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1. Improved survival and MRD remission with blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL

Author

Locatelli, F, Zugmaier, G, Rizzari, C, Morris, J, Gruhn, B, Klingebiel, T, Parasole, R, Linderkamp, C, Flotho, C, Petit, A, Micalizzi, C, Zeng, Y, Desai, R, Kormany, W, Eckert, C, Moricke, A, Sartor, M, Hrusak, O, Peters, C, Saha, V, Vinti, L, von Stackelberg, A, Locatelli F., Zugmaier G., Rizzari C., Morris J. D., Gruhn B., Klingebiel T., Parasole R., Linderkamp C., Flotho C., Petit A., Micalizzi C., Zeng Y., Desai R., Kormany W. N., Eckert C., Moricke A., Sartor M., Hrusak O., Peters C., Saha V., Vinti L., von Stackelberg A., Locatelli, F, Zugmaier, G, Rizzari, C, Morris, J, Gruhn, B, Klingebiel, T, Parasole, R, Linderkamp, C, Flotho, C, Petit, A, Micalizzi, C, Zeng, Y, Desai, R, Kormany, W, Eckert, C, Moricke, A, Sartor, M, Hrusak, O, Peters, C, Saha, V, Vinti, L, von Stackelberg, A, Locatelli F., Zugmaier G., Rizzari C., Morris J. D., Gruhn B., Klingebiel T., Parasole R., Linderkamp C., Flotho C., Petit A., Micalizzi C., Zeng Y., Desai R., Kormany W. N., Eckert C., Moricke A., Sartor M., Hrusak O., Peters C., Saha V., Vinti L., and von Stackelberg A.

Published
2023

2. Blinatumomab in Children and Adolescents with Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia: A Real-Life Multicenter Retrospective Study in Seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Centers

Author

Beneduce, G, De Matteo, A, Stellato, P, Testi, A, Bertorello, N, Colombini, A, Putti, M, Rizzari, C, Cesaro, S, Cellini, M, Barisone, E, Petruzziello, F, Menna, G, Parasole, R, Beneduce G., De Matteo A., Stellato P., Testi A. M., Bertorello N., Colombini A., Putti M. C., Rizzari C., Cesaro S., Cellini M., Barisone E., Petruzziello F., Menna G., Parasole R., Beneduce, G, De Matteo, A, Stellato, P, Testi, A, Bertorello, N, Colombini, A, Putti, M, Rizzari, C, Cesaro, S, Cellini, M, Barisone, E, Petruzziello, F, Menna, G, Parasole, R, Beneduce G., De Matteo A., Stellato P., Testi A. M., Bertorello N., Colombini A., Putti M. C., Rizzari C., Cesaro S., Cellini M., Barisone E., Petruzziello F., Menna G., and Parasole R.

Abstract

Five-year event-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) currently exceeds 80–85%. However, 15–20% of patients still experience a relapsed/refractory disease. From 1 January 2015 to 31 December 2020, thirty-nine patients, 0–21 years old with r/r BCP-ALL were treated with blinatumomab with the aim of inducing remission (n = 13) or reducing MRD levels (n = 26) in the frame of different multiagent chemotherapy schedules, in seven AIEOP centers. Patients were treated in compassionate and/or off-label settings and were not enrolled in any controlled clinical trials. Treatment was well tolerated; 22 (56.4%) patients reported adverse events (AE) on a total of 46 events registered, of which 27 (58.7%) were ≤2 grade according to CTCAE. Neurological AEs were 18 (39.1%); only two patients required transient blinatumomab discontinuation. Complete remission (CR) rate was 46% for the 13 patients treated with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with blasts < 5%. Median relapse-free survival was 33.4 months (95% CI; 7.5–59.3); median overall survival was not reached over a mean follow-up of 16 months. In our study, as in other real-life experiences, blinatumomab proved to be effective and well-tolerated, able to induce a high rate of CR and MRD negativity.

Published
2022

3. Improved survival and MRD remission with blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL

Author

Locatelli, Franco, Zugmaier, G., Rizzari, C., Morris, J. D., Gruhn, B., Klingebiel, T., Parasole, R., Linderkamp, C., Flotho, C., Petit, A., Micalizzi, C., Zeng, Y., Desai, R., Kormany, W. N., Eckert, C., Moricke, A., Sartor, M., Hrusak, O., Peters, C., Saha, V., Vinti, L., von Stackelberg, A., Locatelli F. (ORCID:0000-0002-7976-3654), Locatelli, Franco, Zugmaier, G., Rizzari, C., Morris, J. D., Gruhn, B., Klingebiel, T., Parasole, R., Linderkamp, C., Flotho, C., Petit, A., Micalizzi, C., Zeng, Y., Desai, R., Kormany, W. N., Eckert, C., Moricke, A., Sartor, M., Hrusak, O., Peters, C., Saha, V., Vinti, L., von Stackelberg, A., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2023

5. Recurrent genetic fusions redefine MLL germ line acute lymphoblastic leukemia in infants

Author

Fazio, G, Bardini, M, De Lorenzo, P, Grioni, A, Quadri, M, Pedace, L, Corral Abascal, L, Palamini, S, Palmi, C, Buldini, B, Vinti, L, Parasole, R, Barisone, E, Zecca, M, Favre, C, Locatelli, F, Conter, V, Rizzari, C, Valsecchi, M, Biondi, A, Cazzaniga, G, Fazio G., Bardini M., De Lorenzo P., Grioni A., Quadri M., Pedace L., Corral Abascal L., Palamini S., Palmi C., Buldini B., Vinti L., Parasole R., Barisone E., Zecca M., Favre C., Locatelli F., Conter V., Rizzari C., Valsecchi M. G., Biondi A., Cazzaniga G., Fazio, G, Bardini, M, De Lorenzo, P, Grioni, A, Quadri, M, Pedace, L, Corral Abascal, L, Palamini, S, Palmi, C, Buldini, B, Vinti, L, Parasole, R, Barisone, E, Zecca, M, Favre, C, Locatelli, F, Conter, V, Rizzari, C, Valsecchi, M, Biondi, A, Cazzaniga, G, Fazio G., Bardini M., De Lorenzo P., Grioni A., Quadri M., Pedace L., Corral Abascal L., Palamini S., Palmi C., Buldini B., Vinti L., Parasole R., Barisone E., Zecca M., Favre C., Locatelli F., Conter V., Rizzari C., Valsecchi M. G., Biondi A., and Cazzaniga G.

Abstract

B-cell precursor (BCP) acute lymphoblastic leukemia (BCP-ALL) in infants (ie, children age <1 year) is a rare disease traditionally subdivided into MLL-rearranged (alias KMT2A; MLL-R) and MLL germ line (MLL-G) subtypes. MLL gene rearrangements occur in ∼75% of infants with BCP-ALL1-3 and are typically associated with a mixed-lineage phenotype.4 MLL rearrangements originate prenatally in utero5 and play a role in transcription factor dysregulation.6 MLL-R BCP-ALL in infants is associated with dismal outcomes.1-3 Infants with MLL-G ALL treated with intensive therapies in the Interfant-06 protocol may have a relatively favorable prognosis, with a 6-year event-free survival (EFS) rate of 73.9%,2 slightly inferior to that observed in older children with BCP-ALL.1,2 Of interest, a recent study from the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial reported more favorable outcomes in infants

Published
2021

6. P359: IMPROVED OVERALL SURVIVAL AND MRD CLEARANCE WITH BLINATUMOMAB VS CHEMOTHERAPY AS PRE-TRANSPLANT CONSOLIDATION IN PEDIATRIC HIGH-RISK FIRST-RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL)

