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1. MIS-A: Beware of non-lymphoma

Author

Cantoni, S, Greco, R, Mancini, V, Russo, V, Capasso, A, Travi, G, Vanzulli, A, Cairoli, R, Cantoni, S, Greco, R, Mancini, V, Russo, V, Capasso, A, Travi, G, Vanzulli, A, and Cairoli, R

Subjects
Lymphoma, SARS-CoV-2, MIS-A
Published
2023

2. The ERK1/2 Regulator WNK2 Shows Novel Alternative Splicing Aberrations That Support Tumor Growth in MYD88 Mutated Waldenström's Macroglobulinemia

Author

Guerrera, ML, Liu, X, Morelli, E, Richardson, K, Tsakmaklis, N, Kofides, A, Munshi, M, Liu, SR, Yang, G, Patterson, CJ, Castillo, JJ, Sarosiek, S, Flynn, CA, Meid, K, Gustine, J, Branagan, AR, Trojani, A, Tedeschi, A, Cairoli, R, Sewastianik, T, Carrasco, RD, Anderson, KC, Munshi, NC, Treon, SP, Hunter, ZR, Guerrera, M, Liu, X, Morelli, E, Richardson, K, Tsakmaklis, N, Kofides, A, Munshi, M, Liu, S, Yang, G, Patterson, C, Castillo, J, Sarosiek, S, Flynn, C, Meid, K, Gustine, J, Branagan, A, Trojani, A, Tedeschi, A, Cairoli, R, Sewastianik, T, Carrasco, R, Anderson, K, Munshi, N, Treon, S, and Hunter, Z

Subjects
Immunology, Cell Biology, Hematology, Waldenstrom, WNK2, Biochemistry
Published
2022

3. Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV

Author

Zappasodi P, Cattaneo C, Ferretti V, Mina R, Ferreri AJ, Merli F, Oberti M, Krampera M, Romano A, Zerbi C, Ferrari J, Cavo M, Marco Salvini M, Bertù L, Fracchiolla N, Marchesi F, Massaia M, Marasco V, Cairoli R, Scattolin AM, Vannucchi AM, Gambacorti-Passerini C, Musto P, Gherlinzoni F, Cuneo A, Pinto A, Trentin L, Bocchia M, Galimberti, Coviello E, Morotti A, Falini B, Turrin M, Tafuri A, Billio A, Gentile M, Lemoli M, Venditti A, Della Porta M, Lanza F, Rigacci L, Tosi P, Mohamed S, Corso A, Luppi M, Giuliani N, Busca A, Pagano L, Bruno R, Grossi P, Corradini P, Passamonti F, Arcaini L., Zappasodi, P, Cattaneo, C, Ferretti, V, Mina, R, Ferreri, A, Merli, F, Oberti, M, Krampera, M, Romano, A, Zerbi, C, Ferrari, J, Cavo, M, Marco Salvini, M, Bertù, L, Fracchiolla, N, Marchesi, F, Massaia, M, Marasco, V, Cairoli, R, Scattolin, A, Vannucchi, A, Gambacorti-Passerini, C, Musto, P, Gherlinzoni, F, Cuneo, A, Pinto, A, Trentin, L, Bocchia, M, Galimberti, Coviello, E, Mc, Morotti, A, Falini, B, Turrin, M, Tafuri, A, Billio, A, Gentile, M, Lemoli, M, Venditti, A, Della Porta, M, Lanza, F, Rigacci, L, Tosi, P, Mohamed, S, Corso, A, Luppi, M, Giuliani, N, Busca, A, Pagano, L, Bruno, R, Grossi, P, Corradini, P, Passamonti, F, Arcaini, L, Zappasodi, Patrizia, Cattaneo, Chiara, Ferretti, Virginia Valeria, Mina, Roberto, Ferreri, Andrés José María, Merli, Francesco, Oberti, Margherita, Krampera, Mauro, Romano, Alessandra, Zerbi, Caterina, Ferrari, Jacqueline, Cavo, Michele, Salvini, Marco, Bertù, Lorenza, Fracchiolla, Nicola Stefano, Marchesi, Francesco, Massaia, Massimo, Marasco, Vincenzo, Cairoli, Roberto, Scattolin, Anna Maria, Vannucchi, Alessandro Maria, Gambacorti-Passerini, Carlo, Musto, Pellegrino, Gherlinzoni, Filippo, Cuneo, Antonio, Pinto, Antonello, Trentin, Livio, Bocchia, Monica, Galimberti, Sara, Coviello, Elisa, Tisi, Maria Chiara, Morotti, Alessandro, Falini, Brunangelo, Turrini, Mauro, Tafuri, Agostino, Billio, Atto, Gentile, Massimo, Lemoli, Roberto Massimo, Venditti, Adriano, Della Porta, Matteo Giovanni, Lanza, Francesco, Rigacci, Luigi, Tosi, Patrizia, Mohamed, Sara, Corso, Alessandro, Luppi, Mario, Giuliani, Nicola, Busca, Alessandro, Pagano, Livio, Bruno, Raffaele, Grossi, Paolo Antonio, Corradini, Paolo, Passamonti, Francesco, and Arcaini, Luca

Subjects
Cancer Research, Lymphoma, Coinfection, COVID-19, Hematology, General Medicine, Settore MED/15, hematological malignancie, secondary infections, Settore MED/15 - MALATTIE DEL SANGUE, COVID-19 Testing, Oncology, Hematologic Neoplasms, secondary infection, outcome, Humans, hematological malignancies, Aged
Abstract

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Published
2022

4. 'Efficient Strategies for the Reuse of Surgical and FFP2/ KN95 Face Masks during the COVID-19 Pandemic: Home-Made and Ecological Choices for the Community'

Author

Bossi Luca Emanuele, Trojani A, Melluso A, Bruzzone AG, Accarino F, Cairoli R, Bossi Luca, E, Trojani, A, Melluso, A, Bruzzone, A, Accarino, F, and Cairoli, R

Subjects
MED/15 - MALATTIE DEL SANGUE, General Medicine, Face Mask, COVID-19
Abstract

The SARS CoV-2 is responsible for the severe acute respiratory syndrome (COVID-19) which has claimed numerous victims worldwide. The main symptoms reported in the scientific literature are represented by fever, cough, gastrointestinal disturbances, dysgeusia, and anosmia but currently the symptomatology is not clear, yet. The symptoms vary from one individual to another one, depending mostly on the age of the patients and their co-morbidities. Wearing surgical or FFP2/KN-95 face masks block the interpersonal transmissibility of the droplets containing the virus which are produced during speaking, breathing or coughing. We pondered the regeneration of this personal protective equipment in order to reduce the costs and the biological waste released into the environment. In our paper, we have described four strategies for the decontamination of surgical and FFP2/KN95 face masks. The steam iron and the washing machine are easily reproducible at home, while the thermostatically controlled bath and the autoclave require more advanced structures such as hospitals or scientific institutes. The regeneration methods ensure that both surgical and FFP2/ KN95 face masks maintain the same characteristics of the unused ones. After the regeneration process, we demonstrated the conservation of the structural proprieties of the polypropylene fibers of both masks by light microscope. The microbiological analyses of both regenerated masks showed the absence of the main pathogens that can infect the nasopharyngeal tract. Moreover, we showed that both regenerated surgical and FFP2/KN95 face masks maintained their waterproof properties. Finally, we demonstrated that the regenerated FFP2/KN95 face masks maintained their adequate fit by the qualitative fit testing.

