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105. CLINICAL CHARACTERISTICS AND OUTCOME OF INVASIVE INFECTIONS DUE TO SAPROCHAETE SPECIES IN PATIENTS AFFECTED BY HEMATOLOGICAL MALIGNANCIES. A MULTI-CENTER STUDY ON BEHALF OF SEIFEM/FUNGISCOPE REGISTRY

Author

Del Principe, M. I., Criscuolo, M., Seidel, D., Dargenio, M., Racil, Z., Piedimonte, M., Marchesi, F., Nadali, G., Koehler, P., Fracchiolla, N., Cattaneo, C., Klimko, N., Spolzino, A., Karapinar, D. Yilmaz, Demiraslan, H., Duarte, R., Demeter, J., Stanziani, M., Melillo, L., Basilico, C. M., Cesaro, S., Paterno, G., Oliver Cornely, Califano, C., Delia, M., Busca, A., and Pagano, L.

106. Bcl-2 protein expression and p53 gene mutation in chronic lymphocytic leukemia: correlation with in vitro sensitivity to chlorambucil and purine analogs

Author

Morabito, F., Filangeri, M., Callea, I., Sculli, G., Callea, V., Fracchiolla, N. S., antonino neri, and Brugiatelli, M.

Subjects
Antimetabolites, Antineoplastic, Cell Survival, DNA, Neoplasm, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell, Polymerase Chain Reaction, Neoplasm Proteins, Proto-Oncogene Proteins c-bcl-2, Drug Resistance, Neoplasm, Tumor Cells, Cultured, Cladribine, Humans, Chlorambucil, Antineoplastic Agents, Alkylating, Polymorphism, Single-Stranded Conformational, Vidarabine
Abstract

Bcl-2 oncogenic protein expression plays a major role in blocking the apoptotic mechanism. p53 gene mutations have also been suggested to account for the chlorambucil resistance in CLL. Thus we studied the relationship between bcl-2 protein expression, p53 gene mutations and in vitro drug sensitivity in CLL.Fifty-three samples from untreated CLL patients in early disease stages were tested in vitro for chemosensitivity to chlorambucil (CLB), fludarabine (FAMP) and 2-chlorodeoxyadenosine (2-CDA) using the MTT assay. Intracellular bcl-2 protein expression was evaluated by flow cytometry analysis. p53 gene mutations were detected by using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis.The median LD50 values were 1.55 microM, 4.41 microM and 58.2 microM for 2-CDA, FAMP and CLB, respectively. About 23%, 41% and 11% of samples were defined as being sensitive to FAMP, 2-CDA and CLB, respectively, when samples were clustered for LD50 threshold values corresponding to the plasmatic levels of the drug. No statistically significant difference in bcl-2 protein expression was noted between sensitive and resistant samples for each drug. A p53 gene mutation was detected in 4 of the 30 cases studies and all of them were among samples resistant to CLB.Bcl-2 expression is not an indicator of in vitro response to drugs in CLL; similarly, although the four cases showing a p53 gene mutation were associated with CLB resistance, drug resistant samples were also observed in the group of patients showing wild type p53, suggesting multiple mechanisms of drug resistance in CLL.

109. NELARABINE AS SALVAGE THERAPY AND BRIDGE TO ALLOGENEIC STEM CELLS TRANSPLANTATION IN 118 ADULT PATIENTS WITH RELAPSED/REFRACTORY T-ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA. A CAMPUS-ALL, PHASE 4, STUDY

Author

anna candoni, Lazzarotto, D., Curti, A., Ferrara, F., Lussana, F., Papayannidis, C., Del Principe, M. I., Bonifacio, M., Mosna, F., Delia, M., Minetto, P., Gottardi, M., Fracchiolla, N., Mancini, V., Forghieri, F., Zappasoldi, P., Cerrano, M., Vitale, A., Audisio, E., Trappolini, S., Romani, C., Defina, M., Imbergamo, S., Ciccone, N., Santoro, L., Cambo, B., Iaccarino, S., Dargenio, M., Aprile, L., Elia, L., La Starza, R., Pizzolo, G., and Foa, R.

110. SEIFEM 2015-B: INCIDENCE AND MORTALITY FOR CANDIDEMIA IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

Author

Dragonetti, G., Cattaneo, C., Marchesi, F., Aversa, F., Busca, A., Candoni, A., Castagnola, C., Cesaro, S., Criscuolo, M., Del Principe, M. I., Decembrino, N., Delia, M., Fanci, R., Ferrari, A., Fracchiolla, N. S., Lessi, F., Mancini, V., Martino, B., Melillo, L., Nadali, G., Nosari, A., Perruccio, K., Picardi, M., Prezioso, L., Stanzani, M., Tumbarello, M., Veggia, B., and Livio PAGANO

116. INCIDENCE, TREATMENT AND OUTCOME OF CENTRAL NERVOUS SYSTEM RELAPSE IN ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA TREATED FRONT-LINE WITH PEDIATRIC-INSPIRED REGIMENS. A RETROSPECTIVE MULTI-CENTER STUDY OF THE CAMPUS ALL

Author

Dargenio, M., Bonifacio, M., Chiaretti, S., Vitale, A., Fracchiolla, N., Papayannidis, C., Giglio, F., Salutari, P., Audisio, E., Scappini, B., Zappasodi, P., Defina, M., Forghieri, F., Scattolin, A. M., Todisco, E., Lunghi, M., Fabio Guolo, Del Principe, M. I., Annunziata, M., Lazzarotto, D., Cedrone, M., Pasciolla, C., Imovilli, A., Tanasi, I., Trappolini, S., Cerrano, M., La Starza, R., Pizzolo, G., Ferrara, F., and Foa, R.

122. Outcomes of an Automated Procedure for the Selection of Effective Platelets for Patients Refractory to Random Donors Based on Crossmatching Available Platelet Products.

Author

Rebulla, P., Morelati, F., Revelli, N., Villa, M., Drago, F., Sironi, P., Greppi, N., Marconi, M., Sirchia, G., Cortelezzi, A., Fracchiolla, N., Soligo, D., Tagliaferri, E., and Martinelli, G.

Subjects
BLOOD platelets, BLOOD donors, BLOOD products, HEMATOLOGY
Abstract

Background. In 1998 we modified our policy for the management of patients refractory to random donor platelet support. In this study we evaluated pre- and post-transfusion platelet counts in the 25 consecutive, refractory and HLA allo-immunized hematology patients transfused in the 18 months after implementation of the new policy. Methods. The policy is based on an automated solid-phase cross-match (XM) procedure performed by testing patient's serum vs platelets obtained from supernatants of complete blood count (CBC) samples routinely collected from blood donors. In our institution approximately 100 whole blood donations are collected per day. All units are deprived of the buffy-coats, which are stored overnight at 20-24 C and pooled on the following morning to prepare platelet pools (1 pool=6 donors). After CBC determination, CBC samples are stored overnight in case platelet XM are needed on the next morning. Patients are considered for XM when they develop on 2-3 occasions 20-24 hour post-transfusion platelet count increments lower than 5×10[sup 9]/L. XM is performed by the automated ABS Precis device with the Immucor (Norcross, GA) Capturo-P assay kit. The operator places donor CBC samples after soft centrifugation or overnight sedimentation into racks of the ABS Precis, which dispenses test platelets from the CBC samples supernatants into the kit plate wells, performs incubations and washings, adds patient's serum, indicator red cells, performs final readings and prints results. Platelet pools are finally prepared with buffy-coats from XM negative donors. Average time to XM 1 serum vs 90 donors is 160 min. Results. Mean ± SD pre-transfusion, 1-hour and 24-hour post-transfusion platelet counts (x10[sup 9]/L) of the 336 XM negative transfusions containing a mean of 302×10[sup 9] platelets, given to the 25 refractory patients, were: 8±6, 32±23, 16±15 respectively. Increments were significantly higher (p<0.05, t-test) than those observed in the same patients with 225 random platelet pools (mean dose 326×10[sup 9] platelets) immediately before the use of XM negative platelets: pre 8±9, 1-hour 15±16, 24-hour 10±13. Conclusions. The automated platelet XM program is a useful tool to rapidly select effective platelets for refractory patients from local inventory. [ABSTRACT FROM AUTHOR]

