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1. Hearing chimeras

Author

Di Bona, E

Subjects
Auditory streams, Philosophy, Perception, Musical experience, Auditory experience, Musical streams, Rich view, Gestalt principles, General Social Sciences
Abstract

I argue that chimericity is a property that we typically experience when listening to multi-instrumental music. It is the property of hearing as a unified whole a melody or a harmony that does not belong to any single sound source but instead consists of the assembling of melodic or harmonic fragments coming from different sources. Chimericity is not reducible to the low-level audible properties of pitch and loudness; it is cognized at the perceptual level thanks to the auditory mechanism of primitive grouping. My aim is to show that chimericity is a perceptual property, one that we can genuinely hear. In developing this view, I engage with the debate within the philosophy of sense perception between rich vs thin views of the content of perceptual experience.

Published
2022

4. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2020

5. Increased tumor burden in patients with chronic myeloid leukemia after 36 months of imatinib discontinuation

Author

Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti Passerini, C, Diral E., Mori S., Antolini L., Abruzzese E., Le Coutre P., Martino B., Pungolino E., Elena C., Bergamaschi M., Assouline S., Di Bona E., Gozzini A., Andrade-Campos M., Stagno F., Iurlo A., Pirola A., Fontana D., Petiti J., Bonanomi M. L., Crivori P., Piazza R., Fava C., Gambacorti Passerini C., Diral, E, Mori, S, Antolini, L, Abruzzese, E, Le Coutre, P, Martino, B, Pungolino, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Gozzini, A, Andrade-Campos, M, Stagno, F, Iurlo, A, Pirola, A, Fontana, D, Petiti, J, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti Passerini, C, Diral E., Mori S., Antolini L., Abruzzese E., Le Coutre P., Martino B., Pungolino E., Elena C., Bergamaschi M., Assouline S., Di Bona E., Gozzini A., Andrade-Campos M., Stagno F., Iurlo A., Pirola A., Fontana D., Petiti J., Bonanomi M. L., Crivori P., Piazza R., Fava C., and Gambacorti Passerini C.

Abstract

TO THE EDITOR: The Imatinib Suspension and Validation (ISAV) study1 is a multicenter trial of imatinib discontinuation (ID) among patients with chronic myeloid leukemia (CML) in undetectable deep molecular remission (U-DMR). After 12 months of follow-up, 48% of patients relapsed (total n = 107), with the majority of relapses occurring within the first 9 months. An inverse relationship between patient age and risk of relapse was also observed at this timepoint. Here we report the final results of ISAV after a median follow-up of 49 months, as well as the dynamics of leukemic tumor load as determined by digital polymerase chain reaction (dPCR) in nonrelapsed patients. This trial is registered at www.clinicaltrials.gov (NCT01578213). Eligible patients were 18 years and older and had CML, either in chronic or accelerated phase, with U-DMR of at least 18 months’ duration and at least...

Published
2020

7. Increased Tumour Burden over a 36 Month Period in Chronic Myeloid Leukemia Patients Following Imatinib Discontinuation: Role of Digital PCR

Author

Diral, E, Le Coutre, P, Gottardi, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Petiti, J, Stagno, F, Iurlo, A, Kim, D, Pirola, A, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti-Passerini, C, Diral E., Le Coutre P., Gottardi E. M., Elena C., Bergamaschi M., Assouline S., Di Bona E., Petiti J., Stagno F., Iurlo A., Kim D. -W., Pirola A., Bonanomi M. L., Crivori P., Piazza R., Fava C., Gambacorti-Passerini C., Diral, E, Le Coutre, P, Gottardi, E, Elena, C, Bergamaschi, M, Assouline, S, Di Bona, E, Petiti, J, Stagno, F, Iurlo, A, Kim, D, Pirola, A, Bonanomi, M, Crivori, P, Piazza, R, Fava, C, Gambacorti-Passerini, C, Diral E., Le Coutre P., Gottardi E. M., Elena C., Bergamaschi M., Assouline S., Di Bona E., Petiti J., Stagno F., Iurlo A., Kim D. -W., Pirola A., Bonanomi M. L., Crivori P., Piazza R., Fava C., and Gambacorti-Passerini C.

Published
2019

8. VERY LONG-TERM RESULTS OF ALL-TRANS RETINOIC ACID AND ARSENIC TRIOXIDE IN NON-HIGH RISK ACUTE PROMYELOCYTIC LEUKEMIA: LATEST UPDATE OF THE ITALIAN-GERMAN APL0406 RANDOMIZED TRIAL

Author

Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, Lo-Coco F., Cicconi, L, Platzbecker, U, Avvisati, G, Paoloni, F, Thiede, C, Vignetti, M, Fazi, P, Ferrara, F, Divona, M, Albano, F, Efficace, F, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Annibali, O, Wattad, M, Lubbert, M, Brandts, C, Hanel, M, Rollig, C, Schmitz, N, Lin, H, Frairia, C, Fozza, C, Maria D’Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Dohner, K, Ganser, A, Dohner, H, Amadori, S, Mandelli, F, Teresa Voso, M, Ehninger, G, Schlenk, R, Lo-Coco, F, Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts C, Hanel M, Rollig C, Schmitz N, Lin H, Frairia C, Fozza C, Maria D’Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Teresa Voso M, Ehninger G, Schlenk RF, and Lo-Coco F.

Published
2019

11. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: Final results of the randomized Italian-German APL0406 trial

Author

Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F., Platzbecker, U, Avvisati, G, Cicconi, L, Thiede, C, Paoloni, F, Vignetti, M, Ferrara, F, Divona, M, Albano, F, Efficace, F, Fazi, P, Sborgia, M, Di Bona, E, Breccia, M, Borlenghi, E, Cairoli, R, Rambaldi, A, Melillo, L, La Nasa, G, Fiedler, W, Brossart, P, Hertenstein, B, Salih, H, Wattad, M, Lübbert, M, Brandts, C, Hänel, M, Röllig, C, Schmitz, N, Link, H, Frairia, C, Pogliani, E, Fozza, C, D'Arco, A, Di Renzo, N, Cortelezzi, A, Fabbiano, F, Döhner, K, Ganser, A, Döhner, H, Amadori, S, Mandelli, F, Ehninger, G, Schlenk, R, Lo-Coco, F, Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, and Lo-Coco F.

Abstract

Purpose: The initial results of the APL0406 trial showed that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods: The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 109/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results: Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively (P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively (P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion: These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

Published
2017

14. Sustained response to low-dose rituximab in idiopathic autoimmune hemolytic anemia

Author

Barcellini, W, Zaja, Francesco, Zaninoni, A, Imperiali, Fg, Di Bona, E, Fattizzo, B, Consonni, D, Cortelezzi, A, Zanella, A., Barcellini, W, Zaja, Francesco, Zaninoni, A, Imperiali, Fg, Di Bona, E, Fattizzo, B, Consonni, D, Cortelezzi, A, and Zanella, A.

