Search

Your search keyword '"Forconi, F."' showing total 394 results
Start Over Author "Forconi, F."
394 results on '"Forconi, F."'

2. Robust Bruton’s tyrosine kinase (BTK) degradation with NX‐5948, an oral BTK degrader, in a first‐in‐human phase 1a trial in relapsed/refractory B cell malignancies

Author

Linton, K., primary, Forconi, F., additional, Lewis, D., additional, Riches, J., additional, El‐Sharkawi, D., additional, Gleeson, M., additional, Injac, S. G., additional, Nandakumar, S., additional, Tan, M., additional, Cherala, G., additional, and Collins, G. P., additional

Published
2023
Full Text
View/download PDF

3. FOXO1‐RICTOR AXIS INDUCES AKT PHOSPHORYLATION DURING CLL CELL ADAPTATION TO BCR INHIBITORS: IMPLICATIONS FOR COMBINATORIAL THERAPY

Author

Ondrisova, L., primary, Seda, V., additional, Hoferkova, E., additional, Chiodin, G., additional, Hlavac, K., additional, Kostalova, L., additional, Pavlasova, G. Mladonicka, additional, Filip, D., additional, Zeni, P. Faria, additional, Oppelt, J., additional, Panovska, A., additional, Plevova, K., additional, Pospisilova, S., additional, Simkovic, M., additional, Vrbacky, F., additional, Lysak, D., additional, Fernandes, S. M., additional, Davids, M. S., additional, Maiques‐Diaz, A., additional, Charalampopoulou, S., additional, Martin‐Subero, J. I., additional, Brown, J. R., additional, Doubek, M., additional, Forconi, F., additional, Mayer, J., additional, and Mraz, M., additional

Published
2023
Full Text
View/download PDF

8. S145: THE COMBINATION OF IBRUTINIB PLUS VENETOCLAX RESULTS IN A HIGH RATE OF MRD NEGATIVITY IN PREVIOUSLY UNTREATED CLL: THE RESULTS OF THE PLANNED INTERIM ANALYSIS OF THE PHASE III NCRI FLAIR TRIAL

Author

Hillmen, P., primary, Pitchford, A., additional, Bloor, A., additional, Pettitt, A., additional, Patten, P., additional, Forconi, F., additional, Schuh, A., additional, Fox, C., additional, Elmusharaf, N., additional, Gatto, S., additional, Kennedy, B., additional, Gribben, J., additional, Pemberton, N., additional, Sheehy, O., additional, Preston, G., additional, Howard, D., additional, Hockaday, A., additional, Cairns, D., additional, Jackson, S., additional, Greatorex, N., additional, Webster, N., additional, Dalal, S., additional, Shingles, J., additional, Cwynarski, K., additional, Paneesha, S., additional, Allsup, D., additional, Rawstron, A., additional, and Munir, T., additional

Published
2022
Full Text
View/download PDF

9. P1130: ACALABRUTINIB IN TREATMENT-NAIVE OR RELAPSED/REFRACTORY WALDENSTRÖM MACROGLOBULINEMIA: 5-YEAR FOLLOW-UP OF A PHASE 2, SINGLE-ARM STUDY

Author

Owen, R., primary, McCarthy, H., additional, Rule, S., additional, D’Sa, S., additional, Thomas, S., additional, Tournilhac, O., additional, Forconi, F., additional, José Kersten, M., additional, Luigi Zinzani, P., additional, Iyengar, S., additional, Kothari, J., additional, Minnema, M., additional, Kastritis, E., additional, Cheson, B., additional, Walter, H., additional, Greewald, D., additional, Calvo, R., additional, Wun, C.-C., additional, and Furman, R., additional

Published
2022
Full Text
View/download PDF

10. Development of a distributed international patient data registry for hairy cell leukemia

Author

Andritsos, LA, Anghelina, M, Neal, J, Blachly, JS, Mathur, P, Lele, O, Dearden, C, Iyengar, S, Cross, M, Zent, CS, Rogers, KA, Epperla, N, Lozanski, G, Oakes, CC, Kraut, E, Ruppert, AS, Zhao, Q, Bhat, SA, Forconi, F, Banerji, V, Handunnetti, S, Tam, CS, Seymour, JF, Else, M, Kreitman, RJ, Saven, A, Call, T, Parikh, SA, Ravandi, F, Johnston, JB, Tiacci, E, Troussard, X, Tallman, MS, Dietrich, S, Tadmor, T, Gozzetti, A, Zinzani, PL, Robak, T, Quest, G, Demeter, J, Rai, K, Fernandez, SA, Grever, M, Andritsos, LA, Anghelina, M, Neal, J, Blachly, JS, Mathur, P, Lele, O, Dearden, C, Iyengar, S, Cross, M, Zent, CS, Rogers, KA, Epperla, N, Lozanski, G, Oakes, CC, Kraut, E, Ruppert, AS, Zhao, Q, Bhat, SA, Forconi, F, Banerji, V, Handunnetti, S, Tam, CS, Seymour, JF, Else, M, Kreitman, RJ, Saven, A, Call, T, Parikh, SA, Ravandi, F, Johnston, JB, Tiacci, E, Troussard, X, Tallman, MS, Dietrich, S, Tadmor, T, Gozzetti, A, Zinzani, PL, Robak, T, Quest, G, Demeter, J, Rai, K, Fernandez, SA, and Grever, M

Abstract

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder, comprising only 2% of all leukemias. The Hairy Cell Leukemia Foundation (HCLF) has developed a patient data registry to enable investigators to better study the clinical features, treatment outcomes, and complications of patients with HCL. This system utilizes a centralized registry architecture. Patients are enrolled at HCL Centers of Excellence (COE) or via a web-based portal. All data are de-identified, which reduces regulatory burden and increases opportunities for data access and re-use. To date, 579 patients have been enrolled in the registry. Efforts are underway to engage additional COE's to expand access to patients across the globe. This international PDR will enable researchers to study outcomes in HCL in ways not previously possible due to the rarity of the disease and will serve as a platform for future prospective research.

