Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma

Abstract

In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction increases event-free survival in the subgroups with T-cell lymphoblastic lymphoma and whether therapy duration could be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here we report on the secondary aims of the trial: whether the results of the NHL-BFM90 study could be reproduced and evaluation of disease features and prognostic factors. Three hundred and nineteen patients (66 with precursor B-cell lymphoblastic lymphoma, 233 with T-cell lymphoblastic lymphoma, 12 with mixed phenotype, 8 not classifiable) were enrolled. In induction, 215 patients received prednisone and 104 patients received dexamethasone. The median follow-up was 6.8 years (range, 3.0–10.3). The 5-year event-free survival was 82±2% [12 toxic deaths, 5 secondary malignancies, 43 non-response/relapse (central nervous system n=9; all received prednisone during induction)]. The event-free survival rate was 80±5% for patients with precursor B-cell lymphoblastic lymphoma, 82±3% for those with T-cell lymphoblastic lymphoma, and 100% for patients with a mixed phenotype. During induction, significantly more grade III/IV toxicities were observed in patients receiving dexamethasone, resulting in significant treatment delays. The number of toxic deaths did not differ significantly. The only variable associated with outcome was performance status at diagnosis. The 90% event-free survival rate for patients with T-cell lymphoblastic lymphoma shown in study NHL-BFM90 was not replicated, mainly due to more toxic deaths and central nervous system relapses. Dexamethasone in induction may prevent central nervous system relapse more effectively than prednisone but produces a higher burden of toxicity. (#NCT00275106).

Primary central nervous system lymphoma: initial features, outcome, and late effects in 75 children and adolescents

“…28 Fifty-eight patients (77%) were treated according to NHL-subtypedirected protocols (pediatric type, n 5 57; adult type, n 5 1; B-NHL-block therapy: B-NHLs, n 5 38, ALCL, n 5 14; leukemiatype therapy: LBL, n 5 4, PTCL, n 5 2), and 17 patients (23%) received miscellaneous therapies. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Thirty-one patients (41%) were treated with chemotherapy only, 15 (20%) were treated with chemotherapy 1 rituximab, 24 (32%) were treated with chemotherapy 1 radiotherapy, and 2 (3%) were treated with chemotherapy 1 rituximab 1 radiotherapy. One patient underwent observation alone after total resection, 1 received no therapy for 3 months for logistic reasons, and 1 patients remained without therapy.…”

“…EFS of 74% 6 5% for the entire cohort is comparable to that of children with CNS 1 systemic NHL and similar to the 2-year progression-free survival of 61% that was reported by the International PCNSL Collaborative Group in 29 2-to 21-year-old PCNSL patients. [11][12][13]15,16,23,29 Our favorable outcome has been achieved by histological subtype-directed polychemotherapy in most patients, suggesting that pediatric PCNSL can be successfully managed by protocols designed for children with CNS 1 systemic NHL, usually including high-dose methotrexate and high-dose cytarabine, steroids, and no irradiation (except for ALCL). [11][12][13]15,16,23,29 Our evaluation of prognostic factors found preexisting disorders to be associated with inferior EFS and OS.…”

“…In contrast, usage of high-dose methotrexate, high-dose cytarabine, and alkylators, which are fundamental drugs of all pediatric NHL-subtype protocols/trials, were associated with improved prognosis. [11][12][13]15,16,21,23,29 Our study has limitations, including its retrospective nature, with potential for reporting bias. For subanalyses, patient numbers were small and included different histologic entities.…”

“…For patients enrolled in national trials/registries, data collection was approved by the respective ethics committees. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In nontrial/nonregistry patients, the retrospective data collection was performed with local Institutional Review Board approval.…”

Novel targeted therapeutic agents for the treatment of childhood, adolescent and young adult non‐Hodgkin lymphoma

“…T‐cell receptor antigens are frequently not expressed and CD3 is more often detected in the cytoplasm than on the cell surface. With intensive frontline treatment, r/r disease occurs in 10–20% of patients (Landmann et al , ). NOTCH1 and FBXW7 mutations (Callens et al , ) and loss of heterozygosity at chromosome 6q (Bonn et al , ) were shown to be promising prognostic parameters of paediatric T‐LL.…”