Published
2001

123. COVID-19 elicits an impaired antibody response against SARS-CoV-2 in patients with haematological malignancies

Author

Francesco Zaja, Filippo Gherlinzoni, Anna Maria Scattolin, Luca Arcaini, Roberto Cairoli, Mario Luppi, Carmen Fava, Patrizia Zappasodi, Matteo G. Della Porta, Monica Bocchia, Valeria Cardinali, Nicola Stefano Fracchiolla, Francesco Passamonti, Giuseppe Visani, M. Ladetto, Enrico Derenzini, Lorenza Bertù, Roberto Mina, Daniele Armiento, B. Mora, Anna Candoni, Alessandro Corso, A. M. Vannucchi, Paolo Corradini, Francesco Lanza, Pellegrino Musto, Agostino Tafuri, Carlo Visco, E. Coviello, Francesco Marchesi, Roberto M. Lemoli, Chiara Cattaneo, Alessandro Busca, Marco Salvini, Sara Galimberti, I. Romano, M. Merli, Mauro Krampera, Alessandra Romano, Paolo Grossi, Michele Cavo, E. O. La Barbera, Mauro Turrini, Livio Pagano, Adriano Venditti, Antonio Pinto, Patrizia Tosi, F. Farina, Riccardo Bruna, L. Petrucci, Massimo Massaia, Monia Marchetti, Carlo Gambacorti Passerini, Francesco Merli, Passamonti, F, Romano, A, Salvini, M, Merli, F, Porta, M, Bruna, R, Coviello, E, Romano, I, Cairoli, R, Lemoli, R, Farina, F, Venditti, A, Busca, A, Ladetto, M, Massaia, M, Pinto, A, Arcaini, L, Tafuri, A, Marchesi, F, Fracchiolla, N, Bocchia, M, Armiento, D, Candoni, A, Krampera, M, Luppi, M, Cardinali, V, Galimberti, S, Cattaneo, C, La Barbera, E, Mina, R, Lanza, F, Visani, G, Musto, P, Petrucci, L, Zaja, F, Grossi, P, Bertu, L, Pagano, L, Corradini, P, Derenzini, E, Marchetti, M, Scattolin, A, Corso, A, Tosi, P, Gherlinzoni, F, Gambacorti Passerini, C, Cavo, M, Fava, C, Turrini, M, Visco, C, Zappasodi, P, Merli, M, Mora, B, Vannucchi, A, Passamonti F., Romano A., Salvini M., Merli F., Porta M.G.D., Bruna R., Coviello E., Romano I., Cairoli R., Lemoli R., Farina F., Venditti A., Busca A., Ladetto M., Massaia M., Pinto A., Arcaini L., Tafuri A., Marchesi F., Fracchiolla N., Bocchia M., Armiento D., Candoni A., Krampera M., Luppi M., Cardinali V., Galimberti S., Cattaneo C., La Barbera E.O., Mina R., Lanza F., Visani G., Musto P., Petrucci L., Zaja F., Grossi P.A., Bertu L., Pagano L., Corradini P., Derenzini E., Marchetti M., Scattolin A.M., Corso A., Tosi P., Gherlinzoni F., Passerini C.G., Cavo M., Fava C., Turrini M., Visco C., Zappasodi P., Merli M., Mora B., Vannucchi A.M., Passamonti, F., Romano, A., Salvini, M., Merli, F., Porta, M. G. D., Bruna, R., Coviello, E., Romano, I., Cairoli, R., Lemoli, R., Farina, F., Venditti, A., Busca, A., Ladetto, M., Massaia, M., Pinto, A., Arcaini, L., Tafuri, A., Marchesi, F., Fracchiolla, N., Bocchia, M., Armiento, D., Candoni, A., Krampera, M., Luppi, M., Cardinali, V., Galimberti, S., Cattaneo, C., La Barbera, E. O., Mina, R., Lanza, F., Visani, G., Musto, P., Petrucci, L., Zaja, F., Grossi, P. A., Bertu, L., Pagano, L., Corradini, P., Derenzini, E., Marchetti, M., Scattolin, A. M., Corso, A., Tosi, P., Gherlinzoni, F., Passerini, C. G., Cavo, M., Fava, C., Turrini, M., Visco, C., Zappasodi, P., Merli, M., Mora, B., and Vannucchi, A. M.

Subjects
Male, Myeloid, Antibodies, Viral, Gastroenterology, SARS‐CoV‐2, 80 and over, Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma, Viral, Covid‐19, Aged, 80 and over, biology, Hematology, Plasma cell neoplasm, Middle Aged, Adult, Aged, COVID-19, Female, Hematologic Neoplasms, Humans, Immunoglobulin G, Seroconversion, Young Adult, Antibody Formation, Leukemia, medicine.anatomical_structure, Antibody, Human, medicine.medical_specialty, Short Report, Antibodies, NO, Chemoimmunotherapy, Internal medicine, medicine, Hematologic Neoplasm, business.industry, Odds ratio, Settore MED/15, medicine.disease, Covid-19, SARS-CoV-2, leukemia, lymphoma, myeloma, Lymphoma, Settore MED/15 - MALATTIE DEL SANGUE, biology.protein, business
Abstract

COVID-19 is associated with high mortality in patients with haematological malignancies (HM) and rate of seroconversion is unknown. The ITA-HEMA-COV project (NCT04352556) investigated patterns of seroconversion for SARS-CoV-2 IgG in patients with HMs. A total of 237 patients, SARS-CoV-2 PCR-positive with at least one SARS-CoV-2 IgG test performed during their care, entered the analysis. Among these, 62 (26·2%) had myeloid, 121 (51·1%) lymphoid and 54 (22·8%) plasma cell neoplasms. Overall, 69% of patients (164 of 237) had detectable IgG SARS-CoV-2 serum antibodies. Serologically negative patients (31%, 73 of 237) were evenly distributed across patients with myeloid, lymphoid and plasma cell neoplasms. In the multivariable logistic regression, chemoimmunotherapy [odds ratio (OR), 3·42; 95% confidence interval (CI), 1·04–11·21; P=0·04] was associated with a lower rate of seroconversion. This effect did not decline after 180days from treatment withdrawal (OR, 0·35; 95% CI: 0·11–1·13; P=0·08). This study demonstrates a low rate of seroconversion in HM patients and indicates that treatment-mediated immune dysfunction is the main driver. As a consequence, we expect a low rate of seroconversion after vaccination and thus we suggest testing the efficacy of seroconversion in HM patients.

Published
2021

124. High Throughput Molecular Characterization of Normal Karyotype Acute Myeloid Leukemia in the Context of the Prospective Trial 02/06 of the Northern Italy Leukemia Group (NILG)

Author

Renato Bassan, Chiara Pavoni, Pamela Zanghì, Elisabetta Todisco, Nicola Stefano Fracchiolla, Anna Michelato, Leonardo Campiotti, Federico Lussana, Roberta Cavagna, Annamaria Scattolin, Giacomo Gianfaldoni, Chiara Caprioli, Erika Borlenghi, Fabio Ciceri, Ernesta Audisio, Alessandro Rambaldi, Lorella De Paoli, Tamara Intermesoli, Elisabetta Terruzzi, Orietta Spinelli, Ksenija Buklijas, Lara Elidi, Silvia Salmoiraghi, Paola Stefanoni, Paolo Corradini, Daniele Mattei, Irene Cavattoni, Monica Tajana, Elena Oldani, Salmoiraghi, S, Cavagna, R, Zanghì, P, Pavoni, C, Michelato, A, Buklijas, K, Elidi, L, Intermesoli, T, Lussana, F, Oldani, E, Caprioli, C, Stefanoni, P, Gianfaldoni, G, Audisio, E, Terruzzi, E, De Paoli, L, Borlenghi, E, Cavattoni, I, Mattei, D, Scattolin, A, Tajana, M, Ciceri, F, Todisco, E, Campiotti, L, Corradini, P, Fracchiolla, N, Bassan, R, Rambaldi, A, Spinelli, O, Salmoiraghi, S., Cavagna, R., Zanghi, P., Pavoni, C., Michelato, A., Buklijas, K., Elidi, L., Intermesoli, T., Lussana, F., Oldani, E., Caprioli, C., Stefanoni, P., Gianfaldoni, G., Audisio, E., Terruzzi, E., Paoli, L. D., Borlenghi, E., Cavattoni, I., Mattei, D., Scattolin, A., Tajana, M., Ciceri, F., Todisco, E., Campiotti, L., Corradini, P., Fracchiolla, N., Bassan, R., Rambaldi, A., and Spinelli, O.

Subjects
Oncology, Acute Myeloid Leukemia, Cancer Research, medicine.medical_specialty, NPM1, Context (language use), Gene mutation, Molecular marker, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Prospective cohort study, molecular marker, business.industry, Induction chemotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Transplantation, Leukemia, 030220 oncology & carcinogenesis, NGS, embryonic structures, business, 030215 immunology, Cohort study
Abstract

By way of a Next-Generation Sequencing NGS high throughput approach, we defined the mutational profile in a cohort of 221 normal karyotype acute myeloid leukemia (NK-AML) enrolled into a prospective randomized clinical trial, designed to evaluate an intensified chemotherapy program for remission induction. NPM1, DNMT3A, and FLT3-ITD were the most frequently mutated genes while DNMT3A, FLT3, IDH1, PTPN11, and RAD21 mutations were more common in the NPM1 mutated patients (p &lt, 0.05). IDH1 R132H mutation was strictly associated with NPM1 mutation and mutually exclusive with RUNX1 and ASXL1. In the whole cohort of NK-AML, no matter the induction chemotherapy used, by multivariate analysis, the achievement of complete remission was negatively affected by the SRSF2 mutation. Alterations of FLT3 (FLT3-ITD) and U2AF1 were associated with a worse overall and disease-free survival (p &lt, 0.05). FLT3-ITD positive patients who proceeded to alloHSCT had a survival probability similar to FLT3-ITD negative patients and the transplant outcome was no different when comparing high and low-AR-FLT3-ITD subgroups in terms of both OS and DFS. In conclusion, a comprehensive molecular profile for NK-AML allows for the identification of genetic lesions associated to different clinical outcomes and the selection of the most appropriate and effective treatment strategies, including stem cell transplantation and targeted therapies.