Published
2022

5. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Author

Passamonti, F, Cattaneo, C, Arcaini, L, Bruna, R, Cavo, M, Merli, F, Angelucci, E, Krampera, M, Cairoli, R, Della Porta MG, Fracchiolla, N, Ladetto, M, Gambacorti Passerini, C, Salvini, M, Marchetti, M, Lemoli, R, Molteni, A, Busca, A, Cuneo, A, Romano, A, Giuliani, N, Galimberti, S, Corso, A, Morotti, A, Falini, B, Billio, A, Gherlinzoni, F, Visani, G, Tisi, Mc, Tafuri, A, Tosi, P, Lanza, F, Massaia, M, Turrini, M, Ferrara, F, Gurrieri, C, Vallisa, D, Martelli, M, Derenzini, E, Guarini, A, Conconi, A, Cuccaro, A, Cudillo, L, Russo, D, Ciambelli, F, Scattolin, Am, Luppi, M, Selleri, C, Ortu La Barbera, E, Ferrandina, C, Di Renzo, N, Olivieri, A, Bocchia, M, Gentile, M, Marchesi, F, Musto, P, Federici, Ab, Candoni, A, Venditti, A, Fava, C, Pinto, A, Galieni, P, Rigacci, L, Armiento, D, Pane, F, Oberti, M, Zappasodi, P, Visco, C, Franchi, M, Grossi, Pa, Bertù, L, Corrao, G, Pagano, L, Corradini, P, ITA-HEMA-COV, Investigators., Passamonti, F., Cattaneo, C., Arcaini, L., Bruna, R., Cavo, M., Merli, F., Angelucci, E., Krampera, M., Cairoli, R., Della Porta, M. G., Fracchiolla, N., Ladetto, M., Gambacorti Passerini, C., Salvini, M., Marchetti, M., Lemoli, R., Molteni, A., Busca, A., Cuneo, A., Romano, A., Giuliani, N., Galimberti, S., Corso, A., Morotti, A., Falini, B., Billio, A., Gherlinzoni, F., Visani, G., Tisi, M. C., Tafuri, A., Tosi, P., Lanza, F., Massaia, M., Turrini, M., Ferrara, F., Gurrieri, C., Vallisa, D., Martelli, M., Derenzini, E., Guarini, A., Conconi, A., Cuccaro, A., Cudillo, L., Russo, D., Ciambelli, F., Scattolin, A. M., Luppi, M., Selleri, C., Ortu La Barbera, E., Ferrandina, C., Di Renzo, N., Olivieri, A., Bocchia, M., Gentile, M., Marchesi, F., Musto, P., Federici, A. B., Candoni, A., Venditti, A., Fava, C., Pinto, A., Galieni, P., Rigacci, L., Armiento, D., Pane, F., Oberti, M., Zappasodi, P., Visco, C., Franchi, M., Grossi, P. A., Bertu, L., Corrao, G., Pagano, L., Corradini, P., Passamonti F., Cattaneo C., Arcaini L., Bruna R., Cavo M., Merli F., Angelucci E., Krampera M., Cairoli R., Della Porta M.G., Fracchiolla N., Ladetto M., Gambacorti Passerini C., Salvini M., Marchetti M., Lemoli R., Molteni A., Busca A., Cuneo A., Romano A., Giuliani N., Galimberti S., Corso A., Morotti A., Falini B., Billio A., Gherlinzoni F., Visani G., Tisi M.C., Tafuri A., Tosi P., Lanza F., Massaia M., Turrini M., Ferrara F., Gurrieri C., Vallisa D., Martelli M., Derenzini E., Guarini A., Conconi A., Cuccaro A., Cudillo L., Russo D., Ciambelli F., Scattolin A.M., Luppi M., Selleri C., Ortu La Barbera E., Ferrandina C., Di Renzo N., Olivieri A., Bocchia M., Gentile M., Marchesi F., Musto P., Federici A.B., Candoni A., Venditti A., Fava C., Pinto A., Galieni P., Rigacci L., Armiento D., Pane F., Oberti M., Zappasodi P., Visco C., Franchi M., Grossi P.A., Bertu L., Corrao G., Pagano L., Corradini P., Passamonti, F, Cattaneo, C, Arcaini, L, Bruna, R, Cavo, M, Merli, F, Angelucci, E, Krampera, M, Cairoli, R, Della Porta, M, Fracchiolla, N, Ladetto, M, Gambacorti Passerini, C, Salvini, M, Marchetti, M, Lemoli, R, Molteni, A, Busca, A, Cuneo, A, Romano, A, Giuliani, N, Galimberti, S, Corso, A, Morotti, A, Falini, B, Billio, A, Gherlinzoni, F, Visani, G, Tisi, M, Tafuri, A, Tosi, P, Lanza, F, Massaia, M, Turrini, M, Ferrara, F, Gurrieri, C, Vallisa, D, Martelli, M, Derenzini, E, Guarini, A, Conconi, A, Cuccaro, A, Cudillo, L, Russo, D, Ciambelli, F, Scattolin, A, Luppi, M, Selleri, C, Ortu La Barbera, E, Ferrandina, C, Di Renzo, N, Olivieri, A, Bocchia, M, Gentile, M, Marchesi, F, Musto, P, Federici, A, Candoni, A, Venditti, A, Fava, C, Pinto, A, Galieni, P, Rigacci, L, Armiento, D, Pane, F, Oberti, M, Zappasodi, P, Visco, C, Franchi, M, Grossi, P, Bertu, L, Corrao, G, Pagano, L, and Corradini, P

