Effective multiagent chemotherapy in children with advanced B‐cell lymphoma: who remains the high risk patient?

Abstract

Between 1981 and 1985, 50 patients, mainly children and adolescents, with advanced B-cell lymphoma were entered on a protocol comprising eight drugs: cyclophosphamide, vincristine, prednisolone, high dose methotrexate, adriamycin, BCNU, cytosine arabinoside and thioguanine. Treatment to the central nervous system consisted of intrathecal methotrexate and cytosine-arabinoside in association with high dose methotrexate without irradiation. Data was collected prospectively with regard to response rate, treatment related complications and survival. Histology was reviewed in all referred cases and in 21 there was supportive evidence from immunological and cytogenetic studies. The overall complete response rate was 86%: 31/36 stage III and 12/14 stage IV. There were four treatment related deaths. The overall disease-free survival is 75% with a median follow up of 32 months. In the group of stage IV patients 5/7 with only marrow involvement, 2/4 with isolated CNS involvement and 1/3 with combined CNS and marrow infiltration survive. All the patients with CNS involvement at presentation underwent consolidation treatment with high dose chemotherapy and bone marrow transplant. These results demonstrate the very high curability of B-cell lymphoma using intensive multiagent therapy even with advanced abdominal disease. Bone marrow infiltration does not appear to be an adverse prognostic factor in isolation from bulk disease or CNS involvement. There remain, however, two groups of patients in whom further intensification of therapy is indicated, namely, those with initial CNS involvement, especially in combination with marrow infiltration, and those with extensive multiorgan involvement at presentation who fail to achieve remission with initial therapy. For the other patients, the large majority, a reduction in the intensity and duration of therapy is currently under study.

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol

“…The limited number of patients with known LDH might have contributed to the lack of prognostic significance of LDH level. Another aim of the study was to attempt to reduce early toxic death rate by preventing tumour lysis syndrome during early induction and aggressive treatment of infectious and renal complications, which had appeared to be higher in the previous UKCCSG experience (Hann et al, 1990;Pinkerton et al, 1991), than with the LMB studies (Philip et al, 1987). Three patients (2.7%) died due to treatment-related toxicity, compared with reported rates of 6-8% in previous UKCCSG studies.…”

“…In the last decade the emphasis has been on trying to find prognostic factors that help to stratify patients and to deliver treatment according to risk group. The SFOP classification subdivided patients with stage III disease into two main groups, namely IIIA and IIIB, according to the extent of primary disease (Philip et al, 1987). The German BFM group used a similar approach by dividing patients with stage III B-NHL into two risk groups based on LDH levels less than or more than 500 u l -1 (Reiter et al, 1995).…”

“…Ages at diagnosis ranged from 2.2 to 17.5 years (median 8.3 years). For the purpose of this study, patients were substaged according to the French Society of Paediatric Oncology (SFOP) classification, into two groups according to the extent of primary disease (Philip et al, 1987). Thirty-nine patients were stage IIIA as defined by the presence of limited but unresectable disease usually localized to the abdomen with or without ascites.…”

Burkitt's lymphoma between African and American types in Turkish children: Clinical, viral (EBV), and molecular studies

“…BL is known to be one of the lymphomas most responsive to chemotherapy; however, it is difficult to cure patients in advanced stages [3,7,10,20,21,24,26,27,28]. The most important prognostic factors in BL are the stage and probably the age of the patients [3,11,25,26]. Magrath et al demonstrated that elevated anti-EA titer and LDH concentrations also correlated with prognosis in African patients [ 111.…”

Outcome in stage III non-Hodgkin's lymphoma in children (UKCCSG study NHL 86) – how much treatment is needed?

“…The It has been suggested (Philip et al, 1987) was given as an out-patient. By contrast, in MACHO there is considerable dose escalation with administration of high dose methotrexate between courses of myelosuppressive therapy.…”