Published
2020

125. AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia

Author

Todisco, Elisabetta, Papayannidis, Cristina, Fracchiolla, Nicola, Petracci, Elisabetta, Zingaretti, Chiara, Vetro, Calogero, Martelli, Maria Paola, Zappasodi, Patrizia, Di Renzo, Nicola, Gallo, Susanna, Audisio, Ernesta, Griguolo, Davide, Cerchione, Claudio, Selleri, Carmine, Mattei, Daniele, Bernardi, Massimo, Fumagalli, Monica, Rizzuto, Giuliana, Facchini, Luca, Basilico, Claudia Maria, Manfra, Ilenia, Borlenghi, Erika, Cairoli, Roberto, Salutari, Prassede, Gottardi, Michele, Molteni, Alfredo, Martini, Vincenza, Lunghi, Monia, Fianchi, Luana, Cilloni, Daniela, Lanza, Francesco, Abruzzese, Elisabetta, Cascavilla, Nicola, Rivellini, Flavia, Ferrara, Felicetto, Maurillo, Luca, Nanni, Jacopo, Romano, Alessandra, Cardinali, Valeria, Gigli, Federica, Roncoroni, Elisa, Federico, Vincenzo, Marconi, Giovanni, Volpi, Roberta, Sciumè, Mariarita, Tarella, Corrado, Rossi, Giuseppe, Martinelli, Giovanni, Todisco, Elisabetta, Papayannidis, Cristina, Fracchiolla, Nicola, Petracci, Elisabetta, Zingaretti, Chiara, Vetro, Calogero, Martelli, Maria Paola, Zappasodi, Patrizia, Di Renzo, Nicola, Gallo, Susanna, Audisio, Ernesta, Griguolo, Davide, Cerchione, Claudio, Selleri, Carmine, Mattei, Daniele, Bernardi, Massimo, Fumagalli, Monica, Rizzuto, Giuliana, Facchini, Luca, Basilico, Claudia Maria, Manfra, Ilenia, Borlenghi, Erika, Cairoli, Roberto, Salutari, Prassede, Gottardi, Michele, Molteni, Alfredo, Martini, Vincenza, Lunghi, Monia, Fianchi, Luana, Cilloni, Daniela, Lanza, Francesco, Abruzzese, Elisabetta, Cascavilla, Nicola, Rivellini, Flavia, Ferrara, Felicetto, Maurillo, Luca, Nanni, Jacopo, Romano, Alessandra, Cardinali, Valeria, Gigli, Federica, Roncoroni, Elisa, Federico, Vincenzo, Marconi, Giovanni, Volpi, Roberta, Sciumè, Mariarita, Tarella, Corrado, Rossi, Giuseppe, Martinelli, Giovanni, Todisco, E, Papayannidis, C, Fracchiolla, N, Petracci, E, Zingaretti, C, Vetro, C, Martelli, M, Zappasodi, P, Di Renzo, N, Gallo, S, Audisio, E, Griguolo, D, Cerchione, C, Selleri, C, Mattei, D, Bernardi, M, Fumagalli, M, Rizzuto, G, Facchini, L, Basilico, C, Manfra, I, Borlenghi, E, Cairoli, R, Salutari, P, Gottardi, M, Molteni, A, Martini, V, Lunghi, M, Fianchi, L, Cilloni, D, Lanza, F, Abruzzese, E, Cascavilla, N, Rivellini, F, Ferrara, F, Maurillo, L, Nanni, J, Romano, A, Cardinali, V, Gigli, F, Roncoroni, E, Federico, V, Marconi, G, Volpi, R, Sciumè, M, Tarella, C, Rossi, G, and Martinelli, G

Subjects
Cancer Research, hypomethylating agents, Oncology, hypomethylating agent, relapsed and refractory AML, venetoclax, real-life data, acute myeloid leukemia
Abstract

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia. Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax+HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here. Results: In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE-A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60days of therapy. Infections were confirmed as the most common nonhematologic adverse event. Conclusions: Real-life data show that the combination of venetoclax and HMA offers an expectation of remission and long-term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax+HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax+HMA effectiveness and toxicities in real life.

Published
2023

126. Validation of the 'fitness criteria' for the treatment of older patients with acute myeloid leukemia: A multicenter study on a series of 699 patients by the Network Rete Ematologica Lombarda (REL)

Author

Chiara Pagani, Erika Borlenghi, Matteo Claudio Da Via, Chiara Cattaneo, Fabio Ciceri, Roberto Cairoli, Francesco Passamonti, Massimo Bernardi, Claudia Basilico, Nicola Stefano Fracchiolla, Valentina Mancini, Mauro Turrini, Mariarita Sciumè, Elisabetta Todisco, Giuseppe Rossi, Patrizia Zappasodi, Elisa Cerqui, Margherita Sciumé, Borlenghi, E, Pagani, C, Zappasodi, P, Bernardi, M, Basilico, C, Cairoli, R, Fracchiolla, N, Todisco, E, Turrini, M, Cattaneo, C, Da Via, M, Ciceri, F, Passamonti, F, Mancini, V, Sciume, M, Cerqui, E, and Rossi, G

Subjects
medicine.medical_specialty, Multivariate analysis, Fitne, Concordance, Karyotype, Comorbidity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Fitness, medicine, Humans, 030212 general & internal medicine, Exercise, Aged, Retrospective Studies, Acute myeloid leukemia, Performance status, business.industry, Older, Treatment, Myeloid leukemia, Retrospective cohort study, medicine.disease, Clinical trial, Leukemia, Myeloid, Acute, Leukemia, Oncology, 030220 oncology & carcinogenesis, Geriatrics and Gerontology, business
Abstract

Objectives: Treatment of older patients with acute myeloid leukemia (AML) is still controversial. To facilitate treatment decisions, the “fitness criteria” proposed by Ferrara et al. (Leukemia, 2013), including age > 75 years, performance status and comorbidities, were verified retrospectively in 699 patients with AML (419 de-novo, 280 secondary AML), diagnosed at 8 Hematological Centers (REL). Methods: Patients were categorized in FIT to intensive chemotherapy (i-T) (292, 42.5%), UNFIT to i-T (289, 42.1%), or unfit even to non-intensive therapy (non i-T) (FRAIL) (105, 15.3%). Biological characteristics and treatment actually received by patients [i-T, 274 patients (39.2%); non i-T, 134 (19.2%), best-supportive care (BSC), 291 (41.6%)] were recorded. Results: “Fitness criteria” were easily applicable in 98.1% of patients. Overall concordance between “fitness criteria” and treatment actually received by patients was high (79.4%), 76% in FIT, 82.7% in UNFIT and 80% in FRAIL patients. Fitness independently predicted survival (median survival: 10.9, 4.2 and 1.8 months in FIT, UNFIT and FRAIL patients, respectively; p = 0.000), as confirmed also by multivariate analysis. In FRAIL patients, survival with any treatment was no better than with BSC, in UNFIT non i-T was as effective as i-T and better than BSC, and in FIT patients i-T was better than non i-T or BSC. In addition, a non-adverse risk AML, an ECOG PS

Published
2021

127. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study

Author

Marco Cerrano, Massimiliano Bonifacio, Matteo Olivi, Antonio Curti, Michele Malagola, Michelina Dargenio, Anna Maria Scattolin, Cristina Papayannidis, Fabio Forghieri, Carmela Gurrieri, Ilaria Tanasi, Patrizia Zappasodi, Roberta La Starza, Nicola Stefano Fracchiolla, Patrizia Chiusolo, Luisa Giaccone, Maria Ilaria Del Principe, Fabio Giglio, Marzia Defina, Claudio Favre, Carmelo Rizzari, Barbara Castella, Giovanni Pizzolo, Felicetto Ferrara, Sabina Chiaretti, Robin Foà, Cerrano, M, Bonifacio, M, Olivi, M, Curti, A, Malagola, M, Dargenio, M, Scattolin, A, Papayannidis, C, Forghieri, F, Gurrieri, C, Tanasi, I, Zappasodi, P, Starza, R, Fracchiolla, N, Chiusolo, P, Giaccone, L, Del Principe, M, Giglio, F, Defina, M, Favre, C, Rizzari, C, Castella, B, Pizzolo, G, Ferrara, F, Chiaretti, S, and Foa, R

Subjects
Humans, Antibodies, Monoclonal, Hematology, MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Human, Retrospective Studies
Published
2022

128. A prognostic model for patients with lymphoma and COVID-19: a multicentre cohort study

Author

Francesco Merli, Carlo Visco, Annarita Conconi, Daniele Vallisa, Elettra Ortu La Barbera, Sara Galimberti, Roberto Mina, Marianna Sassone, Anna Guidetti, Adriano Venditti, Alessandro Corso, Francesco Marchesi, Pellegrino Musto, Agostino Tafuri, Valentina Bonuomo, Filippo Gherlinzoni, Francesco Lanza, Monia Marchetti, Safaa M. Ramadan, Marco Salvini, Massimo Massaia, Elisa Coviello, Alessandro Busca, Luigi Petrucci, Daniele Armiento, Mauro Turrini, Alessandra Romano, Chiara Cattaneo, Francesco Passamonti, Matteo G. Della Porta, Anna Candoni, Luigi Rigacci, Luca Arcaini, Livio Trentin, Valeria Cardinali, Maria Chiara Tisi, Carmine Selleri, Carlo Gambacorti-Passerini, Andrés J.M. Ferreri, Patrizia Tosi, Riccardo Bruna, Mauro Krampera, Antonio Cuneo, Nicola Stefano Fracchiolla, Daniela Cilloni, Lorenza Bertù, Paolo Corradini, Annamaria Scattolin, Roberto Cairoli, Giuseppe Visani, Domenico Penna, Marco Ladetto, Antonello Pinto, Michele Cavo, Monica Bocchia, Sofia Pilerci, Luigi Marcheselli, Visco, C, Marcheselli, L, Mina, R, Sassone, M, Guidetti, A, Penna, D, Cattaneo, C, Bonuomo, V, Busca, A, Ferreri, A, Bruna, R, Petrucci, L, Cairoli, R, Salvini, M, Bertu, L, Ladetto, M, Pilerci, S, Pinto, A, Ramadan, S, Marchesi, F, Cavo, M, Arcaini, L, Coviello, E, Romano, A, Musto, P, Massaia, M, Fracchiolla, N, Marchetti, M, Scattolin, A, Tisi, M, Cuneo, A, Porta, M, Trentin, L, Turrini, M, Gherlinzoni, F, Tafuri, A, Galimberti, S, Bocchia, M, Cardinali, V, Cilloni, D, Corso, A, Armiento, D, Rigacci, L, La Barbera, E, Gambacorti Passerini, C, Visani, G, Vallisa, D, Venditti, A, Selleri, C, Conconi, A, Tosi, P, Lanza, F, Candoni, A, Krampera, M, Corradini, P, Passamonti, F, and Merli, F