Author

Locatelli, F., primary, Zugmaier, G., additional, Rizzari, C., additional, Morris, J., additional, Gruhn, B., additional, Klingebiel, T., additional, Parasole, R., additional, Linderkamp, C., additional, Flotho, C., additional, Petit, A., additional, Micalizzi, C., additional, Zeng, Y., additional, Desai, R., additional, Kormany, W., additional, Eckert, C., additional, Möricke, A., additional, Sartor, M., additional, Hrusak, O., additional, Peters, C., additional, Saha, V., additional, Vinti, L., additional, and von Stackelberg, A., additional

Published
2022
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8. FLT3-ITD in Children with Early T-cell Precursor (ETP) Acute Lymphoblastic Leukemia: Incidence and Potential Target for Monitoring Minimal Residual Disease (MRD)

Author

Locatelli, F, Lo Nigro, L, Andriano, N, Buldini, B, Silvestri, D, Villa, T, Parasole, R, Barisone, E, Testi, A, Biondi, A, Valsecchi, M, Rizzari, C, Conter, V, Basso, G, Cazzaniga, G, Locatelli, Franco, Lo Nigro, Luca, Andriano, Nellina, Buldini, Barbara, Silvestri, Daniela, Villa, Tiziana, Parasole, Rosanna, Barisone, Elena, Testi, Anna Maria, Biondi, Andrea, Valsecchi, Maria Grazia, Rizzari, Carmelo, Conter, Valentino, Basso, Giuseppe, Cazzaniga, Giovanni, Locatelli, F, Lo Nigro, L, Andriano, N, Buldini, B, Silvestri, D, Villa, T, Parasole, R, Barisone, E, Testi, A, Biondi, A, Valsecchi, M, Rizzari, C, Conter, V, Basso, G, Cazzaniga, G, Locatelli, Franco, Lo Nigro, Luca, Andriano, Nellina, Buldini, Barbara, Silvestri, Daniela, Villa, Tiziana, Parasole, Rosanna, Barisone, Elena, Testi, Anna Maria, Biondi, Andrea, Valsecchi, Maria Grazia, Rizzari, Carmelo, Conter, Valentino, Basso, Giuseppe, and Cazzaniga, Giovanni

Abstract

Early T‐cell precursor (ETP) is an aggressive form of acute lymphoblastic leukemia (ALL), associated with high risk of relapse. This leukemia subtype shows a higher prevalence of mutations, typically associated with acute myeloid leukemia (AML), including RAS and FLT3 mutations. FLT3‐ ITD was identified in 35% cases of adult ETP‐ALL, but data in the pediatric counterpart are lacking. ETPs frequently lack immunoglobulin (IG) and T‐cell receptor (TR) gene rearrangements, used for minimal residual disease (MRD) monitoring. Among 718 T‐ALL enrolled in Italy into AIEOP‐BFM‐ ALL2000, AIEOP‐ALLR2006, and AIEOP‐BFM‐ALL2009 consecutive protocols, 86 patients (12%) were identified as ETP and 77 out of 86 children were studied for the presence of FLT3‐ITD. A total of 10 out of 77 (13%) ETP cases were FLT3‐ITD positive. IG/TR MRD monitoring was feasible only in four cases. FLT3‐ITD MRD monitoring was performed using real‐time PCR in all FLT3‐ITD positive ETP cases. A comparison between IG/TR and FLT3‐ITD resulted in comparable findings. Our study demonstrated that the FLT3‐ITD prevalence in children was lower (13%) than that reported in adult ETP‐ALL. FLT3‐ITD can be used as a marker for sensitive molecular MRD monitoring in ETP‐ALL when IG/TR markers are not available, potentially selecting those patients who should spare allogeneic hematopoietic stem cell transplantation (HSCT). Finally, the FLT3 pathway is a robust druggable target in this aggressive form of leukemia.

Published
2022

9. Brentuximab vedotin in combination with bendamustine in pediatric patients or young adults with relapsed or refractory Hodgkin lymphoma

Author

Vinti, L., Pagliara, D., Buffardi, S., Di Ruscio, V., Stocchi, F., Mariggio, E., Parasole, R., Di Matteo, A., Petruzziello, F., Paganelli, V., De Vito, R., Del Bufalo, F., Strocchio, L., Locatelli, Franco, Locatelli F. (ORCID:0000-0002-7976-3654), Vinti, L., Pagliara, D., Buffardi, S., Di Ruscio, V., Stocchi, F., Mariggio, E., Parasole, R., Di Matteo, A., Petruzziello, F., Paganelli, V., De Vito, R., Del Bufalo, F., Strocchio, L., Locatelli, Franco, and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Although children and young adults with Hodgkin's lymphoma usually have a favorable prognosis, patients with primary refractory disease and some subsets of relapsed patients still have a dismal outcome. Brentuximab vedotin (BV) in combination with bendamustine may represent a suitable salvage therapy; data on 32 patients aged less than 25 years were retrospectively analyzed. Patients received up to six cycles of treatment of BV 1.8 mg/kg on day 1 and bendamustine 90–120 mg/m2 on days 2 and 3. At the end of treatment, the overall response rate was 81%. The 3-year overall and progression-free survivals are 78.1% and 67%, respectively.

Published
2022

10. FLT3‐ITD in Children with Early T‐cell Precursor (ETP) Acute Lymphoblastic Leukemia: Incidence and Potential Target for Monitoring Minimal Residual Disease (MRD)

Author

Lo Nigro, L., Andriano, N., Buldini, B., Silvestri, D., Villa, T., Locatelli, Franco, Parasole, R., Barisone, E., Testi, A. M., Biondi, A., Valsecchi, M. G., Rizzari, C., Conter, V., Basso, G., Cazzaniga, G., Locatelli F. (ORCID:0000-0002-7976-3654), Lo Nigro, L., Andriano, N., Buldini, B., Silvestri, D., Villa, T., Locatelli, Franco, Parasole, R., Barisone, E., Testi, A. M., Biondi, A., Valsecchi, M. G., Rizzari, C., Conter, V., Basso, G., Cazzaniga, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Early T‐cell precursor (ETP) is an aggressive form of acute lymphoblastic leukemia (ALL), associated with high risk of relapse. This leukemia subtype shows a higher prevalence of mutations, typically associated with acute myeloid leukemia (AML), including RAS and FLT3 mutations. FLT3‐ ITD was identified in 35% cases of adult ETP‐ALL, but data in the pediatric counterpart are lacking. ETPs frequently lack immunoglobulin (IG) and T‐cell receptor (TR) gene rearrangements, used for minimal residual disease (MRD) monitoring. Among 718 T‐ALL enrolled in Italy into AIEOP‐BFM‐ ALL2000, AIEOP‐ALLR2006, and AIEOP‐BFM‐ALL2009 consecutive protocols, 86 patients (12%) were identified as ETP and 77 out of 86 children were studied for the presence of FLT3‐ITD. A total of 10 out of 77 (13%) ETP cases were FLT3‐ITD positive. IG/TR MRD monitoring was feasible only in four cases. FLT3‐ITD MRD monitoring was performed using real‐time PCR in all FLT3‐ITD positive ETP cases. A comparison between IG/TR and FLT3‐ITD resulted in comparable findings. Our study demonstrated that the FLT3‐ITD prevalence in children was lower (13%) than that reported in adult ETP‐ALL. FLT3‐ITD can be used as a marker for sensitive molecular MRD monitoring in ETP‐ALL when IG/TR markers are not available, potentially selecting those patients who should spare allogeneic hematopoietic stem cell transplantation (HSCT). Finally, the FLT3 pathway is a robust druggable target in this aggressive form of leukemia.