Abstract

ObjectivesTo evaluate the sustained response to low-dose (LD) rituximab in autoimmune hemolytic anemia (AIHA), the ex vivo effect on anti-RBC antibody production by mitogen-stimulated direct antiglobulin test (MS-DAT), and the in vitro dose effect of the drug on the production of anti-RBC antibodies. MethodsThirty two patients, 18 warm (W) AIHA and 14 cold hemagglutinin disease (CHD), were treated with LD rituximab (100mg fixed dose x4 weekly infusions) along with a short course of oral prednisone. Complete clinical examination, blood counts, and hemolytic markers were performed at enrollment and at month 6, 12, 24, and 36. ResultsHematological parameters significantly improved at all time points compared to enrollment. The overall response was 90%, 100%, 100%, and 89% and the relapse-free survival 87%, 79%, 68%, and 68% at 6, 12, 24, and 36months, respectively. Response rates were slightly better in WAIHA than in CHD, and relapse risk was greater in cold than warm forms (HR 2.1, 95% CI 0.6-7.9). Four patients were retreated (one patient twice), all achieving a response, lasting a median of 18months (range 9-30). Treatment was well tolerated without adverse events or infections. Anti-RBC antibody production by MS-DAT significantly decreased over time. In vitro studies showed that rituximab effectively inhibited anti-RBC antibody production at 50g/mL, 1/6 of the drug concentration after therapy with standard doses. ConclusionsThese data confirm that LD rituximab treatment is effective and induces sustained responses in AIHA, and that a lower dose of the drug is enough to down-regulate autoantibody production.

Published
2013

15. Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib

Author

Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., on behalf of the GIMEMA CML Working Party (Lucarelli, G., Polimeno, G., Ladetto, M., Pini, M., Rupoli, S., Scortechini, A. R., Galieni, P., Bigazzi, C., Cantore, N., Palmieri, F., Specchia, G., Russo, Rossi., Rambaldi, A., Ferrari, M. L., Palandri, F., Luatti, S., Iacobucci, I., Bochicchio, M. T., Apolinari, M., Fogli, M., Cervello, I., Capucci, A., Giuliani, G., Malpignano, A., Girasoli, M., Angelucci, E., Usala, E., De Biasi, E., Tagariello, G., Sartori, R., Di Raimondo, F., Vigneri, P., Molica, S., Lentini, M., Lanza, F., Viganò, C., Grasso, M., Rapezzi, D., Cuneo, A., Ciccone, M., Bosi, A., Gozzini, A., Gobbi, M., Pierri, I., Chianese, R., De Blasio, A., Ciccone, F., Capochiani, E., Pelosini, M., Musolino, C., Russo, S., Cortelezzi, A., Luppi, M., Marasca, R., Pogliani, E. M., Gambacorti-Passerini, C., Luciano, L., Izzo, B., Ferrara, F., Annunziata, M., Mettivier, V., Sessa, U., Latte, G., Noli, D., Rege-Cambrin, G., Fava, C., Semenzato, G., Binotto, G., Fabbiano, F., Turri, D., Siragusa, S., Caracciolo, C., Musso, M., Porretto, F., Cazzola, M., Orlandi, E., Falini, B., Falzetti, F., Visani, G., Isidor, I., Di Bartolomeo, P., Di Lorenzo, R., Vallisa, D., Trabacch, I., Pizzuti, M., Zuffa, E., Salvucci, M., Ronco, F., Lelo, D., Merli, F., Avanzini, P., Tosi, P., Merli, A., Sica, S., Sorà, F., Latagliata, R., De Fabritiis, P., Trawiska, M., Amadori, S., Cantonetti, M., Majolino, I., Pacilli, L., Ronci, B., Cedrone, M., Mengarelli, A., Romano, A., Tafuri, A., Montefusc, O., Iuliano, F., Infusino, S., Dore, F., Fozza, C., Bocchia, M., Defina, M., Liberati, Am., Luzi, D., Boccadoro, M., Ferrero, D., Vitolo, U., Nicolosi, M., Gottardi, M., Calistri, E., Fanin, R., Tiribelli, M., Pizzolo, G., Bonifacio, M., Rodeghiero, F., Di Bona, E. )., Castagnetti, F, Gugliotta, G., Breccia, M., Stagno, F., Iurlo, A., Albano, F., Abruzzese, E., Martino, B., Levato, L., Intermesoli, T., Pregno, P., Rossi, G., Gherlinzoni, F., Leoni, P., Cavazzini, F., Venturi, C., Soverini, S., Testoni, N., Alimena, G., Cavo, M., Martinelli, G., Pane, F., Saglio, G., Rosti, G., Baccarani, M., and on behalf of the GIMEMA CML Working Party [, Palandri F.], Pane, Fabrizio, Gugliotta, G, Breccia, M, Stagno, F, Iurlo, A, Albano, F, Abruzzese, E, Martino, B, Levato, L, Intermesoli, T, Pregno, P, Rossi, G, Gherlinzoni, F, Leoni, P, Cavazzini, F, Venturi, C, Soverini, S, Testoni, N, Alimena, G, Cavo, M, Martinelli, G, Pane, F, Saglio, G, Rosti, G, Baccarani, M, and GAMBACORTI PASSERINI, C

Subjects
DIAGNOSED CHRONIC-PHASE, Oncology, Male, Cancer Research, Time Factors, bcr-abl, Fusion Proteins, bcr-abl, Antineoplastic Agent, Hematology, Anesthesiology and Pain Medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Cumulative incidence, Young adult, Chronic, Aged, 80 and over, Leukemia, PATIENTS RECEIVING IMATINIB, CHRONIC MYELOGENOUS LEUKEMIA, TYROSINE KINASE INHIBITORS, BCR-ABL1 TRANSCRIPT LEVELS, EARLY MOLECULAR RESPONSE, CML WORKING PARTY, 3-YEAR FOLLOW-UP, EUROPEAN LEUKEMIANET, 400 MG, Myeloid leukemia, Middle Aged, Prognosis, Treatment Outcome, Retreatment, Imatinib Mesylate, Female, Tyrosine kinase, Human, medicine.drug, Adult, medicine.medical_specialty, Time Factor, Adolescent, Prognosi, Protein Kinase Inhibitor, Socio-culturale, Antineoplastic Agents, Treatment results, Follow-Up Studie, Young Adult, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal medicine, medicine, Humans, Protein Kinase Inhibitors, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Fusion Proteins, Imatinib, Follow-Up Studies, Surgery, Imatinib mesylate, BCR-ABL Positive, business, Myelogenous
Abstract

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (⩽10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients.