Subjects
Adult, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Aged, Aged, 80 and over, Cohort Studies, Humans, Middle Aged, Prognosis, SARS-CoV-2, Young Adult, COVID-19, Lymphoma, Lymphocyte, medicine.medical_treatment, Disease, NO, lymphoma, COVID-19, multicentre cohort study, SARS-CoV-2, Internal medicine, medicine, 80 and over, lymphoma, covid-19, anti-cd20, business.industry, Regular Article, Immunosuppression, Hematology, Settore MED/15, medicine.disease, medicine.anatomical_structure, Cohort, Prognostic model, business, Cohort study
Abstract

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Published
2022

129. SARS-CoV-2 infection in patients with chronic lymphocytic leukemia: The Italian Hematology Alliance on COVID-19 cohort

Author

Michele Merli, Isacco Ferrarini, Francesco Merli, Alessandro Busca, Roberto Mina, Brunangelo Falini, Riccardo Bruna, Roberto Cairoli, Monia Marchetti, Alessandra Romano, Michele Cavo, Luca Arcaini, Livio Trentin, Chiara Cattaneo, Enrico Derenzini, Nicola Stefano Fracchiolla, Francesco Marchesi, Annamaria Scattolin, Atto Billio, Monica Bocchia, Massimo Massaia, Carlo Gambacorti‐Passerini, Francesca Romana Mauro, Massimo Gentile, Sara Mohamed, Matteo Giovanni Della Porta, Elisa Coviello, Daniela Cilloni, Giuseppe Visani, Augusto Bramante Federici, Maria Chiara Tisi, Laura Cudillo, Sara Galimberti, Filippo Gherlinzoni, Livio Pagano, Anna Guidetti, Lorenza Bertù, Paolo Corradini, Francesco Passamonti, Carlo Visco, Merli, M, Ferrarini, I, Merli, F, Busca, A, Mina, R, Falini, B, Bruna, R, Cairoli, R, Marchetti, M, Romano, A, Cavo, M, Arcaini, L, Trentin, L, Cattaneo, C, Derenzini, E, Fracchiolla, N, Marchesi, F, Scattolin, A, Billio, A, Bocchia, M, Massaia, M, Gambacorti-Passerini, C, Mauro, F, Gentile, M, Mohamed, S, Della Porta, M, Coviello, E, Cilloni, D, Visani, G, Federici, A, Tisi, M, Cudillo, L, Galimberti, S, Gherlinzoni, F, Pagano, L, Guidetti, A, Bertu, L, Corradini, P, Passamonti, F, and Visco, C

Subjects
Settore MED/15 - MALATTIE DEL SANGUE, Cancer Research, BTK inhibitors, Oncology, chronic lymphocytic leukemia, COVID-19, outcome, SARS-CoV-2, BTK inhibitor, Hematology, General Medicine
Abstract

COVID-19, the disease caused by SARS-CoV-2, is still afflicting thousands of people across the globe. Few studies on COVID-19 in chronic lymphocytic leukemia (CLL) are available. Here, we analyzed data from the CLL cohort of the Italian Hematology Alliance on COVID-19 (NCT04352556), which included 256 CLL patients enrolled between 25 February 2020 and 1 February 2021. Median age was 70 years (range 38–94) with male preponderance (60.1%). Approximately half of patients (n = 127) had received at least one line of therapy for CLL, including 108 (83.7%) who were on active treatment at the time of COVID-19 or received their last therapy within 12 months. Most patients (230/256, 89.9%) were symptomatic at COVID-19 diagnosis and the majority required hospitalization (n = 176). Overall, after a median follow-up of 42 days (IQR 24–96), case fatality rate was 30.1%, and it was 37.5% and 24.4% in the first (25 February 2020–22 June 2020) and second wave (23 June 2020–1 February 2021), respectively (p = 0.03). At multivariate analysis, male sex (HR 1.82, 95% CI 1.03–3.24, p = 0.04), age over than 70 years (HR 2.23, 95% CI 1.23–4.05, p = 0.01), any treatment for CLL given in the last 12 months (HR 1.72, 95% CI 1.04–2.84, p = 0.04) and COVID-19 severity (severe: HR 5.66, 95% CI 2.62–12.33, p < 0.0001; critical: HR 15.99, 95% CI 6.93–36.90, p < 0.0001) were independently associated with poor survival. In summary, we report a dismal COVID-related outcome in a significant fraction of CLL patients, that can be nicely predicted by clinical parameters.

Published
2022

130. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author

Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract

Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2021

131. CPX-351 treatment in secondary acute myeloblastic leukemia is effective and improves the feasibility of allogeneic stem cell transplantation: results of the Italian compassionate use program

Author

Paola Minetto, Carmela Gurreri, Fabio Guolo, Anna Candoni, Giovanni Rossi, Giambattista Bertani, Marco Cerrano, Patrizia Zappasodi, Francesco Grimaldi, Atto Bilio, Anna Maria Scattolin, Barbara Scappini, Pellegrino Musto, Marino Clavio, Agostino Tafuri, Livio Pagano, Crescenza Pasciolla, Giuseppe Pietrantuono, Monica Morselli, Alessandro Cignetti, Roberto M. Lemoli, Sara Galimberti, Ernesta Audisio, Nicola Stefano Fracchiolla, Fabrizio Carnevale-Schianca, Felicetto Ferrara, Stefano D'Ardia, Giuseppe Rossi, Francesca Pavesi, Manuela Caizzi, Michele Gottardi, Luana Fianchi, Giuliana Rizzuto, Michela Rondoni, Michela Dargenio, Caterina Alati, Guolo, F., Fianchi, L., Minetto, P., Clavio, M., Gottardi, M., Galimberti, S., Rizzuto, G., Rondoni, M., Bertani, G., Dargenio, M., Bilio, A., Scappini, B., Zappasodi, P., Scattolin, A. M., Grimaldi, F., Pietrantuono, G., Musto, P., Cerrano, M., D'Ardia, S., Audisio, E., Cignetti, A., Pasciolla, C., Pavesi, F., Candoni, A., Gurreri, C., Morselli, M., Alati, C., Fracchiolla, N., Rossi, G., Caizzi, M., Carnevale-Schianca, F., Tafuri, A., Ferrara, F., Pagano, L., and Lemoli, R. M.

Subjects
Compassionate Use Trials, Male, medicine.medical_specialty, medicine.medical_treatment, neoplasms, acute myeloid - leukemia, minimal residual disease, myelodysplastic syndrome, molar ratiotherapy, neoplasms, cytarabine, daunorubicin, Drug development, Hematopoietic stem cell transplantation, Gene mutation, lcsh:RC254-282, Disease-Free Survival, Article, molar ratiotherapy, Internal medicine, Medicine, Secondary Acute Myeloid Leukemia, Humans, Cumulative incidence, Survival rate, Aged, Leukemia, business.industry, Mortality rate, Daunorubicin, Cytarabine, Hematopoietic Stem Cell Transplantation, Neoplasms, Second Primary, Hematology, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Allografts, Transplantation, Survival Rate, Settore MED/15 - MALATTIE DEL SANGUE, Regimen, Leukemia, Myeloid, Acute, Combination drug therapy, Oncology, Italy, Female, business, Follow-Up Studies
Abstract

Secondary acute myeloid leukemia (sAML) poorly responds to conventional treatments and allogeneic stem cell transplantation (HSCT). We evaluated toxicity and efficacy of CPX-351 in 71 elderly patients (median age 66 years) with sAML enrolled in the Italian Named (Compassionate) Use Program. Sixty days treatment-related mortality was 7% (5/71). The response rate at the end of treatment was: CR/CRi in 50/71 patients (70.4%), PR in 6/71 (8.5%), and NR in 10/71 (19.7%). After a median follow-up of 11 months relapse was observed in 10/50 patients (20%) and 12 months cumulative incidence of relapse (CIR) was 23.6%. Median duration of response was not reached. In competing risk analysis, CIR was reduced when HSCT was performed in first CR (12 months CIR of 5% and 37.4%, respectively, for patients receiving (=20) or not (=30) HSCT, p = 0.012). Twelve-months OS was 68.6% (median not reached). In landmark analysis, HSCT in CR1 was the only significant predictor of longer survival (12 months OS of 100 and 70.5%, for patients undergoing or not HSCT in CR1, respectively, p = 0.011). In conclusion, we extend to a real-life setting, the notion that CPX is an effective regimen for high risk AML patients and may improve the results of HSCT.

