Fabian Knörr1, Laurence Brugières2, Marta Pillon3, Martin Zimmermann4, Stephanie Ruf5, Andishe Attarbaschi6, Karin Mellgren7, G Amos A Burke8, Anne Uyttebroeck9, Grażyna Wróbel10, Auke Beishuizen11, Nathalie Aladjidi12, Alfred Reiter5, Wilhelm Woessmann1. 1. Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Germany. 2. Department of Children and Adolescents Oncology, Gustave Roussy University Hospital, Paris-Saclay University, Villejuif, France. 3. Pediatric Hematology and Oncology, University Hospital of Padova, Italy. 4. Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany. 5. Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany. 6. Pediatric Hematology and Oncology, St Anna Children's Hospital, Medical University of Vienna, Austria. 7. Department of Pediatric Oncology and Hematology, The Queen Silvia Children's Hospital, Göteborg, Sweden. 8. Department of Pediatric Hematology, Oncology and Palliative Care, Cambridge University Hospital NHS Trust, Cambridge, United Kingdom. 9. Department of Pediatric Oncology & Hematology, University Hospitals Leuven, Belgium. 10. Department of Bone Marrow Transplantation, Children's Oncology and Hematology, Wroclaw Medical University, Poland. 11. Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. 12. Department of Pediatric Hematology and Oncology, CIC1401, INSERM CICP, University Hospital of Bordeaux, France.
Abstract
PURPOSE: To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408) stratified patients according to the time of relapse and CD3 expression to prospectively test reinduction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy. PATIENTS AND METHODS: Patients with progression during frontline therapy (very high risk) or a CD3-positive relapse (high risk) were scheduled for allogeneic SCT after reinduction chemotherapy. Patients with a CD3-negative relapse within 1 year after initial diagnosis or prior exposure to vinblastine (intermediate risk) received autologous SCT after carmustine-etoposide-cytarabine-melphalan. This arm was terminated prematurely, and subsequent patients received vinblastine monotherapy instead. Patients with a CD3-negative relapse > 1 year after initial diagnosis (low risk) received vinblastine monotherapy. RESULTS: One hundred sixteen patients met the inclusion criteria; 105 evaluable patients with CNS-negative disease had a 5-year event-free survival (EFS) of 53% ± 5% and a 5-year overall survival (OS) of 78% ± 4%. Before termination of autologous SCT, EFS rates of patients in the very-high- (n = 17), high- (n = 26), intermediate- (n = 32), and low- (n = 21) risk groups were 41% ± 12%, 62% ± 10%, 44% ± 9%, and 81% ± 9%; the respective OS rates were 59% ± 12%, 73% ± 9%, 78% ± 7%, and 90% ± 6%. Analyzing only the patients in the intermediate-risk group consolidated per protocol by autologous SCT, EFS and OS of 23 patients were 30% ± 10% and 78% ± 9%, respectively. All 5 patients with intermediate risk receiving vinblastine monotherapy after the amendment experienced relapse again. CONCLUSION: Shorter time to relapse was the strongest predictor of subsequent relapse. Allogeneic SCT offers a chance for cure in patients with high-risk ALCL relapse. For early relapsed ALCL autologous SCT was not effective. Vinblastine monotherapy achieved cure in patients with late relapse; however, it was not effective for early relapses.
PURPOSE: To analyze the efficacy of a risk-stratified treatment of children with relapsed anaplastic large cell lymphoma (ALCL). The ALCL-Relapse trial (ClinicalTrials.gov identifier: NCT00317408) stratified patients according to the time of relapse and CD3 expression to prospectively test reinduction approaches combined with consolidation by allogeneic or autologous hematopoietic stem cell transplantation (SCT) and vinblastine monotherapy. PATIENTS AND METHODS: Patients with progression during frontline therapy (very high risk) or a CD3-positive relapse (high risk) were scheduled for allogeneic SCT after reinduction chemotherapy. Patients with a CD3-negative relapse within 1 year after initial diagnosis or prior exposure to vinblastine (intermediate risk) received autologous SCT after carmustine-etoposide-cytarabine-melphalan. This arm was terminated prematurely, and subsequent patients received vinblastine monotherapy instead. Patients with a CD3-negative relapse > 1 year after initial diagnosis (low risk) received vinblastine monotherapy. RESULTS: One hundred sixteen patients met the inclusion criteria; 105 evaluable patients with CNS-negative disease had a 5-year event-free survival (EFS) of 53% ± 5% and a 5-year overall survival (OS) of 78% ± 4%. Before termination of autologous SCT, EFS rates of patients in the very-high- (n = 17), high- (n = 26), intermediate- (n = 32), and low- (n = 21) risk groups were 41% ± 12%, 62% ± 10%, 44% ± 9%, and 81% ± 9%; the respective OS rates were 59% ± 12%, 73% ± 9%, 78% ± 7%, and 90% ± 6%. Analyzing only the patients in the intermediate-risk group consolidated per protocol by autologous SCT, EFS and OS of 23 patients were 30% ± 10% and 78% ± 9%, respectively. All 5 patients with intermediate risk receiving vinblastine monotherapy after the amendment experienced relapse again. CONCLUSION: Shorter time to relapse was the strongest predictor of subsequent relapse. Allogeneic SCT offers a chance for cure in patients with high-risk ALCL relapse. For early relapsed ALCL autologous SCT was not effective. Vinblastine monotherapy achieved cure in patients with late relapse; however, it was not effective for early relapses.
Authors: Stephan Mathas; Lukas Kenner; Olaf Merkel; Huan-Chang Liang; Mariantonia Costanza; Nicole Prutsch; Mark W Zimmerman; Elisabeth Gurnhofer; Ivonne A Montes-Mojarro; Brian J Abraham; Nina Prokoph; Stefan Stoiber; Simone Tangermann; Cosimo Lobello; Jan Oppelt; Ioannis Anagnostopoulos; Thomas Hielscher; Shahid Pervez; Wolfram Klapper; Francesca Zammarchi; Daniel-Adriano Silva; K Christopher Garcia; David Baker; Martin Janz; Nikolai Schleussner; Falko Fend; Šárka Pospíšilová; Andrea Janiková; Jacqueline Wallwitz; Dagmar Stoiber; Ingrid Simonitsch-Klupp; Lorenzo Cerroni; Stefano Pileri; Laurence de Leval; David Sibon; Virginie Fataccioli; Philippe Gaulard; Chalid Assaf; Fabian Knörr; Christine Damm-Welk; Wilhelm Woessmann; Suzanne D Turner; A Thomas Look Journal: Nat Commun Date: 2021-09-22 Impact factor: 17.694
Authors: Eric J Lowe; Anne F Reilly; Megan S Lim; Thomas G Gross; Lauren Saguilig; Donald A Barkauskas; Rui Wu; Sarah Alexander; Catherine M Bollard Journal: Blood Date: 2021-07-01 Impact factor: 22.113