Published
2022

11. Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Author

Ravandi, F, Kreitman, RJ, Tiacci, E, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, SA, Blachly, JS, Broccoli, A, Call, T, Chihara, D, Dearden, C, Demeter, J, Dietrich, S, Else, M, Epperla, N, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Jorgensen, J, Juliusson, G, Lauria, F, Lozanski, G, Parikh, SA, Park, JH, Polliack, A, Quest, G, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Thompson, PA, Troussard, X, Zent, CS, Zenz, T, Zinzani, PL, Woermann, B, Rai, K, Grever, M, Ravandi, F, Kreitman, RJ, Tiacci, E, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, SA, Blachly, JS, Broccoli, A, Call, T, Chihara, D, Dearden, C, Demeter, J, Dietrich, S, Else, M, Epperla, N, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Jorgensen, J, Juliusson, G, Lauria, F, Lozanski, G, Parikh, SA, Park, JH, Polliack, A, Quest, G, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Thompson, PA, Troussard, X, Zent, CS, Zenz, T, Zinzani, PL, Woermann, B, Rai, K, and Grever, M

Abstract

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.

Published
2022

12. Long-term benefit of IGHV mutated patients in a real-life multicenter cohort of FCR-treated chronic lymphocytic leukemia

Author

Moia, R., Dondolin, R., De Propris, M. S., Talotta, D., Mouhssine, S., Perutelli, F., Reda, G., Mattiello, V., Rigolin, G. M., Motta, M., Olivieri, J., Fanin, R., Perbellini, O., Ferrarini, I., Mauro, F. R., Del Giudice, I., Laurenti, Luca, Tomasso, Annamaria, Gentile, M., Frustaci, A. M., Tedeschi, Alessandra, Gozzetti, A., Stelitano, C., Visco, C., Moreno, C., Forconi, F., Marasca, R., Coscia, M., Rossi, Dario, Foa, Robin, Gaidano, G., Laurenti L. (ORCID:0000-0002-8327-1396), Tomasso A., Tedeschi A., Rossi D., Foa R., Moia, R., Dondolin, R., De Propris, M. S., Talotta, D., Mouhssine, S., Perutelli, F., Reda, G., Mattiello, V., Rigolin, G. M., Motta, M., Olivieri, J., Fanin, R., Perbellini, O., Ferrarini, I., Mauro, F. R., Del Giudice, I., Laurenti, Luca, Tomasso, Annamaria, Gentile, M., Frustaci, A. M., Tedeschi, Alessandra, Gozzetti, A., Stelitano, C., Visco, C., Moreno, C., Forconi, F., Marasca, R., Coscia, M., Rossi, Dario, Foa, Robin, Gaidano, G., Laurenti L. (ORCID:0000-0002-8327-1396), Tomasso A., Tedeschi A., Rossi D., and Foa R.

Abstract

NA

Published
2022

16. Insertion of atypical glycans into the tumor antigen-binding site identifies DLBCLs with distinct origin and behavior

Author

Chiodin, G., Allen, J.D., Bryant, D.J., Rock, P., Martino, E.A., Valle-Argos, B., Duriez, P.J., Watanabe, Y., Henderson, I., Blachly, J.S., McCann, K.J., Strefford, J.C., Packham, G., Geijtenbeek, T.B.H., Figdor, C.G., Wright, G.W., Staudt, L.M., Burack, R., Bowden, T.A., Crispin, M., Stevenson, F.K., Forconi, F., Chiodin, G., Allen, J.D., Bryant, D.J., Rock, P., Martino, E.A., Valle-Argos, B., Duriez, P.J., Watanabe, Y., Henderson, I., Blachly, J.S., McCann, K.J., Strefford, J.C., Packham, G., Geijtenbeek, T.B.H., Figdor, C.G., Wright, G.W., Staudt, L.M., Burack, R., Bowden, T.A., Crispin, M., Stevenson, F.K., and Forconi, F.

Abstract

Item does not contain fulltext, Glycosylation of the surface immunoglobulin (Ig) variable region is a remarkable follicular lymphoma-associated feature rarely seen in normal B cells. Here, we define a subset of diffuse large B-cell lymphomas (DLBCLs) that acquire N-glycosylation sites selectively in the Ig complementarity-determining regions (CDRs) of the antigen-binding sites. Mass spectrometry and X-ray crystallography demonstrate how the inserted glycans are stalled at oligomannose-type structures because they are buried in the CDR loops. Acquisition of sites occurs in approximately 50% of germinal-center B-cell-like DLBCL (GCB-DLBCL), mainly of the genetic EZB subtype, irrespective of IGHV-D-J use. This markedly contrasts with the activated B-cell-like DLBCL Ig, which rarely has sites in the CDR and does not seem to acquire oligomannose-type structures. Acquisition of CDR-located acceptor sites associates with mutations of epigenetic regulators and BCL2 translocations, indicating an origin shared with follicular lymphoma. Within the EZB subtype, these sites are associated with more rapid disease progression and with significant gene set enrichment of the B-cell receptor, PI3K/AKT/MTORC1 pathway, glucose metabolism, and MYC signaling pathways, particularly in the fraction devoid of MYC translocations. The oligomannose-type glycans on the lymphoma cells interact with the candidate lectin dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN), mediating low-level signals, and lectin-expressing cells form clusters with lymphoma cells. Both clustering and signaling are inhibited by antibodies specifically targeting the DC-SIGN carbohydrate recognition domain. Oligomannosylation of the tumor Ig is a posttranslational modification that readily identifies a distinct GCB-DLBCL category with more aggressive clinical behavior, and it could be a potential precise therapeutic target via antibody-mediated inhibition of the tumor Ig interaction with DC-SIGN-expressing M2-po