Published
2020

132. Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimale residual disease-oriented GIMEMA LAL1913

Author

Roberto Cairoli, Robin Foà, Orietta Spinelli, Enrico Crea, Antonella Vitale, Alessandra Santoro, Loredana Elia, Monica Messina, Maria Ctristina Puzzolo, Sabina Chiaretti, Michela Ansuinelli, Chiara Cattaneo, Nicola Stefano Fracchiolla, Marzia Cavalli, Valerio Apicella, Valentina Pierini, Paolo de Fabritiis, Guglielmo Albertini Petroni, Alfonso Piciocchi, Cristina Mecucci, Irene Della Starza, Cristina Papayannidis, Anna Guarini, Luciana Cafforio, Alessia Lauretti, Daniele Mattei, Akram Taherinasab, Renato Bassan, Francesco Di Raimondo, Martina Canichella, Saveria Capria, Roberta La Starza, Alessandro Rambaldi, Marco Cerrano, Anna Candoni, Paola Fazi, Chiaretti, S, Messina, M, Della Starza, I, Piciocchi, A, Cafforio, L, Cavalli, M, Taherinasab, A, Ansuinelli, M, Elia, L, Petroni, G, La Starza, R, Canichella, M, Lauretti, A, Puzzolo, M, Pierini, V, Santoro, A, Spinelli, O, Apicella, V, Capria, S, Di Raimondo, F, De Fabritiis, P, Papayannidis, C, Candoni, A, Cairoli, R, Cerrano, M, Fracchiolla, N, Mattei, D, Cattaneo, C, Vitale, A, Crea, E, Fazi, P, Mecucci, C, Rambaldi, A, Guarini, A, Bassan, R, and Foa, R

Subjects
Adult, medicine.medical_specialty, Minimal Residual Disease Persistence, Neoplasm, Residual, Philadelphia-Like Acute Lymphoblastic Leukemia, Gastroenterology, Disease-Free Survival, Article, 03 medical and health sciences, 0302 clinical medicine, MED/15 - MALATTIE DEL SANGUE, Internal medicine, hemic and lymphatic diseases, medicine, Adults, Neoplasm, Humans, Philadelphia Chromosome, Child, Adult all, business.industry, Minimal residual disease, Editorials, Complete remission, breakpoint cluster region, Ph-like, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Settore MED/15, Prognosis, medicine.disease, Ph-like ALL, GIMEMA LAL, minimal residual disease-oriented, Adult Acute Lymphoblastic Leukemia, 030220 oncology & carcinogenesis, Acute Disease, business, Human, 030215 immunology
Abstract

Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)- driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission rate was significantly lower in Ph-like compared to non-Phlike cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for transplant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents that Ph-like patients have a lower complete remission rate, event-free survival and disease-free survival, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies. Clinicaltrials gov. Identifier: 02067143.

Published
2020

133. Considerations on antimicrobial prophylaxis in patients with lymphoproliferative diseases: A SEIFEM group position paper

Author

Elena De Carolis, Michele Malagola, Livio Pagano, Angelica Spolzino, Monica Piedimonte, Angela Maria Quinto, Roma Rosa Fanci, Eleonora Ceresoli, Francesca Farina, Ilaria Del Principe, Fabio Trastulli, Francesco Marchesi, Marco Picardi, Maria Chiara Tisi, Patrizia Zappasodi, Mario Delia, Anna Candoni, Mario Tumbarello, Lucia Prezioso, Marianna Criscuolo, Gianpaolo Nadali, Chiara Cattaneo, Roberta Della Pepa, Alessandro Busca, Claudia Giordano, Enrico Maria Trecarichi, Massimo Offidani, Nicola Stefano Fracchiolla, Busca, A., Cattaneo, C., De Carolis, E., Nadali, G., Offidani, M., Picardi, M., Candoni, A., Ceresoli, E., Criscuolo, M., Delia, M., Della Pepa, R., Del Principe, I., Fanci, R. R., Farina, F., Fracchiolla, N., Giordano, C., Malagola, M., Marchesi, F., Piedimonte, M., Prezioso, L., Quinto, A. M., Spolzino, A., Tisi, M. C., Trastulli, F., Trecarichi, E. M., Zappasodi, P., Tumbarello, M., and Pagano, L.

Subjects
Anti-Infective Agent, Lymphoproliferative disorders, 0301 basic medicine, medicine.medical_specialty, Antimicrobial prophylaxis, Antimicrobial stewardship, Bacterial, Fungal and viral infections, 03 medical and health sciences, 0302 clinical medicine, Fungal and viral infection, Anti-Infective Agents, Anti-Bacterial Agent, medicine, Humans, Antimicrobial prophylaxi, Antibiotic prophylaxis, Intensive care medicine, Antiinfective agent, business.industry, Anti-Bacterial Agents, Lymphoproliferative Disorders, Hematology, Settore MED/15, Antimicrobial, medicine.disease, Multiple drug resistance, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Lymphoproliferative disorder, Oncology, 030220 oncology & carcinogenesis, Position paper, business, Human
Abstract

The therapeutic armamentarium for the treatment of patients with lymphoproliferative diseases has grown considerably over the most recent years, including a large use of new immunotherapeutic agents. As a consequence, the epidemiology of infectious complications in this group of patients is poorly documented, and even more importantly, the potential benefit of antimicrobial prophylaxis remains a matter of debate when considering the harmful effect from the emergence of multidrug resistant pathogens. The present position paper is addressed to all hematologists treating patients affected by lymphoproliferative malignancies with the aim to provide clinicians with a useful tool for the prevention of bacterial, fungal and viral infections.

Published
2021

134. Clinical management of peripherally inserted central catheters compared to conventional central venous catheters in patients with hematological malignancies: A large multicenter study of the REL GROUP (Rete Ematologica Lombarda - Lombardy Hematologic Network, Italy)

Author

Francesca Guidotti, Laura Marbello, Dario Consonni, Nicola Stefano Fracchiolla, Massimo Bernardi, Nicola Orofino, Agostino Cortelezzi, Andrea Bilancia, Sara Gandolfi, Armando Santoro, Elisabetta Todisco, Roberto Cairoli, Andrea Assanelli, Valentina Mancini, Fracchiolla, N, Todisco, E, Bilancia, A, Gandolfi, S, Orofino, N, Guidotti, F, Mancini, V, Marbello, L, Assanelli, A, Bernardi, M, Santoro, A, Cairoli, R, Consonni, D, and Cortelezzi, A

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Hematologic Neoplasms, 030204 cardiovascular system & hematology, Catheterization, Central Venou, 03 medical and health sciences, 0302 clinical medicine, Central Venous Catheter, Upper Extremity Deep Vein Thrombosis, medicine, In patient, Child, Hematologic Neoplasm, Aged, Aged, 80 and over, business.industry, Hematology, Middle Aged, medicine.disease, Thrombosis, Surgery, Clinical trial, Multicenter study, Italy, 030220 oncology & carcinogenesis, Female, business, Infection, Human
Published
2017

135. Isavuconazole in Hematological Patients: Results of a Real-Life Multicentre Observational Seifem Study

Author

Nicola Stefano Fracchiolla, Monica Piedimonte, Valentina Mancini, Anna Candoni, Mario Tumbarello, Margherita Sciumé, Giuseppe Rossi, Livio Pagano, Stelvio Ballanti, Massimo Offidani, Chiara Pagani, Doriana Gramegna, Rosa Fanci, Francesco Marchesi, Maria Ilaria Del Principe, Francesca Farina, Alessandro Busca, Attilio Olivieri, Marco Picardi, Gianpaolo Nadali, Angelica Spolzino, Chiara Cattaneo, Marianna Criscuolo, Maria Chiara Tisi, Mario Delia, Cattaneo, C., Busca, A., Gramegna, D., Farina, F., Candoni, A., Piedimonte, M., Fracchiolla, N., Pagani, C., Principe, M. I. D., Tisi, M. C., Offidani, M., Fanci, R., Ballanti, S., Spolzino, A., Criscuolo, M., Marchesi, F., Nadali, G., Delia, M., Picardi, M., Sciume, M., Mancini, V., Olivieri, A., Tumbarello, M., Rossi, G., and Pagano, L.

Subjects
Response rate (survey), medicine.medical_specialty, Acute leukemia, Multivariate analysis, lcsh:RC633-647.5, business.industry, isavuconazole, Retrospective cohort study, lcsh:Diseases of the blood and blood-forming organs, isavuconazole, hematological malignancies, Hematology, Settore MED/15, Settore MED/17 - MALATTIE INFETTIVE, Article, Discontinuation, Tolerability, Internal medicine, Medicine, Observational study, hematological malignancies, business, Adverse effect
Abstract

Invasive fungal diseases (IFDs) remain a major clinical issue in patients with hematological malignancies (HMs). To confirm the efficacy and safety of the new azole isavuconazole (ISV) in a clinical care setting, we planned a multicenter retrospective study; we collected data on all possible/probable/proven IFDs in patients with HMs treated with ISV in 17 centers. Between July 2016 and November 2018, 128 patients were enrolled, and 122 were fully evaluable. ISV was employed as the 1st line therapy in 43 (35%) patients and as a subsequent therapy in 79 (65%) patients. The response rate was 82/122 patients (67.2%); it was similar when using ISV as a 1st or 2nd line treatment (60.5% vs 70.9%, respectively; p = 0.24). In multivariate analysis, both female sex (OR: 2.992; CI: 1.22–7.34) and induction phase of treatment (OR: 3.953; CI: 1.085–14.403) were predictive of a favorable response. At a median follow-up of 5 months, 43 (35.2%) patients were dead; the 1-year overall survival (OS) was 49.9%. In multivariate analysis, the response to ISV (OR: 0.103; CI: 0.041–0.262) and IFD refractoriness to previous antifungals (OR: 3.413; CI: 1.318–8.838) were statistically significant for OS. Adverse events (AEs) were reported in 15/122 patients (12.3%); grade 3–4 AEs were reported in 5 (4%) and led to ISV discontinuation. Our study confirms the safety and tolerability of ISV, also in diseases other than acute leukemia. Phase of hematological disease, gender and refractoriness to previous antifungals are the main predictive factors for the aforementioned response and outcome.