Published
2015

16. PML-RAR alpha kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy

Author

Cicconi, L, Divona, M, Ciardi, C, Ottone, T, Ferrantini, A, Lavorgna, S, Alfonso, V, Paoloni, F, Piciocchi, A, Avvisati, G, Ferrara, F, Di Bona, E, Albano, F, Breccia, M, Cerqui, E, Sborgia, M, Kropp, Mg, Santoro, A, Levis, A, Sica, Simona, Amadori, S, Voso, Mt, Mandelli, F, Lo-Coco, F, Sica, S (ORCID:0000-0003-2426-3465), Cicconi, L, Divona, M, Ciardi, C, Ottone, T, Ferrantini, A, Lavorgna, S, Alfonso, V, Paoloni, F, Piciocchi, A, Avvisati, G, Ferrara, F, Di Bona, E, Albano, F, Breccia, M, Cerqui, E, Sborgia, M, Kropp, Mg, Santoro, A, Levis, A, Sica, Simona, Amadori, S, Voso, Mt, Mandelli, F, Lo-Coco, F, and Sica, S (ORCID:0000-0003-2426-3465)

Abstract

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-alpha (PML-RAR alpha) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARa transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P = 0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RAR alpha transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P = 0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

Published
2016

17. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation

Author

Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, Morra, E, Trojani A, Ripamonti CB, Penco S, Beghini A, Nadali G, Di Bona E, Viola A, Castagnola C, Colapietro P, Grillo G, Pezzetti L, Ravelli E, Patrosso MC, Marocchi A, Cuneo A, Ferrara F, Lazzarino M, Pizzolo G, Cairoli R, Morra E., Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, Morra, E, Trojani A, Ripamonti CB, Penco S, Beghini A, Nadali G, Di Bona E, Viola A, Castagnola C, Colapietro P, Grillo G, Pezzetti L, Ravelli E, Patrosso MC, Marocchi A, Cuneo A, Ferrara F, Lazzarino M, Pizzolo G, Cairoli R, and Morra E.

Abstract

Background: Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. Patients and Methods: In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. Results: Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. Conclusion: These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.

Published
2008

18. Improved Clinical Outcome of Adult Patients with Ph plus ALL After a Combined Imatinib-Chemotherapy Induction/Consolidation Program Followed by Allogeneic Hematopoietic Stem Cell Transplantation: Results From a Prospective Study of the Northern Italy Leukemia Group

Author

Rambaldi A, Spinelli O, Oldani E, Grassi A, Rossi G, Pogliani EM, Di Bona E, Angelucci E, Cavattoni I, Lambertenghi Deliliers G, Mannelli F, Levis A, Mattei D, Borlenghi E, Terruzzi E, Borghero C, Romani C, Tosi M, Bussini A, Intermesoli T, Bassan R., CICERI , FABIO, Rambaldi, A, Spinelli, O, Oldani, E, Grassi, A, Rossi, G, Pogliani, Em, Di Bona, E, Angelucci, E, Cavattoni, I, Lambertenghi Deliliers, G, Mannelli, F, Levis, A, Ciceri, Fabio, Mattei, D, Borlenghi, E, Terruzzi, E, Borghero, C, Romani, C, Tosi, M, Bussini, A, Intermesoli, T, and Bassan, R.

Published
2010

20. Minimal residual disease (MRD)-oriented therapy of adult, acute lymphoblastic leukemia (ALL): Final results of northern Italy leukemia group study 09/00

Author

Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Peruta B, Guerini V, Rossi G, Pogliani E, Di Bona E, Fabris P, Cortelezzi A, Chisesi T, Angelucci E, Leoni F, Mattei D, Barbui T, Rambaldi A., CICERI , FABIO, Bassan, R, Spinelli, O, Oldani, E, Intermesoli, T, Tosi, M, Peruta, B, Guerini, V, Rossi, G, Pogliani, E, Di Bona, E, Fabris, P, Cortelezzi, A, Chisesi, T, Angelucci, E, Leoni, F, Ciceri, Fabio, Mattei, D, Barbui, T, and Rambaldi, A.

Published
2007

21. Minimal residual disease (MRD) and risk-oriented therapy in adult acute lymphoblastic leukemia (ALL)

Author

Bassan R, Spinelli O, Oldani E, Intermesoli T, Tosi M, Giuseppe R, Pogliani EM, Angelucci E, Fabris P, Lambertenghi Deliliers G, Polistena P, Di Bona E, Leoni F, Minotto C, Mattei D, Musso M, Barbui T, Rambaldi A., CICERI , FABIO, Bassan, R, Spinelli, O, Oldani, E, Intermesoli, T, Tosi, M, Giuseppe, R, Pogliani, Em, Angelucci, E, Fabris, P, Lambertenghi Deliliers, G, Polistena, P, Di Bona, E, Ciceri, Fabio, Leoni, F, Minotto, C, Mattei, D, Musso, M, Barbui, T, and Rambaldi, A.

Published
2005

22. Nonrelapse-related mortality (NRM) among 1,201 adult patients with acute leukemia treated over a 23 year period

Author

Oldani E, Di Bona E, Rossi G, Pogliani EM, Fabris P, Sancetta R, Minotto C, Morandi S, Cortelezzi A, Gallamini A, Gallo E, Angelucci E, Musso M, Barbui T, Bassan R., CICERI , FABIO, Oldani, E, Di Bona, E, Rossi, G, Pogliani, Em, Fabris, P, Sancetta, R, Minotto, C, Morandi, S, Cortelezzi, A, Ciceri, Fabio, Gallamini, A, Gallo, E, Angelucci, E, Musso, M, Barbui, T, and Bassan, R.

Published
2003

23. SIMILAR BUT NOT THE SAME: CHROMOSOMAL ABNORMALITIES T(8;21)(Q22;Q22) AND INV(16)(P13;Q22)/T(16;16)(P13;Q22) IDENTIFY SUBTYPES OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA CHARACTERIZED BY DIFFERENT SURVIVAL AND PROGNOS- TIC FACTORS

Author

Mosna, Federico, Gottardi M, 1, Papayannidis C, 1, Di Bona E, 2, Tecchio, Cristina, Can doni A, 4, Forghieri F, 5, Galieni P, 6, Visani G, 7, Zambello R, 8, Volpato F, 9, Martinelli G, 1, and Gherlinzoni F, 2

Subjects
CORE BINDING FACTOR, ACUTE MYELOID LEUKEMIA
Published
2013

24. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance

Author

Avvisati, G, Lo Coco, F, Paoloni, Fp, Petti, Mc, Diverio, D, Vignetti, M, Latagliata, R, Specchia, G, Baccarani, M, Di Bona, E, Fioritoni, G, Marmont, F, Rambaldi, A, DI RAIMONDO, Francesco, Kropp, Mg, Pizzolo, G, Pogliani, Em, Rossi, G, Cantore, N, Nobile, F, Gabbas, A, Ferrara, F, Fazi, P, Amadori, S, Mandelli, F, Gimema, Aieop, and EORTC Cooperative Groups

Published
2011

25. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group

Author

LO COCO, F, Avvisati, G, Vignetti, M, Breccia, M, Gallo, E, Rambaldi, A, Paoloni, F, Fioritoni, G, Ferrara, F, Specchia, G, Cimino, G, Diverio, D, Borlenghi, E, Martinelli, G, DI RAIMONDO, Francesco, DI BONA, E, Fazi, P, Peta, A, Bosi, A, Carella, Am, Fabbiano, F, Pogliani, Em, Petti, Mc, Amadori, S, Mandelli, F, and ITALIAN GIMEMA COOPERATIVE GROUP

Published
2010

26. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes

Author

Efficace, F, Mandelli, F, Avvisati, G, Cottone, F, Ferrara, F, Di Bona, E, Specchia, G, Breccia, M, Levis, A, Sica, Simona, Finizio, O, Kropp, Mg, Fioritoni, G, Cerqui, E, Vignetti, M, Amadori, S, Schlenk, Rf, Platzbecker, U, Lo Coco, F., Sica, Simona (ORCID:0000-0003-2426-3465), Efficace, F, Mandelli, F, Avvisati, G, Cottone, F, Ferrara, F, Di Bona, E, Specchia, G, Breccia, M, Levis, A, Sica, Simona, Finizio, O, Kropp, Mg, Fioritoni, G, Cerqui, E, Vignetti, M, Amadori, S, Schlenk, Rf, Platzbecker, U, Lo Coco, F., and Sica, Simona (ORCID:0000-0003-2426-3465)

Abstract

A randomized clinical trial compared efficacy and toxicity of standard all-trans-retinoic acid (ATRA) plus chemotherapy versus ATRA plus arsenic trioxide in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL). Here, we report health-related quality-of-life (HRQOL) results.