Subjects
Male, Lymphoma, Comorbidity, 0302 clinical medicine, COVID-19, risk factors, death's rates, haematological malignancies, Retrospective Studie, Risk Factors, Neoplasms, 80 and over, haematological malignancies, Viral, Aged, 80 and over, education.field_of_study, Leukemia, Mortality rate, Lymphoma, Non-Hodgkin, Hazard ratio, Hematology, Plasma cell neoplasm, Middle Aged, Italy, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Cohort, Plasma Cell, Female, Inpatient, Coronavirus Infections, Cohort study, Human, Adult, medicine.medical_specialty, Population, Pneumonia, Viral, Non-Hodgkin, Article, NO, Follow-Up Studie, 03 medical and health sciences, Betacoronavirus, Young Adult, COVID-19 haematological malignancies, Internal medicine, COVID-19, haematological malignancies, multicentre, retrospective, cohort study, Multivariable Cox, medicine, Humans, education, Hematologic Neoplasm, Neoplasms, Plasma Cell, Pandemics, Myeloproliferative Disorder, Aged, Retrospective Studies, Inpatients, Follow-Up Studies, Myeloproliferative Disorders, death's rates, Betacoronaviru, business.industry, Coronavirus Infection, SARS-CoV-2, Risk Factor, COVID-19, haematological malignancies, risk factors, COVID-19, Retrospective cohort study, Pneumonia, Settore MED/15, COVID-19 Drug Treatment, Settore MED/15 - MALATTIE DEL SANGUE, Standardized mortality ratio, business, 030215 immunology
Abstract

Summary Background Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. Methods This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov , NCT04352556 , and the prospective part of the study is ongoing. Findings We enrolled 536 patients with a median follow-up of 20 days (IQR 10–34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77–2·34) in our whole study cohort and 3·72 (2·86–4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1–44·9). Older age (hazard ratio 1·03, 95% CI 1·01–1·05); progressive disease status (2·10, 1·41–3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56–7·81), indolent non-Hodgin lymphoma (2·19, 1·07–4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34–4·89), or plasma cell neoplasms (2·48, 1·31–4·69), and severe or critical COVID-19 (4·08, 2·73–6·09) were associated with worse overall survival. Interpretation This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. Funding Associazione italiana contro le leucemie, linfomi e mieloma–Varese Onlus.

Published
2020

6. Cytomegalovirus and Epstein-Barr Virus DNA Kinetics in Whole Blood and Plasma of Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Author

Lazzarotto T, Chiereghin A, Piralla A, Piccirilli G, Girello A, Campanini G, Gabrielli L, Costa C, Prete A, Bonifazi F, Busca A, Cairoli R, Colombo AA, Zecca M, Sidoti F, Bianco G, Paba P, Perno CF, Cavallo R, Baldanti F, AMCLI-GLaIT working group., Lazzarotto T, Chiereghin A, Piralla A, Piccirilli G, Girello A, Campanini G, Gabrielli L, Costa C, Prete A, Bonifazi F, Busca A, Cairoli R, Colombo AA, Zecca M, Sidoti F, Bianco G, Paba P, Perno CF, Cavallo R, Baldanti F, AMCLI-GLaIT working group., Tiziana, L, Angela, C, Antonio, P, Giulia, P, Alessia, G, Giulia, C, Liliana, G, Cristina, C, Arcangelo, P, Francesca, B, Alessandro, B, Cairoli, R, Anna Amelia, C, Marco, Z, Francesca, S, Gabriele, B, Pierpaolo, P, Carlo Federico, P, Rossana, C, and Fausto, B

Subjects
Adult, Male, 0301 basic medicine, Herpesvirus 4, Human, medicine.medical_specialty, medicine.medical_treatment, 030106 microbiology, Congenital cytomegalovirus infection, Allogeneic hematopoietic stem cell transplantation, CMV and EBV DNA kinetics, Plasma, Whole blood, Hematology, Transplantation, Cytomegalovirus, Hematopoietic stem cell transplantation, Virus Replication, Virus, 03 medical and health sciences, chemistry.chemical_compound, Internal medicine, medicine, Humans, Aged, Retrospective Studies, CMV and EBV DNA kinetic, business.industry, Hematopoietic Stem Cell Transplantation, virus diseases, Middle Aged, Allografts, medicine.disease, Virology, Transplant Recipients, Kinetics, Blood, 030104 developmental biology, chemistry, Viral replication, DNA, Viral, Female, business, DNA
Abstract

Currently, no consensus has been reached on the optimal blood compartment to be used for surveillance of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNAemia. Although several comparative studies have been performed correlating CMV and EBV DNA loads in whole blood (WB) versus plasma, to our knowledge, no studies to date have analyzed the kinetics of both viruses in the 2 blood compartments. In this retrospective noninterventional multicenter cohort study, the kinetics of CMV and EBV DNA in 121 hematopoietic stem cell transplantation (HSCT) recipients were investigated by analyzing in parallel 569 and 351 paired samples from 80 and 58 sequential episodes of CMV and EBV DNAemia, respectively. Unlike previous studies, this study used a single automated molecular method that was CE-marked and Food and Drug Administration-approved for use in quantifying CMV and EBV DNA in both plasma and WB. Furthermore, the complete viral replication kinetics of all episodes (including both the ascending and the descending phases of the active infection) was examined in each patient. The previously observed overall correlation between CMV DNA levels in WB and plasma was confirmed (Spearman's ρ =.85; P

Published
2018

7. Predicting the probability of Gaucher disease in subjects with splenomegaly and thrombocytopenia

Author

Motta I, Consonni D, Stroppiano M, Benedetto C, Cassinerio E, Tappino B, Ranalli P, Borin L, Facchini L, Patriarca A, Barcellini W, Lanza F, Filocamo M, Cappellini MD, Farina F, Codeluppi K, Rivolti E, Simonetti F, Lunghi F, Perrone T, Sgherza N, Carrai V, Cafro AM, Cairoli R, Amendola A, Trabacchi E, Vallisa D, Burgo I, Federici AB, Carbone C, D’Adda M, Mannina D, Di Giacomo V, Lupparelli G, Lombardo A., Motta, I, Consonni, D, Stroppiano, M, Benedetto, C, Cassinerio, E, Tappino, B, Ranalli, P, Borin, L, Facchini, L, Patriarca, A, Barcellini, W, Lanza, F, Filocamo, M, Cappellini, M, Farina, F, Codeluppi, K, Rivolti, E, Simonetti, F, Lunghi, F, Perrone, T, Sgherza, N, Carrai, V, Cafro, A, Cairoli, R, Amendola, A, Trabacchi, E, Vallisa, D, Burgo, I, Federici, A, Carbone, C, D’Adda, M, Mannina, D, Di Giacomo, V, Lupparelli, G, and Lombardo, A

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Science, Population, Diseases, Disease, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hematologist, education, education.field_of_study, Gaucher Disease, Multidisciplinary, biology, Transferrin saturation, business.industry, beta-Glucosidase, Middle Aged, Thrombocytopenia, Dried blood spot, Algorithm, Ferritin, Multicenter study, 030220 oncology & carcinogenesis, Splenomegaly, biology.protein, Medicine, Female, business, Haematological diseases, Algorithms, Human, 030215 immunology
Abstract

Hematologists are frequently involved in the diagnostic pathway of Gaucher disease type 1 (GD1) patients since they present several hematological signs. However, GD1 is mainly underdiagnosed because of a lack of awareness. In this multicenter study, we combine the use of a diagnostic algorithm with a simple test (β-glucosidase activity on Dried Blood Spot) in order to facilitate the diagnosis in a population presenting to the hematologist with splenomegaly and/or thrombocytopenia associated with other hematological signs. In this high-risk population, the prevalence of GD1 is 3.3%. We propose an equation that predicts the probability of having GD1 according to three parameters that are routinely evaluated: platelet count, ferritin, and transferrin saturation.