Published
2022

11. Prognostic value of minimal residual disease measured by flow-cytometry in two cohorts of infants with acute lymphoblastic leukemia treated according to either MLL-Baby or Interfant protocols

Author

Popov, A, Buldini, B, De Lorenzo, P, Disaro, S, Verzhbitskaya, T, Movchan, L, Giarin, E, Shorikov, E, Di Meglio, A, Tsaur, G, Parasole, R, Miakova, N, Boichenko, E, Kondratchik, K, Aleinikova, O, Karachunskiy, A, Roumiantsev, A, Locatelli, F, Biondi, A, Pieters, R, Valsecchi, M, Fechina, L, Basso, G, Popov A., Buldini B., De Lorenzo P., Disaro S., Verzhbitskaya T., Movchan L., Giarin E., Shorikov E., Di Meglio A., Tsaur G., Parasole R., Miakova N., Boichenko E., Kondratchik K., Aleinikova O., Karachunskiy A., Roumiantsev A., Locatelli F., Biondi A., Pieters R., Valsecchi M. G., Fechina L., Basso G., Popov, A, Buldini, B, De Lorenzo, P, Disaro, S, Verzhbitskaya, T, Movchan, L, Giarin, E, Shorikov, E, Di Meglio, A, Tsaur, G, Parasole, R, Miakova, N, Boichenko, E, Kondratchik, K, Aleinikova, O, Karachunskiy, A, Roumiantsev, A, Locatelli, F, Biondi, A, Pieters, R, Valsecchi, M, Fechina, L, Basso, G, Popov A., Buldini B., De Lorenzo P., Disaro S., Verzhbitskaya T., Movchan L., Giarin E., Shorikov E., Di Meglio A., Tsaur G., Parasole R., Miakova N., Boichenko E., Kondratchik K., Aleinikova O., Karachunskiy A., Roumiantsev A., Locatelli F., Biondi A., Pieters R., Valsecchi M. G., Fechina L., and Basso G.

Published
2020

12. Collateral effects of COVID-19 pandemic in pediatric hematooncology: Fatalities caused by diagnostic delay

Author

Parasole, R, Stellato, P, Conter, V, De Matteo, A, D'Amato, L, Colombini, A, Pecoraro, C, Bencivenga, C, Raimondo, M, Silvestri, S, Tipo, V, Annicchiarico Petruzzelli, L, Giagnuolo, G, Curatolo, A, Biondi, A, Menna, G, Parasole R., Stellato P., Conter V., De Matteo A., D'Amato L., Colombini A., Pecoraro C., Bencivenga C., Raimondo M., Silvestri S., Tipo V., Annicchiarico Petruzzelli L., Giagnuolo G., Curatolo A., Biondi A., Menna G., Parasole, R, Stellato, P, Conter, V, De Matteo, A, D'Amato, L, Colombini, A, Pecoraro, C, Bencivenga, C, Raimondo, M, Silvestri, S, Tipo, V, Annicchiarico Petruzzelli, L, Giagnuolo, G, Curatolo, A, Biondi, A, Menna, G, Parasole R., Stellato P., Conter V., De Matteo A., D'Amato L., Colombini A., Pecoraro C., Bencivenga C., Raimondo M., Silvestri S., Tipo V., Annicchiarico Petruzzelli L., Giagnuolo G., Curatolo A., Biondi A., and Menna G.

Published
2020

13. Randomized post-induction and delayed intensification therapy in high-risk pediatric acute lymphoblastic leukemia: long-term results of the international AIEOP-BFM ALL 2000 trial

Author

Attarbaschi, A, Mann, G, Zimmermann, M, Bader, P, Barisone, E, Basso, G, Biondi, A, Cario, G, Cazzaniga, G, Colombini, A, Flotho, C, Kuhlen, M, Lang, P, Lauten, M, Linderkamp, C, Locatelli, F, Lo Nigro, L, Moricke, A, Niggli, F, Panzer-Grumayer, R, Parasole, R, Peters, C, Caterina Putti, M, Rizzari, C, Suttorp, M, Valsecchi, M, Conter, V, Schrappe, M, Attarbaschi A., Mann G., Zimmermann M., Bader P., Barisone E., Basso G., Biondi A., Cario G., Cazzaniga G., Colombini A., Flotho C., Kuhlen M., Lang P., Lauten M., Linderkamp C., Locatelli F., Lo Nigro L., Moricke A., Niggli F., Panzer-Grumayer R., Parasole R., Peters C., Caterina Putti M., Rizzari C., Suttorp M., Valsecchi M. G., Conter V., Schrappe M., Attarbaschi, A, Mann, G, Zimmermann, M, Bader, P, Barisone, E, Basso, G, Biondi, A, Cario, G, Cazzaniga, G, Colombini, A, Flotho, C, Kuhlen, M, Lang, P, Lauten, M, Linderkamp, C, Locatelli, F, Lo Nigro, L, Moricke, A, Niggli, F, Panzer-Grumayer, R, Parasole, R, Peters, C, Caterina Putti, M, Rizzari, C, Suttorp, M, Valsecchi, M, Conter, V, Schrappe, M, Attarbaschi A., Mann G., Zimmermann M., Bader P., Barisone E., Basso G., Biondi A., Cario G., Cazzaniga G., Colombini A., Flotho C., Kuhlen M., Lang P., Lauten M., Linderkamp C., Locatelli F., Lo Nigro L., Moricke A., Niggli F., Panzer-Grumayer R., Parasole R., Peters C., Caterina Putti M., Rizzari C., Suttorp M., Valsecchi M. G., Conter V., and Schrappe M.

Published
2020

14. Treatment of Poor-Risk Neuroblastoma with Intensive Chemotherapy and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor

Author

Lanino, E., Parasole, R., Garaventa, A., Arrighini, A., Bagnulo, S., Carli, M., Comis, S., di Montezemolo, L. Cordero, Di Tullio, M. T., Massolo, F., Mazzanti, P., Paolucci, P., Pasino, M., Boni, L., Tamaro, P., De Bernardi, B., Freund, Mathias, editor, Link, Hartmut, editor, Schmidt, Reinhold E., editor, and Welte, Karl, editor

Published
1992
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16. Outcome of adolescent patients with acute lymphoblastic leukaemia aged 10–14 years as compared with those aged 15–17 years: Long-term results of 1094 patients of the AIEOP-BFM ALL 2000 study

Author

Testi, A, Attarbaschi, A, Valsecchi, M, Moricke, A, Cario, G, Niggli, F, Silvestri, D, Bader, P, Kuhlen, M, Parasole, R, Putti, M, Lang, P, Flotho, C, Mann, G, Rizzari, C, Barisone, E, Locatelli, F, Linderkamp, C, Lauten, M, Suttorp, M, Zimmermann, M, Basso, G, Biondi, A, Conter, V, Schrappe, M, Testi A. M., Attarbaschi A., Valsecchi M. G., Moricke A., Cario G., Niggli F., Silvestri D., Bader P., Kuhlen M., Parasole R., Putti M. C., Lang P., Flotho C., Mann G., Rizzari C., Barisone E., Locatelli F., Linderkamp C., Lauten M., Suttorp M., Zimmermann M., Basso G., Biondi A., Conter V., Schrappe M., Testi, A, Attarbaschi, A, Valsecchi, M, Moricke, A, Cario, G, Niggli, F, Silvestri, D, Bader, P, Kuhlen, M, Parasole, R, Putti, M, Lang, P, Flotho, C, Mann, G, Rizzari, C, Barisone, E, Locatelli, F, Linderkamp, C, Lauten, M, Suttorp, M, Zimmermann, M, Basso, G, Biondi, A, Conter, V, Schrappe, M, Testi A. M., Attarbaschi A., Valsecchi M. G., Moricke A., Cario G., Niggli F., Silvestri D., Bader P., Kuhlen M., Parasole R., Putti M. C., Lang P., Flotho C., Mann G., Rizzari C., Barisone E., Locatelli F., Linderkamp C., Lauten M., Suttorp M., Zimmermann M., Basso G., Biondi A., Conter V., and Schrappe M.