Published
2019

136. Treatment of Elderly Patients with Acute Promyelocytic Leukemia: A Real Life Experience of the 'Rete Ematologica Lombarda'

Author

Patrizia Zappasodi, Erika Ravelli, Roberto Cairoli, Monica Fumagalli, Mauro Turrini, Federico Lussana, Elisabetta Todisco, Erika Borlenghi, Massimo Bernardi, Silvia Cantoni, Valentina Mancini, Chiara Cattaneo, Nicola Stefano Fracchiolla, Livia Leuzzi, Giuseppe Rossi, Giambattista Bertani, Claudia Basilico, Mancini, V, Borlenghi, E, Leuzzi, L, Basilico, C, Bernardi, M, Zappasodi, P, Fumagalli, M, Todisco, E, Cattaneo, C, Lussana, F, Bertani, G, Ravelli, E, Fracchiolla, N, Turrini, M, Rossi, G, Cantoni, S, and Cairoli, R

Subjects
Response rate (survey), medicine.medical_specialty, education.field_of_study, Performance status, business.industry, Proportional hazards model, medicine.medical_treatment, Immunology, Population, Cell Biology, Hematology, Biochemistry, Chemotherapy regimen, Log-rank test, Internal medicine, Medicine, business, Adverse effect, education, Neoadjuvant therapy
Abstract

Background Acute promyelocytic leukemia (APL) in the elderly has a favourable outcome in a significant proportion of patients (pts). Elderly and frail pts are usually treated with attenuated treatment schedules, mostly "according to medical judgment". The combination of all-trans retinoic (ATRA) and anthracycline-based chemotherapy (CT) has been the mainstay of treatment for many years. Alternative approaches, such as arsenic trioxide (ATO) and gentuzumab ozogamicin (GO) have recently been tested with success in this setting, even though no large series of elderly pts treated with CT-free first-line treatment have been published yet. Moreover, neither a "standard of care approach" nor a specific prognostic score system have been developed to guide physician in choosing the most adequate treatment schedule in this setting. Objective Aim of the present preliminary survey was to assess genetic and clinical features of APL in pts over 60 yrs. This cut off reflects the definition of "elderly patient" in most Italian APL GIMEMA trials. Moreover, both the real life outcome and safety data after either conventional anthracycline-based CT or alternative CT-free approaches were analysed. OS, response rate to either regimens and adverse event occurrence were collected. Methods This retrospective multicenter REL (Rete Ematologica Lombarda) survey, enrolled a total of 101 consecutive APL pts aged ≥60, treated between 2000-2018. Demographics, clinical data and therapy outcome data were recorded in a dedicated patient's report form. Statistical analysis was performed using the Kaplan Maier method, Log-rank test and Cox regression. Results For analysis, pts were grouped into different categories according to age and fitness. Tables 1 and 2 summarise clinical charcteristics and treatment administered. Performance status (PS) and number of comorbidities increase with age. Twentynine of 102 (28,4%) and 9/102 (8,8%) pts had a history of or subsequently developed a solid tumor respectively. High frequency of additive cytogenetic abnormalities was observed as well. CT+ATRA was preferentially administered, mostly with attenuated intensity, to younger pts with better PS, while ATO+ATRA was preferred in pts with reduced cardiac function and ATRA monotherapy was reserved to frail or over 80 yrs old pts. Rates of differentiation syndrome or infections or cardiac events were similar in the different treatment groups. Overall, complete remission (CR) rate after induction therapy was 94.16% [CI95%: 87,5%-97,8% ]. At a median follow-up of 40 mos (range 0-199), the overall relapse rate was 24%. Median time to relapse was 7 mos in 1/8 (12,5%) ATRA monotherapy treated pts and 13 mos (range 5-66) in the 23/68 (33,8%) pts receiving CT+ATRA. No relapse occurred among the 22 pts treated with ATO+ATRA (p 0.005). OS and EFS were significantly associated with pts' age (HR 9% and 7.6%; p Conclusion This survey confirms that elderly and frail APL pts may benefit from ATO-based regimens. Reduced-dose antracycline-based CT, appears to be less effective, with high rate of relapse in elderly pts. Scoring systems and prospective data are needed in order to better define treatment strategies aiming to further improve outcome in this challenging but growing population. Disclosures Rossi: Daiichi-Sankyo: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: 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; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria.

Published
2019

137. Peripherally Inserted Central Catheters (PICCs) Implantation in the Clinical Management of Oncohematologic Patients: Results of a Large Multicenter, Retrospective Study of the REL Group (Rete Ematologica Lombarda - Lombardy Hematologic Network, Italy)

Author

Nicola Orofino, Ramona Cassin, Mariarita Sciumè, Massimo Bernardi, Francesca Guidotti, Fabio Ciceri, Agostino Cortelezzi, Roberto Cairoli, Elisabetta Todisco, Armando Santoro, Andrea Bilancia, Nicola Stefano Fracchiolla, Sara Gandolfi, Valentina Mancini, Giuseppe Rossi, Laura Marbello, Andrea Assanelli, Fracchiolla, N, Todisco, E, Bilancia, A, Gandolfi, S, Mancini, V, Marbello, L, Bernardi, M, Assanelli, A, Orofino, N, Cassin, R, Sciume, M, Guidotti, F, Cairoli, R, Ciceri, F, Santoro, A, Cortelezzi, A, and Rossi, G

Subjects
medicine.medical_specialty, business.industry, hematology, medicine.medical_treatment, Immunology, Lumen (anatomy), Cell Biology, medicine.disease, Biochemistry, Peripherally inserted central catheter, Thrombosis, Surgery, Catheter, Venous thrombosis, Pneumothorax, Intravenous therapy, medicine, Complication, business
Abstract

Background: PICCs are vascular devices inserted from a peripheral vein of the upper third of the arm under ultrasound guide, and provide a central venous access (CVA) with an intermediate duration between short term central venous catheters (CVCs), such as jugular or subclavian CVCs, and long term ones (port-a-caths). PICC insertion is ease and safe with no pneumothorax or hemothorax risk. Their extremity reaches a central vein, and can be used for cytostatic drugs, hyperosmolar solutions, and antibiotics infusion. Furthermore, patients (pts) at high risk of hemorrhage for thrombocytopenia or coagulopathy are eligible for PICC insertion. Nevertheless, some concern exists about the risk of infectious and thrombotic complications associated with PICC use in immunocompromised cancer pts characterized by a prothrombotic state. In particular, few clinical data from large oncohematologic pts series are available on PICCs' implants and their complications. Aims: To analyze the results of a large multicenter, retrospective study of the REL group (Rete Ematologica Lombarda-Lombardy Hematologic Network, Italy) aimed at clinically characterizing PICC use in oncohematologic patients management. Methods: Four REL Hematology Centers participate to the study. The clinical data of 453 implanted PICCs from January 2010 to June 2015, were retrospectively collected, for a total of 44,577 catheter days. Pts median age was 61 yrs (range 10-88). Patients' diagnoses were 197 non-Hodgkin's lymphoma, 10 chronic lymphocytic leukemia, 105 acute myeloid leukemia, 45 acute lymphoblastic leukemia, 33 Hodgkin's lymphoma, 39 multiple myeloma, 12 myelodysplastic/myeloproliferative syndrome, 6 miscellaneous. All pts received intravenous chemotherapy, long term anti infectious drugs (antibiotics and antifungals), and hypertonic solutions. PICCs were inserted by ultrasound-guided puncture of a peripheral vein of the arm, by microintroducer technique, under strict asepsis. Chest X-ray was performed to verify correct tip location (ideally in the proximity of cavo-atrial junction). Data on PICCs' lumen number are available in 423 cases: 292 (69%) were single-lumen and 131 were double-lumen (31%). Results: Median PICC life-span was 90 days (range 1-760, Kaplan-Meier method). No major insertion-related complications were observed. Late complications occurred in 172/453 PICCs (38%, 3.8/1000 catheter days): 93 infectious (20%, 2/1000 catheter days), 38 thrombotic (8%, 0.8/1000 catheter days), 37 mechanical (8%, 0.8/1000 catheter days), 5 (1%, 0.1/1000 catheter days) miscellaneous complications (patient intolerance, local pain and hematoma). Among infectious complications, we reported 24 cases (5%, 0.5/1000 catheter days) of fever of unknown origin (FUO) and 69 (15%, 1.5/1000 catheter days) catheter-related bloodstream infections. Mechanical complications consisted of 3 (1%) catheter dislocations, 19 accidental removals (4%), 16 (3%) lumen occlusions and 3 (1%) breakages of the external section of PICC. In 376/453 (83%) cases PICC was removed due to end of intravenous therapy in 160 patients (35%), death in 98 (22%) and to various complications in 118 (26%) cases. Specifically, FUO lead to PICC removal in 10 (2%), infection in 40 (9%), venous thrombosis in 25 (5%) cases, catheter dislocation or accidental removal in 22 (5%), lumen occlusion in 13 (3%), breakage of the external section of PICC in 2 (0,5%), other mechanical complication in 4 (1%), local pain and miscellaneous 2 (0,5%) each. In the case of a complication occured, the incidence of PICC removal was 68% (118/172): FUO/infections represented the removal cause in 50/172 (29%), mechanical complications in 40/172 (23%), thrombosis in 25/172 (14%) cases. Conclusions: Traditional CVCs are associated with significant complications, reported at varying frequencies in highly heterogeneous oncohematologic pts series: infections are reported from 4.6 to 23% and thromboses from 1.2 to 30.2% of the cases. We have clinically characterized a large series of PICCs in oncohematologic patients. Our data suggest that their implant, as an alternative to traditional CVCs, is a safe and effective way to provide oncohematologic patients at high risk of hemorrhagic and infective complications with a CVA. PICCs compare favorably with traditional CVCs reported complications, and facilitate the proper management of complex and prolonged therapeutic programs. Disclosures No relevant conflicts of interest to declare.

