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32 results on '"Bassan, R"'

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

Author

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

Published
2021

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

Author

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, Foa, R, Chiaretti S, Messina M, Della Starza I, Piciocchi A, Cafforio L, Cavalli M, Taherinasab A, Ansuinelli M, Elia L, Petroni GA, La Starza R, Canichella M, Lauretti A, Puzzolo MC, 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, Foa R, 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, Foa, R, Chiaretti S, Messina M, Della Starza I, Piciocchi A, Cafforio L, Cavalli M, Taherinasab A, Ansuinelli M, Elia L, Petroni GA, La Starza R, Canichella M, Lauretti A, Puzzolo MC, 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

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-Ph-like 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.

Published
2021

3. 14q32 rearrangements deregulating BCL11B mark a distinct subgroup of T-lymphoid and myeloid immature acute leukemia

Author

Di Giacomo, D, La Starza, R, Gorello, P, Pellanera, F, Kalender Atak, Z, De Keersmaecker, K, Pierini, V, Harrison, C, Arniani, S, Moretti, M, Testoni, N, De Santis, G, Roti, G, Matteucci, C, Bassan, R, Vandenberghe, P, Aerts, S, Cools, J, Bornhauser, B, Bourquin, J, Piazza, R, Mecucci, C, Di Giacomo D., La Starza R., Gorello P., Pellanera F., Kalender Atak Z., De Keersmaecker K., Pierini V., Harrison C. J., Arniani S., Moretti M., Testoni N., De Santis G., Roti G., Matteucci C., Bassan R., Vandenberghe P., Aerts S., Cools J., Bornhauser B., Bourquin J. -P., Piazza R., Mecucci C., Di Giacomo, D, La Starza, R, Gorello, P, Pellanera, F, Kalender Atak, Z, De Keersmaecker, K, Pierini, V, Harrison, C, Arniani, S, Moretti, M, Testoni, N, De Santis, G, Roti, G, Matteucci, C, Bassan, R, Vandenberghe, P, Aerts, S, Cools, J, Bornhauser, B, Bourquin, J, Piazza, R, Mecucci, C, Di Giacomo D., La Starza R., Gorello P., Pellanera F., Kalender Atak Z., De Keersmaecker K., Pierini V., Harrison C. J., Arniani S., Moretti M., Testoni N., De Santis G., Roti G., Matteucci C., Bassan R., Vandenberghe P., Aerts S., Cools J., Bornhauser B., Bourquin J. -P., Piazza R., and Mecucci C.

Abstract

Acute leukemias (ALs) of ambiguous lineage are a heterogeneous group of high-risk leukemias characterized by coexpression of myeloid and lymphoid markers. In this study, we identified a distinct subgroup of immature acute leukemias characterized by a broadly variable phenotype, covering acute myeloid leukemia (AML, M0 or M1), T/myeloid mixed-phenotype acute leukemia (T/M MPAL), and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Rearrangements at 14q32/BCL11B are the cytogenetic hallmark of this entity. In our screening of 915 hematological malignancies, there were 202 AML and 333 T-cell acute lymphoblastic leukemias (T-ALL: 58, ETP; 178, non-ETP; 8, T/M MPAL; 89, not otherwise specified). We identified 20 cases of immature leukemias (4% of AML and 3.6% of T-ALL), harboring 4 types of 14q32/BCL11B translocations: t(2,14)(q22.3;q32) (n = 7), t(6;14)(q25.3;q32) (n = 9), t(7;14)(q21.2;q32) (n = 2), and t(8;14)(q24.2;q32) (n = 2). The t(2;14) produced a ZEB2-BCL11B fusion transcript, whereas the other 3 rearrangements displaced transcriptionally active enhancer sequences close to BCL11B without producing fusion genes. All translocations resulted in the activation of BCL11B, a regulator of T-cell differentiation associated with transcriptional corepressor complexes in mammalian cells. The expression of BCL11B behaved as a disease biomarker that was present at diagnosis, but not in remission. Deregulation of BCL11B co-occurred with variants at FLT3 and at epigenetic modulators, most frequently the DNMT3A, TET2, and/or WT1 genes. Transcriptome analysis identified a specific expression signature, with significant downregulation of BCL11B targets, and clearly separating BCL11B AL from AML, T-ALL, and ETP-ALL. Remarkably, an ex vivo drug-sensitivity profile identified a panel of compounds with effective antileukemic activity.