Published
2021

17. Hairy cell leukemia and COVID-19 adaptation of treatment guidelines

Author

Grever, M, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, S, Blachly, JS, Call, T, Cross, M, Dearden, C, Demeter, J, Dietrich, S, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Juliusson, G, Kraut, E, Kreitman, RJ, Lauria, F, Lozanski, G, Parikh, SA, Park, J, Polliack, A, Ravandi, F, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Tiacci, E, Troussard, X, Zent, C, Zenz, T, Zinzani, PL, Wormann, B, Grever, M, Andritsos, L, Banerji, V, Barrientos, JC, Bhat, S, Blachly, JS, Call, T, Cross, M, Dearden, C, Demeter, J, Dietrich, S, Falini, B, Forconi, F, Gladstone, DE, Gozzetti, A, Iyengar, S, Johnston, JB, Juliusson, G, Kraut, E, Kreitman, RJ, Lauria, F, Lozanski, G, Parikh, SA, Park, J, Polliack, A, Ravandi, F, Robak, T, Rogers, KA, Saven, A, Seymour, JF, Tadmor, T, Tallman, MS, Tam, CS, Tiacci, E, Troussard, X, Zent, C, Zenz, T, Zinzani, PL, and Wormann, B

Abstract

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.

Published
2021

18. The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome

Author

Fundación Memoria de D. Samuel Solorzano Barruso, Universidad de Salamanca, European Commission, Instituto de Salud Carlos III, Cancer Research UK, Asociación Española Contra el Cáncer, Associazione Italiana per la Ricerca sul Cancro, Rodríguez-Caballero, Arancha, Fuentes-Herrero, Blanca, Oliva-Ariza, Guillermo, Criado, Ignacio, Alcoceba, Miguel, Prieto, Carlos, Pérez-Caro, M., García-Montero, Andrés, González, Marcos, Forconi, F., Sarmento-Ribeiro, Ana Bela, Almeida, Julia, Orfao, Alberto, Fundación Memoria de D. Samuel Solorzano Barruso, Universidad de Salamanca, European Commission, Instituto de Salud Carlos III, Cancer Research UK, Asociación Española Contra el Cáncer, Associazione Italiana per la Ricerca sul Cancro, Rodríguez-Caballero, Arancha, Fuentes-Herrero, Blanca, Oliva-Ariza, Guillermo, Criado, Ignacio, Alcoceba, Miguel, Prieto, Carlos, Pérez-Caro, M., García-Montero, Andrés, González, Marcos, Forconi, F., Sarmento-Ribeiro, Ana Bela, Almeida, Julia, and Orfao, Alberto

Abstract

The HCDR3 sequences of the B-cell receptor (BCR) undergo constraints in length, amino acid use, and charge during maturation of B-cell precursors and after antigen encounter, leading to BCR and antibodies with high affinity to specific antigens. Chronic lymphocytic leukemia consists of an expansion of B-cells with a mixed immature and “antigen-experienced” phenotype, with either a mutated (M-CLL) or unmutated (U-CLL) tumor BCR, associated with distinct patient outcomes. Here, we investigated the hydropathy index of the BCR of 138 CLL patients and its association with the IGHV mutational status and patient outcome. Overall, two clearly distinct subgroups of M-CLL patients emerged, based on a neutral (mean hydropathy index of -0.1) vs. negatively charged BCR (mean hydropathy index of -1.1) with molecular features closer to those of B-cell precursors and peripheral/mature B-cells, respectively. Despite that M-CLL with neutral HCDR3 did not show traits associated with a mature B-cell repertoire, important differences in IGHV gene usage of tumor cells and patient outcome were observed in this subgroup of patients once compared to both U-CLL and M-CLL with negatively charged HCDR3 sequences. Compared to M-CLL with negatively charged HCDR3 sequences, M-CLL with neutral HCDR3 sequences showed predominance of men, more advanced stages of the disease, and a greater frequency of genetic alterations—e.g., del(17p)—together with a higher rate of disease progression and shorter time to therapy (TTT), independently of other prognostic factors. Our data suggest that the hydropathy index of the HCDR3 sequences of CLL cells allows the identification of a subgroup of M-CLL with intermediate prognostic features between U-CLL and the more favorable subgroup of M-CLL with a negatively charged BCR.

Published
2021

21. BTK and PLCG2 mutations in patients with Chronic Lymphocytic Leukemia relapsing on Ibrutinib: a European Research Initiative on CLL (ERIC) study based on real-world evidence

Author

Scarfò, L, Bonfiglio, S, A Sutton, L, Ljungstrom, V, Pandzic, T, Cortese, D, Gaidano, G, Trentin, L, Bonello, L, Reda, G, Panayiotidis, P, Forconi, F, Stavroyianni, N, Bödör, C, Tam, C, Iyengar, S, Österborg, A, Coscia, M, Ysebaert, L, Jaksic, O, Ringshausen, I, Mulligan, S, Tedeschi, A, Strugov, V, Davis, Z, Pavlovsky, C, Marasca, R, Capasso, A, Ranghetti, P, Stamatopoulos, K, Rosenquist, R, and Ghia, P

Published
2020

22. Acalabrutinib monotherapy in patients with Waldenström macroglobulinemia: a single-arm, multicentre, phase 2 study

Author

Owen, R.G. McCarthy, H. Rule, S. D'Sa, S. Thomas, S.K. Tournilhac, O. Forconi, F. Kersten, M.J. Zinzani, P.L. Iyengar, S. Kothari, J. Minnema, M.C. Kastritis, E. Aurran-Schleinitz, T. Cheson, B.D. Walter, H. Greenwald, D. Chen, D.-Y. Frigault, M.M. Hamdy, A. Izumi, R. Patel, P. Wei, H. Lee, S.K. Mittag, D. Furman, R.R.

