Overall survival of children and adolescents with mature B cell non‐Hodgkin lymphoma who had refractory or relapsed disease during or after treatment with FAB/LMB 96: A report from the FAB/LMB 96 study group

Abstract

We determined the risk factors associated with poor survival in children and adolescents with de novo mature B cell non-Hodgkin lymphoma (B-NHL) who had refractory or relapsed disease during or after the French-American-British mature lymphoma B (FAB/LMB) 96 multi-agent chemotherapy. Among the 1 111 registered on study, 104 patients (9·4%) had refractory disease or disease relapse after first complete remission. Among these 104 patients, 28 (27%) patients had refractory disease and 76 (73%) had relapsed disease. The estimated 1- and 2-year overall survival (OS) (95% confidence interval) was 31·5% (23·3-41·0%) and 22·3% (15·3-31·4%), respectively. Prognostic analysis of OS using a Cox multivariate model showed that factors independently associated with OS included lactate dehydrogenase ≥2 upper normal limit [hazard ratio (HR) = 2·86 (1·57-5·2), P = 0·0006]; time to failure (>6 months) [HR = 0·59 (0·36-0·97), P = 0·038]; and failure in bone marrow [HR = 2·78 (1·65-4·68), P = 0·0001]. New therapeutic strategies are required to significantly reduce refractory disease and disease relapse in patients with newly diagnosed mature B-NHL and, more importantly, there is a critical need to develop novel retrieval approaches in patients with chemotherapy-resistant disease.

Outcome of relapse in children and adolescents with B‐cell non‐Hodgkin lymphoma and mature acute leukemia: A report from the French LMB study

“…However, when comparing with survivals from previous relapsed BL cohorts published before the rituximab era, it ranged from 22% to 30%, which is very similar to our findings. 1,[8][9][10][11][12][13][14][15][16][17]20 Even with historical comparison, this shows the lack of benefit from rituximab in relapsed BL. While it is not clear why rituximab does not have such an effect in relapsed when compared with newly diagnosed BL, several hypotheses may be proposed.…”

“…It is generally accepted that good response to salvage chemotherapy is crucial, meaning that the treatment of patients with progressive disease should not be intensified 1,11,13,20,27 and that survival post HDC is mainly dependent on disease status before consolidation, with better outcomes for patients in CR2. 10,20,[27][28][29][30][31] This study, even with small numbers, emphasizes that being in CR is essential before HDC;…”

Advances in cellular and humoral immunotherapy – implications for the treatment of poor risk childhood, adolescent, and young adult B‐cell non‐Hodgkin lymphoma

“…There was, however, a small cadre of 104 CAYA amongst the 1111 studied who had primary refractory disease or disease relapse after first complete remission (CR). The probability of 1‐ and 2‐year overall survival (OS) in this group was a dismal 31·5% and 23·3%, respectively (Cairo et al , ). Those patients with lactate dehydrogenase ≥2 times upper limit of normal at diagnosis, patients with relapsed or refractory disease within 6 months of diagnosis and/or those patients with relapsed or refractory disease with bone marrow involvement had a significantly decreased OS (Cairo et al , ).…”

“…The probability of 1‐ and 2‐year overall survival (OS) in this group was a dismal 31·5% and 23·3%, respectively (Cairo et al , ). Those patients with lactate dehydrogenase ≥2 times upper limit of normal at diagnosis, patients with relapsed or refractory disease within 6 months of diagnosis and/or those patients with relapsed or refractory disease with bone marrow involvement had a significantly decreased OS (Cairo et al , ). Cellular and humoral immunotherapy for these high‐risk populations include haematopoietic stem cell transplantation (HSCT), bispecific antibodies, viral‐derived cytotoxic T cells, chimeric antigen receptor (CAR) T cells and natural killer (NK) cell therapy.…”

Epidemiology, outcome, targeted agents and immunotherapy in adolescent and young adult non‐Hodgkin and Hodgkin lymphoma

“…While a large proportion of patients with HL can be retrieved with or without high dose chemotherapy and autologous stem cell transplantation (ASCT) after failure to front line therapy, particularly those that only received low intensity therapy or relapse more than a year after completion of therapy, there is a number of patients that will fail ASCT (Satwani et al , ). Patients with NHL have an even gloomier outcome after failing front‐line therapies requiring SCT (Gross et al , ), particularly those with mature B‐cell lymphomas that relapse within 6 months from diagnosis, have bone marrow involvement at the time of relapse or have an elevated lactate dehydrogenase at diagnosis (Cairo et al , ). For these patients, further intensification of therapy is not likely to improve outcome, rather novel treatment approaches are needed to overcome resistance.…”