Abstract
We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.
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Acknowledgements
We are grateful to all parents associations and charities, which continuously supported the clinical and research work. This study has been partly supported by grants from the Ministero Università Ricerca Scientifica e Tecnologica (MURST), Grant 9906152551-007, AIRC (MGV) and PRIN (GB).
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Appendix
Appendix
The following institutions enrolled patients in AIEOP-ALL studies:
Ancona, Div. Pediatria (Dr P Pierani)
Bari, Clinica Pediatrica (Prof. D De Mattia, Dr N Santoro)
Bergamo, Div. Pediatria (Dr M Provenzi)
Bologna, Clinica Pediatrica (Prof. A Pession, Dr R Rondelli)
Brescia, Clinica Pediatrica (Dr F Porta)
Cagliari, Servizio Oncoematologia Pediatrica (Prof. PF Biddau, Dr R Mura)
Catania, Div. Oncoematologia Pediatrica (Prof G Schilirò, Dr L Lo Nigro)
Catanzaro, Div. Ematologia (Dr C Consarino)
Cosenza, U.O. Pediatria (Dr D Sperlì)
Firenze, Ospedale Meyer, Dip. Pediatria, U.O. Oncoematologia Pediatrica (Dr M Aricò, Dr A Lippi)
Genova, Ist ‘G.Gaslini’ (Dr G Dini, Dr C Micalizzi)
Milano, Clinica Pediatrica ‘De Marchi’ (Dr D Portaleone)
Milano, Divisione di Pediatria, Ospedale Niguarda, (Dr F Fedeli)
Modena, Clinica Pediatrica (Prof. P Paolucci)
Monza, Clinica Pediatrica (Prof. G Masera, Dr V Conter, Prof. A Biondi, Dr M Jankovic, Dr C Rizzari)
Napoli, Divisione di Oncoematologia Pediatrica, Ospedale Pausillipon (Dr V Poggi, Dr R Parasole)
Napoli, II Università, Dip. Pediatria, Servizio Autonomo Oncologia Pediatrica (Prof. MT Di Tullio, Prof. F Casale)
Padova, Clinica Pediatrica II (Prof. M Carli, Prof. C Messina)
Palermo, Clinica Pediatrica I ( Dr P D’Angelo)
Parma, Clinica Pediatrica (Dr G Izzi, Dr P Bertolini)
Pavia, Clinica Pediatrica (Prof. F Locatelli, Dr G Giorgiani, Dr M Zecca)
Perugia, Div. Oncoematologia Pediatrica, Ospedale Silvestrini (Prof. F Aversa)
Pesaro, Divisione di Pediatria (Dr L Felici)
Pesaro, Ematologia, Ospedale di Muraglia (Dr G Visani)
Pescara, Divisione di Pediatria (Dr P Di Bartolomeo)
Pisa, Clinica Pediatrica III (Dr C Favre)
Reggio Calabria, Div. Ematologia, Ospedali Riuniti (Prof. F Nobile, Dr M Comis)
Roma, Div. Ematologia Pediatrica, Osp. ‘Bambin Gesù’ (Dr G De Rossi, Dr M Luciani)
Roma, Cattedra Ematologia (Prof. R Foà, Dr AM Testi)
Roma, Clinica Pediatrica (Prof. M Castello)
Roma, Oncologia Pediatrica, Policlinico Gemelli (Prof. R Riccardi)
San Giovanni Rotondo, Div. Pediatria, Ospedale Casa Sollievo della Sofferenza (Dr S Ladogana)
Siena, Clinica Pediatrica (Prof. A Acquaviva)
Sassari, Clinica Pediatrica (Prof. D Gallisai, Dr C Cosmi)
Torino, Clinica Pediatrica (Prof. E Madon, Dr E Barisone)
Trieste, Clinica Pediatrica (Prof. P Tamaro, Dr. GA Zanazzo)
Varese, Clinica Pediatrica (Prof. L Nespoli)
Verona, Clinica Pediatrica (Dr P Marradi)
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Conter, V., Aricò, M., Basso, G. et al. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia. Leukemia 24, 255–264 (2010). https://doi.org/10.1038/leu.2009.250
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DOI: https://doi.org/10.1038/leu.2009.250
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