Abstract

Background: Chemoimmunotherapy is typically the standard of care for patients with Waldenström macroglobulinemia; however, infectious and hematologic toxic effects are problematic. Acalabrutinib is a selective, potent Bruton tyrosine-kinase inhibitor. The aim of this trial was to evaluate the activity and safety of acalabrutinib in patients with Waldenström macroglobulinemia. Methods: This single-arm, multicentre, phase 2 trial was done in 19 European academic centres in France, Italy, Greece, the Netherlands, and the UK, and eight academic centres in the USA. Eligible patients were 18 years or older and had treatment naive (declined or not eligible for chemoimmunotherapy) or relapsed or refractory (at least one previous therapy) Waldenström macroglobulinemia that required treatment, an Eastern Cooperative Oncology Group performance status of 2 or less, and received no previous Bruton tyrosine-kinase inhibitor therapy. Patients received 100 mg oral acalabrutinib twice per day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed overall response (at least a minor response) according to the 6th International Workshop for Waldenström Macroglobulinemia (IWWM) and the modified 3rd IWWM workshop criteria. The primary outcome and safety were assessed in all patients who received at least one dose of treatment. This study is registered with ClinicalTrials.gov, number NCT02180724, and is ongoing, but no longer enrolling. Findings: Between Sept 8, 2014, and Dec 24, 2015, 122 patients were assessed for eligibility, of which 106 (87%) patients were given acalabrutinib (14 were treatment naive and 92 had relapsed or refractory disease). With a median follow-up of 27·4 months (IQR 26·0–29·7), 13 (93% [95% CI 66–100]) of 14 treatment naive patients achieved an overall response and 86 (93% [86–98]) of 92 relapsed or refractory patients per both the modified 3rd and 6th IWWM criteria. Seven (50%) of 14 treatment naive patients and 23 (25%) of 92 relapsed or refractory patients discontinued treatment on study. Grade 3–4 adverse events occurring in more than 5% of patients were neutropenia (17 [16%] of 106 patients) and pneumonia (7 [7%]). Grade 3–4 atrial fibrillation occurred in one (1%) patient and grade 3–4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7 [7%]), pneumonia (n=7 [7%]), pyrexia (n=4 [4%]), cellulitis (n=3 [3%]), fall (n=3 [3%]), and sepsis (n=3 [3%]). Pneumonia (n=5 [5%]) and lower respiratory tract infection (n=4 [4%]) were considered treatment related. One treatment-related death was reported (intracranial hematoma). Interpretation: This study provides evidence that acalabrutinib is active as single-agent therapy with a manageable safety profile in patients with treatment-naive, or relapse or refractory Waldenström macroglobulinemia. Further studies are needed to establish its efficacy against current standard treatments and to investigate whether outcomes can be improved with combination therapies. Funding: Acerta Pharma. © 2020 Elsevier Ltd

Published
2020

27. Kinobead Profiling Reveals Reprogramming of B-cell Receptor Signaling in Response to Therapy Within Primary Chronic Lymphocytic Leukemia Cells

Author

Linley, AJ, primary, Karydis, LI, additional, Mondru, A, additional, D’Avola, A, additional, Cicconi, S, additional, Griffin, R, additional, Forconi, F, additional, Pettitt, AR, additional, Kalakonda, N, additional, Rawstron, A, additional, Hillmen, P, additional, Steele, AJ, additional, MacEwan, DJ, additional, Packham, G, additional, Prior, IA, additional, and Slupsky, JR, additional

Published
2019
Full Text
View/download PDF

30. INTERNATIONAL PROGNOSTIC SCORE FOR EARLY STAGE CHRONIC LYMPHOCYTIC LEUKEMIA (IPS-A)

Author

Condoluci, A., primary, Terzi di Bergamo, L., additional, Langerbeins, P., additional, Hoechstetter, M., additional, Herling, C., additional, De Paoli, L., additional, Delgado, J., additional, Gentile, M., additional, Doubek, M., additional, Mauro, F.R., additional, Chiodin, G., additional, Mattsson, M., additional, Bahlo, J., additional, Cutrona, G., additional, Kotaskova, J., additional, Deambrogi, C., additional, Moia, R., additional, Gerber, B., additional, Zucca, E., additional, Ghielmini, M., additional, Cavalli, F., additional, Stüssi, G., additional, Neri, A., additional, Ferrarini, M., additional, Rosenquist, R., additional, Forconi, F., additional, Foà, R., additional, Pospisilova, S., additional, Morabito, F., additional, Wierda, W.G., additional, Montserrat, E., additional, Gaidano, G., additional, Hallek, M., additional, and Rossi, D., additional

Published
2019
Full Text
View/download PDF

33. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib: a GIMEMA, ERIC and UK CLL FORUM study

