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1. Role of bone marrow biopsy in staging of patients with classical Hodgkin’s lymphoma undergoing positron emission tomography/computed tomography

Author

Puccini, B ., Nassi, L., Minoia, C., Volpetti, S., Ciancia, R., Riccomagno, P. C., Di Rocco, A., Mulè, A., Toldo, C., Sassone, M. C., Guariglia, R., Filì, C., Finolezzi, E., Falorio, S., Zanon, S., Furlan, A., Doa, G., Zaja, F., and on behalf of the Fondazione Italiana Linfomi Postgraduate Master course

Published
2017
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8. MULTI-GENOTYPING OF MINOR HISTOCOMPATIBILITY ANTIGENS (MHAGS) IN ALLOGENEIC STEM CELL TRANSPLANTATION AND THEIR ROLE IN DETERMINING GRAFT VERSUS HOST DISEASE (GVHD) AND GRAFT VERSUS LEUKEMIA (GVL) EFFECT: PH-P109

Author

Cattina, F., Skert, C., Bernardi, S., Malagola, M., Ottaviani, E., Bochicchio, M. T., Iacobucci, I., Soverini, S., Bonifazi, F., Bandini, G., Arpinati, M., Motta, M. R., Toffoletti, E., Damiani, D., Santoro, A., Fabbiano, F., Pastore, D., Specchia, G., Console, G., Bruno, M., Carella, G., Malagoli, A., Guadagnuolo, V., De Benedittis, C., Bergonzi, C., Filì, C., Turra, A., Ribolla, R., Cancelli, V., Alghisi, E., Perucca, S., Di Palma, A., Martinelli, G., and Russo, D.

Published
2014

12. PS997 A NEW BIOMARKER OF RESPONSE TO 5-AZACITIDINE THERAPY IN MDS AND AML PATIENTS: SIRPB1

Author

Cerchione, C., primary, Guadagnuolo, V., additional, Papayannidis, C., additional, Iacobucci, I., additional, Padella, A., additional, Simonetti, G., additional, Paolini, S., additional, Abbenante, M., additional, Parisi, S., additional, Volpato, F., additional, Fontana, M.C., additional, Ottaviani, E., additional, Testoni, N., additional, Baldazzi, C., additional, Delledonne, M., additional, Filì, C., additional, Malagola, M., additional, Cattina, F., additional, Bernardi, S., additional, Russo, D., additional, and Martinelli, G., additional

Published
2019
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14. PI-PLCBETA1 GENE METHYLATION AND EXPRESSION AS A RELIABLE AND DYNAMIC MARKER OF CLINICAL RESPONSE TO 5-AZACYTIDINE IN PATIENTS WITH LOW-RISK MYELODYSPLASTIC SYNDROMES

Author

Follo, My, Malagola, Michele, Filì, C, Finelli, C, Iacobucci, I, Martinelli, G, Cattina, F, Clissa, C, Candoni, A, Fanin, R, Gobbi, M, Bocchia, M, Defina, M, Spedini, P, Skert, C, Manzoli, L, Cocco, L, Russo, Domenico, Follo MY, Malagola M, Filì C, Finelli C, Iacobucci I, Martinelli G, Cattina F, Clissa C, Candoni A, Fanin R, Gobbi M, Bocchia M, Defina M, Spedini P, Skert C, Manzoli L, Cocco L, and Russo D