Published
2014

27. Different molecular levels of post-induction minimal residual disease may predict hematopoietic stem cell transplantation outcome in adult Philadelphia-negative acute lymphoblastic leukemia

Author

Bassan, R, primary, Spinelli, O, additional, Oldani, E, additional, Intermesoli, T, additional, Tosi, M, additional, Peruta, B, additional, Borlenghi, E, additional, Pogliani, E M, additional, Di Bona, E, additional, Cassibba, V, additional, Scattolin, A M, additional, Romani, C, additional, Ciceri, F, additional, Cortelezzi, A, additional, Gianfaldoni, G, additional, Mattei, D, additional, Audisio, E, additional, and Rambaldi, A, additional

Published
2014
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28. The Italian Way of Treating Acute Promyelocytic Leukemia (APL), Final Act

Author

Avvisati, G., Petti, M. C., LO COCO, F., Testi, A. M., Fazi, P., Specchia, G., Malagola, M., DI BONA, E., Recchia, A., Marmont, F., Buelli, M., Lazzarino, M., DI RAIMONDO, Francesco, Leoni, F., Kropp, M. G., Veneri, D., Micolis, I., Rossi, G., Venditti, A., and Mandelli, F.

Published
2003

30. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

Author

Pagano, L, Valentini, C, Pulsoni, A, Fisogni, S, Carluccio, P, Mannelli, F, Lunghi, M, Pica, G, Onida, F, Cattaneo, C, Piccaluga, P, Di Bona, E, Todisco, E, Musto, P, Spadea, A, D'Arco, A, Pileri, S, Leone, G, Amadori, S, Facchetti, F, Berti, E, BERTI, EMILIO, Pagano, L, Valentini, C, Pulsoni, A, Fisogni, S, Carluccio, P, Mannelli, F, Lunghi, M, Pica, G, Onida, F, Cattaneo, C, Piccaluga, P, Di Bona, E, Todisco, E, Musto, P, Spadea, A, D'Arco, A, Pileri, S, Leone, G, Amadori, S, Facchetti, F, Berti, E, and BERTI, EMILIO

Abstract

The objective of this study was to evaluate the clinical features, prognostic factors, and efficacy of treatments in patients with blastic plasmacytoid dendritic cell neoplasm with a leukemic presentation at onset of the disease. In order to do this, a retrospective multicenter study was performed from 2005-2011 in 28 Italian hematology divisions in which 43 cases were collected. Forty-one patients received an induction therapy, consisting of an acute myeloid leukemia-type regimen in 26 patients (60%) and acute lymphoid leukemia/lymphoma-type regimen in 15 patients (35%). Six patients (14%) underwent allogeneic hematopoietic stem cell transplantation. Seventeen patients (41%) achieved a complete remission: seven after acute myeloid leukemia-type treatment and 10 after an acute lymphoid leukemia/lymphoma-type regimen, with a significant advantage for acute lymphoid leukemia/lymphoma-type chemotherapy (P=0.02). Relapse occurred in six of the 17 patients (35%) who achieved complete remission, more frequently after acute lymphoid leukemia/lymphoma-type chemotherapy. The median overall survival was 8.7 months (range, 0.2-32.9). The patients treated with an acute myeloid leukemia-type regimen had an overall survival of 7.1 months (range, 0.2-19.5), whereas that of the patients receiving acute lymphoid leukemia/lymphoma-type chemotherapy was 12.3 months (range, 1-32.9) (P=0.02). The median overall survival of the allogeneic hematopoietic stem cell transplant recipients was 22.7 months (range, 12-32.9), and these patients had a significant survival advantage compared to the non-transplanted patients (median 7.1 months, 0.2-21.3; P=0.03). In conclusion, blastic plasmacytoid dendritic cell neoplasm with bone-marrow involvement is an aggressive subtype of high-risk acute leukemia. The rarity of this disease does not enable prospective clinical trials to identify the better therapeutic strategy, which, at present, is based on clinicians' experience.

Published
2013

31. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia

Author

Lo Coco, F, Avvisati, G, Vignetti, M, Thiede, C, Orlando, Sm, Iacobelli, S, Ferrara, F, Fazi, P, Cicconi, L, Di Bona, E, Specchia, G, Sica, Simona, Divona, M, Levis, A, Fiedler, W, Cerqui, E, Breccia, M, Fioritoni, G, Salih, Hr, Cazzola, M, Melillo, L, Carella, Am, Brandts, Ch, Morra, E, Von Lilienfeld Toal, M, Hertenstein, B, Wattad, M, Lübbert, M, Hänel, M, Schmitz, N, Link, H, Kropp, Mg, Rambaldi, A, La Nasa, G, Luppi, M, Ciceri, F, Finizio, O, Venditti, A, Fabbiano, F, Döhner, K, Sauer, M, Ganser, A, Amadori, S, Mandelli, F, Döhner, H, Ehninger, G, Schlenk, Rf, Platzbecker, U., Sica, Simona (ORCID:0000-0003-2426-3465), Lo Coco, F, Avvisati, G, Vignetti, M, Thiede, C, Orlando, Sm, Iacobelli, S, Ferrara, F, Fazi, P, Cicconi, L, Di Bona, E, Specchia, G, Sica, Simona, Divona, M, Levis, A, Fiedler, W, Cerqui, E, Breccia, M, Fioritoni, G, Salih, Hr, Cazzola, M, Melillo, L, Carella, Am, Brandts, Ch, Morra, E, Von Lilienfeld Toal, M, Hertenstein, B, Wattad, M, Lübbert, M, Hänel, M, Schmitz, N, Link, H, Kropp, Mg, Rambaldi, A, La Nasa, G, Luppi, M, Ciceri, F, Finizio, O, Venditti, A, Fabbiano, F, Döhner, K, Sauer, M, Ganser, A, Amadori, S, Mandelli, F, Döhner, H, Ehninger, G, Schlenk, Rf, Platzbecker, U., and Sica, Simona (ORCID:0000-0003-2426-3465)

Abstract

All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity.