Abstract

Background: Adolescents (aged 10–17 years) with acute lymphoblastic leukaemia (ALL) have unfavourable disease features and an inferior outcome when compared with younger children, but it is still unclear if differences in disease biology and prognosis exist between adolescents older or younger than 15 years. Methods: We retrospectively analysed outcomes of 1094 adolescents with ALL, aged 10–17 years, treated within the AIEOP-BFM ALL 2000 trial, overall and by the age groups 10–14 and 15–17 years. Findings: Compared with younger children (aged 1–9 years, n = 3647), adolescents had a statistically inferior 5-year event-free survival (EFS) [74.6% (1.3) vs. 84.4% (0.6)] and overall survival (OS) [83.4% (1.1) vs. 92.7% (0.4); p < 0.001]. Clinical and biological disease characteristics did not differ between the two subgroups of adolescents, including minimal residual disease (MRD) results during initial therapy, except for ETV6-RUNX1 frequency and gender. With a median follow-up of 8.8 years, the 5-year EFS and OS were 76.2% (1.5) and 84.9% (1.3), respectively, for those aged 10–14 years and 70.0% (2.8) and 78.8% (2.5) for those aged 15–17 years (p = 0.06; 0.05). There was no significant difference in the cumulative incidence of relapses [17.8% (1.4) and 18.3% (2.4); p = 0.98], while the incidence of treatment-related deaths as a first event was 2.6% (0.6) versus 7.4% (1.6) (p < 0.001) with, in particular, a higher incidence in the high-risk arm. Interpretation: Further prospective studies and biological investigations are required to define optimal treatment for adolescents, in particular for those aged 15–17 years. Newer agents (immunotherapy, targeted therapy) in early treatment phases of patients at higher risk of treatment failure could replace most toxic treatment elements, with the aim of reducing both toxicity and the risk of relapses.

Published
2019

17. Recurrent genetic fusions redefine MLL germ line acute lymphoblastic leukemia in infants

Author

Fazio, G., Bardini, M., De Lorenzo, P., Grioni, A., Quadri, M., Pedace, L., Corral Abascal, L., Palamini, S., Palmi, C., Buldini, B., Vinti, L., Parasole, R., Barisone, E., Zecca, M., Favre, C., Locatelli, Franco, Conter, V., Rizzari, C., Valsecchi, M. G., Biondi, A., Cazzaniga, G., Locatelli F. (ORCID:0000-0002-7976-3654), Fazio, G., Bardini, M., De Lorenzo, P., Grioni, A., Quadri, M., Pedace, L., Corral Abascal, L., Palamini, S., Palmi, C., Buldini, B., Vinti, L., Parasole, R., Barisone, E., Zecca, M., Favre, C., Locatelli, Franco, Conter, V., Rizzari, C., Valsecchi, M. G., Biondi, A., Cazzaniga, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2021

21. Correspondence: Osteonecrosis in childhood acute lymphoblastic leukemia: a retrospective cohort study of the Italian Association of Pediatric Haemato-Oncology (AIEOP)

Author

Parasole, R, Valsecchi, M, Silvestri, D, Locatelli, F, Barisone, E, Petruzziello, F, Putti, M, Micalizzi, C, Colombini, A, Mura, R, Mina, T, Testi, A, Notarangelo, L, Santoro, N, Casini, T, Consarino, C, Nigro, L, Ziino, O, Giagnuolo, G, Rizzari, C, Conter, V, Parasole R., Valsecchi M. G., Silvestri D., Locatelli F., Barisone E., Petruzziello F., Putti M. C., Micalizzi C., Colombini A., Mura R., Mina T., Testi A. M., Notarangelo L. D., Santoro N., Casini T., Consarino C., Nigro L. L., Ziino O., Giagnuolo G., Rizzari C., Conter V., Parasole, R, Valsecchi, M, Silvestri, D, Locatelli, F, Barisone, E, Petruzziello, F, Putti, M, Micalizzi, C, Colombini, A, Mura, R, Mina, T, Testi, A, Notarangelo, L, Santoro, N, Casini, T, Consarino, C, Nigro, L, Ziino, O, Giagnuolo, G, Rizzari, C, Conter, V, Parasole R., Valsecchi M. G., Silvestri D., Locatelli F., Barisone E., Petruzziello F., Putti M. C., Micalizzi C., Colombini A., Mura R., Mina T., Testi A. M., Notarangelo L. D., Santoro N., Casini T., Consarino C., Nigro L. L., Ziino O., Giagnuolo G., Rizzari C., and Conter V.

Published
2018

23. Randomized post-induction and delayed intensification therapy in high-risk pediatric acute lymphoblastic leukemia: long-term results of the international AIEOP-BFM ALL 2000 trial

Author

Attarbaschi, A., Mann, G., Zimmermann, M., Bader, P., Barisone, E., Basso, G., Biondi, A., Cario, G., Cazzaniga, G., Colombini, A., Flotho, C., Kuhlen, M., Lang, P., Lauten, M., Linderkamp, C., Locatelli, Franco, Lo Nigro, L., Moricke, A., Niggli, F., Panzer-Grumayer, R., Parasole, R., Peters, C., Caterina Putti, M., Rizzari, C., Suttorp, M., Valsecchi, M. G., Conter, V., Schrappe, M., Locatelli F. (ORCID:0000-0002-7976-3654), Attarbaschi, A., Mann, G., Zimmermann, M., Bader, P., Barisone, E., Basso, G., Biondi, A., Cario, G., Cazzaniga, G., Colombini, A., Flotho, C., Kuhlen, M., Lang, P., Lauten, M., Linderkamp, C., Locatelli, Franco, Lo Nigro, L., Moricke, A., Niggli, F., Panzer-Grumayer, R., Parasole, R., Peters, C., Caterina Putti, M., Rizzari, C., Suttorp, M., Valsecchi, M. G., Conter, V., Schrappe, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2020

24. Prognostic value of minimal residual disease measured by flow-cytometry in two cohorts of infants with acute lymphoblastic leukemia treated according to either MLL-Baby or Interfant protocols

Author

Popov, A., Buldini, B., De Lorenzo, P., Disaro, S., Verzhbitskaya, T., Movchan, L., Giarin, E., Shorikov, E., Di Meglio, A., Tsaur, G., Parasole, R., Miakova, N., Boichenko, E., Kondratchik, K., Aleinikova, O., Karachunskiy, A., Roumiantsev, A., Locatelli, Franco, Biondi, A., Pieters, R., Valsecchi, M. G., Fechina, L., Basso, G., Locatelli F. (ORCID:0000-0002-7976-3654), Popov, A., Buldini, B., De Lorenzo, P., Disaro, S., Verzhbitskaya, T., Movchan, L., Giarin, E., Shorikov, E., Di Meglio, A., Tsaur, G., Parasole, R., Miakova, N., Boichenko, E., Kondratchik, K., Aleinikova, O., Karachunskiy, A., Roumiantsev, A., Locatelli, Franco, Biondi, A., Pieters, R., Valsecchi, M. G., Fechina, L., Basso, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2020

29. Outcome of adolescent patients with acute lymphoblastic leukaemia aged 10–14 years as compared with those aged 15–17 years: Long-term results of 1094 patients of the AIEOP-BFM ALL 2000 study

