Retrospective and prospective studies of clinical manifestations and disease course were performed in 100 children with certain categories of NHL (Burkitt's lymphoma (BL; 46.7%); lymphoblastic lymphoma (LBL; 27.8%), anaplastic large T(0)-cell lymphoma (ALCL; 15.5%), diffuse large B-cell lymphoma (DLBCL; 10.0%)). NHL in 10% of those patients had developed in association with immunodeficiency due to chromosomal instability syndromes (CIS; Nijmegen breakage syndrome, ataxia-telangiectasia).
The results of the clinical research show different clinical manifestations of the subtypes of pediatric NHL. It is typical for LBL to have a generalized lymph node affection (84% of children), and for T-LBL there are involved the mediastinum lymph nodes (44%) with the compression syndrome. It is typical for mature B-cell NHL (LB and DLBCL) to have an extremely rapid beginning with involvement of the gastrointestinal tract organs (71% and 56% respectively). ALCL, with the invasion of lymph nodes, is characterized by skin, soft tissue, and bone lesions (64%). One child with LBL had a single tumor site (stage І according St. Jude classification). Six (6.7%) patients with NHL were at clinical stage ІІ. The largest group of the children was evaluated at stage ІІІ [48 (53.3%)]. On the basis of the great tumor extension, bone marrow, CNS and bones invasion, 35 (38.9%) children were diagnosed at stage ІV of NHL.
The results of the complex imaging (sonography, X-ray, CТ, MRI) and laboratory examinations of the tumor substrate (cytological, histological, immunophenotyping and immunohistochemistry) should be the basis for the NHL diagnostics and determination of its category. Cytomorphological analysis of the tumor substrate, bone marrow aspirate, cells of the cerebrospinal fluid and pathologic exudates could only be the argument for diagnosing of LBL (in 12% of the patients) and LB (31%), because lymphoblasts L1/L2 type (FAB-classification) and Burkitt’s cells (lymphoblasts L3) are easy to identify. Histomorphological analysis of the tumor substrate allowed to detect the subcftegories of LB (typical, atypical), DLBCL (centroblastic, immunoblastic), ALCL (classical, lymphohistiocytic). Immunocyto(histo)chemical research of tumor cells allowed to determine its B- or T-cellular origin, to distinguish them from other neoplastic cells and to detect the separate subtypes of children’s NHL. T-LBL was diagnosed in 61% of the children, pre B-LBL in 39%. There were detected in patients suffering from LB the classic immunophenotype (panB+sIgM+CD10+CD23–; 43% of children), acceptable (panB+sIgM+CD10+CD23+; 14% of children), compatible with LB diagnosis (panB+sIgM+CD10–CD23–; 43%); expression Кі-67+>90%. In children with DLBCL, there were pan-B markers (CD19+CD20+CD22+CD79a+), without Т-cell markers expression, CD30–ALK– on lymphoma cells. Typical ALCL cells show aberrant expression of Т-cell markers (CD2+CD5+CD3+CD7+CD4+CD8–), they exhibit CD45+, CD30+ and/or ALK+.
Treatment of the children with NHL was conducted according to the program of BFM-group. From 90 children, who were primarily diagnosed with NHL, remission I was attained in 62 (68,9%) with long-term outcome. At first terms of the cytostatic therapy 8 (8,9%) patients died due to the acute tumor lysis syndrome and severe infectious complications, 8 (8,9%) patients – as a result of lymphoma progression. The relapse of NHL was diagnosed in 12 (13,3%) children. Treatment response in relapses was worse and remission II was achieved only in 5 of the patients. Event-free survival (EFS) rate for the whole group of childhood NHL is reached 0,69; overall survival (OS) index – 0,74, including the patients with LBL – 0,88, LB – 0,72, DLBCL – 0,78, ALCL – 0,56.
The unique group of 10 children with NHL associated with CIS and severe combined immunodeficiency was firstly presented in Ukraine. This group includes 3 children with LBL (2 – Т-LBL), 6 children with DLBCL and one child with the lymphoma classified as a diffuse mixed small and large cell (by WF). NHL in the children had the aggressive course and involved the peripheral and abdominal lymph nodes, mediastinum with a spread on the lungs and compression syndrome, and was accompanied with severe infection processes. Only four patients were successfully treated according BFM-protocol and achieved remission (3 with LBL, one – DLBCL); two children died before starting and three children – at first time of the cytostatic treatment, one child died due to the lymphoma progression. It is proven that the specific treatment of NHL associated with CIS is possible and efficient when using individually corrected dosages and schedules for maintenance cytostatic therapy, also including the adequate attendant therapy.
