Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD <10−3 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL-1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL-2000 and LAL-0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric-inspired and MRD-oriented protocol is feasible and effective for Ph- AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.

Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric-like GIMEMA LAL-1308 trial / Testi, A. M.; Canichella, M.; Vitale, A.; Piciocchi, A.; Guarini, A.; Starza, I. D.; Cavalli, M.; De Propris, M. S.; Messina, M.; Elia, L.; Moleti, M. L.; Martino, B.; Luppi, M.; D'Aloisio, M.; Candoni, A.; Conter, V.; Fazi, P.; Vignetti, M.; Chiaretti, S.; Foa, R.. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - 96:3(2021), pp. 292-301. [10.1002/ajh.26066]

Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric-like GIMEMA LAL-1308 trial

Testi A. M.
;
Canichella M.;Piciocchi A.;Guarini A.;Cavalli M.;Messina M.;Elia L.;Vignetti M.;Chiaretti S.;Foa R.
2021

Abstract

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) represent a unique patient population with specific characteristics and needs. Growing evidences suggest that pediatric-inspired approaches improve the outcome in AYA. These results prompted the design of a pediatric AIEOP-BFM ALL 2000-based regimen - the GIMEMA LAL-1308 protocol - for newly diagnosed AYA (range 18-35 years) with Philadelphia negative (Ph-) ALL. The protocol included minimal residual disease (MRD) analysis at two different time-points (TP), that is, at the end of induction IA and consolidation IB, and a modulation in post-consolidation intensity according to MRD. Seventy-six patients were eligible between September 2010 and October 2014. The regimen was well tolerated, with 2.7% induction deaths and no deaths in the post-consolidation phase. The complete response (CR) rate was 92%; the 48-month overall survival (OS) and disease-free survival (DFS) were 60.3% and 60.4%. Both OS and DFS were significantly better in T-ALL than B-ALL. A molecular MRD <10−3 at TP1 was associated with a significantly better OS and DFS (77% vs 39% and 71.9% vs 34.4%, respectively);similar results were documented at TP2 (OS and DFS 74.5% vs 30.6% and 71.5% vs 25.7%, respectively). The LAL-1308 results were compared to those from similar historic AYA populations undergoing the two previous GIMEMA LAL-2000 and LAL-0904 protocols. Both OS and DFS improved significantly compared to the two previous protocols. These results indicate that this pediatric-inspired and MRD-oriented protocol is feasible and effective for Ph- AYA ALL patients, and underline the prognostic value of MRD determinations at specific TPs.
adolescent; adult; allografts; antineoplastic combined chemotherapy protocols; asparaginase; combined modality therapy; cranial irradiation; cyclophosphamide; cytarabine; dexamethasone; disease-free survival; doxorubicin; female; hematopoietic stem cell transplantation; humans; italy; kaplan-meier estimate; male; mercaptopurine; methotrexate; neoplasm, residual; precursor cell lymphoblastic leukemia-lymphoma; prednisone; treatment outcome; vincristine; young adult
01 Pubblicazione su rivista::01l Trial clinico
Adolescent and young adult acute lymphoblastic leukemia. Final results of the phase II pediatric-like GIMEMA LAL-1308 trial / Testi, A. M.; Canichella, M.; Vitale, A.; Piciocchi, A.; Guarini, A.; Starza, I. D.; Cavalli, M.; De Propris, M. S.; Messina, M.; Elia, L.; Moleti, M. L.; Martino, B.; Luppi, M.; D'Aloisio, M.; Candoni, A.; Conter, V.; Fazi, P.; Vignetti, M.; Chiaretti, S.; Foa, R.. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - 96:3(2021), pp. 292-301. [10.1002/ajh.26066]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1624501
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