Published
2015

138. Molecular analysis of cutaneous B- and T-cell lymphomas

Author

Alketa Boletini, Lucia Perletti, Elena Roscetti, Luca Baldini, Dino Trecca, Antonino Neri, Silvia Garatti, Nicola Stefano Fracchiolla, Anna Teresa Maiolo, Emilio Berti, Neri, A, Fracchiolla, N, Roscetti, E, Garatti, S, Trecca, D, Boletini, A, Perletti, L, Baldini, L, Maiolo, A, and Berti, E

Subjects
Adult, Male, Lymphoma, B-Cell, Skin Neoplasms, Tumor suppressor gene, Immunology, DNA Mutational Analysis, Molecular Sequence Data, Locus (genetics), Gene mutation, Biology, Lymphoma, T-Cell, Biochemistry, Polymerase Chain Reaction, law.invention, DNA Mutational Analysi, law, MED/15 - MALATTIE DEL SANGUE, MED/35 - MALATTIE CUTANEE E VENEREE, medicine, Humans, Skin Neoplasm, Gene, Polymerase chain reaction, Oncogene, Polymorphism, Single-Stranded Conformational, Southern blot, Aged, Sequence Deletion, Genetics, Aged, 80 and over, Gene Rearrangement, Base Sequence, Genes, Immunoglobulin, Cell Biology, Hematology, Gene rearrangement, DNA, Neoplasm, Oncogenes, Middle Aged, medicine.disease, Genes, p53, Molecular biology, Lymphoma, Cell Transformation, Neoplastic, Female, Human
Abstract

Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.

Published
1995

139. bcl-1, bcl-2, p53, c-myc, and lyt-10 analysis in cutaneous lymphomas

Author

Dino Trecca, Emilio Berti, Elena Roscetti, Nicola Stefano Fracchiolla, S. A. Garatti, Antonino Neri, Garbe, C, Schmitz, S, Orfanos, CE, Garatti, S, Roscetti, E, Trecca, D, Fracchiolla, N, Neri, A, and Berti, E

Subjects
Lymphoma, B-Cell, Receptors, Antigen, T-Cell, alpha-beta, Molecular Sequence Data, Cutaneous B-cell lymphoma, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Genes, myc, Biology, Gene Rearrangement, T-Lymphocyte, Polymerase Chain Reaction, Chromosome Aberration, Cutaneous lymphoma, DNA Mutational Analysi, NF-kappa B p52 Subunit, MED/15 - MALATTIE DEL SANGUE, hemic and lymphatic diseases, MED/35 - MALATTIE CUTANEE E VENEREE, medicine, Cyclin D1, Skin Neoplasm, Anaplastic large-cell lymphoma, Oncogene, Polymorphism, Single-Stranded Conformational, Mycosis fungoides, Mycosis Fungoide, Proto-Oncogene Protein, Genes, Immunoglobulin, Base Sequence, Cutaneous T-cell lymphoma, NF-kappa B, Receptors, Antigen, T-Cell, gamma-delta, Gene rearrangement, DNA, Neoplasm, medicine.disease, Genes, p53, Lymphoma, Lymphoma, T-Cell, Cutaneous, Proto-Oncogene Proteins c-bcl-2, Tumor progression, Immunology, Cancer research, MED/06 - ONCOLOGIA MEDICA, Human
Abstract

In the present study we investigated the pathogenetic role of c-myc, bcl-2, and lyt-10 oncogenes, bcl-1 locus, and p53 suppressor gene in a representative panel of cutaneous lymphomas, including 25 cases of cutaneous B cell lymphoma (CBCL) and 29 cases of cutaneous T cell lymphoma (CTCL). In our analysis four cases of CBCL were found rearranged for bcl-2 and two for the bcl-1 locus. Two cases of CTCL and one case of CBCL were found rearranged for lyt-10. No rearrangements of c-myc oncogene were found in CBCL. Analysis of p53 gene showed mutation only in one case of mycosis fungoides in tumoral stage, at codon 163 of p53 gene (TAC-->CAC; Tyr--> Asp). Our data suggest that in primary CBCL bcl-2 oncogenes and bcl-1 locus are rarely involved. Furthermore, in primary CTCL p53 gene is not affected at significant frequency. The occurrence of p53 mutation in a patient affected by mycosis fungoides in tumoral stage may represent an involvement of p53 gene in tumor progression of CTCL, a finding observed in several types of human cancer.

Published
1995

140. Structural alterations of the NF-kappa B transcription factor lyt-10 in lymphoid malignancies

Author

Ns, Fracchiolla, Lombardi L, Salina M, Migliazza A, Luca Baldini, Berti E, Cro L, Polli E, At, Maiolo, Neri A, Fracchiolla, N, Lombardi, L, Salina, M, Migliazza, A, Baldini, L, Berti, E, Cro, L, Polli, E, Maiolo, A, and Neri, A

Subjects
Lymphoma, B-Cell, Base Sequence, Transcription Factor, Intron, Molecular Sequence Data, NF-kappa B, Exon, Proto-Oncogene, Exons, Gene Rearrangement, T-Lymphocyte, Proto-Oncogene Mas, Introns, Lymphoma, T-Cell, Cutaneous, Blotting, Southern, Structure-Activity Relationship, NF-kappa B p52 Subunit, Proto-Oncogenes, Humans, Amino Acid Sequence, Gene Rearrangement, B-Lymphocyte, Multiple Myeloma, Human, Transcription Factors
Abstract

We have previously reported the identification of a novel putative proto-oncogene involved in the breakpoint of a t(10;14)(q24;q32) chromosomal translocation in a case of B-cell lymphoma. This gene, called lyt-10 (NFKB2/p52), is a member of the NF-kappa B family of transcription factors and displays a high degree of homology with the NFKB1/p50. Here we describe the genomic organization of the lyt-10 gene based on the restriction analysis of genomic phage clones and the sequence determination of exon-intron boundaries. The lyt-10 gene spans a genomic region of about 8 kb on 10q24, and contains 24 exons, ranging in size between 41 and 258 base pairs. To improve the understanding of the role of lyt-10 in lymphomagenesis, we performed Southern blot analysis to detect alterations of the lyt-10 gene in a large panel of cases representative of different types of lymphoid malignancies. We found rearrangements in 5 of 228 (approximately 2%) cases analysed: two cases of B-cell lymphoma, one case of multiple myeloma and two cases of T-cell lymphoma. The use of various probes specific for different regions of the lyt-10 locus revealed that rearrangements in positive cases lead to the partial or total deletion of the carboxy-terminal region containing the ankyrin domain. Taken together, our results indicate that lyt-10 gene rearrangements represent a recurrent lesion that may be involved in the pathogenesis of both B- and T-cell malignancies, and suggest that truncation of the ankyrin domain may be a common mechanism of lesion leading to abnormal lyt-10 activation in lymphoid neoplasia.

Published
1993

141. Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression

Author

Mozzanica, N., Cattaneo, A., Nicola S. Fracchiolla, Boneschi, V., Berti, E., Gronda, E., Mangiavacchi, M., Finzi, A. F., Neri, A., Mozzanica, N, Cattaneo, A, Fracchiolla, N, Boneschi, V, Berti, E, Gronda, E, Mangiavacchi, M, Finzi, A, and Neri, A

Subjects
Male, Herpesvirus 4, Human, Lymphoma, B-Cell, Skin Neoplasms, Prognosi, Opportunistic Infection, Acyclovir, Opportunistic Infections, Antiviral Agents, Drug Administration Schedule, Immunosuppressive Agent, Postoperative Complications, MED/15 - MALATTIE DEL SANGUE, MED/35 - MALATTIE CUTANEE E VENEREE, Humans, Skin Neoplasm, Antiviral Agent, Herpesviridae Infection, Dose-Response Relationship, Drug, Tumor Virus Infection, Herpesviridae Infections, Middle Aged, Prognosis, MED/23 - CHIRURGIA CARDIACA, Tumor Virus Infections, Heart Transplantation, Drug Therapy, Combination, Postoperative Complication, Immunosuppressive Agents, Human
Abstract

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

142. Prognostic and Predictive Models in Myelofibrosis.

Author

Mora B, Bucelli C, Cattaneo D, Bellani V, Versino F, Barbullushi K, Fracchiolla N, Iurlo A, and Passamonti F

Subjects
Humans, Prognosis, Disease Progression, Primary Myelofibrosis mortality, Primary Myelofibrosis diagnosis, Primary Myelofibrosis therapy
Abstract

Purpose of Review: Myelofibrosis (MF) includes prefibrotic primary MF (pre-PMF), overt-PMF and secondary MF (SMF). Median overall survival (OS) of pre-PMF, overt-PMF and SMF patients is around 14 years, seven and nine years, respectively. Main causes of mortality are non-clonal progression and transformation into blast phase., Recent Findings: Discoveries on the impact of the biological architecture on OS have led to the design of integrated scores to predict survival in PMF. For SMF, OS estimates should be calculated by the specific MYSEC-PM (MYelofibrosis SECondary-prognostic model). Information on the prognostic role of the molecular landscape in SMF is accumulating. Crucial treatment decisions for MF patients could be now supported by multivariable predictive algorithms. OS should become a relevant endpoint of clinical trials. Prognostic models guide prediction of OS and treatment planning in MF, therefore, their timely application is critical in the personalized approach of MF patients., (© 2024. The Author(s).)

