Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations

Abstract

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.

The follicular lymphoma epigenome regulates its microenvironment

“…Thus, for clinical translation, their effects must be restricted to the targeted tumor population and their off-target effects strongly reduced by using natural nanomaterials (such as HDL-based nanoparticles). Moreover, although epigenetic modifying agents represent an interesting therapeutic option for FL, their complete response rates, as single agents, have been low [ 56 , 57 ]. Hence, combination therapies targeting the epigenetic dysregulations (upstream), the immunological synapse (downstream), and FL metabolic pathway would help to better attack all the pro-tumor mechanisms of FL.…”

Management of Aggressive Non-Hodgkin Lymphomas in the Pediatric, Adolescent, and Young Adult Population: An Adult vs. Pediatric Perspective

“…NHL in pediatric and adolescent patients is distinct type from the NHLs seen in adults. While the outcomes of pediatric and adolescent patients with primary NHLs such Burkitt lymphoma and DLBCL are outstanding, survival rates markedly decrease following relapse [ 89 ]. HSCT provides some hope for patients with R/R disease, although the results depend on the type of pediatric NHL.…”

“…However, outcomes were markedly different among disease types: patients with ALCL had the best outcomes, with 77% DFS and 83% OS, while the five included patients with Burkitt lymphoma all died 1–3 months following HSCT. Taken together, these studies demonstrate that HSCT, regardless of transplant source, represents a chance for cure with patients with R/R ALCL and DLBCL (OS rates of about 70% and 60%, respectively) but less so for patients with Burkitt lymphoma (OS of about 30%) [ 89 , 95 , 96 , 97 ]. In contrast, in pediatric and adolescent patients that relapse or fail to respond following first-line chemotherapy and do not progress to HSCT, overall survival is significantly lower at less than 25% underscoring the importance of HSCT to provide greater chance of survival [ 98 ].…”

“…Although primary Burkitt lymphoma and DLBCL have 5-year EFS rates of nearly 90% in the pediatric population, patients with R/R NHL have substantially worse outcomes, with a cure rate of about 30% [ 87 , 88 , 89 ]. Among pediatric patients with R/R NHLs, those with PMLBCL have the best chance of survival; a study by Burkhardt et al [ 89 ] evaluated over 600 patients and found 8-year survival rates of 57% for PMLBCL, 28% for Burkitt lymphoma, and 50% for DLBCL. In the same study, patients with DLBCL who did not undergo HSCT did not survive at 8 years.…”

Other (Non-CNS/Testicular) Extramedullary Localizations of Childhood Relapsed Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma—A Report from the ALL-REZ Study Group

“…Survival improved slightly over the last years in T-LBL patients treated on intensive relapse protocols and currently reaches 27% 8-year OS. However, cure for most patients is unattainable, and more effective treatments for T-cell LBL patients are urgently needed [40]. Intensifying induction chemotherapy and improved molecular characterization [41,42] might lead to more efficient therapies.…”