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

Purpose To compare the efficacy and safety of two methotrexate doses and administration schedules in children with anaplastic large-cell lymphoma (ALCL). Patients and Methods This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma–Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m2 over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m2 over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/lymphoma study groups and a Japanese group. Results Overall, 352 patients (96% ALK positive) were recruited between 1999 and 2005; 175 were randomly assigned to the MTX1 arm, and 177 were assigned to the MTX3 arm. Ninety-two percent of patients received protocol treatment. Median follow-up time is 3.7 years. Event-free survival (EFS) curves were superimposed with 2-year EFS rates (73.6% and 74.5% in the MTX1 and MTX3 arms, respectively; hazard ratio = 0.98; 91.76% CI, 0.69 to 1.38). Two-year overall survival rates were 90.1% and 94.9% in MTX1 and MTX3, respectively. Only two CNS relapses occurred (both in the MTX1 arm). Toxicity was assessed after 2,050 courses and included grade 4 hematologic toxicity after 79% and 64% of MTX1 and MTX3 courses, respectively (P < .0001); infection after 50% and 32% of courses, respectively (P < .0001); and grade 3 to 4 stomatitis after 21% and 6% of courses, respectively (P < .0001). Conclusion 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.

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Vinblastine in Children and Adolescents With High-Risk Anaplastic Large-Cell Lymphoma: Results of the Randomized ALCL99-Vinblastine Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.5999 ◽

2010 ◽

Vol 28 (25) ◽

pp. 3987-3993 ◽

Cited By ~ 114

Author(s):

Marie-Cécile Le Deley ◽

Angelo Rosolen ◽

Denise M. Williams ◽

Keizo Horibe ◽

Grazyna Wrobel ◽

...

Keyword(s):

High Risk ◽

Children And Adolescents ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Hematologic Toxicity ◽

Increased Risk ◽

Large Cell Lymphoma ◽

The Impact ◽

To Receive

Purpose The impact of adding vinblastine to a 4-month chemotherapy regimen, based on the Non-Hodgkin's Lymphoma Berlin-Frankfurt-Münster 90 protocol, in childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed. Patients and Methods Children and adolescents with high-risk ALCL, defined by mediastinal, lung, liver, spleen, or skin involvement, were eligible for the trial. After a prephase and one chemotherapy course, patients were randomly assigned to receive either five further chemotherapy courses without vinblastine or the same regimen with one vinblastine injection (6 mg/m2) during each course followed by weekly vinblastine to complete a total of 1 year of treatment. The primary end point was event-free survival (EFS), analyzed on the intent-to-treat population. Results Between November 1999 and June 2006, 110 patients were randomly assigned to receive vinblastine, and 107 were randomly assigned not to receive vinblastine. Median follow-up was 4.8 years. Patients in the vinblastine arm had a significantly reduced risk of events during the first year (hazard ratio [HR] = 0.31; 95% CI, 0.15 to 0.67; P = .002) followed by an increased risk thereafter (HR = 4.98; 95% CI, 1.65 to 15.0; P = .003). Consequently, EFS at 1 year differed significantly (91% in the vinblastine group v 74% in the no-vinblastine group), with no difference at 2 years (73% and 70%, respectively). Overall EFS curves did not differ significantly (HR = 0.91; 95% CI, 0.55 to 1.5; P = .71). Thirty-one percent of weekly doses of vinblastine were reduced as a result of hematologic toxicity, although vinblastine was discontinued for toxicity in only three patients. Conclusion Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure.

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Advanced stage anaplastic large cell lymphoma in children and adolescents: Results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: A report from the children's oncology group

Pediatric Blood & Cancer ◽

10.1002/pbc.25187 ◽

2014 ◽

Vol 61 (12) ◽

pp. 2236-2242 ◽

Cited By ~ 41

Author(s):

Sarah Alexander ◽

Jacqueline M. Kraveka ◽

Sheila Weitzman ◽

Eric Lowe ◽

Lynette Smith ◽

...

Keyword(s):

Children And Adolescents ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Phase Iii ◽

Advanced Stage ◽

Oncology Group ◽

Phase Iii Trial ◽

Large Cell Lymphoma

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Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: Final results of children's cancer group study 5941

Pediatric Blood & Cancer ◽

10.1002/pbc.21817 ◽

2009 ◽

Vol 52 (3) ◽

pp. 335-339 ◽

Cited By ~ 74

Author(s):

Eric J. Lowe ◽

Richard Sposto ◽

Sherrie L. Perkins ◽

Thomas G. Gross ◽

Jonathan Finlay ◽

...

Keyword(s):

Children And Adolescents ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

Intensive Chemotherapy ◽

Cancer Group ◽

Large Cell Lymphoma

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Relapsed or Refractory Anaplastic Large-Cell Lymphoma in Children and Adolescents After Berlin-Frankfurt-Muenster (BFM)–Type First-Line Therapy: A BFM-Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2011.34.8417 ◽

2011 ◽

Vol 29 (22) ◽

pp. 3065-3071 ◽

Cited By ~ 64

Author(s):

Willi Woessmann ◽

Martin Zimmermann ◽

Meike Lenhard ◽

Birgit Burkhardt ◽

Claudia Rossig ◽

...

Keyword(s):

Children And Adolescents ◽

Anaplastic Large Cell Lymphoma ◽

Cell Lymphoma ◽

Large Cell ◽

First Line ◽

Hematopoietic Stem ◽

First Line Therapy ◽

Line Therapy ◽

First Relapse ◽

Large Cell Lymphoma

Purpose To evaluate risk factors for outcome in children and adolescents with relapse of anaplastic large-cell lymphoma (ALCL) after comparable first-line therapy. Patients and Methods We analyzed a population-based cohort of 74 children with relapsed ALCL after Berlin-Frankfurt-Muenster–type first-line therapy between April 1990 and December 2003. The recommended salvage strategy was reinduction chemotherapy followed by autologous hematopoietic stem-cell transplantation (SCT). Results With a median follow-up time of 8.4 years (range, 4.5 to 16.4 years), the 5-year overall survival (OS) rate after first relapse was 57% ± 6%. Survival correlated with time of relapse and clinically advanced dissemination. Five-year OS of 16 patients who experienced progression during first-line therapy was 25% ± 11% compared with 66% ± 6% for 58 patients with a later relapse (P = .002). Five-year OS of 11 patients with bone marrow or CNS involvement was 27% ± 13% compared with 62% ± 6% for 63 patients without involvement (P = .001). Five-year event-free survival (EFS) and OS of 39 children who received the recommended autologous SCT were 59% ± 8% and 77% ± 7%, respectively. EFS after autologous SCT was significantly associated with time to relapse (progression: n = 3; EFS, 0; later relapse: n = 36; EFS, 64% ± 8%; P = .014) and CD3 expression (CD3 negative: n = 25; EFS, 72% ± 9%; CD3 positive: n = 11; EFS, 18% ± 12%; P < .001), but not with site of relapse, conditioning regimen, or graft manipulation. No relapses occurred among 10 patients with relapsed CD3-positive ALCL treated with allogeneic SCT. Conclusion Reinduction chemotherapy followed by autologous SCT proved feasible and efficacious for patients with a first relapse of CD3-negative ALCL after first-line therapy. Patients with progression during first-line therapy or relapsed CD3-positive ALCL may benefit from allogeneic SCT.

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