Author

Testi, A. M., Attarbaschi, A., Valsecchi, M. G., Moricke, A., Cario, G., Niggli, F., Silvestri, D., Bader, P., Kuhlen, M., Parasole, R., Putti, M. C., Lang, P., Flotho, C., Mann, G., Rizzari, C., Barisone, E., Locatelli, Franco, Linderkamp, C., Lauten, M., Suttorp, M., Zimmermann, M., Basso, G., Biondi, A., Conter, V., Schrappe, M., Locatelli F. (ORCID:0000-0002-7976-3654), Testi, A. M., Attarbaschi, A., Valsecchi, M. G., Moricke, A., Cario, G., Niggli, F., Silvestri, D., Bader, P., Kuhlen, M., Parasole, R., Putti, M. C., Lang, P., Flotho, C., Mann, G., Rizzari, C., Barisone, E., Locatelli, Franco, Linderkamp, C., Lauten, M., Suttorp, M., Zimmermann, M., Basso, G., Biondi, A., Conter, V., Schrappe, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background: Adolescents (aged 10–17 years) with acute lymphoblastic leukaemia (ALL) have unfavourable disease features and an inferior outcome when compared with younger children, but it is still unclear if differences in disease biology and prognosis exist between adolescents older or younger than 15 years. Methods: We retrospectively analysed outcomes of 1094 adolescents with ALL, aged 10–17 years, treated within the AIEOP-BFM ALL 2000 trial, overall and by the age groups 10–14 and 15–17 years. Findings: Compared with younger children (aged 1–9 years, n = 3647), adolescents had a statistically inferior 5-year event-free survival (EFS) [74.6% (1.3) vs. 84.4% (0.6)] and overall survival (OS) [83.4% (1.1) vs. 92.7% (0.4); p < 0.001]. Clinical and biological disease characteristics did not differ between the two subgroups of adolescents, including minimal residual disease (MRD) results during initial therapy, except for ETV6-RUNX1 frequency and gender. With a median follow-up of 8.8 years, the 5-year EFS and OS were 76.2% (1.5) and 84.9% (1.3), respectively, for those aged 10–14 years and 70.0% (2.8) and 78.8% (2.5) for those aged 15–17 years (p = 0.06; 0.05). There was no significant difference in the cumulative incidence of relapses [17.8% (1.4) and 18.3% (2.4); p = 0.98], while the incidence of treatment-related deaths as a first event was 2.6% (0.6) versus 7.4% (1.6) (p < 0.001) with, in particular, a higher incidence in the high-risk arm. Interpretation: Further prospective studies and biological investigations are required to define optimal treatment for adolescents, in particular for those aged 15–17 years. Newer agents (immunotherapy, targeted therapy) in early treatment phases of patients at higher risk of treatment failure could replace most toxic treatment elements, with the aim of reducing both toxicity and the risk of relapses.

Published
2019

30. Complicanze infettive gravi nei pazienti affetti da leucemia linfoblastica acuta (LLA) arruolati nel protocollo AIEOP-BFM ALL 2009: incidenza ed esito. Hematology Reports 2018; 10 (s1): 67

Author

Colombini, A., Brivio, E., Barisone, E., Barone, A., Cellini, M., Kiren, V., La-Spina, M., Mina, T., Muggeo, P., Mura, R., Parasole, R., Putti, M. C., Rizzari, C., Silvestri, D., Vinti, L., Conter, V., and Cesaro, S.

Subjects
leucemia linfoblastica acuta, pediatria, infezioni batteriche, leucemia linfoblastica acuta, pediatria, infezioni batteriche
Published
2018

33. Multidisciplinary treatment of primary orbital rhabdomyosarcoma: a single-institution experience

Author

Fiorillo, Amedeo, Migliorati, R., Grimaldi, M., Vassallo, P., Canale, G., Tranfa, F., Uccello, G., Fiore, M., Muto, P., Menna, G., Parasole, R., and Bonavolonta, G.

Subjects
Eye cancer -- Care and treatment, Cancer in children -- Care and treatment, Chemotherapy, Combination -- Evaluation, Rhabdomyosarcoma -- Care and treatment, Health
Abstract

Overall, rhabdomyosarcomas are not common, but they are among the most frequent tumors of muscle tissue. Among children, rhabdomyosarcomas account for four to eight percent of cancers. While many rhabdomyosarcomas have a poor prognosis, patients enjoy a far better prognosis if the disease is limited to the eye socket, or orbit. Published studies indicate a two-year survival rate of about 90 percent. In a retrospective evaluation of the treatment of 12 children, the authors indicate that the current treatment method, which combines radiotherapy with chemotherapy, can be completely effective when properly applied. Ten of the 12 patients were immediately treated with radiation and combined chemotherapy upon diagnosis, and two patients were treated with radiotherapy upon recurrence. The authors view the treatment of these two patients as corrective, in that the initial treatment was not properly applied. All 12 patients are alive without evidence of disease at follow-up periods ranging from 7 to 123 months. Eleven of the 12 patients received a radiation dose of 6,000 cGy (a Gy, or Gary, is one Joule of energy absorbed per kilogram of tissue). This level of radiation, when administered to the eye, is believed to cause cataracts. In the present series of patients, cataract formation was observed in only one patient, and lens opacities occurred in another two. An additional eight patients retain good visual acuity; the remaining patient had almost total lack of vision prior to treatment. The excellent preservation of vision is attributed to immediate treatment with radiotherapy. The ability of the eye to recover from radiation exposure may be compromised if radiotherapy is delayed until after chemotherapy. Therefore, treatment should not be delayed once a diagnosis of rhabdomyosarcoma of the orbit is confirmed. The authors suggest that the currently available treatment methods are already optimal and require only proper administration. (Consumer Summary produced by Reliance Medical Information, Inc.)

Published
1991

34. Correspondence: Osteonecrosis in childhood acute lymphoblastic leukemia: a retrospective cohort study of the Italian Association of Pediatric Haemato-Oncology (AIEOP)

Author

Parasole, R., Valsecchi, M. G., Silvestri, D., Locatelli, Franco, Barisone, E., Petruzziello, F., Putti, M. C., Micalizzi, C., Colombini, A., Mura, R., Mina, T., Testi, A. M., Notarangelo, L. D., Santoro, N., Casini, T., Consarino, C., Nigro, L. L., Ziino, O., Giagnuolo, G., Rizzari, C., Conter, V., Locatelli F. (ORCID:0000-0002-7976-3654), Parasole, R., Valsecchi, M. G., Silvestri, D., Locatelli, Franco, Barisone, E., Petruzziello, F., Putti, M. C., Micalizzi, C., Colombini, A., Mura, R., Mina, T., Testi, A. M., Notarangelo, L. D., Santoro, N., Casini, T., Consarino, C., Nigro, L. L., Ziino, O., Giagnuolo, G., Rizzari, C., Conter, V., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2018

35. Reduced-Intensity delayed intensification in standard-Risk pediatric acute lymphoblastic leukemia defined by undetectable minimal residual disease: Results of an international randomized trial (AIEOP-BFM ALL 2000)

