Marta Pillon1, Maurizio Aricò2, Lara Mussolin3, Elisa Carraro1, Valentino Conter4, Alessandra Sala4, Salvatore Buffardi5, Alberto Garaventa6, Paolo D'Angelo7, Luca Lo Nigro8, Nicola Santoro9, Matilde Piglione10, Alessandra Lombardi11, Fulvio Porta12, Simone Cesaro13, Maria L Moleti14, Fiorina Casale15, Rossella Mura16, Emanuele S G d'Amore17, Giuseppe Basso1, Angelo Rosolen1. 1. Clinic of Pediatric Hemato-Oncology, Department of Women's and Children's Health, University of Padova, Padova, Italy. 2. Azienda Sanitaria Provinciale, Ragusa, Italy. 3. Istituto di Ricerca Pediatrica, Fondazione Citt, à, della Speranza, Padova, Italy. 4. Clinica Pediatrica, Università degli Studi di Milano-Bicocca, Azienda Ospedaliera San Gerardo, Monza, Italy. 5. Pediatric Oncology Department, Santobono-Pausilipon Hospital of Napoli, Napoli, Italy. 6. Department of Hematology-Oncology, Istituto Giannina Gaslini, Genova, Italy. 7. Department of Oncology, Pediatric Hematology and Oncology Unit, A.R.N.A.S. Ospedali Civico Di Cristina e Benfratelli, Palermo, Italy. 8. Pediatric Hematology-Oncology, Policlinico di Catania, Catania, Italy. 9. Division of Paediatric Haematology-Oncology, Department of Pediatrics, Bari, Italy. 10. Division of Pediatric Onco-Hematology, Regina Margherita Children's Hospital, Torino, Italy. 11. Dipartimento di Onco-Ematologia Pediatrica, Ospedale Bambino Gesù, Roma, Italy. 12. Oncology-Haematology and BMT Unit, Ospedale dei Bambini, Spedali Civili, Brescia, Italy. 13. Pediatric Hematology-Oncology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy. 14. Hematology, Department of Cellular Biotechnologies and Hematology, Roma, Italy. 15. Pediatric Oncology Service,, Pediatric Department, Second University of Napoli, Napoli, Italy. 16. Pediatric Hematology-Oncology, Ospedale Pediatrico Microcitemico, Cagliari, Italy. 17. Department of Pathology, San Bortolo Hospital, Vicenza, Italy.
Abstract
BACKGROUND: Treatment intensification was considered a suitable strategy to increase the cure rate of lymphoblastic lymphoma (LBL) in children. PROCEDURE: The AIEOP LNH-97 trial was run between 1997 and 2007 for newly diagnosed LBL in patients aged less than 18 years. Treatment schedule was based on the previous, LSA2-L2 derived, AIEOP LNH-92 protocol. Modifications included: increased dose of upfront cyclophosphamide and methotrexate, use of l-Asparaginase during induction therapy, intensive block therapy for slow responders, and late intensification ("Reinduction") for patients with advanced stage disease. Total therapy duration was 12 months for stage I and II, and 24 months for stage III and IV. Central nervous system prophylaxis did not include cranial irradiation. RESULTS: 114 eligible patients were enrolled, 84 males and 30 females; median age was 9 years. Complete remission was obtained in 98% of patients. After a median follow-up time of seven years, 29 patients failed due to progression of disease (n = 2), relapse (n = 25), or second malignancy (n = 2). The 7-year overall survival was 82% (standard error [SE] 4%) and the 7-year event-free survival was 74% (SE 4%). No subgroup showed significantly different event free survival. None of the patients died of front line chemotherapy-related toxicity. CONCLUSIONS: Treatment intensification was associated with good outcome in children and adolescents with LBL, with limited toxicity. Prognosis after relapse was better for patients who underwent allogeneic hematopoietic stem cell transplantation. Measurements of biological markers and treatment response are necessary for achieving further improvement through more accurate identification and stratification of patients at risk of disease relapse.