Published
2021

4. Immature immunoglobulin gene rearrangements are recurrent in B precursor adult acute lymphoblastic leukemia carrying TP53 molecular alterations

Author

Salmoiraghi, S, Cavagna, R, Montalvo, M, Ubiali, G, Tosi, M, Peruta, B, Intermesoli, T, Oldani, E, Salvi, A, Pavoni, C, Giussani, U, Bassan, R, Rambaldi, A, Spinelli, O, Salmoiraghi S., Cavagna R., Montalvo M. L. G., Ubiali G., Tosi M., Peruta B., Intermesoli T., Oldani E., Salvi A., Pavoni C., Giussani U., Bassan R., Rambaldi A., Spinelli O., Salmoiraghi, S, Cavagna, R, Montalvo, M, Ubiali, G, Tosi, M, Peruta, B, Intermesoli, T, Oldani, E, Salvi, A, Pavoni, C, Giussani, U, Bassan, R, Rambaldi, A, Spinelli, O, Salmoiraghi S., Cavagna R., Montalvo M. L. G., Ubiali G., Tosi M., Peruta B., Intermesoli T., Oldani E., Salvi A., Pavoni C., Giussani U., Bassan R., Rambaldi A., and Spinelli O.

Abstract

Here, we describe the immunoglobulin and T cell receptor (Ig/TCR) molecular rearrangements identified as a leukemic clone hallmark for minimal residual disease assessment in relation to TP53 mutational status in 171 Ph-negative Acute Lymphoblastic Leukemia (ALL) adult patients at diagnosis. The presence of a TP53 alterations, which represents a marker of poor prognosis, was strictly correlated with an immature DH/JH rearrangement of the immunoglobulin receptor (p < 0.0001). Furthermore, TP53-mutated patients were classified as pro-B ALL more frequently than their wild-type counterpart (46% vs. 25%, p = 0.05). Although the reasons for the co-presence of immature Ig rearrangements and TP53 mutation need to be clarified, this can suggest that the alteration in TP53 is acquired at an early stage of B-cell maturation or even at the level of pre-leukemic transformation.

Published
2020

5. Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06

Author

Caprioli, C, Lussana, F, Salmoiraghi, S, Cavagna, R, Buklijas, K, Elidi, L, Zanghi', P, Michelato, A, Delaini, F, Oldani, E, Intermesoli, T, Grassi, A, Gianfaldoni, G, Mannelli, F, Ferrero, D, Audisio, E, Terruzzi, E, De Paoli, L, Cattaneo, C, Borlenghi, E, Cavattoni, I, Tajana, M, Scattolin, A, Mattei, D, Corradini, P, Campiotti, L, Ciceri, F, Bernardi, M, Todisco, E, Cortelezzi, A, Falini, B, Pavoni, C, Bassan, R, Spinelli, O, Rambaldi, A, Caprioli, Chiara, Lussana, Federico, Salmoiraghi, Silvia, Cavagna, Roberta, Buklijas, Ksenija, Elidi, Lara, Zanghi', Pamela, Michelato, Anna, Delaini, Federica, Oldani, Elena, Intermesoli, Tamara, Grassi, Anna, Gianfaldoni, Giacomo, Mannelli, Francesco, Ferrero, Dario, Audisio, Ernesta, Terruzzi, Elisabetta, De Paoli, Lorella, Cattaneo, Chiara, Borlenghi, Erika, Cavattoni, Irene, Tajana, Monica, Scattolin, Anna Maria, Mattei, Daniele, Corradini, Paolo, Campiotti, Leonardo, Ciceri, Fabio, Bernardi, Massimo, Todisco, Elisabetta, Cortelezzi, Agostino, Falini, Brunangelo, Pavoni, Chiara, Bassan, Renato, Spinelli, Orietta, Rambaldi, Alessandro, Caprioli, C, Lussana, F, Salmoiraghi, S, Cavagna, R, Buklijas, K, Elidi, L, Zanghi', P, Michelato, A, Delaini, F, Oldani, E, Intermesoli, T, Grassi, A, Gianfaldoni, G, Mannelli, F, Ferrero, D, Audisio, E, Terruzzi, E, De Paoli, L, Cattaneo, C, Borlenghi, E, Cavattoni, I, Tajana, M, Scattolin, A, Mattei, D, Corradini, P, Campiotti, L, Ciceri, F, Bernardi, M, Todisco, E, Cortelezzi, A, Falini, B, Pavoni, C, Bassan, R, Spinelli, O, Rambaldi, A, Caprioli, Chiara, Lussana, Federico, Salmoiraghi, Silvia, Cavagna, Roberta, Buklijas, Ksenija, Elidi, Lara, Zanghi', Pamela, Michelato, Anna, Delaini, Federica, Oldani, Elena, Intermesoli, Tamara, Grassi, Anna, Gianfaldoni, Giacomo, Mannelli, Francesco, Ferrero, Dario, Audisio, Ernesta, Terruzzi, Elisabetta, De Paoli, Lorella, Cattaneo, Chiara, Borlenghi, Erika, Cavattoni, Irene, Tajana, Monica, Scattolin, Anna Maria, Mattei, Daniele, Corradini, Paolo, Campiotti, Leonardo, Ciceri, Fabio, Bernardi, Massimo, Todisco, Elisabetta, Cortelezzi, Agostino, Falini, Brunangelo, Pavoni, Chiara, Bassan, Renato, Spinelli, Orietta, and Rambaldi, Alessandro