Published
2013

32. Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: an Italian multicenter study

Author

Pagano, Livio, Valentini, Chiara, Pulsoni, A, Fisogni, S, Carluccio, P, Mannelli, F, Lunghi, M, Pica, G, Onida, F, Cattaneo, C, Piccaluga, Pp, Di Bona, E, Todisco, E, Musto, P, Spadea, A, D'Arco, A, Pileri, S, Leone, Giuseppe, Amadori, S, Facchetti, F., Pagano, Livio (ORCID:0000-0001-8287-928X), Pagano, Livio, Valentini, Chiara, Pulsoni, A, Fisogni, S, Carluccio, P, Mannelli, F, Lunghi, M, Pica, G, Onida, F, Cattaneo, C, Piccaluga, Pp, Di Bona, E, Todisco, E, Musto, P, Spadea, A, D'Arco, A, Pileri, S, Leone, Giuseppe, Amadori, S, Facchetti, F., and Pagano, Livio (ORCID:0000-0001-8287-928X)

Abstract

Purpose: To evaluate the clinical features, the prognostic factors, and the efficacy of treatments in patients (pts) with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) with leukemic presentation. Methods: A retrospective multicenter study was carried out during the period 2005-2011 in 28 Italian hematology divisions among GIMEMA centres. Results: A total of 43 cases were collected (M/F 31/12; median age 68 yo).At diagnosis the median bone-marrow infiltration was 73%; 33 pts (77%) had peculiar skin lesions; lymph nodes and/or spleen involvements were documented in 24 (56%), and extramedullary disease in 9 (21%). In 28 pts (65%) cytogenetic study was performed, revealing an unfavourable karyotype in 12. Forty-one pts received an induction therapy (2 died early), consisting of AML-type regimen in 26 (60%), and ALL/lymphoma-type in 15 (35%); 6 pts (14%) underwent allo-HSCT. Complete remission (CR) was achieved in 17 pts (41%), registering 7 CR after AML-type and 10 after ALL/lymphoma-type regimen, with a significant advantage for ALL/lymphoma-type chemotherapy (p=0.02). The median OS was 8.7 months (range 0.2-32.9):7.1 months (range 0.2-19.5) and 12.3 months (range 1-32.9) in pts received AML-type and ALL/lymphoma-type regimen, respectively (p=0.02). In HSCT-pts the median OS was 22.7 months (range 12-32.9), with a significant advantage with respect to the non-transplanted (median 7.1 months, range 0.2-21.3, p=0.03). Conclusions: BPDCN with bone-marrow involvement is an aggressive subtype of high-risk acute leukemia.With intensive therapy according to ALL/lymphoma-type induction the rate of CR increases. Allo-HSCT performed in first remission may lead to long-term survival in selected cases, but more data are needed.

Published
2012

33. Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia

Author

DI BONA, E., Avvisati, G., Castaman, G., Vegna, Ml, DE SANCTIS, Vitaliana, Rodeghiero, F., and Mandelli, Franco

Subjects
Adult, Male, Time Factors, Adolescent, Antineoplastic Agents, Hemorrhage, Tretinoin, Leukemia, Promyelocytic, Acute, Humans, Prospective Studies, Child, Aged, Antibiotics, Antineoplastic, Platelet Count, Incidence, Remission Induction, Fibrinogen, Infant, Middle Aged, Italy, Evaluation Studies as Topic, Child, Preschool, Multivariate Analysis, Drug Therapy, Combination, Female, Morbidity, Idarubicin
Abstract

A total of 622 consecutive patients with acute promyelocytic leukaemia (APL) treated within the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group during 1989-97 have been reviewed to assess the clinical effectiveness of all-trans retinoic acid (ATRA) on the incidence of early haemorrhagic deaths and on APL-associated coagulopathy. Of them, 499 were treated with idarubicin plus ATRA (study A) and 123 with Idarubicin alone (study B). In both studies, similar guidelines for supportive treatment were used. Haemorrhagic symptoms were evaluated according to a reproducible score system. Deaths occurring within 10 d of starting treatment were 19 (3.8%) in study A and nine (7.3%) in study B (P = 0.09), with 15 (3%) and five (4.1%) (P not significant) due to haemorrhage. Overall, induction mortality was 7.6% and 16.2% respectively (P0.003). In study A, days with platelet counts/= 20 x 109/l or with fibrinogen/= 1 g/L were reduced by about 30%, the haemorrhagic score by 50% and the consumption of blood products by about 40%, and fewer patients were treated with antihaemorrhagic drugs (39% vs. 61%; P0.001). On multivariate analysis, early deaths were influenced by blast count at diagnosis30 x 109/l (P0.001) in both studies, and by a haemorrhagic score of 3 in study A (P0.001). Although the reduction of early fatal haemorrhages was not significant, a substantial clinical improvement was evident in terms of reduction of the severity of bleeding symptoms, blood product consumption and overall induction mortality when ATRA was combined with idarubicin.

Published
2000

35. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00

Author

Bassan, R, Rossi, G, Pogliani, E, Di Bona, E, Angelucci, E, Cavattoni, I, Lambertenghi Deliliers, G, Mannelli, F, Levis, A, Ciceri, F, Mattei, D, Borlenghi, E, Terruzzi, E, Borghero, C, Romani, C, Spinelli, O, Tosi, M, Oldani, E, Intermesoli, T, Rambaldi, A, POGLIANI, ENRICO MARIA, Rambaldi, A., Bassan, R, Rossi, G, Pogliani, E, Di Bona, E, Angelucci, E, Cavattoni, I, Lambertenghi Deliliers, G, Mannelli, F, Levis, A, Ciceri, F, Mattei, D, Borlenghi, E, Terruzzi, E, Borghero, C, Romani, C, Spinelli, O, Tosi, M, Oldani, E, Intermesoli, T, Rambaldi, A, POGLIANI, ENRICO MARIA, and Rambaldi, A.

Abstract

Purpose: Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. Patients and Methods: Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. Results: CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. Conclusion: This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure. © 2010 by American Society of Clinical Oncology.

Published
2010

36. Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL)

Author

Bassan, R, Spinelli, O, Oldani, E, Intermesoli, T, Tosi, M, Peruta, B, Rossi, G, Borlenghi, E, Pogliani, E, Terruzzi, E, Fabris, P, Cassibba, V, Lambertenghi Deliliers, G, Cortelezzi, A, Bosi, A, Gianfaldoni, G, Ciceri, F, Bernardi, M, Gallamini, A, Mattei, D, Di Bona, E, Romani, C, Scattolin, A, Barbui, T, Rambaldi, A, POGLIANI, ENRICO MARIA, Scattolin, AM, Rambaldi, A., Bassan, R, Spinelli, O, Oldani, E, Intermesoli, T, Tosi, M, Peruta, B, Rossi, G, Borlenghi, E, Pogliani, E, Terruzzi, E, Fabris, P, Cassibba, V, Lambertenghi Deliliers, G, Cortelezzi, A, Bosi, A, Gianfaldoni, G, Ciceri, F, Bernardi, M, Gallamini, A, Mattei, D, Di Bona, E, Romani, C, Scattolin, A, Barbui, T, Rambaldi, A, POGLIANI, ENRICO MARIA, Scattolin, AM, and Rambaldi, A.