Published
2021

8. 'MOLTO', A MULTICENTER, OPEN LABEL, UNCONTROLLED, PHASE II CLINICAL TRIAL ON VENETOCLAX, ATEZOLIZUMAB, OBINUTUZUMAB (AVO) COMBINATION IN RICHTER TRANSFORMATION: SAFETY INTERIM ANALYSIS

Author

Frustaci, AM, Tedeschi, A, Zinzani, PL, Pietrasanta, D, Coscia, M, Zenz, T, Motta, M, Gaidano, G, Scarfo, L, Deodato, M, Zamprogna, G, Vitale, C, Cairoli, R, Rossi, D, Montillo, M, Frustaci, A, Tedeschi, A, Zinzani, P, Pietrasanta, D, Coscia, M, Zenz, T, Motta, M, Gaidano, G, Scarfo, L, Deodato, M, Zamprogna, G, Vitale, C, Cairoli, R, Rossi, D, and Montillo, M

Subjects
Hematology
Published
2021

9. INTERIM RESULTS OF PROSPECTIVE OBSERVATIONAL SEIFEM STUDY ON CLINICAL OUTCOME AND INFECTIOUS COMPLICATIONS IN 230 UNFIT AML PATIENTS TREATED IN FIRST-LINE WITH HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX

Author

Candoni A, Piccin M, Lazzarotto D, Bonuomo V, Fracchiolla N, Dargenio M, Riva M, Melillo L, Papayannidis C, Stulle M, Lessi F, Dragonetti G, Del Principe MI, Cerqui E, Pasciolla C, De Marchi R, Delia M, Tisi MC, Fanci R, Nadali G, Sciume M, Di Renzo N, Cairoli R, Valente D, Basilico, C (Basilico, C.) 18 Spadea, A (Spadea, A.) 19 Sartor, C (Sartor, C.) 8 Griguolo, D (Griguolo, D.) 9 Sarlo, C (Sarlo, C.) 20 Olivieri, A (Olivieri, A.) 21 Piccioni AL, Pagano L, Candoni, A, Piccin, M, Lazzarotto, D, Bonuomo, V, Fracchiolla, N, Dargenio, M, Riva, M, Melillo, L, Papayannidis, C, Stulle, M, Lessi, F, Dragonetti, G, Del Principe, M, Cerqui, E, Pasciolla, C, De Marchi, R, Delia, M, Tisi, M, Fanci, R, Nadali, G, Sciume, M, Di Renzo, N, Cairoli, R, Valente, D, Basilico, C,, C., ), A,, A., ), D,, D., ), and Pagano, L

Subjects
Hematology
Published
2021

10. Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996

Author

Piciocchi, A., Messina, M., Elia, L., Vitale, A., Soddu, S., Testi, A. M., Chiaretti, S., Mancini, M., Albano, F., Spadano, A., Krampera, M., Bonifacio, M., Cairoli, R., Vetro, C., Colella, F., Ferrara, F., Cimino, G., Bassan, R., Fazi, P., Vignetti, M., Piciocchi, A, Messina, M, Elia, L, Vitale, A, Soddu, S, Testi, A, Chiaretti, S, Mancini, M, Albano, F, Spadano, A, Krampera, M, Bonifacio, M, Cairoli, R, Vetro, C, Colella, F, Ferrara, F, Cimino, G, Bassan, R, Fazi, P, and Vignetti, M

Subjects
Adult, Male, Oncogene Proteins, Fusion, Prognosi, DNA-Binding Protein, bcr-abl, Fusion Proteins, bcr-abl, Histone-Lysine N-Methyltransferase, MED/15 - MALATTIE DEL SANGUE, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, DNA-binding proteins, adult, female, fusion proteins, bcr-abl, humans, male, Female, Survival Analysi, Transcriptional Elongation Factors, fusion proteins, Myeloid-Lymphoid Leukemia Protein, Human
Published
2021

12. VENETOCLAX IN MULTI-RELAPSED MANTLE CELL LYMPHOMA PATIENTS: A REAL-LIFE MULTICENTRIC EXPERIENCE

Author

Galimberti, S, Marchi E, Pelosini, M, Benedetti, E, Urso, A, Cuneo, A, Musuraca, G, Martinelli, G, Quaglia, FM, Visco, C, Vallone, R, Muzi, C, Cairoli, R, Loseto, G, Guarini, A, Clerico, M, Ferrero, S, Petrini, M, Galimberti, S, Marchi, E, Pelosini, M, Benedetti, E, Urso, A, Cuneo, A, Musuraca, G, Martinelli, G, Quaglia, F, Visco, C, Vallone, R, Muzi, C, Cairoli, R, Loseto, G, Guarini, A, Clerico, M, Ferrero, S, and Petrini, M

Subjects
Hematology
Published
2021

13. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M. T., Cucci, R., Messina, M., Santoro, A., Divona, M., Albano, F., Ottaviani, E., Roberta Bertorelle, Guerrasio, A., Gottardi, E., Izzo, B., Tarantini, G., Scardocci, A., Siragusa, S., Forghieri, F., Cairoli, R., Cambo, B., Vallisa, D., Venditti, A., Ferrara, F., Mannina, D., Cilloni, D., La Sala, E., Piciocchi, A., Falini, B., Pane, F., Saglio, G., Vignetti, M., Amadori, S., Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, and Amadori, S

Subjects
Hematology
Published
2021

14. Safety and efficacy of NEPA and dexamethasone in Hodgkin's lymphoma patients: a single-center real-life experience

Author

Zilioli V, Muzi C, Minga P, Codega P, Crucitti L, Meli E, Esposito A, Panico C, Rusconi C, Cairoli R, Zilioli, V, Muzi, C, Minga, P, Codega, P, Crucitti, L, Meli, E, Esposito, A, Panico, C, Rusconi, C, and Cairoli, R

Subjects
Hodgkin’s lymphoma, CINV, NEPA, ABVD, netupitant, palonosetron
Abstract

We analyzed safety of NEPA (netupitant/palonosetron) and dexamethasone (NEPA+DEX) for the management of chemotherapy-induced nausea and vomiting (CINV) in classical Hodgkin's lymphoma patients that experienced CINV with a prophylaxis with palonosetron (PALO + DEX). In a retrospective, monocentric, noncomparative study, we analyzed adverse events and CINV grading in patients who switched from PALO + DEX to NEPA + DEX. Among 32 patients treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) during the study period, 47% did not properly control CINV with PALO + DEX and were shifted to NEPA + DEX. Among these, 53.3% properly controlled CINV is for all the remaining chemotherapy cycles. We did not observe an increase of adverse events after switching to NEPA. In our study, NEPA did not show drug-drug interaction with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy agents and NEPA administration was well tolerated with mild and transient adverse events.