Author

Schrappe, M., Bleckmann, K., Zimmermann, M., Biondi, A., Moricke, A., Locatelli, Franco, Cario, G., Rizzari, C., Attarbaschi, A., Valsecchi, M. G., Bartram, C. R., Barisone, E., Niggli, F., Niemeyer, C., Testi, A. M., Mann, G., Ziino, O., Schafer, B., Panzer-Grumayer, R., Beier, R., Parasole, R., Gohring, G., Ludwig, W. -D., Casale, F., Schlegel, P. -G., Basso, G., Conter, V., Locatelli F. (ORCID:0000-0002-7976-3654), Schrappe, M., Bleckmann, K., Zimmermann, M., Biondi, A., Moricke, A., Locatelli, Franco, Cario, G., Rizzari, C., Attarbaschi, A., Valsecchi, M. G., Bartram, C. R., Barisone, E., Niggli, F., Niemeyer, C., Testi, A. M., Mann, G., Ziino, O., Schafer, B., Panzer-Grumayer, R., Beier, R., Parasole, R., Gohring, G., Ludwig, W. -D., Casale, F., Schlegel, P. -G., Basso, G., Conter, V., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). Cumulative drug doses of P-III were reduced by 30% for dexamethasone and 50% for vincristine, doxorubicin, and cyclophosphamide, which shortened the treatment duration from 49 to 29 days. The study aimed at noninferiority of reduced-intensity P-III; analyses were performed according to treatment given. Results For P-III and P-II, respectively, the 8-year rate of disease-free survival (6 SE) was 89.2 6 1.3% and 92.3 6 1.2% (P = .04); cumulative incidence of relapse, 8.7 6 1.2% and 6.4 6 1.1% (P = .09); and overall survival, 96.1 6 0.8% and 98.0 6 0.6% (P = .06). Patients with ETV6-RUNX1–positive ALL and patients 1 to 6 years of age performed equally well in both arms. The incidence of death during remission was comparable, which indicates equivalent toxicity. The 8-year cumulative incidence rate of secondary malignancies was 1.3 6 0.5% and 0.6 6 0.4% for P-III and P-II, respectively (P = .37). Conclusion Although the criteria used for the standard-risk definition in this trial identified patients with exceptionally good prognosis, reduction of chemotherapy was not successful mainly because of an increased rate of relapse. The data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity of t

Published
2018

36. DNA variants in DHFR gene and response to treatment in children with childhood B ALL: Revisited in AIEOP-BFM protocol

Author

Ceppi, F, Gagné, V, Douyon, L, Quintin, C, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, Krajinovic, M, Ceppi, Francesco, Gagné, Vincent, Douyon, Laurance, Quintin, Camille J., Colombini, Antonella, Parasole, Rosanna, Buldini, Barbara, Basso, Giuseppe, Conter, Valentino, Cazzaniga, Giovanni, Krajinovic, Maja, Ceppi, F, Gagné, V, Douyon, L, Quintin, C, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, Krajinovic, M, Ceppi, Francesco, Gagné, Vincent, Douyon, Laurance, Quintin, Camille J., Colombini, Antonella, Parasole, Rosanna, Buldini, Barbara, Basso, Giuseppe, Conter, Valentino, Cazzaniga, Giovanni, and Krajinovic, Maja

Abstract

Aim: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. Methods: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome. Results: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype ∗1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%). Conclusion: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment.

Published
2018

37. Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing

Author

Abaji, R, Ceppi, F, Patel, S, Gagné, V, Xu, C, Spinella, J, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, Leclerc, J, Laverdière, C, Sinnett, D, Krajinovic, M, Abaji, Rachid, Ceppi, Francesco, Patel, Swati, Gagné, Vincent, Xu, Chang J., Spinella, Jean-François, Colombini, Antonella, Parasole, Rosanna, Buldini, Barbara, Basso, Giuseppe, Conter, Valentino, Cazzaniga, Giovanni, Leclerc, Jean-Marie, Laverdière, Caroline, Sinnett, Daniel, Krajinovic, Maja, Abaji, R, Ceppi, F, Patel, S, Gagné, V, Xu, C, Spinella, J, Colombini, A, Parasole, R, Buldini, B, Basso, G, Conter, V, Cazzaniga, G, Leclerc, J, Laverdière, C, Sinnett, D, Krajinovic, M, Abaji, Rachid, Ceppi, Francesco, Patel, Swati, Gagné, Vincent, Xu, Chang J., Spinella, Jean-François, Colombini, Antonella, Parasole, Rosanna, Buldini, Barbara, Basso, Giuseppe, Conter, Valentino, Cazzaniga, Giovanni, Leclerc, Jean-Marie, Laverdière, Caroline, Sinnett, Daniel, and Krajinovic, Maja

Abstract

Aim: To identify genetic markers associated with vincristine-induced peripheral neuropathy (VIPN) in childhood acute lymphoblastic leukemia. Patients & methods: Whole-exome sequencing data were combined with exome-wide association study to identify predicted-functional germline variants associated with high-grade VIPN. Genotyping was then performed for top-ranked signals (n = 237), followed by validation in independent replication group (n = 405). Results: Minor alleles of rs2781377/SYNE2 (p = 0.01) and rs10513762/MRPL47 (p = 0.01) showed increased risk, whereas that of rs3803357/BAHD1 had a protective effect (p = 0.007). Using a genetic model based on weighted genetic risk scores, an additive effect of combining these loci was observed (p = 0.003). The addition of rs1135989/ACTG1 further enhanced model performance (p = 0.0001). Conclusion: Variants in SYNE2, MRPL47 and BAHD1 genes are putative new risk factors for VIPN in childhood acute lymphoblastic leukemia.

Published
2018

38. Reduced-Intensity delayed intensification in standard-Risk pediatric acute lymphoblastic leukemia defined by undetectable minimal residual disease: Results of an international randomized trial (AIEOP-BFM ALL 2000)

Author

Schrappe, M, Bleckmann, K, Zimmermann, M, Biondi, A, Möricke, A, Locatelli, F, Cario, G, Rizzari, C, Attarbaschi, A, Valsecchi, M, Bartram, C, Barisone, E, Niggli, F, Niemeyer, C, Testi, A, Mann, G, Ziino, O, Schäfer, B, Panzer-Grümayer, R, Beier, R, Parasole, R, Göhring, G, Ludwig, W, Casale, F, Schlegel, P, Basso, G, Conter, V, Valsecchi, MG, Bartram, CR, Testi, AM, Ludwig, WD, Schlegel, PG, Schrappe, M, Bleckmann, K, Zimmermann, M, Biondi, A, Möricke, A, Locatelli, F, Cario, G, Rizzari, C, Attarbaschi, A, Valsecchi, M, Bartram, C, Barisone, E, Niggli, F, Niemeyer, C, Testi, A, Mann, G, Ziino, O, Schäfer, B, Panzer-Grümayer, R, Beier, R, Parasole, R, Göhring, G, Ludwig, W, Casale, F, Schlegel, P, Basso, G, Conter, V, Valsecchi, MG, Bartram, CR, Testi, AM, Ludwig, WD, and Schlegel, PG

Abstract

Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). Cumulative drug doses of P-III were reduced by 30% for dexamethasone and 50% for vincristine, doxorubicin, and cyclophosphamide, which shortened the treatment duration from 49 to 29 days. The study aimed at noninferiority of reduced-intensity P-III; analyses were performed according to treatment given. Results For P-III and P-II, respectively, the 8-year rate of disease-free survival (6 SE) was 89.2 6 1.3% and 92.3 6 1.2% (P = .04); cumulative incidence of relapse, 8.7 6 1.2% and 6.4 6 1.1% (P = .09); and overall survival, 96.1 6 0.8% and 98.0 6 0.6% (P = .06). Patients with ETV6-RUNX1–positive ALL and patients 1 to 6 years of age performed equally well in both arms. The incidence of death during remission was comparable, which indicates equivalent toxicity. The 8-year cumulative incidence rate of secondary malignancies was 1.3 6 0.5% and 0.6 6 0.4% for P-III and P-II, respectively (P = .37). Conclusion Although the criteria used for the standard-risk definition in this trial identified patients with exceptionally good prognosis, reduction of chemotherapy was not successful mainly because of an increased rate of relapse. The data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity o