Abstract

Clinical risk classification is inaccurate in predicting relapse in adult patients with acute lymphoblastic leukemia, sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation (SCT). We studied minimal residual disease (MRD) as a predictive factor for recurrence and as a decisional tool for postconsolidation maintenance (in MRD(neg)) or SCT (in MRD(pos)). MRD was tested at weeks 10, 16, and 22 using real-time quantitative polymerase chain reaction with 1 or more sensitive probes. Only patients with t(9;22) or t(4;11) were immediately eligible for allogeneic SCT. Of 280 registered patients (236 in remission), 34 underwent an early SCT, 60 suffered from relapse or severe toxicity, and 142 were evaluable for MRD at the end of consolidation. Of these, 58 were MRD(neg), 54 MRD(pos), and 30 were not assessable. Five-year overall survival/disease-free survival rates were 0.75/0.72 in the MRD(neg) group compared with 0.33/0.14 in MRD(pos) (P = .001), regardless of the clinical risk class. MRD was the most significant risk factor for relapse (hazard ratio, 5.22). MRD results at weeks 16 to 22 correlated strongly with the earlier time point (P = .001) using a level of 10(-4) or higher to define persistent disease. MRD analysis during early postremission therapy improves risk definitions and bolsters risk-oriented strategies. ClinicalTrials.gov identifier: NCT00358072

Published
2009

37. Acute promyelocytic leukaemia: epidemiology and risk factors. A report of the GIMEMA Italian archive of adult acute leukaemia. GIMEMA Cooperative Group

Author

Pulsoni, Alessandro, Stazi, A., Cotichini, R., Allione, B., Cerri, R., Di Bona, E., Nosari, A. M., Pagano, L., Recchia, A., Ribersani, M., Rocchi, L., Veneri, D., Visani, G., Mandelli, Franco, and Mele, A.

Subjects
Adult, Male, Adolescent, Italy, Leukemia, Promyelocytic, Acute, Risk Factors, Age Factors, Humans, Female, Middle Aged, Aged
Abstract

Acute promyelocytic leukaemia (APL) exhibits peculiar epidemiological, clinical, cytogenetic and molecular features, compared to the other acute myeloid leukaemias (AML). Data on epidemiology and occupational risk factors for APL desumed from the GIMEMA archive are reported and compared with those of the other AML. An exploratory case-case study was designed on AML patients from 56 haematology centres in Italy. Overall, 4296 patients older than 15 yr with a new diagnosis of acute leukaemia were recorded between July 1992 and July 1997. Of these, 335 were classified as APL, and 2894 as other AML. The median age of APL patients was 43 compared to 59 yr for the other AML (p0.00001). In order to identify peculiar risk factors for APL development, different parameters were compared in the 2 groups. After adjusting by age no significant differences were observed with regard to education, lifetime prevalence of cancer among siblings and previous diseases in the patient's history. Occupational exposure as a possible risk factor for APL showed no increased risk compared to other AML among farmers, builders and leather workers. A significant association was found in electricians (OR=4.4, 95% CI=2.0-9.7) and a weak association was found in wood workers (OR=3.2, 95% CI=0.8-10.8). The proportion of APL with respect to other AML was significantly higher in the north east of Italy compared to the rest of the country (OR=1.7, 95% CI=1.3-2.2). These data confirm the younger age of APL patients compared to the other AML. A possible role of electromagnetic fields is suggested by the higher risk of APL in electrical workers and in the more industrialized areas of the country.

Published
1998

38. IMPACT OF KIT MUTATIONS IN ACUTE MYELOID LEUKAEMIA WITH INV(16)

Author

Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Bertani, G, Ravelli, E, Nador, G, Castagnola, C, Cattaneo, C, Ottaviani, E, Pioltelli, P, Viola, A, Cuneo, A, Ferrara, F, Martinelli, G, Lazzarino, M, Rossi, G, Pizzolo, G, Morra, E, Ripamonti, CB, Bertani, GB, Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Bertani, G, Ravelli, E, Nador, G, Castagnola, C, Cattaneo, C, Ottaviani, E, Pioltelli, P, Viola, A, Cuneo, A, Ferrara, F, Martinelli, G, Lazzarino, M, Rossi, G, Pizzolo, G, Morra, E, Ripamonti, CB, and Bertani, GB

Published
2008

39. High cure rates in Burkitt lymphoma and leukemia: a Northern Italy Leukemia Group study of the German short intensive rituximab-chemotherapy program

Author

Intermesoli, T., primary, Rambaldi, A., additional, Rossi, G., additional, Delaini, F., additional, Romani, C., additional, Pogliani, E. M., additional, Pagani, C., additional, Angelucci, E., additional, Terruzzi, E., additional, Levis, A., additional, Cassibba, V., additional, Mattei, D., additional, Gianfaldoni, G., additional, Scattolin, A. M., additional, Di Bona, E., additional, Oldani, E., additional, Parolini, M., additional, Gokbuget, N., additional, and Bassan, R., additional

Published
2013
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40. Prevalence and prognostic impact of KIT mutations in acute myeloid leukaemia with inv(16). A retrospective study

Author

Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Bertani, G, Ravelli, E, Cuneo, A, Ottaviani, E, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, Morra, E, Ripamonti, CB, Martinelli, GN, Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Bertani, G, Ravelli, E, Cuneo, A, Ottaviani, E, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, Morra, E, Ripamonti, CB, and Martinelli, GN

Abstract

Introduction Several studies have recently pointed out the adverse impact of KIT mutations (mutKIT) on relapse incidence (RI) and overall survival (OS) in AML pts with t(8;21). By contrast, the prognostic significance of mutKIT in pts with inv(16) remains unclear. Purpose of this study is to evaluate the prevalence and the prognostic impact of mutKIT in inv(16)(p13q22). Patients and Methods Fifty adults with inv(16) AML at diagnosis (median age 46.6 yrs, range: 17–88; M/F: 30 /20), were centrally analyzed for mutKIT in exon 2, 8, 10, 11 and 17. Mutations were detected using sequencing and other sensitive assays such as ARMS (amplification refractory mutation system) PCR for D816Y and D816H and enzymatic digestion with HINFI for D816V and with Tsp509I for N822K. Results Data showed a prevalence of KIT mutation of 34% (17/50 pts). Among the mutKIT cases, we detected mutations in exon 17 (n=12), exon 8 (n= 4) and exon 10 (n=1). There was no difference between the mutKIT vs the unmutated (KIT-) patients in the median of WBC count at presentation (WBC 13.9 x109/L, range 4.4 to 277.5 vs 19.4 x109/L, range 2.5 to 130; Mann-Whitney U test: p = 0.649). Of the 42 patients (age < 60 years) who received intensive chemotherapy, 13 resulted mutKIT upon mutational screening. Complete remission (CR) was achieved in 13/13 (100%) mutKIT vs 27/29 (93%) KIT- patients (Fisher’s exact test: p > 0.999). At a median follow-up of 26 months (range: 2–144), 9/13 (69%) mutKIT and 8/27 (29%)KIT- pts relapsed;the Kaplan-Meier plots revealed KIT mutations to be a significant factor adversely affecting RI (log-rank test: p = 0.017) but not OS (61% in mutKIT vs 75% in KIT-;log-rank test: p = 0.331). Conclusion KIT mutations are associated with a greater probability of relapse following CR, without affecting OS, in AML pts with inv(16) aged <60 years.

