Impact of the Methotrexate Administration Dose on the Need for Intrathecal Treatment in Children and Adolescents With Anaplastic Large-Cell Lymphoma: Results of a Randomized Trial of the EICNHL Group

Abstract

The results of the NHL-BFM90 study were reproduced in this large international trial. The methotrexate schedule of the NHL-BFM90 protocol including IT therapy can be safely replaced by a less toxic schedule of methotrexate 3 g/m2 in a 3-hour infusion without IT therapy.

Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood

“…The AIEOP LNH-97 protocol used higher doses of chemotherapy compared to the ALCL99 protocol, but achieved comparable outcome (5-year EFS 68% vs. 2-year EFS 71%). This confirms the results of the randomized use of two different doses and schedules of high-dose MTX and of the addition of vinblastine, evaluated prospectively in the ALCL-99 trial, which failed to demonstrate any significant difference in terms of efficacy [19,20]. These observations raise the question of whether dose intensity, or dose of specific agents, such as MTX, may play a role in ALCL therapy or whether other characteristics in the treatment strategy, such as continuous lowdose chemotherapy, might be most important for the overall outcome.…”

“…In the early nineties, like in North America, our group treated patients with ALCL with prolonged, repeated-pulse chemotherapy, based on a modified LSA-L2 protocol [10][11][12]. The results of the randomized clinical trial ALCL99 showed that a NHL-B-like therapy, based on six cycles of chemotherapy for 5 days each with MTX 3 g/m 2 in 4-hour infusion, showed the same efficacy when MTX was given at 1 g/m 2 in 24-hour infusion [19]. This study also showed that intrathecal prophylaxis is not necessary to prevent disease recurrence to the CNS.…”

“…Adding vinblastine to the same therapy backbone significantly delayed the occurrence of relapse but did not reduce the risk of failure [20]. The event-free survival (EFS) rate ranges from 60% to 75% for most of the studies and recurrence is observed in up to 35% of patients [7][8][9][10][11][12][16][17][18][19]. Patients who suffer a relapse can be successfully treated with second line therapy, ranging from weekly vinblastine…”

Anaplastic large cell lymphoma: pathology, genetics, and clinical aspects

“…Some groups conducted prospective studies on pediatric patients. 19,[161][162][163][164][165][166] The pediatric data have been thoroughly reviewed elsewhere. 18 Thus, in this review, we will focus on therapeutic approaches for adult patients.…”

Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma

“…1 The relapse rate of ALCL in children and adolescents is 25% to 35% following a first-line treatment strategy based on short-pulse chemotherapy over a period of 3 to 6 months. 4,5 According to retrospective analyses, patients with ALCL relapse have a 30% to 60% chance of reaching a second continuous remission with relapse therapies as variable as maintenance treatment with vinblastine, autologous or allogeneic hematopoietic stem cell transplantation. 6,7 Clinical risk factors have been defined and used for therapy stratification.…”