Published
2020

15. New Insights from CAR-T: An Economic and Organizational Perspective

Author

Foglia E., Garagiola E, Ferrario LB, Ladisa V, Scorza A, Rambaldi A, Cairoli R, Medaglia ML, Simona M, Sale EO, Omodeo E, Zinzani PL, Esposti M, Alberti L, Marcias M, Mulas MF, Satta V, Melis E, Onnis S, Croce D, Foglia, E, Garagiola, E, Ferrario, L, Ladisa, V, Scorza, A, Rambaldi, A, Cairoli, R, Medaglia, M, Simona, M, Sale, E, Omodeo, E, Zinzani, P, Esposti, M, Alberti, L, Marcias, M, Mulas, M, Satta, V, Melis, E, Onnis, S, and Croce, D

Subjects
Business Economic, Health Care Sciences Services
Published
2020

17. Prospective Evaluation of a Continuation Therapy with Midostaurin in Adult Patients with Core-Binding Factor Leukemia and Integrated Genetic Analysis: A Multi Center Phase II Study. Preliminary Results

Author

Cairoli R, Krampera M, Zappasodi P, Todisco E, Borlenghi E, Molteni A, Fumagalli M, Ubezio M, Bernardi M, Greco Ravelli, E (Ravelli, Erika), Mancini V, Grillo G, Riva M, De Marco B, Cassaro A, Brando B, Gatti A, Veronese SM, Beghini A, Cairoli, R, Krampera, M, Zappasodi, P, Todisco, E, Borlenghi, E, Molteni, A, Fumagalli, M, Ubezio, M, Bernardi, M, Greco, R, E,, Erika), Mancini, V, Grillo, G, Riva, M, De Marco, B, Cassaro, A, Brando, B, Gatti, A, Veronese, S, and Beghini, A

Subjects
medicine.medical_specialty, business.industry, Immunology, Phases of clinical research, Consolidation Chemotherapy, Cell Biology, Hematology, Neutropenia, medicine.disease, Biochemistry, chemistry.chemical_compound, Regimen, chemistry, Maintenance therapy, Internal medicine, Cytarabine, Medicine, Midostaurin, business, Adverse effect, medicine.drug
Abstract

Genetic and Clinical Background: The clinical outcome of Core Binding Factor Leukemia (CBFL) seems influenced by the mutational status of KIT. In fact, several retrospective studies, in addition to our own, as well as a systematic review, indicate that KIT mutations have a negative prognostic impact in AML with t(8;21) or, to a lesser extent, with inv(16)/t(16;16). In addition, gene expression studies found KIT to be highly expressed in CBFL regardless of its mutational status. Furthermore, recent studies have identified novel recurrent somatic mutations co-occurring with KITmut. In-vitro studies revealed that Midostaurin (Mido) is effective in inhibiting both wild type (WT) and a range of KIT mutants. In addition, it is proven to be effective in KIT-positive malignancies such as Aggressive Systemic Mastocytosis (ASM), Mast Cell Leukemia (MCL), and SM with Associated Hematological Neoplasm (SM-AHN). With this background, we designed a Phase II trial to evaluate the safety and efficacy of Mido in association with Intensive Chemotherapy (IC), in CBFL regardless of KIT mutational status. Methods: The inclusion criteria were the following: age 18 to 60 years, diagnosis of de-novo CBFL, adequate organ function, signed informed consent. The exclusion criteria were: central nervous system involvement, uncontrolled infections, other active malignancies, a Qtc value greater than 470 ms (according to Bazett formula) at the electrocardiogram, significant uncontrolled or active cardiovascular diseases. Patients received standard induction therapy with an anthracycline containing regimen ("7+3"-like) + Mido, three cycles of post-remission consolidation chemotherapy with high-dose cytarabine + Mido, and 12 months of Mido as Maintenance. The Mido dosage was: 50 mg orally twice a day, on days 8-21, in association with IC, and 50 mg orally twice a day as single agent maintenance. In order to attain a reduction in 2 years Relapse Incidence (RI), from the historical value of 48% to 28% (Primary Objective of the Study), we plan to enrol 39 patients (power 82%, alpha error 4,6%). At diagnosis all patients were studied by a comprehensive NGS panel targeting 40 DNA genes and 29 RNA fusion driver genes. MRD status was assessed by qPCR and high-resolution multicolor flow cytometry at established check-points during consolidation and maintenance therapy. Results: 17 patients were enrolled between December 2018 to April 2020 (table1). Overall, the CR rate was 94.2%. At a median follow-up of 9 months (range 3-19 months), we recorded a RI of 12.5%, an OS of 93.7%, and a DFS of 81.2%. 16 patients continue on study and 14 patients are in 1st CR, MRD-negative by flow cytometry and qPCR. Six patients (35.2 %) experienced 12 Treatment Emergent Adverse Event (TEAE), 10 out of whom were infections, with grade 3-4 neutropenia (Table 2). We only recorded one death from SARS-Cov2 infection (Interstitial Pneumonia) in a patient in MRD-negative complete remission. There were no treatment-related deaths. Conclusion: In patients with CBFL, the regimen consisting of intensive chemotherapy and consolidation chemotherapy in association with Mido, followed by Mido maintenance, had an acceptable safety profile and excellent response rates with a significant proportion of patients in MRD-negative complete remission. Trial is continuing to accrue (EudraCT Number 2017-002094-18; ClinicalTrials ID: NCT 03686345). This work was supported by a grant from Fondazione Regionale per la Ricerca Biomedica (FRRB 2015). Disclosures Krampera: Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Todisco:Jannsen, Abbvie, Jazz: Membership on an entity's Board of Directors or advisory committees. Veronese:Novartis: Other: Travel Expenses; Bayer: Honoraria; AstraZeneca: Other: Travel Expenses; Janssen Cilag: Honoraria. OffLabel Disclosure: Midostaurin for treatment of Core Binding Factor Leukemia. The drug has been used as KIT inhibitor.