Author

Cuneo, A, Follows, G, Rigolin, GM, Piciocchi, A, Tedeschi, A, Trentin, L, Perez, AM, Coscia, M, Laurenti, L, Musuraca, G, Farina, L, Delgado, AR, Orlandi, EM, Galieni, P, Mauro, FR, Visco, C, Amendola, A, Billio, A, Marasca, R, Chiarenza, A, Meneghini, V, Ilariucci, F, Marchetti, M, Molica, S, Re, F, Gaidano, G, Gonzalez, M, Forconi, F, Ciolli, S, Cortelezzi, A, Montillo, M, Smolej, L, Schuh, A, Eyre, TA, Kennedy, B, Bowles, KM, Vignetti, M, de la Seam, J, Moreno, C, Foa, R, Ghia, P, GIMEMA, European Res Initiative CLL ERIC, and UK CLL Forum

Abstract

We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion. (Registered at clinicaltrials.gov identifier: 02491398)

Published
2018

34. Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

Author

Jacob, A, Bloor, A, Whiteway, A, Milne, AE, Kirkwood, AA, Hodson, A, Duncombe, AS, Schuh, A, von Barsewisch, B, Fegan, C, Fox, CP, Pocock, C, William, C, Dearden, C, Hutchinson, C, Balotis, C, De Lord, C, Kennedy, DB, Tucker, D, Vendenberghe, E, Maughan, E, Kumar, E, McNichol, F, Scott, F, Forconi, F, Campbell, G, Follows, GA, Pratt, G, Knight, H, Parry, H, Ringshausen, I, Whalley, I, Nielson, J, Allen, J, Arnold, J, Gribbon, J, Wallis, J, Blundell, J, Cwynarski, K, Bowles, KM, Ewings, M, Karanth, M, Dyer, MJ, Hamblin, M, Leach, M, Badat, M, Mir, N, Morley, N, Bienz, N, and Philpott, N

Abstract

In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression.

Published
2016

35. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukemia

Author

Parker, H., Rose-Zerilli, M.J.J., Larrayoz, M., Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, V., Wojdacz, T.K., Chaplin, T., Roghanian, A., Davis, Z., Parker, A., Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A.J., Packham, G., Rodriquez-Vicente, A.E., Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M.S., Chelala, C., Oakes, C.C., Rosenquist, R., Stamatopoulos, K., Stilgenbauer, S., Knight, S., Schuh, A., Oscier, D.G., and Strefford, J.C.

Abstract

Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumors including haematological malignancies. Using high-resolution SNP-arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2-deletions or mutations were often observed as a 56 clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy, had reduced progression-free and overall survival compared to cases wild-type for all three genes. Consistent with its postulated role as a tumor suppressor, our data highlights SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease.