Subjects
SIGNAL TRANSDUCTION, MYELODISPLASTIC SYNDROME
Abstract

Hypomethylating agents, such as 5-Azacytidine (AZA), significantly modified the therapeutic approach to MDS, primarily in older patients with higher risk disease for whom intensive chemotherapy and allogeneic stem cell transplantation are not an option. In low-risk MDS, 5- AZA aims to reduce transfusion dependency, improve quality of life and hopefully the survival, but it is still unclear if this therapeutic approach would be cost-effective. At a molecular level, the mechanisms underlying the effect of epigenetic therapy are not completely understood, although it is well known that DNA methyltransferase inhibitors can induce the expression of Phosphoinositide-Phospholipase C (PIPLC) beta1 in high-risk MDS. Here, we prospectively investigated the efficacy and safety of AZA in low-risk MDS patients. AZA was administered at a lower intensity schedule, that is 75 mg/sqm/day subcutaneous for 5 days every 28, for a total of 8 cycles, and response was assessed at the 4th and 8th cycle of AZA. Moreover, PI-PLCbeta1 promoter methylation and gene expression levels were quantified before and after each cycle of 5-AZA. The study included 32 patients, and 26 cases completed 8 cycles of AZA. ORR was 47% (15/32) on intention to treat and 58% (15/26) for patients completing the treatment program. In this latter group, 5 (19%) cases achieved CR and 10 (38%) had HI, according to the IWG criteria. Interestingly, three patients have maintained their HI after 37, 34 and 33 months without other treatments. At a molecular level, although baseline PI-PLCbeta1 levels were not correlated to clinical response, 5d-AZA induced a statistically significant decrease in PI-PLCbeta1 promoter methylation in 14/15 responders, which corresponded to a significant increase in PI-PLCbeta1 mRNA. In 9/14 (64%) responsive patients, the first molecular increase in PI-PLCbeta1 level was observed between the 3rd and 4th cycle, therefore anticipating the clinical evaluation. In addition, 8 cases showed a loss of the response after the end of therapy (8th cycle) and these cases displayed a significant reduction of PI-PLCbeta1 levels, below the pre-treatment values, already before the clinical loss of the response. Taken together, our results show that 5d-AZA is safe and effective in a proportion of low risk MDS patients. PI-PLCbeta1 gene expression is a reliable and dynamic marker of response that can be useful to optimize AZA therapy.

Published
2013

15. IS PI-PLC 1 EXPRESSION A RELIABLE PREDICTOR OF RESPONSE IN LOW RISK MDS PATIENTS TREATED WITH LOW-DOSE AZACITIDINE? RESULTS OF A PROSPECTIVE MULTICENTRIC STUDY

Author

Filì, C., Follo, My, Martinelli, G., Iacobucci, I., Cattina, F., Skert, C., Bergonzi, C., Michele Malagola, Finelli, C., Gobbi, M., Candoni, A., Lauria, F., Lanza, F., Turra, A., Ribolla, R., Simona Bernardi, Cocco, L., Russo, Domenico, Filì C, Follo MY, Martinelli G, Iacobucci I, Cattina F, Skert C, Bergonzi C, Malagola M, Finelli C, Gobbi M, Candoni A, Lauria F, Lanza F, Turra A, Ribolla R, Bernardi S, Cocco L, and Russo D

Subjects
SIGNAL TRANSDUCTION, MYELODISPLASTIC SYNDROME
Abstract

Background. The use of hypomethylating agents significantly modified the therapeutic approach to MDS patients, primarily in high-risk MDS patients. In low-risk MDSs the use of AZA hypomethylating agent is less understood. Epigenetic regulation of Phosphoinositide-Phospholipase C (PI-PLC) beta1 promoter and key molecules involved in the nuclear inositide signalling pathways seems to play an important role for the activity of AZA demethylating therapy. Aims. We prospectively evaluated the efficacy and safety of AZA low-dose in Low or Int-1 risk MDS patients who were symptomatic and/or unresponsive to previous treatments. In the same study we evaluated the molecular effects of AZA on PI-PLCbeta1 promoter methylation, in order to investigate a possibly correlation with the response to the drug. Methods. AZA was administered at a dose of 75 mg/mq/daily s.c for 5 consecutive days every 28 days for a total of 8 cycles. Final response was checked at the end of the 8th course. PI-PLC beta1 gene expression was evaluated on peripheral blood samples from patients at baseline, and monthly until the 8th cycle of AZA administration. Results. Between September 2008 and February 2010, 32 MDS patients with IPSS risk Low- or Int-1 were enrolled into the study. Most patients had a normal karyotype (63%) by metaphase cytogenetics, were BRC transfusion-dependent (81%), receiving a median of 4 units/mo, and were previously unresponsive to treatment including ESAs (69%). Twenty-six patients (81%) completed the treatment plan (8 cycles). The Overall Response Rate after the 8th cycle was 58% (15/26 pts) whereas 42% of patients maintained a stable disease; no patient progressed towards a high-risk MDS or AML. Five (19%) patients reached a complete remission whereas 10 (38%) achieved an hematological improvement. Transfusion independent was achieved in 8/26 patients (31%). The median duration of the response was 10 months; five patients maintain their response, that is CR in 2 cases (+24 and +30 months) and HI-E in 3 cases (+14, +25,+26 months) without any treatment or supportive therapy. No clinical or hematologic factor showed a correlation with the response. PI-PLCbeta1 gene expression was quantified in MDS patients at baseline and during AZA treatment. Results were calculated as a percentage ratio of PI-PLCbeta1 expression during AZA treatment compared to baseline. All but one patients (14/15) who achieved an hematologic response during treatment with AZA showed a statistically significant increase in PI-PLCbeta1 mRNA expression (P