Published
2018

39. 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

Author

Conter V., Aricò M., Basso G., Biondi A., Barisone E., Messina C., Parasole R., De Rossi G., Locatelli F., Santoro N., Micalizzi C., Citterio M., Rizzari C., Silvestri D., Rondelli R., Lo Nigro L., Ziino O., Testi A.M., Masera G., Valsecchi M.G., Associazione Italiana di Ematologia ed Oncologia Pediatrica, PESSION, ANDREA, Conter V., Aricò M., Basso G., Biondi A., Barisone E., Messina C., Parasole R., De Rossi G., Locatelli F., Pession A., Santoro N., Micalizzi C., Citterio M., Rizzari C., Silvestri D., Rondelli R., Lo Nigro L., Ziino O., Testi AM., Masera G., Valsecchi MG., Associazione Italiana di Ematologia ed Oncologia Pediatrica., Conter, V, Aricò, M, Basso, G, Biondi, A, Barisone, E, Messina, C, Parasole, R, De Rossi, G, Locatelli, F, Pession, A, Santoro, N, Micalizzi, C, Citterio, M, Rizzari, C, Silvestri, D, Rondelli, R, Lo Nigro, L, Ziino, O, Testi, A, Masera, G, and Valsecchi, M

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Pediatrics, acute lymphoblastic leukemia, childhood, long-term results, Time Factors, Adolescent, Time Factor, Prognosi, Medical Oncology, Systemic therapy, Follow-Up Studie, Risk Factors, Internal medicine, Acute lymphocytic leukemia, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Child, Survival rate, Childhood Acute Lymphoblastic Leukemia, Antineoplastic Combined Chemotherapy Protocol, Hematology, business.industry, Risk Factor, Remission Induction, Infant, Cancer, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, medicine.disease, Minimal residual disease, Survival Rate, Treatment Outcome, Italy, El Niño, Child, Preschool, Female, Cranial Irradiation, business, Follow-Up Studies, Human
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.

Published
2010

40. Infezioni Clinicamente rilevanti durante la terapia di induzione sono associate con un aumento del rischio di recidiva. Studio di 1999 pazienti arruolati nel protocollo AIEOP-LLA-2000

Author

Caselli, D., Colombini, A., Silvestri, D., Vinti, L., Parasole, R., Putti, M. C., Barisone, E., Lo Nigro, L., Santoro, N., Ziino, O., Decembrino, N., Castagnola, E., Cesaro, Simone, Aricò, M., and Conter, V. .

Subjects
leucemia linfoblastica acuta, chemioterapia, Infezioni, Infezioni, chemioterapia, leucemia linfoblastica acuta
Published
2016

41. Pharmacogenetics and induction/consolidation therapy toxicities in acute lymphoblastic leukemia patients treated with AIEOP-BFM ALL 2000 protocol

Author

Franca, R., Rebora, P., Bertorello, N., Fagioli, F., Conter, V., Biondi, A., Colombini, A., Micalizzi, C., Zecca, M., Parasole, R., Petruzziello, F., Basso, G., Putti, M. C., Locatelli, Franco, D'Adamo, P., Valsecchi, M. G., Decorti, G., Rabusin, M., Locatelli F. (ORCID:0000-0002-7976-3654), Franca, R., Rebora, P., Bertorello, N., Fagioli, F., Conter, V., Biondi, A., Colombini, A., Micalizzi, C., Zecca, M., Parasole, R., Petruzziello, F., Basso, G., Putti, M. C., Locatelli, Franco, D'Adamo, P., Valsecchi, M. G., Decorti, G., Rabusin, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Drug-related toxicities represent an important clinical concern in chemotherapy, genetic variants could help tailoring treatment to patient. A pharmacogenetic multicentric study was performed on 508 pediatric acute lymphoblastic leukemia patients treated with AIEOP-BFM 2000 protocol: 28 variants were genotyped by VeraCode and Taqman technologies, deletions of GST-M1 and GST-T1 by multiplex PCR. Toxicities were derived from a central database: 251 patients (49.4%) experienced at least one gastrointestinal (GI) or hepatic (HEP) or neurological (NEU) grade III/IV episode during the remission induction phase: GI occurred in 63 patients (12.4%); HEP in 204 (40.2%) and NEU in 44 (8.7%). Logistic regression model adjusted for sex, risk and treatment phase revealed that ITPA rs1127354 homozygous mutated patients showed an increased risk of severe GI and NEU. ABCC1 rs246240 and ADORA2A rs2236624 homozygous mutated genotypes were associated to NEU and HEP, respectively. These three variants could be putative predictive markers for chemotherapy-related toxicities in AIEOP-BFM protocols.

Published
2017

42. Protocol II vs protocol III given twice during reinduction therapy in children with medium-risk ALL

Author

Locatelli, Franco, Valsecchi, M. G., Moricke, A., Zimmermann, M., Gruhn, B., Biondi, A., Kulozik, A. E., Silvestri, D., Bodmer, N., Putti, M. C., Burdach, S., Micalizzi, C., Teigler-Schlegel, A., Ritter, J., Pession, A., Cario, G., Bielack, S., Basso, G., Klingebiel, T., Vinti, L., Rizzari, C., Attarbaschi, A., Santoro, N., Parasole, R., Mann, G., Karawajew, L., Haas, O. A., Conter, V., Schrappe, M., Locatelli F. (ORCID:0000-0002-7976-3654), Locatelli, Franco, Valsecchi, M. G., Moricke, A., Zimmermann, M., Gruhn, B., Biondi, A., Kulozik, A. E., Silvestri, D., Bodmer, N., Putti, M. C., Burdach, S., Micalizzi, C., Teigler-Schlegel, A., Ritter, J., Pession, A., Cario, G., Bielack, S., Basso, G., Klingebiel, T., Vinti, L., Rizzari, C., Attarbaschi, A., Santoro, N., Parasole, R., Mann, G., Karawajew, L., Haas, O. A., Conter, V., Schrappe, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2017

43. Protocol II vs protocol III given twice during reinduction therapy in children with medium-risk ALL

Author

Locatelli, F, Valsecchi, M, Möricke, A, Zimmermann, M, Gruhn, B, Biondi, A, Kulozik, A, Silvestri, D, Bodmer, N, Putti, M, Burdach, S, Micalizzi, C, Teigler-Schlegel, A, Ritter, J, Pession, A, Cario, G, Bielack, S, Basso, G, Klingebiel, T, Vinti, L, Rizzari, C, Attarbaschi, A, Santoro, N, Parasole, R, Mann, G, Karawajew, L, Haas, O, Conter, V, Schrappe, M, Valsecchi, MG, Kulozik, AE, Putti, MC, Locatelli, F, Valsecchi, M, Möricke, A, Zimmermann, M, Gruhn, B, Biondi, A, Kulozik, A, Silvestri, D, Bodmer, N, Putti, M, Burdach, S, Micalizzi, C, Teigler-Schlegel, A, Ritter, J, Pession, A, Cario, G, Bielack, S, Basso, G, Klingebiel, T, Vinti, L, Rizzari, C, Attarbaschi, A, Santoro, N, Parasole, R, Mann, G, Karawajew, L, Haas, O, Conter, V, Schrappe, M, Valsecchi, MG, Kulozik, AE, and Putti, MC

Published
2017

44. Andamento dei livelli di GATA-1 e WT-1 in corso di emopatie pediatriche

Author

Petruzziello F, Ambrosio R, Giovannone ED, Parasole R, Menna G, De Simone G, Poggi V, SESSA, RAFFAELE, IZZO, PAOLA, GROSSO, MICHELA, Petruzziello, F, Sessa, Raffaele, Ambrosio, R, Giovannone, Ed, Parasole, R, Menna, G, De Simone, G, Poggi, V, Izzo, Paola, and Grosso, Michela

Published
2012

45. Bone lesions in Langerhans cell histiocytosis

Author

Fiorillo, A., Sadile, F., De Chiara, C., Parasole, R., Simeone, D., D'Amore, R., D'Alvano, L., and Cigala, F.