Published
2016

36. Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis

Author

Eichhorst, Barbara F, Fischer, Kirsten, Fink, Anna Maria, Elter, Thomas, Wendtner, Clemens M, Goede, Valentin, Bergmann, Manuela, Stilgenbauer, Stephan, Hopfinger, Georg, Ritgen, Matthias, Bahlo, Jasmin, Busch, Raymonde, Hallek, Michael, Oduncu, F, Dreyling, M, Forstpointner, R, Schneller, F, Bogner, C, Peschel, C, Ringshausen, I, Götze, K, Goebeler, Me, Rückle, Lanz, Ritgen, M, Schawitzke, A, Heydrich, B, Kern, K, Böttcher, S, Irmer, S, Strack, U, Borries, V, Klima, Km, Scholz, C, Herold, M, Härtwig, K, Dürig, J, Dührsen, U, Müller Beissenhirtz, H, Noppeney, R, Schüttrumpf, S, Hohloch, K, Binder, C, Hasenkamp, J, Trümper, L, Bäsecke, J, Rieger, M, Witzens Harig, M, Friedrichs, B, Rieger, K, Uharek, L, Kubuschok, B, Murawski, N, Held, G, Zwick, C, Pfreundschuh, M, Fingerle Rowson, G, Reiser, M, Elter, T, Eichhorst, B, Pallasch, C, Hallek, M, Borchmann, P, Hacker, U, Schinkel, S, Wieker, K, Sökler, M, Wolf, Hh, Eucker, J, Staib, P, Schlegel, F, Kropff, M, Kahl, C, Hess, G, Beck, J, Wölfel, T, Bokemeyer, C, Schilling, G, Dierlamm, J, Schüler, F, Busemann, C, Dölken, G, Trendelenburg, Tk, Bühler, A, Stilgenbauer, S, Viardot, A, Greiner, J, Zenz, T, Gaidzik, V, Langer, C, Döhner, H, Werner, I, Dienst, A, Habersang, K, Härtel, N, Leitner, A, Kehrer, G, Middeke, H, Heinisch, K, Adorf, D, Ismer, B, Hering Schubert, C, Jäckle, J, Aulmann, C, Söllner, S, Majunke, P, Fuss, H, Käfer, G, Potenberg, J, Dietrich, G, Hartung, E, Pronath, A, Riedhammer, Fj, Zehrfeld, T, Prümmer, O, Gatter, J, Meier, A, Wattad, M, Heit, W, Sauer, I, Hilgers, K, Geissler, M, Bauer, J, Stein, W, Voigtmann, R, Natt, F, Nickelsen, M, Zeis, M, Schmitz, N, Lange, E, Stoltefuss, A, Schubert, J, Dürk, Ha, Kloke, O, Fauser, A, Roemer, E, Kraut, L, Musch, E, Kohl, S, Link, H, Kirsch, Jf, Schatz, M, Mezger, J, Kempf, B, Heil, G, Derigs, Hg, Roll, C, Kettner, E, Dübbers, Hw, Lutz, L, Hentrich, M, Hoffmann, U, Ibe, M, Falge, C, Schäfer Eckart, K, Rothmann, F, Raghavachar, A, Beckmann, K, Behringer, D, Stauder, H, Hempfling, C, Matzdorff, A, Hähling, D, Kaesberger, Kj, Mück, R, Waladkhani, Ar, Clemens, M, Kraft, J, Ehlert, T, N. N., Schloen, A, Sandritter, B, Scholz, Diekmann, C, Pflüger, Kh, Hausner, G, Fetscher, S, Aulitzky, W, Brugger, W, Frickhofen, N, Fuhr, Lange, C, Lambertz, H, Schulz, L, Schmier, M, Bentz, M, Tauchmann, Gm, Schmidt, M, Meiler, J, Sandmann, M, Kürschner, D, Maier Bay, B, Lindemann, W, Diers, J, Riemeier Sievers, C, Daun, M, Mergenthaler, Hg, Hiller, S, Schirmer, V, Kirchner, H, Langer, W, Günther, B, Gassmann, W, Franke, K, Burghardt, F, Abele, U, Celikel Becker, D, von Weikersthal LF, Brög, G, Hauch, U, Heinrich, B, Brudler, O, Häcker, B, Eckart, Mj, Bolouri, H, Göttler, B, Kindler, M, Zuchold, K, Strohbach, F, Plingen, Ml, Seibt Jung, H, Kirsch, A, Herrenberger, J, Doering, G, von Grünhagen, U, Franke, H, Weniger, J, Kerzel, W, Schmalfeld, M, Rohrberg, R, Hurtz, Hj, Gehbauer, G, Hahnfeld, S, Vehling Kaiser, U, Abenhardt, W, Bosse, D, Böning, L, Schmidt, B, Schick, Hd, Jacobs, G, Stauch, M, Hoffmann, R, Müller, S, Hahn, M, Freier, W, Dietzfelbinger, H, Rassmann, I, Söling, U, Siehl, S, Rudolph, R, Weinert, R, Sauer, A, Meyer, B, Eschenburg, H, Schadeck Gressel, C, Grabenhorst, U, Perker, M, Otremba, B, Reschke, D, Hinrichs, Hf, Zirpel, I, Höring, E, Respondek, M, Köppler, H, Heymanns, J, Weide, R, Hünermund, K, Thiel, C, Reiber, T, Spohn, C, Springer, G, Fiechtner, H, Hübner, A, Kurschel, E, Weiss, J, Schlag, R, Schäfer, E, Hartwich, G, Schmitz, S, Steinmetz, T, Kim, Ts, Lerchenmüller, C, Wehmeyer, J, Laubenstein, Hp, Rendenbach, B, Lebahn, H, Kröning, H, Uhle, R, Balló, H, Gaede, B, Zumbrink, S, Eckert, R, Kamp, T, Reimann, B, Burkhard, O, Mittermüller, J, Hansen, R, Hitz, H, Schliesser, G, Schmitt, Hr, Forstbauer, H, Grundeis, M, Schulze, M, Baldus, M, Lakner, V, Haen, M, Müller, C, Dörfel, S, Göhler, T, Welslau, M, Achtzehn, V, Culmann, H, Gerhardt, S, Ulshöfer, T, Koschuth, A, Schmidt, P, Müller, L, Schneider, M, Koniczek, K, Porowski, P, Glados, M, Knoblich, J, Ben Yehuda, D, Jäger, U, Gaiger, A, Schwarzmeier, J, Nösslinger, T, Smith, M, Patton, N, Gibbons, S, Bouabdallah, R, Gandhi, M, Marlton, P, Mills, T, Angelucci, E, Sorano, Gg, Casula, P, Berneman, Z, Kohser, P, Hudcova Burgetova, A, Machová, R, Papajik, T, Kubová, Z, Fineman, R, Mayer, J, Doubek, M, Brychtova, Y, Ciceri, F, Caligaris Cappio, F, Crocchiolo, R, Dauriac, C, Bernard, M, Escoffre Barbe, M, Lamy, T, Zikesova, E, Karban, J, Salkova, J, Trnený, M, Pytlik, R, Tiley, C, Forsyth, C, Vokurka, S, Koza, V, Van Hoof, A, Selleslag, D, Sebban, C, Baker, B, Belada, D, Jebavy, L, Smolej, L, Pavel, Z, Di Ianni, M, Castaigne, S, Del Poeta, G, Amadori, S, Catalano, J, Ganju, V, Hertzberg, M, Laurenti, L, Dalseg, Am, Bron, D, Morton, J, Durrant, S, Casado, Lf, Theunissen, K, Atias, D, Berkhan, L, Seymour, J, Wolf, M, Bosly, A, Osma Cordoba MM, Portois, C, Jaubert, J, Ferrant, A, Lambert, C, Maerevoet, E, Van den Neste, E, Gadeberg, O, Carney, B, Cannell, P, Eghbali, H, Legouffe, E, Bordessoule, D, Chaury, M, Moreau, S, Pierri, I, Gobbi, M, Berrebi, A, Lishner, M, Yerushazim, R, Yermiaku, T, Kosolov, V, Ambrosetti, Achille, Andreoli, Al, Huguet, F, Laurent, G, Orsucci, L, Forconi, F, Musuraca, G, Zinzani, Pl, Loscertales, J, Mcquillan, A, Cordingley, F, Leahy, M, Cazin, B, Taylor, Mulligan, S, Herbrecht, Cull, G, Seldon, M, Rowlings, P, Ludwig, H, Zojer, N, Solal Céligny, P, Pomponi, F, Savdkova, L, Kozák, T, Christiansen, I, Pérez, I, Campbell, P, Canales Albendea, M, De Paz, R, Arthur, C, Gisselbrecht, C., Eichhorst B.F., Fischer K., Fink A.M., Elter T., Wendtner C.M., Goede V., Bergmann M., Stilgenbauer S., Hopfinger G., Ritgen M., Bahlo J., Busch R., Hallek M., and Zinzani P.L.