Published
2020

18. 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 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, and Lo-Coco, F

Subjects
Hematology
Published
2019

19. IDENTIFICAZIONE DI MIRNA E GENI TARGET NELL’ANALISI TRASCRITTOMICA DELLE CELLULE CD34+/LIN- DI PAZIENTI CON LEUCEMIA MIELOIDE CRONICA IN FASE CRONICA DOPO 12 MESI DI TERAPIA CON NILOTINIB

Author

Trojani A, Pungolino E, Dal Molin A, Bossi LE, Rossi G, D'Adda M, Perego A, Elena C, Turrini M, Borin L, Bucelli C, Malato S, Carraro MC, Spina F, Latargia ML, Artale S, Spedini P, Anghilieri M, Di Camillo B, Baruzzo G, De Canal G, Iurlo A, Morra E, Cairoli R, Trojani, A, Pungolino, E, Dal Molin, A, Bossi, L, Rossi, G, D'Adda, M, Perego, A, Elena, C, Turrini, M, Borin, L, Bucelli, C, Malato, S, Carraro, M, Spina, F, Latargia, M, Artale, S, Spedini, P, Anghilieri, M, Di Camillo, B, Baruzzo, G, De Canal, G, Iurlo, A, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2019

20. PROGNOSTIC CORRELATION OF CELL-OF-ORIGIN AND MYC, BCL-2 AND BCL-6 STATUS IN HIV-ASSOCIATED DIFFUSE LARGE B-CELL LYMPHOMAS

Author

Rusconi C, Crucitti L, Re A, Bandiera L, Spina M, Gini G, Paulli M, Lucioni M, Facchetti F, Goteri G, Canzonieri V, Lorenzi L, Balzarini P, Fisogni S, Riboni R, Malfitano A, Bonfichi M, Moioli MC, Nichelatti M, Melle F, Motta G, Pileri SA, Cairoli R, Rusconi, C, Crucitti, L, Re, A, Bandiera, L, Spina, M, Gini, G, Paulli, M, Lucioni, M, Facchetti, F, Goteri, G, Canzonieri, V, Lorenzi, L, Balzarini, P, Fisogni, S, Riboni, R, Malfitano, A, Bonfichi, M, Moioli, M, Nichelatti, M, Melle, F, Motta, G, Pileri, S, and Cairoli, R

Subjects
Hematology
Published
2019

21. Identification of genes differently expressed between bone marrow CD34+/LIN-cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs 12 months of first-line nilotinib treatment

Author

Trojani A., Pungolino E., Rossi G., D'Adda M., Lodola M., Di Camillo B., Perego A., Turrini M., Orlandi E., Borin L., Iurlo A., Bucelli C., Malato S., Spina F., Latargia M.L., Lanza F., Artale S., Anghilieri M., Carraro M.C., De Canal G., Morra E., Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Bucelli, C, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, De Canal, G, Morra, E, and Cairoli, R

Subjects
CML
Published
2018

22. SENSITIVE AND EARLY DETECTION OF THE PML-A216V MUTATION BY DROPLET DIGITAL PCR IN ARSENIC TRIOXIDE RESISTANT ACUTE PROMYELOCYTIC LEUKEMIA

Author

Alfonso, V., Iaccarino, L., Ottone, T., Cicconi, L., Lavorgna, S., Divona, M., Cairoli, R., Cristiano, A., Ciardi, C., Patrizia Chiusolo, Venditti, A., Arcese, W., Voso, M. T., Lo Coco, F., Alfonso, V, Iaccarino, L, Ottone, T, Cicconi, L, Lavorgna, S, Divona, M, Cairoli, R, Cristiano, A, Ciardi, C, Chiusolo, P, Venditti, A, Arcese, W, Voso, M, and Lo Coco, F

Subjects
hematology
Published
2018

24. IDENTIFICATION OF MIRNA AND TARGET GENES IN THE TRANSCRIPTOME ANALYSIS OF CD34+/LIN- CELLS OF PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN THE CHRONIC PHASE AFTER 12 MONTHS OF NILOTINIB THERAPY

Author

Trojani, A., Pungolino, E., Dal Molin, A., Luca Emanuele Bossi, Rossi, G., D Adda, M., Perego, A., Elena, C., Turrini, M., Borin, L., Bucelli, C., Malato, S., Carraro, M. C., Spina, F., Latargia, M. L., Artale, S., Spedini, P., Anghilieri, M., Di Camillo, B., Baruzzo, G., Canal, G., Iurlo, A., Morra, E., and Cairoli, R.

Published
2019

28. SEQUENTIAL USE OF THROMBOPOIETIN RECEPTOR AGONISTS IN ADULT PRIMARY IMMUNE THROMBOCYTOPENIA PATIENTS: A RETROSPECTIVE COLLABORATIVE SURVEY FROM ITALIAN HEMATOLOGY CENTERS

Author

Carpenedo, M, Cantoni, S, Mazzucconi, MG, De Stefano, V, Carrai, V, Ruggeri, M, Specchia, G, Vianelli, N, Pane, F, Consoli, U, Zaja, F, Artoni, A, Trentin, L, Ferrara, F, Barcellini, W, Caramazza, D, Rossi, E, Baldacci, E, Ciminello, A, Carbone, C, Cairoli, R, Carpenedo, M, Cantoni, S, Mazzucconi, M, De Stefano, V, Carrai, V, Ruggeri, M, Specchia, G, Vianelli, N, Pane, F, Consoli, U, Zaja, F, Artoni, A, Trentin, L, Ferrara, F, Barcellini, W, Caramazza, D, Rossi, E, Baldacci, E, Ciminello, A, Carbone, C, and Cairoli, R

Subjects
Hematology
Published
2017

30. Gene Expression Profiling and Cellularity of Bone Marrow CD34+/Lin- Cells of Patients with Chronic-Phase Chronic Myeloid Leukemia at Diagnosis Vs. 12 Months of First-Line Nilotinib Treatment

Author

Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, EM, Borin, LM, Iurlo, A, Malato, S, Spina, F, Latargia, ML, Lanza, F, Artale, S, Anghilieri, M, Carraro, MC, Bucelli, C, De Canal, G, Morra, E, Cairoli R, Trojani, A, Pungolino, E, Rossi, G, D'Adda, M, Lodola, M, Di Camillo, B, Perego, A, Turrini, M, Orlandi, E, Borin, L, Iurlo, A, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bucelli, C, De Canal, G, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2017