Published
2012

16. Treatment of refractory chronic GVHD with rituximab: a GITMO study

Author

ZAJA, Francesco, BACIGALUPO A, PATRIARCA, Francesca, STANZANI M, VAN LINT M. T, FILÌ C, SCIME R, MILONE G, FALDA M, VENER C, LASZLO D, ALESSANDRINO P. E, NARNI F, SICA S, OLIVIERI A, SPEROTTO A, BOSI A, BONIFAZI F, FANIN, Renato, GITMO GRUPPO ITALIANO TRAPIANTO MIDOLLO OSSEO, Zaja, Francesco, Bacigalupo, A, Patriarca, Francesca, Stanzani, M, VAN LINT M., T, Filì, C, Scime, R, Milone, G, Falda, M, Vener, C, Laszlo, D, ALESSANDRINO P., E, Narni, F, Sica, S, Olivieri, A, Sperotto, A, Bosi, A, Bonifazi, F, Fanin, Renato, and GITMO GRUPPO ITALIANO TRAPIANTO MIDOLLO, Osseo

Abstract

The anti-CD20 chimaeric monoclonal antibody Rituximab has recently been shown to induce significant clinical response in a proportion of patients with refractory chronic graft-versus-host disease (cGVHD). We now report 38 patients, median age 48 years (22-61), receiving Rituximab for refractory cGVHD, assessed for clinical response and survival. Median duration of cGVHD before Rituximab was 23 months (range 2-116), the median number of failed treatment lines was 3 (range 1 to > or =6) and the median follow-up after Rituximab was 11 months (1-88). Overall response rate was 65%: skin 17/20 (63%), mouth 10/21 (48%), eyes 6/14 (43%), liver 3/12 (25%), lung 3/8 (37.5%), joints 4/5, gut 3/4, thrombocytopaenia 2/3, vagina 0/2, pure red cell aplasia 0/1 and, myasthenia gravis 1/1. During the study period 8/38 died: causes of death were cGVHD progression (n=3), disease relapse (n=1), infection (n=3), sudden death (n=1). The actuarial 2 year survival is currently 76%. We confirm that Rituximab is effective in over 50% of patients with refractory cGVHD and may have a beneficial impact on survival.

Published
2007

17. Chronic GVHD and sequential study of cytokine patterns and lymphocyte subsets in patients underwent allogeneic stem cell transplantation with reduced intensity conditioning

Author

Skert, C, Damiani, Daniela, Patriarca, Francesca, Michelutti, A, Filì, C, Zaja, Francesco, Sperotto, A, Cerno, M, Geromin, A, Candoni, A, Battista, M, Malagola, M, Roccaro, A, Bergonzi, C, Russo, D, Fanin, R., Skert, C, Damiani, Daniela, Patriarca, Francesca, Michelutti, A, Filì, C, Zaja, Francesco, Sperotto, A, Cerno, M, Geromin, A, Candoni, A, Battista, M, Malagola, M, Roccaro, A, Bergonzi, C, Russo, D, and Fanin, R.

Published
2006

19. Late-onset non-infectious pulmonary complcations after unrelated donor stem cell transplantation are strongly associated with chronic graft versus host disease and with the graft versus malignancy effect

Author

Patriarca, Francesca, Skert, C., Sperotto, A., Damiani, Daniela, Cerno, M., Geromin, A., Zaja, Francesco, Prosdocimo, S., Filì, C., Stocchi, R., Fanin, R., Patriarca, Francesca, Skert, C., Sperotto, A., Damiani, Daniela, Cerno, M., Geromin, A., Zaja, Francesco, Prosdocimo, S., Filì, C., Stocchi, R., and Fanin, R.