Abstract

Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization. Among clinically defined de novo AML, 17.6% carried CS mutations (CS-AML) and showed clinical characteristics closer to sAML (older age, lower white blood cell counts and higher rate of multilineage dysplasia). Outcomes in this group were adverse, more similar to those of sAML as compared to de novo AML (overall survival, 30% in CS-AML and 17% in sAML vs 61% in de novo AML, P<0.0001; disease free survival, 26% in CS-AML and 22% in sAML vs 54% of de novo AML, P<0.001) and independently confirmed by multivariable analysis. Allogeneic transplant in first complete remission improved survival in both sAML and CS-AML patients. In conclusion, these findings highlight the clinical significance of identifying CS-AML for improved prognostic prediction and potential therapeutic implications. (NILG AML 02/06: ClinicalTrials.gov Identifier: NCT00495287).

Published
2021

6. 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

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, Silvia, Cavagna, Roberta, Zanghì, Pamela, Pavoni, Chiara, Michelato, Anna, Buklijas, Ksenija, Elidi, Lara, Intermesoli, Tamara, Lussana, Federico, Oldani, Elena, Caprioli, Chiara, Stefanoni, Paola, Gianfaldoni, Giacomo, Audisio, Ernesta, Terruzzi, Elisabetta, De Paoli, Lorella, Borlenghi, Erika, Cavattoni, Irene, Mattei, Daniele, Scattolin, Annamaria, Tajana, Monica, Ciceri, Fabio, Todisco, Elisabetta, Campiotti, Leonardo, Corradini, Paolo, Fracchiolla, Nicola, Bassan, Renato, Rambaldi, Alessandro, Spinelli, Orietta, 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, Silvia, Cavagna, Roberta, Zanghì, Pamela, Pavoni, Chiara, Michelato, Anna, Buklijas, Ksenija, Elidi, Lara, Intermesoli, Tamara, Lussana, Federico, Oldani, Elena, Caprioli, Chiara, Stefanoni, Paola, Gianfaldoni, Giacomo, Audisio, Ernesta, Terruzzi, Elisabetta, De Paoli, Lorella, Borlenghi, Erika, Cavattoni, Irene, Mattei, Daniele, Scattolin, Annamaria, Tajana, Monica, Ciceri, Fabio, Todisco, Elisabetta, Campiotti, Leonardo, Corradini, Paolo, Fracchiolla, Nicola, Bassan, Renato, Rambaldi, Alessandro, and Spinelli, Orietta

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 < 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 < 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

7. Long-term survival of patients with CLL after allogeneic transplantation: A report from the European Society for Blood and Marrow Transplantation