35. Preliminary Experience of Imatinib after Nilotinib in the First Line Treatment of Chronic Myeloid Leukemia

Author

Pungolino, E, D'adda M, Perego A, Orlandi, EM, Turrini, M, Borin, LM, Iurlo, A, Artale, S, Latargia, ML, Anghilieri, M, Malato, S, Trojani, A, Spina, F, Carraro, MC, Pioltelli, ML, Elena, C, Bucelli, C, Spedini, P, Rossi, G, Morra, E, Cairoli, R, Pungolino, E, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Borin, L, Iurlo, A, Artale, S, Latargia, M, Anghilieri, M, Malato, S, Trojani, A, Spina, F, Carraro, M, Pioltelli, M, Elena, C, Bucelli, C, Spedini, P, Rossi, G, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2017

36. Jak-2 and Nfkbia Gene Expression Play a Strategic Role in Chronic Myeloid Leukemia (CML) Molecular Response during Early Nilotinib Treatment: The PhilosoPhi34 Data

Author

Pungolino E, D'adda M, Trojani A, Perego D, Pioltelli ML, Rossi G, Perego A, Elena C, Iurlo A, Malato S, Turrini M, De Canal G, Borin L, Lodola M, Caramella M, Artale S, Spina F, Latargia ML, Anghilieri M, Spedini P, Carraro M, Di Camillo B, Gramegna D, Morra E, Cairoli R, Pungolino, E, D'Adda, M, Trojani, A, Perego, D, Pioltelli, M, Rossi, G, Perego, A, Elena, C, Iurlo, A, Malato, S, Turrini, M, De Canal, G, Borin, L, Lodola, M, Caramella, M, Artale, S, Spina, F, Latargia, M, Anghilieri, M, Spedini, P, Carraro, M, Di Camillo, B, Gramegna, D, Morra, E, and Cairoli, R

Subjects
Janus kinase 2, biology, business.industry, Immunology, NFKBIA Gene, Myeloid leukemia, Cell Biology, Hematology, NFKB1, Biochemistry, Gene expression profiling, medicine.anatomical_structure, Nilotinib, Molecular Response, Cancer research, biology.protein, Medicine, Bone marrow, business, medicine.drug
Abstract

Background Targeted therapy with Tyrosine-Kinase-Inhibitors (TKIs) totally modified the course of treatment of Chronic Myeloid Leukemia (CML). The objectives and the needs of treatment have been modified during the last years and the discontinuation of therapy is now a feasible aim. However, a lot of biological data acquired in the last twenty years, showed that degree and mechanisms of Leukemic Stem Cells (LSCs) clearance during TKI treatment are not clearly established as well as the predictive criteria for a stable and prolonged Treatment Free Remission (TFR). The multicentre, prospective, single-arm PhilosoPhi34 study (EudraCT: 2012-005062-34) was designed by the Rete Ematologica Lombarda (REL), to verify the in-vivo activity and time-course of first-line Nilotinib (NIL) therapy on Bone Marrow (BM) CD34+/lin-Ph+ cells clearance. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells at diagnosis and at 12 months (mos) of treatment, for the first 30 evaluable pts, was included. Preliminary GEP data suggested a correlation between different NFKBIA expression at diagnosis and at 12 mos and the achievement of a deeper Molecular Response (MR) (Pungolino et al, AJH 2018). We report here some results of GEP analysis on all enrolled evaluable pts and their possible correlation with clinical data. Methods BM cells were collected and stored at diagnosis and at 12 mos of treatment. CD34+/lin- cells were purified with a Diamond CD34 Isolation Kit Miltenyi (97% of purity). For GEP analysis we used Affymetrix HG-U133 Plus 2.0 microarray and Genechip platform (Affymetrix) and the Affymetrix GeneChip Scanner 3000. Data was pre-processed and normalized using the Robust Multi-array Average (RMA) algorithm. The Significant Analysis of Microarrays (SAM) was used to identify genes with statistically significant changes in expression. P-values were corrected for multiple testing using false discovery rate, for differentially expressed genes confirmation. We chose to analyse different expression of NFKBIA (the inhibitor of NF-kB onco-gene) in order to confirm the preliminary data reported on the first 30 analysed pts. Pts were monitored according to ELN-recommendation. Biological data were correlated with MR at 3, 12 and 36 mos of therapy. We use Fishers test to compare unbalanced group. Results Out of the 87 enrolled pts, 80 completed the first 12 mos of treatment and 78 (1 failure and 77 CCyR) were evaluable for GEP analysis. We observed 2726 genes symbol differentially expressed of which 1868 are coding genes. Among these, JAK-2 showed a down regulation at 12 mos (p: .024). JAK-2 expression ranged from 2.62 to 4.95 at diagnosis and from 1.48 to 5.58 at 12 mos. Only 26/78 pts increased JAK-2 expression that was > 4 in 1/26 pts, at diagnosis; 2/26 (7.69%) pts showed a H Sokal. Other 52/78 pts decreased JAK-2 expression that was ≥ 4 in 21/52 pts, at diagnosis; 10/52 (19.23%) pts and 6/21 (28,57%) pts showed a H Sokal. Similarly, when we compared low JAK-2 expression (< 3.5) vs vary high expression (≥ 4) 2/21 vs 6/22 pts had H Sokal (9.52% vs 27.27%; p: .0057). Considering the role of JAK-2 and NFKBIA in cell regulation and survival, we evaluated how the combination of their different expression impact on MR (i.e. NFKBIA increased expression/JAK-2 decreased expression vs NFKBIA decreased expression/JAK-2 increased expression). Data are reported in Table 1 and 2. Conclusion GEP analysis showed a down regulation of JAK-2 expression after 12 mos of first line NIL treatment, in 78 early chronic phase CML pts. Data suggest that high expression of JAK-2, at diagnosis, correlate with H Sokal score. However, H Sokal pts with a JAK-2 down regulation, obtain during treatment similar MR compared to L Sokal pts. Additionally, the study confirms our preliminary observation on 30 pts , concerning the role of NKBIA up - regulation in increasing percentage of earlier and deeper MR . The better condition of NFKBIA and JAK-2 expression (up regulation of NFKBIA and down regulation of JAK-2) is associated with a higher percentage of early MR3 and optimal responses over time, despite the higher number of H Sokal pts in this group. A study with NIL as first line treatment combined with low dose of JAK-2 inhibitor and a natural inhibitor of NF-kB (such as curcuma), during the first year of treatment, to increase the deeper MR rate and the probability of TFR is warrented. Disclosures Rossi: Sandoz: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Teva: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Novartis: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Published
2018

37. Outcome of patients with chronic myeloid leukemia and a low-risk score: allogeneic hematopoietic stem cell transplantation in the era of targeted therapy. A report from the EBMT Chronic Malignancies Working Party