Subjects
Reticuloendotheliosis -- Care and treatment, Health
Published
1993

46. Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia : insight on prognostic value of DNA index in the framework of Berlin-Frnkfurt-Munster based chemotherapy

Author

ARICÒ M, VALSECCHI MG, RIZZARI C, BARISONE E, BIONDI A, LOCATELLI F, LO NIGRO L, LUCANI M, MESSINA C, MICALIZZI C, PARASOLE R, PESSION A, SANTORO N, TESTI AM, SILVESTRI D, BASSO G, MASERA G, CONTER V., CASALE, Fiorina, Aricò, M, Valsecchi, Mg, Rizzari, C, Barisone, E, Biondi, A, Casale, Fiorina, Locatelli, F, LO NIGRO, L, Lucani, M, Messina, C, Micalizzi, C, Parasole, R, Pession, A, Santoro, N, Testi, Am, Silvestri, D, Basso, G, Masera, G, and Conter, V.

Published
2008

47. Risultati a lungo termine ottenuti nei bambini con leucemia linfoblastica acuta ( LLA) ad immunofenotipo T arruolati nei protocolli AIEOP LLA 91 e 95

Author

Rizzari C., Conter V., Valsecchi M.G., Aricò M., Barisone E., Basso G., Biondi A., Casale F., Citterio M., De Rossi G., Lo Nigro L., Locatelli F., Messina C., Micalizzi C., Parasole R., Rondelli R., Santoro N., Silvestri D., Testi A.M., Masera G., PESSION, ANDREA, Rizzari C., Conter V., Valsecchi MG., Aricò M., Barisone E., Basso G., Biondi A., Casale F., Citterio M., De Rossi G., Lo Nigro L., Locatelli F., Messina C., Micalizzi C., Parasole R., Pession A., Rondelli R., Santoro N., Silvestri D., Testi AM., and Masera G.

Published
2007

48. Il DNA INDEX ha valore prognostico nella LLA del bambino trattata con chemioterapia intensiva tipo bfm.Risultati finali del protocollo AIEOP-LLA-95

Author

Aricò M., Valsecchi M.G., Rizzari C., Barisone E., Biondi A., Casale F., Locatelli F., Lo Nigro L., Baronci C., Messina C., Micalizzi C., Parasole R., Santoro N., Testi A.M., Silvestri D., Basso G., Masera G., Conter V., PESSION, ANDREA, Aricò M., Valsecchi MG., Rizzari C., Barisone E., Biondi A., Casale F., Locatelli F., Lo Nigro L., Baronci C., Messina C., Micalizzi C., Parasole R., Pession A., Santoro N., Testi AM., Silvestri D., Basso G., Masera G., and Conter V.

Published
2007

49. Risultati del protocollo AIEOP-LLA 95 per il trattamento della leucemia linfoblastica acuta(LLA) dell'età pediatrica

Author

Aricò M., Rizzari C., Valsecchi M.G., Barisone E., Basso G., Biondi A., Casale F., de rossi G., Locatelli F., Lo Nigro L., Messina C., Micalizzi C., parasole R., Rondelli R., Sntoro N., Silvestri S., Testi A.M., Masera G., Conter V., PESSION, ANDREA, Aricò M., Rizzari C., Valsecchi MG., Barisone E., Basso G., Biondi A., Casale F., de rossi G., Locatelli F., Lo Nigro L., Messina C., Micalizzi C., parasole R., Pession A., Rondelli R., Sntoro N., Silvestri S., Testi AM., Masera G., and Conter V.

Published
2006

50. CRLF2 over-expression is a poor prognostic marker in children with high risk T-cell acute lymphoblastic leukemia

Author

Palmi, C, Savino, A, Silvestri, D, Bronzini, I, Cario, G, Paganin, M, Buldini, B, Galbiati, M, Muckenthaler, M, Bugarin, C, Mina, P, Nagel, S, Barisone, E, Casale, F, Locatelli, F, Nigro, L, Micalizzi, C, Parasole, R, Pession, A, Putti, M, Santoro, N, Testi, A, Ziino, O, Kulozik, A, Zimmermann, M, Schrappe, M, Villa, A, Gaipa, G, Basso, G, Biondi, A, Valsecchi, M, Stanulla, M, Conter, V, Kronnie, G, Cazzaniga, G, PALMI, CHIARA, SAVINO, ANGELA MARIA, VILLA, ANTONELLO, GAIPA, GIUSEPPE, BIONDI, ANDREA, VALSECCHI, MARIA GRAZIA, CONTER, VALENTINO, CAZZANIGA, GIOVANNI ITALO, Palmi, C, Savino, A, Silvestri, D, Bronzini, I, Cario, G, Paganin, M, Buldini, B, Galbiati, M, Muckenthaler, M, Bugarin, C, Mina, P, Nagel, S, Barisone, E, Casale, F, Locatelli, F, Nigro, L, Micalizzi, C, Parasole, R, Pession, A, Putti, M, Santoro, N, Testi, A, Ziino, O, Kulozik, A, Zimmermann, M, Schrappe, M, Villa, A, Gaipa, G, Basso, G, Biondi, A, Valsecchi, M, Stanulla, M, Conter, V, Kronnie, G, Cazzaniga, G, PALMI, CHIARA, SAVINO, ANGELA MARIA, VILLA, ANTONELLO, GAIPA, GIUSEPPE, BIONDI, ANDREA, VALSECCHI, MARIA GRAZIA, CONTER, VALENTINO, and CAZZANIGA, GIOVANNI ITALO

Abstract

Pediatric T-ALL patients have a worse outcome compared to BCP-ALL patients and they could benefit from new prognostic marker identification. Alteration of CRLF2 gene, a hallmark correlated with poor outcome in BCP-ALL, has not been reported in T-ALL. We analyzed CRLF2 expression in 212 T-ALL pediatric patients enrolled in AIEOP-BFM ALL2000 study in Italian and German centers. Seventeen out of 120 (14.2%) Italian patients presented CRLF2 mRNA expression 5 times higher than the median (CRLF2-high); they had a significantly inferior event-free survival (41.2%±11.9 vs. 68.9%±4.6, p=0.006) and overall survival (47.1%±12.1 vs. 73.8%±4.3, p=0.009) and an increased cumulative incidence of relapse/resistance (52.9%±12.1 vs. 26.2%±4.3, p=0.007) compared to CRLF2-low patients. The prognostic value of CRLF2 over-expression was validated in the German cohort. Of note, CRLF2 over-expression was associated with poor prognosis in the high risk (HR) subgroup where CRLF2-high patients were more frequently allocated. Interestingly, although in T-ALL CRLF2 protein was localized mainly in the cytoplasm, in CRLF2-high blasts we found a trend towards a stronger TSLP-induced pSTAT5 response, sensitive to the JAK inhibitor Ruxolitinib. In conclusion, CRLF2 over-expression is a poor prognostic marker identifying a subset of HR T-ALL patients that could benefit from alternative therapy, potentially targeting the CRLF2 pathway.

Published
2016

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