Published
2004

20. Intensified full-dose induction therapy (HD-MACHOP+radiotherapy) follwed dy consolidation with BAVC regimen and autologous stem cell transplantation as fron-line therapeutic approach for high risk aggressive non Hodgkin lymphoma

Author

Zaja, Francesco, Sperotto, A., Tomadini, V., Patriarca, Francesca, Filì, C., Kikic, F., Damiani, Daniela, Mestroni, R., Tiribelli, Mario, Fanin, Renato, Zaja, Francesco, Sperotto, A., Tomadini, V., Patriarca, Francesca, Filì, C., Kikic, F., Damiani, Daniela, Mestroni, R., Tiribelli, Mario, and Fanin, Renato

Published
2004

22. Conventional unrelated boine marrow transplantation for patients with haematological disease: probability of finding a donor and outcome of 131 consecutivecases in a single centre

Author

Sperotto, A., Patriarca, Francesca, Cerno, M., Silvestri, F., Zaja, Francesco, Filì, C., Geromin, A., Calistri, E., Stocchi, R., Damiani, Daniela, Fanin, R., Sperotto, A., Patriarca, Francesca, Cerno, M., Silvestri, F., Zaja, Francesco, Filì, C., Geromin, A., Calistri, E., Stocchi, R., Damiani, Daniela, and Fanin, R.

Published
2004

27. Activity of all-trans-retinoic acid in a case of central nervous system extramedullary relapse of acute promyelocytic leukemia

Author

Patriarca, Francesca, Sperotto, A, Filì, C, Zaja, Francesco, Prisdocimo, S, Fanin, Renato, Patriarca, Francesca, Sperotto, A, Filì, C, Zaja, Francesco, Prisdocimo, S, and Fanin, Renato

Abstract

We describe a patient with an acute promyelocytic leukemia (APL) previously treated with two courses of cytarabin, idarubicin and all-trans retinoic acid (ATRA), who presented a medullary and meningeal relapse after 8 months of complete remission. A diagnosis of central nervous system (CNS) involvement was based on the appearance of APL blasts in the cerebrospinal fluid (CSF); magnetic resonance (MR) imaging was negative. The neurological symptoms were not evident at the time of recognition of the medullary recurrence, but appeared a few days later, when the patient had already received a reinduction treatment. When the CSF was first examined, showing atypical promyelocytes, there was no excess of blasts on bone-marrow examination. The patient was treated with ATRA and intrathecal administrations of cytoxic drugs, achieving a complete long-lasting CNS remission. The appearance of mature myeloid cells in the CSF during this treatment suggested a possible differentiating effect of ATRA towards extramedullary relapse.

Published
2002

45. 5-AZACITIDINE FIVE DAYS/MONTHLY SCHEDULE IN SYMPTOMATIC LOW-RISK (IPSS: 0-1) MYELODISPLASTIC (MDS) PATIENTS. CLINICAL AND BIOLOGICAL EFFECTS Authors

Author

Filì, C., Gobbi, 1 M., Martinelli, 2 G., Finelli, 3 C., Iacobucci, 4 I., Ottaviani, 5 E., Cocco, 5 L., Follo, 6 M., Candoni, 6 A., Simeone, 7 E., Damiani, Daniela, Tiribelli, Mario, Miglino, 7 M., Lauria, 2 F., Bocchia, 8 M., Defina, 8 M., Clissa, 8 C., Skert, 9 C., Bergonzi, 10 C., Malagola, 10 M., Peli, 10 A., Turra, 10 A., Cattina, 10 F., Colombi, 10 C., and Russo10, 10 D.

Published
2010

50. Incidence of bacterial and fungal infections in acute myeloid leukemia patients treated with induction regimens including fludarabine: a retrospective analysis of 224 cases

Author

Malagola, Michele, Peli, A, Damiani, D, Candoni, A, Tiribelli, M, Martinelli, G, Piccaluga PP3 Paolini, S, Lauria, F, Bocchia, M, Gobbi, M, Pierri, I, Zaccaria, A, Zuffa, E, Mazza, P, Piccolo, G, Gugliotta, L, Bovini, A, Visani, G, Skert, C, Bergonzi, C, Roccaro, A, Filì, C, Capuzzi, E, Fanin, R, Baccarani, M, and Russo, Domenico

Published
2008

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