Author

Koenecke, C., Heim, D., Biezen, A. van, Heuser, M., Aljurf, M., Kyrcz-Krzemien, S., Volin, L., Souza, C.A. de, Gedde-Dahl, T., Sengeloev, H., Schanz, U., Komarnicki, M., Arroyo, C.H., Tholouli, E., Gluckman, E., Esquirol, A., Yakoub-Agha, I., Gurman, G., Olavarria, E., Kroger, N., Rovira, M., Kahls, P., Alegre, A., Nemet, D., Stamatovic, D., Vitek, A., Hamladji, R., Hellmann, A., Chybicka, A., Wiktor-Jedrzejczak, W., Maiolino, A., Borne, P.V.D., Chevallier, P., Littlewood, T., Crawley, C., Mistrik, M., Schafer-Eckart, K., Orchard, K., Maertens, J., Lint, M. van, Ethell, M., Vettenranta, K., Broom, A., Deconinck, E., Schaap, N., Petersen, E., Espiga, C.R., Bartolomeo, P. di, Brown, P., Beelen, D., Leblond, V., Leleu, X., Carlson, K., Milpied, N., Collin, M., Johansson, J., Cairoli, R., Serwe, H., Schleuning, M., Ozturk, M., Lisukov, I.A., Robinson, S., Uckan-Cetinkaya, D., Rohrlich, P., Visani, G., Merli, F., Sanz, M., Michallet, M., Halaburda, K., O'Brien, T., Jindra, P., Feldman, L., Theobald, M., Favre, C., Rodeghiero, F., Finke, J., Koenecke, C, Heim, D, Van Biezen, A, Heuser, M, Aljurf, M, Kyrcz-Krzemien, S, Volin, L, De Souza, C, Gedde-Dahl, T, Sengeloev, H, Schanz, U, Komarnicki, M, Arroyo, C, Tholouli, E, Gluckman, E, Esquirol, A, Yakoub-Agha, I, Gurman, G, Olavarria, E, Kroger, N, Cairoli, R, and University of Zurich

Subjects
0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Adolescent, 2747 Transplantation, medicine.medical_treatment, 2720 Hematology, Decision Making, Medizin, 610 Medicine & health, Hematopoietic stem cell transplantation, Risk Assessment, Targeted therapy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Humans, Transplantation, Homologous, Molecular Targeted Therapy, Progenitor cell, Child, Transplantation, Homologou, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, medicine.disease, Algorithm, 030104 developmental biology, Graft-versus-host disease, Treatment Outcome, 10032 Clinic for Oncology and Hematology, Immunology, Female, Stem cell, business, Algorithms, Human, 030215 immunology, Chronic myelogenous leukemia
Abstract

Outcome of patients with chronic myeloid leukemia and a low-risk score: allogeneic hematopoietic stem cell transplantation in the era of targeted therapy. A report from the EBMT Chronic Malignancies Working Party

Published
2016

38. DIFFERENT SETS OF GENES WERE ASSOCIATED TO THE MOLECULAR RESPONSE AFTER 3 AND 6 MONTHS OF FIRST-LINE NILOTINIB TREATMENT BY MICROARRAY OF CD34+/LIN- CELLS OF CHRONIC PHASE CML PATIENTS AT DIAGNOSIS

Author

Trojani A, Pungolino E, Lodola M, Di Camillo B, D'Adda M, Perego A, Turrini M, Orlandi E, Elena C, Iurlo A, Bucelli C, Borin L, Malato S, Spina F, Latargia ML, Lanza F, Artale S, Anghilieri M, Carraro MC, Bertinato E, Morra E, Cairoli R, Trojani, A, Pungolino, E, Lodola, M, Di Camillo, B, D'Adda, M, Perego, A, Turrini, M, Orlandi, E, Elena, C, Iurlo, A, Bucelli, C, Borin, L, Malato, S, Spina, F, Latargia, M, Lanza, F, Artale, S, Anghilieri, M, Carraro, M, Bertinato, E, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2016

40. VALIDATING THE PATIENT'S 'FITNESS' CRITERIA PROPOSED TO GUIDE TREATMENT DECISION IN ELDERLY AML: A MULTICENTER STUDY ON A SERIES OF 699 PATIENTS BY THE NETWORK 'RETE EMATOLOGICA LOMBARDA'

Author

Borlenghi, E, Pagani, C, Basilico, C, Bernardi, M, Cairoli, R, Cortelezzi, A, Davia, M, Ferrario, A, Fracchiolla, N, Marbello, L, Messina, C, Santoro, A, Todisco, E, Turrini, M, Zappasodi, P, Cattaneo, C, Lamorgese, C, Rossi, G, Borlenghi, E, Pagani, C, Basilico, C, Bernardi, M, Cairoli, R, Cortelezzi, A, Davia, M, Ferrario, A, Fracchiolla, N, Marbello, L, Messina, C, Santoro, A, Todisco, E, Turrini, M, Zappasodi, P, Cattaneo, C, Lamorgese, C, and Rossi, G

Subjects
Hematology
Published
2016

41. REL-PROTOCOL PHILOSOPHI34 CONFIRMS THAT NILOTINIB RAPIDLY INDUCES CD34+/LIN-PH+ CELLS DISAPPEARANCE IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA (CML) IN CHRONIC PHASE (CP)

Author

Pungolino, E, De Canal, G, D'Adda, M, Perego, A, Orlandi, EM, Turrini, M, Trojani, A, Malato, S, Lodola, M, Borin, L, Iurlo, A, Artale, S, Spina, F, Pioltelli, ML, Latargia, ML, Brusorio, S, Elena, C, Lanza, F, Anghilieri, M, Carraro, MC, Rossi, G, Morra, E, Cairoli, R, Pungolino, E, De Canal, G, D'Adda, M, Perego, A, Orlandi, E, Turrini, M, Trojani, A, Malato, S, Lodola, M, Borin, L, Iurlo, A, Artale, S, Spina, F, Pioltelli, M, Latargia, M, Brusorio, S, Elena, C, Lanza, F, Anghilieri, M, Carraro, M, Rossi, G, Morra, E, and Cairoli, R

Subjects
Hematology
Published
2016

45. THE EFFICACY OF THE 5-AZACITIDINE IN THE THERAPY-RELATED MYELOID NEOPLASIA: A RETROSPECTIVE MULTICENTRIC EXPERIENCE

Author

Riva, M., Molteni, A., Borin, L., Bernardi, M., Pellizzari, A., Freyrie, A., Della Porta, M., Nichelatti, M., Ravano, E., Quaresmini, G., Jacopo Mariotti, Caramazza, D., Ubezio, M., Guarco, S., Gigli, F., Greco, R., Cairoli, R., Riva, M, Molteni, A, Borin, L, Bernardi, M, Pellizzari, A, Freyrie, A, Della Porta, M, Nichelatti, M, Ravano, E, Quaresmini, G, Mariotti, J, Caramazza, D, Ubezio, M, Guarco, S, Gigli, F, Greco, R, and Cairoli, R

Subjects
hematology
Published
2015

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