Published
2007

41. Prevalence and prognostic impact of KIT mutations in acute myeloid leukaemia with INV(16)

Author

Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Ravelli, E, Nador, G, Cuneo, A, Castagnola, C, Viola, A, Ottaviani, E, Colarossi, S, Cattaneo, C, Parma, M, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, Morra, E, Ripamonti, CB, Cairoli, R, Beghini, A, Ripamonti, C, Grillo, G, Nadali, G, Di Bona, E, Colapietro, P, Nichelatti, M, Ravelli, E, Nador, G, Cuneo, A, Castagnola, C, Viola, A, Ottaviani, E, Colarossi, S, Cattaneo, C, Parma, M, Pioltelli, P, Ferrara, F, Lazzarino, M, Rossi, G, Rodeghiero, F, Pizzolo, G, Martinelli, G, Morra, E, and Ripamonti, CB

Published
2007

42. Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients

Author

Di Bona, E, Pogliani, E, Rossi, G, Lerede, T, D'Emilio, A, Vespignani, M, Rodeghiero, F, Barbui, T, Bassan, R, Bassan, R., POGLIANI, ENRICO MARIA, Di Bona, E, Pogliani, E, Rossi, G, Lerede, T, D'Emilio, A, Vespignani, M, Rodeghiero, F, Barbui, T, Bassan, R, Bassan, R., and POGLIANI, ENRICO MARIA

Abstract

Idarubicin-based induction programs in acute lymphoblastic leukemia (ALL) account for 75?-?85% of complete remission rate. A small amount of patients exhibit primary refractoriness, and approximately 60% of those achieving a remission eventually relapse. The present study aimed to review the outcome of patients relapsing after or resistant to an idarubicin-based, induction-consolidation regimen (with/without additional high dose cytarabine). The 'ABC' phase II trial consisted of mitoxantrone (50 mg/m(2) over 5 days) associated with high-dose methotrexate (1.5 g/m(2) over 24 h, followed by folinic acid rescue), high-dose methyl-prednisolone (125 mg b.i.d.) and vincristine, plus granulocyte colony-stimulating factor. Eligible patients were treated with two courses ('A' and 'B', the latter with reduced drug dosages), followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT, 'C'). Thirty-six patients (3 primary resistant, 33 at first marrow relapse) were evaluated. With 'A', 21 achieved a complete remission (CR), 10 were refractory and 5 died early. Eighteen patients received 'B' (with one more CR, for an overall CR rate of 61%) and, eventually, 12 patients had 'C' procedures (7 autologous, 5 allogeneic HSCT). WHO grade >or=3 treatment-related toxicity developed in 50% and 34% of 'A' and 'B' courses, respectively. The median duration of CR was 5.2 (range 0.5-19.7) months and median overall survival was 7.6 (range 0.5-20) months. In spite of 12 HSCTs, there was no long-term survivor. 'ABC' salvage proved feasible and comparable to reported rescue chemotherapic regimens, but the achievement of cure in refractory/relapsing ALL remains an outstanding clinical task.

Published
2005

43. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia

Author

Lo Coco, F, Cimino, G, Breccia, M, Noguera, N, Diverio, D, Finolezzi, E, Pogliani, E, Di Bona, E, Micalizzi, C, Kropp, M, Venditti, A, Tafuri, A, Mandelli, F, Noguera, NI, Mandelli, F., POGLIANI, ENRICO MARIA, Lo Coco, F, Cimino, G, Breccia, M, Noguera, N, Diverio, D, Finolezzi, E, Pogliani, E, Di Bona, E, Micalizzi, C, Kropp, M, Venditti, A, Tafuri, A, Mandelli, F, Noguera, NI, Mandelli, F., and POGLIANI, ENRICO MARIA

Abstract

The anti-CD33 antibody calicheamicinconjugate gemtuzumab ozogamicin (GO) was used to treat 16 patients with acute promyelocytic leukemia (APL) who had relapsed at the molecular level. Of these patients, 8 were experiencing a first, 5 a second, 2 a third, and 1 a fourth relapse. GO was administered at 6 mg/m2 for 2 doses, and patients achieving a new molecular remission (MR) (ie, negativity of the reverse transcriptase-polymerase chain reaction [RT-PCR] test for PML/RARalpha) received a third dose. MR was obtained in 9 (91%) of 11 patients tested after 2 doses and in 13 (100%) of 13 patients tested after the third dose. Of the 3 remaining patients, 1 achieved MR after one GO administration and received no further therapy owing to hepatic toxicity, and 2 showed disease progression during treatment. Quantitative RT-PCR studies showed that responding patients experienced a dramatic decline (at least 2 logs) of the PML/RARalpha transcript after the first GO dose. Of 14 responders, 7 remained in sustained MR for a median of 15 months (range, 7-31 months) while 7 experienced relapse at 3 to 15 months. GO was administered again in 2 patients with relapse, and both obtained a new MR. These data indicate that GO is highly effective as a single treatment for patients with molecularly relapsed APL including those with very advanced disease.

Published
2004

44. Treatment of aplastic anaemia with granulocyte-colony stimulating factor and risk of malignancy. Italian Aplastic Anaemia Study Group

Author

Locasciulli, A, Arcese, W, Locatelli, Franco, Di Bona, E, Bacigalupo, Andrea, Locatelli, F (ORCID:0000-0002-7976-3654), Bacigalupo, A (ORCID:0000-0002-9119-567X), Locasciulli, A, Arcese, W, Locatelli, Franco, Di Bona, E, Bacigalupo, Andrea, Locatelli, F (ORCID:0000-0002-7976-3654), and Bacigalupo, A (ORCID:0000-0002-9119-567X)

Abstract

Granulocyte-colony stimulating factor (G-CSF) is being increasingly used in healthy volunteers to harvest haemopoietic stem cells, A possible role of G-CSF in the development of clonal disorders or leukaemia has been suggested. We analysed 144 patients with aplastic anaemia treated with immunosuppression protocols with or without G-CSF, with normal cytogenetics at diagnosis or immediately after immunosuppression, Our findings indicated that the risk of developing myelodysplasia or leukaemia was similar in patients with aplastic anaemia on immunosuppressive treatment with or without G-CSF. Therefore, it seems unlikely that G-CSF causes leukaemia in healthy volunteers.

Published
2001

45. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO).

Author

Bacigalupo, A, Bruno, Sinopoli, Saracco, P, Di Bona, E, Locasciulli, A, Locatelli, Francesco, Gabbas, A, Dufour, C, Arcese, W, Testi, G, Broccia, G, Carotenuto, M, Coser, P, Barbui, T, Leoni, P, Ferster, Alina, Bacigalupo, A, Bruno, Sinopoli, Saracco, P, Di Bona, E, Locasciulli, A, Locatelli, Francesco, Gabbas, A, Dufour, C, Arcese, W, Testi, G, Broccia, G, Carotenuto, M, Coser, P, Barbui, T, Leoni, P, and Ferster, Alina

Abstract

One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 x 10(9)/L (range, 0-0.5 x 10(9)/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 x 10(9)/L (P =.001) and 88% versus 87% for patients aged less than versus more than 16 years (P =.8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 x 10(9)/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF. (Blood. 2000;95:1931-1934), Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2000

46. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO)