BACKGROUND: Treatment intensification was considered a suitable strategy to increase the cure rate of lymphoblastic lymphoma (LBL) in children. PROCEDURE: The AIEOP LNH-97 trial was run between 1997 and 2007 for newly diagnosed LBL in patients aged less than 18 years. Treatment schedule was based on the previous, LSA2-L2 derived, AIEOP LNH-92 protocol. Modifications included: increased dose of upfront cyclophosphamide and methotrexate, use of l-Asparaginase during induction therapy, intensive block therapy for slow responders, and late intensification ("Reinduction") for patients with advanced stage disease. Total therapy duration was 12 months for stage I and II, and 24 months for stage III and IV. Central nervous system prophylaxis did not include cranial irradiation. RESULTS: 114 eligible patients were enrolled, 84 males and 30 females; median age was 9 years. Complete remission was obtained in 98% of patients. After a median follow-up time of seven years, 29 patients failed due to progression of disease (n = 2), relapse (n = 25), or second malignancy (n = 2). The 7-year overall survival was 82% (standard error [SE] 4%) and the 7-year event-free survival was 74% (SE 4%). No subgroup showed significantly different event free survival. None of the patients died of front line chemotherapy-related toxicity. CONCLUSIONS: Treatment intensification was associated with good outcome in children and adolescents with LBL, with limited toxicity. Prognosis after relapse was better for patients who underwent allogeneic hematopoietic stem cell transplantation. Measurements of biological markers and treatment response are necessary for achieving further improvement through more accurate identification and stratification of patients at risk of disease relapse.
Authors: Robert J Hayashi; Stuart S Winter; Kimberly P Dunsmore; Meenakshi Devidas; Zhiguo Chen; Brent L Wood; Michelle L Hermiston; David T Teachey; Sherrie L Perkins; Rodney R Miles; Elizabeth A Raetz; Mignon L Loh; Naomi J Winick; William L Carroll; Stephen P Hunger; Megan S Lim; Thomas G Gross; Catherine M Bollard Journal: J Clin Oncol Date: 2020-06-17 Impact factor: 44.544
Authors: Andishe Attarbaschi; Elisa Carraro; Leila Ronceray; Mara Andrés; Shlomit Barzilai-Birenboim; Simon Bomken; Laurence Brugières; Birgit Burkhardt; Francesco Ceppi; Alan K S Chiang; Monika Csoka; Alina Fedorova; Janez Jazbec; Edita Kabickova; Jan Loeffen; Karin Mellgren; Natalia Miakova; Olga Moser; Tomoo Osumi; Apostolos Pourtsidis; Charlotte Rigaud; Anne Uyttebroeck; Wilhelm Woessmann; Marta Pillon Journal: Leukemia Date: 2020-05-11 Impact factor: 11.528
Authors: Andishe Attarbaschi; Elisa Carraro; Oussama Abla; Shlomit Barzilai-Birenboim; Simon Bomken; Laurence Brugieres; Eva Bubanska; Birgit Burkhardt; Alan K S Chiang; Monika Csoka; Alina Fedorova; Janez Jazbec; Edita Kabickova; Zdenka Krenova; Jelena Lazic; Jan Loeffen; Georg Mann; Felix Niggli; Natalia Miakova; Tomoo Osumi; Leila Ronceray; Anne Uyttebroeck; Denise Williams; Wilhelm Woessmann; Grazyna Wrobel; Marta Pillon Journal: Haematologica Date: 2016-08-11 Impact factor: 9.941
Authors: Elena Pomari; Federica Lovisa; Elisa Carraro; Simona Primerano; Emanuele S G D'Amore; Paolo Bonvini; Luca Lo Nigro; Rita De Vito; Luciana Vinti; Piero Farruggia; Marta Pillon; Giuseppe Basso; Katia Basso; Lara Mussolin Journal: Oncotarget Date: 2017-11-11