Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL) - results of the UKCCSG 9003 protocol

Abstract

Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with WiskottAldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11 %) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern.Keywords: high risk; paediatric cancer; B-cell acute lymphoblastic leukaemia; B-cell non-Hodgkin's lymphomaThe treatment of B-NHL in children is one of the success stories in paediatric oncology. The cure rate has increased from less than 20% before 1980 (Al-Attar et al, 1979) to over 70% in the 1980s and 1990s (Philip et al, 1982;Al-Attar et al, 1986;Patte et al, 1990). Recent studies have concentrated on improving outcome in the remaining poor-risk subgroups (Hann et al, 1988;Patte et al, 1991;Cairo et al, 1996), reducing early deaths by aggressive treatment of early renal and infectious complications (Lynch et al, 1977;Allegretta et al, 1985) and avoiding debulking surgery (Frappaz et al, 1988;Al-Attar et al, 1989).In 1986, the French paediatric oncology group (SFOP) introduced a regimen for poor-risk patients with increased intensity of early intrathecal (i.t.) therapy and the use of high-dose cytarabine (LMB 86). Before this, results in patients with CNS disease were disappointing, despite the use of craniospinal irradiation with chemotherapy regimen, which was very effective in less advanced disease (Philip et al, 1982;Chilcote et al, 1991). The subsequent results with LMB 86 were dramatic, with a survival rate over 70% (Rubie et al, 1988). Relapse of the underlying disease remains a major cause of treatment failure. The use of high-dose cytarabine and etoposide (CYVE) may he...

Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model

“…The incidence of CTLS in AML patients seems to be lower than that reported in patients with acute lymphoid leukemia (ALL) or high grade non-Hodgkin's lymphoma (NHL), 7,[21][22][23] in whom it ranges from 11% to 25%. Few studies have analyzed the incidence of LTLS in patients with AML.…”

“…Despite these measures, TLS-related morbidity and mortality still occur in a sizeable proportion of patients with hematologic malignancies. [5][6][7] However, few studies on TLS are focused on patients with acute myeloid leukemia (AML), and the incidence and outcome of TLS in this population is not well defined. 8,9 With the introduction into clinical practice of new agents, such as recombinant urate oxidase (rasburicase), 10 for the prevention or treatment of TLS, there has been an increased interest in defining the population at high risk of TLS.…”

Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents

“…4,5,7,8 Reduction therapy with cyclophosphamide, Oncovin (vincristine) and prednisone (COP), induction therapy with cyclophosphamide, Oncovin (vincristine), prednisone, Adriamycin (doxorubicin), and methotrexate (COPADM), and intensification with cytarabine (high dose and continuous infusion) plus etoposide (CYVE 12 ) (Lymphoma Malignancy B [LMB] 86 and 89 group C therapy) was originally introduced by Patte et al and the Société Française d'Oncologie Pédiatrique (SFOP) for advanced (BM with or without CNS) childhood B-NHL and subsequently investigated by Cairo et al in the Children's Cancer Group (CCG) and by Atra et al for the United Kingdom Children's Cancer Study Group (UKCCSG). 4,13,14 However, in view of the high morbidity of this therapy, the exact intensity that is required for optimal results is still unclear. The incidence of advanced (BM with or without CNS) de novo childhood B-NHL, however, is extremely low (Ͻ 75 cases/y in CCG, SFOP, and UKCCSG combined).…”

Cyclophosphamide Metabolism in Children with Non-Hodgkin’s Lymphoma

“…Present treatment schemes for advanced-stage B-cell nonHodgkin's lymphoma (B-NHL) achieve cure in over 75% of children (1)(2)(3). In addition to the universal introduction of central nervous system prophylaxis, improved patient survival has also followed the use of fractionated cyclophosphamide in combination with cytarabine and high-dose methotrexate (4 -6).…”