Author

Van Gelder, M, De Wreede, L, Bornhauser, M, Niederwieser, D, Karas, M, Anderson, N, Gramatzki, M, Dreger, P, Michallet, M, Petersen, E, Bunjes, D, Potter, M, Beelen, D, Cornelissen, J, Yakoub-Agha, I, Russell, N, Finke, J, Schoemans, H, Vitek, A, Urbano-Ispizua, A, Blaise, D, Volin, L, Chevallier, P, Caballero, D, Putter, H, Van Biezen, A, Henseler, A, Schonland, S, Kroger, N, Schetelig, J, Ehninger, G, Jindra, P, Sengeloev, H, Ispizua, A, Arnold, R, Veelken, J, Mufti, G, Milpied, N, Benedetto, B, Schaap, M, Leblond, V, Nikolousis, M, Hallek, M, Passweg, J, Ljungman, P, Masszi, T, Stelljes, M, Browne, P, Glass, B, Espiga, C, Bourhis, J, Roussy, G, Gribben, J, Foa, R, Sierra, J, Mayer, J, Thomson, K, Meijer, E, Blau, W, Holler, E, Bacigalupo, A, Guilhot, F, Carlson, K, Zachee, P, Ifrah, N, Marin, J, Socie, G, Mcquaker, G, Cortelezzi, A, Lenhoff, S, Tischer, J, Irrera, G, Fanin, R, Beguin, Y, Nagler, A, Mackinnon, S, Itala-Remes, M, Deconinck, E, Wulf, G, Corradini, P, Gilleece, M, Wing, B, Peniket, A, Ganser, A, Stuhler, G, Faber, E, Komarnicki, M, Kanz, L, Brune, M, Lamy, T, Sanz, M, Kyrcz-Krzemien, S, Orchard, K, Hunter, A, Sandstedt, A, Fegueux, N, Bandini, G, Robinson, S, Craddock, C, Crawley, C, Griskevicius, L, Bloor, A, Reman, O, Hilgendorf, I, Cannell, P, Ciceri, F, Kalhs, P, Sica, S, Greinix, H, Scime, R, Selleslag, D, Kruger, W, Huynh, A, Einsele, H, Bittenbring, J, Olivieri, A, Hermine, O, Gedde-Dahl, T, Zsiros, J, Guyotat, D, Cordonnier, C, Campos, A, Casini, M, Martinelli, G, Muller, L, Van Imhoff, G, Neubauer, A, Lioure, B, Hamladji, R, Noens, L, Theobald, M, Salvi, F, Ram, R, Poire, X, Or, R, Chalandon, Y, Solano, C, Wilson, K, Santasusana, J, Karakasis, D, Schafer-Eckart, K, Wahlin, A, Mohty, M, Velardi, A, Bron, D, Alegre, A, Cairoli, R, Marotta, G, Lange, A, Narni, F, Fauser, A, Rambaldi, A, Guillerm, G, Heras, I, Snowden, J, Wiktor-Jedrzejczak, W, Schanz, U, Cahn, J, Abecasis, M, Kobbe, G, Salim, R, Junghanss, C, Segel, E, Clement, L, Zak, P, Metzner, B, Espigado, I, Tilly, H, Schroyens, W, Favre, C, Russo, D, Gastl, G, Bay, J, Alessandrino, E, Majolino, I, Bosi, A, Zuckerman, T, Aljurf, M, Thomson, J, Pioltelli, P, Anagnostopoulos, A, Schouten, H, Tholouli, E, Gurman, G, Vural, F, Zver, S, Muniz, S, Afanasyev, B, Pohlreich, D, Hellmann, A, Rosler, W, Martin, S, Apperley, J, Finnegan, D, Renaud, M, Nemet, D, Culligan, D, Castagna, L, Cascavilla, N, Koh, M, Chacon, M, Ozdogu, H, Spencer, A, Llamas, C, Grasso, M, Lopez, S, Benedetti, F, Deeren, D, De Revel, T, Musso, M, Halaburda, K, Sureda, A, Angelucci, E, Diez-Martin, J, Hunter, H, Koc, Y, Bordessoule, D, Fouillard, L, Di Bartolomeo, P, Mazza, P, Novitzky, N, Peschel, C, Lopez, J, Cascon, M, Romeril, K, Schots, R, Brussel, H, Koistinen, P, Arcese, W, Aktan, M, Rodeghiero, F, Butler, A, Pizzuti, M, Melpignano, A, Carella, A, Valcarcel, D, De