Published
2024
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143. Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.

Author

Lazzarotto D, Cerrano M, Papayannidis C, Chiaretti S, Mosna F, Fracchiolla N, Zappasodi P, Imbergamo S, Del Principe MI, Lunghi M, Lussana F, Piccini M, Fumagalli M, Dargenio M, Salutari P, Forghieri F, Da Molin TG, Bonifacio M, Olivi M, Giglio F, Trappolini S, Leoncin M, Mule A, Delia M, Pasciolla C, Grimaldi F, Cambo B, Santoro L, Guolo F, Minetto P, Defina M, Chiusolo P, Fanin M, Mauro E, Aprile L, Mazzone C, Trastulli F, Ciccone M, De Gobbi M, Cignetti A, De Bellis E, Mancini V, Piciocchi A, Vignetti M, Marsili G, Starza ID, Fanin R, Luppi M, Ferrara F, Pizzolo G, Bassan R, Foa R, and Candoni A

Abstract

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Published
2024
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144. Long-Term Results of the Dasatinib-Blinatumomab Protocol for Adult Philadelphia-Positive ALL.

Author

Foà R, Bassan R, Elia L, Piciocchi A, Soddu S, Messina M, Ferrara F, Lunghi M, Mulè A, Bonifacio M, Fracchiolla N, Salutari P, Fazi P, Guarini A, Rambaldi A, and Chiaretti S

Subjects
Adult, Humans, Dasatinib adverse effects, Treatment Outcome, Neoplasm Recurrence, Local drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Antibodies, Bispecific
Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.7%, and 74.6%, respectively. No events have occurred among early molecular responders. A significantly worse outcome was recorded for IKZF1 plus patients. Twenty-nine patients-93.1% being in molecular response (ie, complete molecular response or positive nonquantifiable) after dasatinib/blinatumomab-never received chemotherapy/transplant and continued with a tyrosine kinase inhibitor only; 28 patients remain in long-term complete hematologic response (CHR). An allogeneic transplant was carried out in first CHR mainly in patients with persistent minimal residual disease; 83.3% of patients are in continuous CHR. The transplant-related mortality was 12.5% for patients transplanted in first CHR and 13.7% overall. Nine relapses and six deaths have occurred. ABL1 mutations were found in seven cases. The final analysis of the D-ALBA study shows that a chemotherapy-free induction/consolidation regimen on the basis of a targeted strategy (dasatinib) and immunotherapy (blinatumomab) is effective in inducing durable long-term hematologic and molecular responses in adult Ph+ ALL, paving the way for a new era in the management of these patients.

Published
2024
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145. Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study.

Author

Ocadlikova D, Lussana F, Fracchiolla N, Bonifacio M, Santoro L, Delia M, Chiaretti S, Pasciolla C, Cignetti A, Forghieri F, Grimaldi F, Corradi G, Zannoni L, De Propris S, Borleri GM, Tanasi I, Vadakekolathu J, Rutella S, Guarini AR, Foà R, and Curti A

Subjects
Humans, Bone Marrow metabolism, Remission Induction, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Antibodies, Bispecific pharmacology, Antibodies, Bispecific therapeutic use, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism
Abstract

Blinatumomab is the first bi-specific T-cell engager approved for relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (B-ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty-nine patients with B-ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T-cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T-cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T-cell subsets showed a broader post-treatment subversion, including the modulation of markers associated with a T-cell-exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2023
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146. Pegaspargase-modified risk-oriented program for adult acute lymphoblastic leukemia: results of the GIMEMA LAL1913 trial.

Author

Bassan R, Chiaretti S, Della Starza I, Spinelli O, Santoro A, Paoloni F, Messina M, Elia L, De Propris MS, Scattolin AM, Audisio E, Marbello L, Borlenghi E, Zappasodi P, Mauro E, Martinelli G, Mattei D, Fracchiolla N, Bocchia M, De Fabritiis P, Bonifacio M, Candoni A, Cassibba V, Di Bartolomeo P, Latte G, Trappolini S, Guarini A, Vitale A, Fazi P, Piciocchi A, Rambaldi A, and Foà R

Subjects
Humans, Adult, Disease-Free Survival, Remission Induction, Acute Disease, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Hematopoietic Stem Cell Transplantation
Abstract

Pediatric-inspired chemotherapy is the standard of care for younger adults with Philadelphia chromosome-negative acute lymphoblastic leukemia/lymphoma (Ph- ALL/LL). In LAL1913 trial, the Gruppo Italiano Malattie EMatologiche dell'Adulto added pegaspargase 2000 IU/m2 to courses 1, 2, 5, and 6 of an 8-block protocol for patients aged from 18 to 65 years, with dose reductions in patients aged >55 years. Responders were risk stratified for allogeneic hematopoietic cell transplantation (HCT) or maintenance per clinical characteristics and minimal residual disease (MRD). Of 203 study patients (median age, 39.8 years), 91% achieved a complete remission. The 3-year overall survival, event-free, and disease-free survival (DFS) rates were 66.7%, 57.7%, and 63.3%, respectively, fulfilling the primary study end point of a 2-year DFS >55%. Although based on the intention-to-treat, the DFS being 74% and 50% in the chemotherapy (n = 94) and HCT (n = 91) assignment cohorts, respectively, a time-dependent analysis proved the value of HCT in patients who were eligible (DFS HCT 70% vs no HCT 26%; P <.0001). In multivariate analysis, age and MRD were independent factors predicting DFS rates of 86% (age ≤ 40 and MRD-negative), 64%-65% (MRD-positive or age > 40) and 25% (age > 40 and MRD-positive); P < .0001. Grade ≥2 pegaspargase toxicity was mainly observed at course 1, contributing to induction death in 2 patients but was rare thereafter. This program improved outcomes of patients with Ph- ALL/LL aged up to 65 years in a multicenter national setting. This trial was registered at www.clinicaltrials.gov as #NCT02067143., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Published
2023
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147. A review of prophylactic regimens to prevent invasive fungal infections in hematology patients undergoing chemotherapy or stem cell transplantation.

Author

Criscuolo M, Fracchiolla N, Farina F, Verga L, Pagano L, and Busca A

Subjects
Humans, Antifungal Agents therapeutic use, Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections etiology, Invasive Fungal Infections prevention & control, Invasive Fungal Infections drug therapy, Hematology
Abstract

Introduction: The recent introduction of targeted therapies, including monoclonal antibodies, tyrosine-kinase inhibitors, and immunotherapies has improved the cure rate of hematologic patients. The implication of personalized treatment on primary antifungal prophylaxis will be discussed., Areas Covered: We reviewed the literature for clinical trials reporting the rate of invasive fungal infections during targeted and cellular therapies and stem cell transplant, and the most recent international guidelines for primary antifungal prophylaxis., Expert Opinion: As the use of personalized therapies is growing, the risk of invasive fungal infection has emerged in various clinical settings. Therefore, it is possible that the use of mold-active antifungal prophylaxis would spread in the next years and the risk of breakthrough infections would increase. The introduction of new antifungal agents in the clinical armamentarium is expected to reduce clinical unmet needs concerning the management of primary antifungal prophylaxis and improve outcome of patients.

Published
2023
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148. Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in "Real-Life": The SEIFEM Experience.

Author

Fianchi L, Guolo F, Marchesi F, Cattaneo C, Gottardi M, Restuccia F, Candoni A, Ortu La Barbera E, Fazzi R, Pasciolla C, Finizio O, Fracchiolla N, Delia M, Lessi F, Dargenio M, Bonuomo V, Del Principe MI, Zappasodi P, Picardi M, Basilico C, Piedimonte M, Minetto P, Giordano A, Chiusolo P, Prezioso L, Buquicchio C, Melillo LMA, Zama D, Farina F, Mancini V, Terrenato I, Rondoni M, Urbino I, Tumbarello M, Busca A, and Pagano L

Abstract

In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality-infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [ p -value: 0.004, OR 0.05, 95% CI 0.01-0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality.

Published
2023
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150. Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia-like or acute lymphoblastic leukemia-like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study.

Author

Lazzarotto D, Tanasi I, Vitale A, Piccini M, Dargenio M, Giglio F, Forghieri F, Fracchiolla N, Cerrano M, Todisco E, Papayannidis C, Leoncin M, Defina M, Guolo F, Pasciolla C, Delia M, Chiusolo P, Mulè A, Candoni A, Bonifacio M, Pizzolo G, and Foà R

Subjects
Humans, Acute Disease, Phenotype, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis
Abstract

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)-like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2023
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