, pleural, or thymic) disease, extensive primary intra-abdominal disease, or any paraspinal or epidural tumors.
Stage IV Childhood NHL
In stage IV childhood NHL, tumors involve bone marrow and/or central nervous system (CNS), regardless of other sites of involvement.
Bone marrow involvement has been defined as 5% malignant cells in an otherwise normal bone marrow with normal peripheral blood counts and smears. Patients with lymphoblastic lymphoma with more than 25% malignant cells in the bone marrow are usually considered to have leukemia and may be appropriately treated on leukemia clinical trials.
CNS disease in lymphoblastic lymphoma is defined by criteria similar to that used for acute lymphocytic leukemia (i.e., white blood cell count of at least 5/?L and malignant cells in the cerebrospinal fluid [CSF]). For any other NHL, the definition of CNS disease is any malignant cell present in the CSF regardless of cell count. The Berlin-Frankfurt-Munster (BFM) group analyzed the prevalence, clinical pattern, and outcome of CNS involvement in NHL in over 2,500 patients. Overall, CNS involvement was diagnosed in 6% of patients. Involvement by cell type was as follows:
- Burkitt lymphoma/leukemia: 8.8%
- Precursor B-cell lymphoblastic lymphoma: 5.4%
- T-cell lymphoblastic lymphoma: 3.7%
- Anaplastic large cell lymphoma: 3.3%
- Diffuse large B-cell lymphoma (DLBCL): 2.6%
- Primary mediastinal large B-cell lymphoma: 0%
The probability of event-free survival at 6 years for CNS-positive patients was 64% compared with 86% for CNS-negative patients. Presence of CNS involvement did not impact outcome for T-cell lymphoblastic lymphoma patients, but had significant negative impact on patients with Burkitt lymphoma/leukemia.
Mature B-cell NHL (Burkitt lymphoma and DLBCL) patients have been treated based on features of the disease, other than stage.
Table 3. FAB/LMB and BFM Staging Schemas for B-cell NHL
ALL = acute lymphoblastic leukemia; BFM = Berlin-Frankfurt-Munster; CNS= central nervous system; FAB = French-American-British; LDH = lactate dehydrogenase; NHL = non-Hodgkin lymphoma.
|FAB/LMB International Study[3,4,5]||A||Completely resected stage I and abdominal stage II|
|B||Multiple extra-abdominal sites|
|Nonresected stage I and II, III, IV (marrow <25% blasts, no CNS disease)|
|C||Mature B-cell ALL (>25% blasts in marrow) and/or CNS disease|
|BFM Group||R1||Completely resected stage I and abdominal stage II|
|R2||Nonresected stage I/II and stage III with LDH <500 IU/L|
|R3||Stage III with LDH 500-999 IU/L|
|Stage IV, B-ALL (>25% blasts), no CNS disease, and LDH <1,000 IU/L|
|R4||Stage III, IV, B-cell ALL with LDH >1,000 IU/L|
|Any CNS disease|
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- Salzburg J, Burkhardt B, Zimmermann M, et al.: Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Munster Group Report. J Clin Oncol 25 (25): 3915-22, 2007.
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