Author

Bacigalupo, Andrea, Bruno, B, Saracco, P, Di Bona, E, Locasciulli, A, Locatelli, Franco, Gabbas, A, Dufour, C, Arcese, W, Testi, G, Broccia, G, Carotenuto, M, Coser, P, Barbui, T, Leoni, P, Ferster, A, Bacigalupo, A (ORCID:0000-0002-9119-567X), Locatelli, F (ORCID:0000-0002-7976-3654), Bacigalupo, Andrea, Bruno, B, Saracco, P, Di Bona, E, Locasciulli, A, Locatelli, Franco, Gabbas, A, Dufour, C, Arcese, W, Testi, G, Broccia, G, Carotenuto, M, Coser, P, Barbui, T, Leoni, P, Ferster, A, Bacigalupo, A (ORCID:0000-0002-9119-567X), and Locatelli, F (ORCID:0000-0002-7976-3654)

Abstract

One hundred consecutive patients with severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), 6-methylprednisolone (6Mpred), and granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 16 years (range, 1-72 years) and median neutrophil count was 0.2 x 10(9)/L (range, 0-0.5 x 10(9)/L). Trilineage hematologic recovery (at a median interval of 96 days from treatment) was seen in 77 patients (48 complete, 29 partial) after 1 (n = 50) or more courses of ALG (n = 27). Of the 23 nonresponders, 11 patients died at a median interval of 83 days (range, 16-1132 days), 6 were considered treatment failures and underwent transplantation, and 6 were pancytopenic. Cytogenetic abnormalities were seen in 11% of patients, clonal hematologic disease in 8%, and relapse of marrow aplasia in 9%. The actuarial survival at 5 years was 87% (median follow-up 1424 days): 76% versus 98% for patients with neutrophil counts less than versus greater than 0.2 x 10(9)/L (P =.001) and 88% versus 87% for patients aged less than versus more than 16 years (P =.8). The actuarial probability of discontinuing CyA was 38%. Patients who did not achieve a white blood cell (WBC) count of 5 x 10(9)/L during G-CSF treatment have a low probability of responding (37%) and a high mortality rate (42%). This update confirms a high probability for SAA patients of becoming transfusion independent and of surviving after treatment with ALG, CyA, 6Mpred, and G-CSF, with a significant effect of neutrophil counts on outcome. Problems still remain, such as absent or incomplete responses, clonal evolution, relapse of the original disease, and cyclosporine dependence. Early transplantation, also from alternative donors, may be warranted in patients with poor WBC response to G-CSF. (Blood. 2000;95:1931-1934)

Published
2000

47. Therapy-Related Myelodysplastic Syndrome (sMDS) /Acute Myelogenous Leukemia (sAML) in Acute Promyelocytic Leukemia (APL) Patients with Long-Lasting Molecular Remission: The GIMEMA Experience.

Author

Latagliata, R., primary, Breccia, M., primary, Fazi, P., primary, Gubbiotti, S., primary, Di Bona, E., primary, Specchia, G., primary, Chiarenza, A., primary, Murru, R., primary, Carella, A.M., primary, Ferrara, F., primary, Rossi, G., primary, Melillo, L., primary, Sica, S., primary, Invernizzi, R., primary, Cimino, G., primary, Petti, M.C., primary, Avvisati, G., primary, Lo-Coco, F., primary, and Mandelli, F., primary

Published
2005
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48. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients

Author

Bacigalupo, A., primary, Bruno, B., additional, Saracco, P., additional, Di Bona, E., additional, Locasciulli, A., additional, Locatelli, F., additional, Gabbas, A., additional, Dufour, C., additional, Arcese, W., additional, Testi, G., additional, Broccia, G., additional, Carotenuto, M., additional, Coser, P., additional, Barbui, T., additional, Leoni, P., additional, and Ferster, A., additional

Published
2000
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49. Consistency of responses to repeated DDAVP infusions in patients with von Willebrand's disease and hemophilia A

Author

Rodeghiero, F, Castaman, G, Di Bona, E, and Ruggeri, M

Abstract

The consistency in time of responses to separate desmopressin (DDAVP) infusions in patients with von Willebrand's disease (vWD) and mild or moderate hemophilia A has been the subject of limited investigation. We report here the results of a clinical study undertaken to test the consistency of responses to repeated DDAVP administrations in 22 patients with vWD and 10 with mild or moderate hemophilia A (time interval between first and last infusion ranging from 1 to 77 months; median, 13 months). In patients with vWD, 80% of cases showed a departure of less than 20% from the average VIII:C peak level calculated after the two infusions. A similarly consistent pattern was observed for bleeding times recorded 30 minutes after each infusion. In patients with hemophilia A, some infused on more than two instances, the departure from the average VIII:C peak level was less than 20% in nearly 70% of cases. A good within-family consistency was also demonstrated by analyzing data obtained from seven kindreds with vWD and two with hemophilia A. In conclusion, our study suggests that the pattern of responsiveness observed after a DDAVP test-infusion can be reliably used to decide the future clinical management of the individual patient and that a similar pattern of response is usually observed within the same kindred.

Published
1989
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50. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation

Author

Trojani, A., Ripamonti, C. B., Silvana Penco, Beghini, A., Nadali, G., Di Bona, E., Viola, A., Castagnola, C., Colapietro, P., Grillo, G., Pezzetti, L., Ravelli, E., Patrosso, M. C., Marocchi, A., Cuneo, A., Ferrara, F., Lazzarino, M., Pizzolo, G., Cairoli, R., Morra, E., Trojani, A, Ripamonti, C, Penco, S, Beghini, A, Nadali, G, Di Bona, E, Viola, A, Castagnola, C, Colapietro, P, Grillo, G, Pezzetti, L, Ravelli, E, Patrosso, M, Marocchi, A, Cuneo, A, Ferrara, F, Lazzarino, M, Pizzolo, G, Cairoli, R, and Morra, E

Subjects
Adult, Male, Kit, FLT 3, Leukemia, Receptor, Platelet-Derived Growth Factor alpha, Acute myeloid leukemia, PDGFR, Core Binding Factors, Core-binding factor, Middle Aged, NO, Receptor, Platelet-Derived Growth Factor beta, Proto-Oncogene Proteins c-kit, fms-Like Tyrosine Kinase 3, Leukemia, Myeloid, Acute Disease, Mutation, Humans, Female, PDGFR, acute myeloid leukemia, single-strand conformation polymorphism, core-binding factor, Polymorphism, Single-Stranded Conformational, Single-strand conformation polymorphism, Aged
Abstract

Background: Mutations involving KIT and FLT3 genes, encoding tyrosine kinase (TK) membrane receptors, are detected in core-binding factor leukaemia (CBFL) patients. PDFGRA and PDGFRB encode class III TK receptors and are involved both in physiological processes and in the pathogenesis of haematological and solid tumours. The aim of this study was to investigate if PDGFR mutations are involved in CBFL. Patients and Methods: In order to detect PDGFR mutations in CBFL, 35 patients without KIT or FLT3 mutations patients were screened by rapid and sensitive single-strand conformation polymorphism (SSCP) analysis. Sequence analysis was performed in polymerase chain reaction (PCR) products showing altered mobility in SSCP analysis in order to determine the nucleotide changes. Results: Three types of single-nucleotide polymorphism (SNP) were detected in the PDGFRA gene (exon 12, exon 13 and exon 18) while no mutation of PDGFRB was detected in the tested CBFLs. Conclusion: These data showed that no pathogenic mutations in PDGFRA and PDGFRB were detected in the context of CBFL without KIT and FLT3 mutations. Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients.

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