Subjects
Male, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, Immunology, Medizin, Antineoplastic Combined Chemotherapy Protocols, Blood Cell Count, Disease Progression, Disease-Free Survival, Female, Follow-Up Studies, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, Prognosis, Recurrence, Remission Induction, Tomography, X-Ray Computed, Physical examination, Biochemistry, Chemoimmunotherapy, medicine, Chronic, Tomography, Leukemia, medicine.diagnostic_test, business.industry, B-Cell, Cancer, Cell Biology, Hematology, medicine.disease, Lymphocytic, imaging techniques, X-Ray Computed, Fludarabine, Surgery, chronic lymphocytic leukemia, Radiology, business, Progressive disease, medicine.drug
Abstract

The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.

Published
2011
Full Text
View/download PDF

37. Immunoglobulin genes in chronic lymphocytic leukemia: Key to understanding the disease and improving risk stratification

Author

Sutton, L.-A. (L.), Hadzidimitriou, A. (A.), Baliakas, P. (P.), Agathangelidis, A. (Andreas), Langerak, A.W. (Anton), Stilgenbauer, S. (S.), Pospisilova, D. (Dagmar), Davis, Z. (Zadie), Forconi, F. (Francesco), Davi, F. (Frédéric), Ghia, P. (Paolo), Rosenquist, R. (R.), Stamatopoulos, K. (Kostas), Sutton, L.-A. (L.), Hadzidimitriou, A. (A.), Baliakas, P. (P.), Agathangelidis, A. (Andreas), Langerak, A.W. (Anton), Stilgenbauer, S. (S.), Pospisilova, D. (Dagmar), Davis, Z. (Zadie), Forconi, F. (Francesco), Davi, F. (Frédéric), Ghia, P. (Paolo), Rosenquist, R. (R.), and Stamatopoulos, K. (Kostas)

Published
2017
Full Text
View/download PDF

38. Large genomic aberrations detected by SNP array are independent prognosticators of a shorter time to first treatment in chronic lymphocytic leukemia patients with normal FISH

Author

Mian, M., Rinaldi, A., Mensah, A. A., Rossi, D., Ladetto, M., Forconi, F., Marasca, R., Uhr, M., Stussi, G., Kwee, I., Cavalli, F., Gaidano, G., Zucca, E., Bertoni, F., Mian, M., Rinaldi, A., Mensah, A. A., Rossi, D., Ladetto, M., Forconi, F., Marasca, R., Uhr, M., Stussi, G., Kwee, I., Cavalli, F., Gaidano, G., Zucca, E., and Bertoni, F.

Abstract

Background Genomic complexity can predict the clinical course of patients affected by chronic lymphocytic leukemia (CLL) with a normal FISH. However, large studies are still lacking. Here, we analyzed a large series of CLL patients and also carried out the so far largest comparison of FISH versus single-nucleotide polymorphism (SNP) array in this disease. Patients and methods SNP-array data were derived from a previously reported dataset. Results Seventy-seven of 329 CLL patients (23%) presented with a normal FISH. At least one large (>5 Mb) genomic aberration was detected by SNP array in 17 of 77 patients (22%); this finding significantly affected TTT. There was no correlation with the presence of TP53 mutations. In multivariate analysis, including age, Binet stage, IGHV genes mutational status and large genomic lesion, the latter three factors emerged as independent prognosticators. The concordance between FISH and SNP array varied between 84 and 97%, depending on the specific genomic locus investigated. Conclusions SNP array detected additional large genomic aberrations not covered by the standard FISH panel predicting the outcome of CLL patients

Published
2017

39. Sterotypic B-cell receptor and IGHV4-39 usage represent independent risk factors of chronic lymphocytic leukemia transformation to richter syndrome

Author

Rossi D., Spina V., Cerri M., Rasi S., Deambrogi C., De Paoli L., Laurenti L., Maffei R., Forconi F., Bertoni F, Zucca E., Cabras A., Lucioni M., Martini M., Magni M., Deaglio S., Ladetto M., Nomdedeu J. F., Besson C., Canzonieri V., Paulli M., Marasca R., Larocca L. M., Carbone A., Gattei V., Gaidano G., AGOSTINELLI, CLAUDIO, PILERI, STEFANO, Rossi D., Spina V., Cerri M., Rasi S., Deambrogi C., De Paoli L., Laurenti L., Maffei R., Forconi F., Bertoni F, Zucca E., Agostinelli C., Cabras A., Lucioni M., Martini M., Magni M., Deaglio S., Ladetto M., Nomdedeu J.F., Besson C., Canzonieri V., Paulli M., Marasca R., Larocca L.M., Carbone A., Pileri S.A., Gattei V., and Gaidano G.

Subjects
Sterotypic B-cell receptor, CLL
Published
2009

40. Genome Wide-DNA Profiling of Richter's Syndrome-Diffuse Large B-Cell Lymphoma (RS-DLBCL): Differences with De Novo DLBCL and Possible Mechanisms of Transformation from Chronic Lymphocytic Leukemia

Author

Bertoni F, Scandurra M, Cerri M, Deambrogi C, Rancoita PMV, Rasi S, Forconi F, Montes Moreno S, Piris MA, Inghirami G, Rinaldi A, Zucca E, Kwee I, Gaidano G, Rossi D., PONZONI , MAURILIO, Bertoni, F, Scandurra, M, Cerri, M, Deambrogi, C, Rancoita, Pmv, Rasi, S, Forconi, F, Ponzoni, Maurilio, Montes Moreno, S, Piris, Ma, Inghirami, G, Rinaldi, A, Zucca, E, Kwee, I, Gaidano, G, and Rossi, D.

Published
2008

41. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia

Author

Leukaemia & Lymphoma Research (UK), Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), Swedish Research Council, Swedish Cancer Society, Polysackaridforskning i Uppsala AB, German Research Foundation, Leukaemia Foundation, Wessex Medical Research, Kay Kendall Leukaemia Fund, Cancer Research UK, Parker, H., Rose-Zerilli, M. J. J., Larráyoz, María José, Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, V., Wojdacz, T. K., Chaplin, T., Roghanian, A., Davis, Z., Parker, Antón, Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A. J., Packham, G., Rodríguez-Vicente, Ana Eugenia, Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M. S., Chelala, C., Oakes, C. C., Rosenquist, Richard, Stamatopoulos, Kostas, Stilgenbauer, S., Knight, S., Schuh, A., Oscier, David G., Strefford, Jonathan C., Leukaemia & Lymphoma Research (UK), Royal Marsden NHS Foundation Trust, The Institute of Cancer Research (UK), Swedish Research Council, Swedish Cancer Society, Polysackaridforskning i Uppsala AB, German Research Foundation, Leukaemia Foundation, Wessex Medical Research, Kay Kendall Leukaemia Fund, Cancer Research UK, Parker, H., Rose-Zerilli, M. J. J., Larráyoz, María José, Clifford, R., Edelmann, J., Blakemore, S., Gibson, J., Wang, J., Ljungström, V., Wojdacz, T. K., Chaplin, T., Roghanian, A., Davis, Z., Parker, Antón, Tausch, E., Ntoufa, S., Ramos, S., Robbe, P., Alsolami, R., Steele, A. J., Packham, G., Rodríguez-Vicente, Ana Eugenia, Brown, L., McNicholl, F., Forconi, F., Pettitt, A., Hillmen, P., Dyer, M., Cragg, M. S., Chelala, C., Oakes, C. C., Rosenquist, Richard, Stamatopoulos, Kostas, Stilgenbauer, S., Knight, S., Schuh, A., Oscier, David G., and Strefford, Jonathan C.

Abstract

Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next-generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease.

Published
2016

42. IL-10 production by CLL cells is enhanced in the anergic IGHV mutated subset and associates with reduced DNA methylation of the IL10 locus

Author

Drennan, S, primary, D'Avola, A, additional, Gao, Y, additional, Weigel, C, additional, Chrysostomou, E, additional, Steele, A J, additional, Zenz, T, additional, Plass, C, additional, Johnson, P W, additional, Williams, A P, additional, Packham, G, additional, Stevenson, F K, additional, Oakes, C C, additional, and Forconi, F, additional

Published
2016
Full Text
View/download PDF

44. Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia

Author

Parker, H, primary, Rose-Zerilli, M J J, additional, Larrayoz, M, additional, Clifford, R, additional, Edelmann, J, additional, Blakemore, S, additional, Gibson, J, additional, Wang, J, additional, Ljungström, V, additional, Wojdacz, T K, additional, Chaplin, T, additional, Roghanian, A, additional, Davis, Z, additional, Parker, A, additional, Tausch, E, additional, Ntoufa, S, additional, Ramos, S, additional, Robbe, P, additional, Alsolami, R, additional, Steele, A J, additional, Packham, G, additional, Rodríguez-Vicente, A E, additional, Brown, L, additional, McNicholl, F, additional, Forconi, F, additional, Pettitt, A, additional, Hillmen, P, additional, Dyer, M, additional, Cragg, M S, additional, Chelala, C, additional, Oakes, C C, additional, Rosenquist, R, additional, Stamatopoulos, K, additional, Stilgenbauer, S, additional, Knight, S, additional, Schuh, A, additional, Oscier, D G, additional, and Strefford, J C, additional

Published
2016
Full Text
View/download PDF

45. A Molecular Model to Predict Durable Remission after First Line Fludarabine-Cyclophosphamide-Rituximab Treatment in Chronic Lymphocytic Leukemia

Author

Rossi, D, di Bergamo, Lt, Chiarenza, A, Bulian, P, Visco, C, Mauro, Fr, Morabito, F, Cortelezzi, A, Zaja, F, Forconi, F, Laurenti, L, Del Giudice, I, De Paoli, L, Vincelli, I, Rigolin, Gian Matteo, Marasca, R, Perbellini, O, Moreno, C, Del Poeta, G, Massaia, M, Zinzani, Pl, Montillo, M, Cuneo, Antonio, Foa, R, Gattei, V, and Gaidano, G.

Subjects
CLL, FCR, molecular analysis, FCR, molecular analysis, CLL, NO
Published
2014

46. HLA-G is a component of the CLL escape repertoire to generate immune suppression: impact of HLA-G 14 bp (rs66554220) polymorphism

Author

Rizzo, R., Audrito, Valentina, Vacca, P., Rossi, D., Brusa, Davide, Stignani, M., Bortolotti, D., D' Arena, G., Coscia, Marta, Laurenti, L., Forconi, F., Gaidano, G., Mingari, M. C., Moretta, L., Malavasi, Fabio, and Deaglio, Silvia

Subjects
Settore MED/15 - MALATTIE DEL SANGUE, single nucleotide polymorphism, HLA-G, Chronic Lymphocytic Leukemia, NK cells, tumor immunology
Published
2014

Catalog

Books, media, physical & digital resources
See catalog results