Toledo Codina, J, Galieni, P, Bader, P, Hahn, Cavanna, L, Sucak, G, Broom, A, Garcia, P, Nicolas-Virelizier, E, Rizzoli, V, Witz, F, Collin, M, Ringhoffer, M, Kansu, E, Martin, H, Moraleda, J, Pranger, D, Greil, R, Bazarbachi, A, Ozturk, M, Fagioli, F, Jantunen, E, Yeshurun, M, Altuntas, F, Bassan, R, Rohrlich, P, Jimenez, S, Glaisner, S, Vinante, O, Clausen, J, Lopez-Jimenez, J, Theunissen, K, Specchia, G, Pavone, V, Krauter, J, Edwards, D, Rifon, J, Everaus, H, Da Prada, G, Wattad, M, Milone, G, Walewski, J, Thieblemont, C, Nasa, G, Duchosal, M, Ferrara, F, Devidas, A, Delmer, A, Degos, L, Van Gelder M., De Wreede L. C., Bornhauser M., Niederwieser D., Karas M., Anderson N. S., Gramatzki M., Dreger P., Michallet M., Petersen E., Bunjes D., Potter M., Beelen D., Cornelissen J. J., Yakoub-Agha I., Russell N. H., Finke J., Schoemans H., Vitek A., Urbano-Ispizua A., Blaise D., Volin L., Chevallier P., Caballero D., Putter H., Van Biezen A., Henseler A., Schonland S., Kroger N., Schetelig J., Ehninger G., Jindra P., Sengeloev H., Russell N., Ispizua A. U., Arnold R., Veelken J. H., Mufti G., Milpied N., Benedetto B., Schaap M., Leblond V., Nikolousis M., Hallek M., Passweg J., Ljungman P., Masszi T., Stelljes M., Browne P., Glass B., Espiga C. R., Bourhis J. H., Roussy G., Gribben J., Foa R., Sierra J., Mayer J., Thomson K., Meijer E., Blau W., Holler E., Bacigalupo A., Guilhot F., Carlson K., Zachee P., Ifrah N., Marin J. R. C., Socie G., McQuaker G., Cortelezzi A., Lenhoff S., Tischer J., Irrera G., Fanin R., Beguin Y., Nagler A., Mackinnon S., Itala-Remes M., Deconinck E., Wulf G., Corradini P., Gilleece M., Wing B., Peniket A., Ganser A., Stuhler G., Faber E., Komarnicki M., Kanz L., Brune M., Lamy T., Sanz M., Kyrcz-Krzemien S., Orchard K., Hunter A., Sandstedt A., Fegueux N., Bandini G., Robinson S., Craddock C., Crawley C., Griskevicius L., Bloor A., Reman O., Hilgendorf I., Cannell P., Ciceri F., Kalhs P., Sica S., Greinix H., Scime R., Selleslag D., Kruger W., Huynh A., Einsele H., Bittenbring J., Olivieri A., Hermine O., Gedde-Dahl T., Zsiros J., Guyotat D., Cordonnier C., Campos A., Casini M., Martinelli G., Muller L. P., Van Imhoff G., Neubauer A., Lioure B., Hamladji R. -M., Noens L., Theobald M., Salvi F., Ram R., Poire X., Or R., Chalandon Y., Solano C., Wilson K., Santasusana J. M. R., Karakasis D., Schafer-Eckart K., Wahlin A., Mohty M., Velardi A., Bron D., Alegre A., Cairoli R., Marotta G., Lange A., Narni F., Fauser A., Rambaldi A., Guillerm G., Heras I., Snowden J., Wiktor-Jedrzejczak W., Schanz U., Cahn J. Y., Abecasis M., Kobbe G., Salim R., Junghanss C., Segel E. K., Clement L., Zak P., Metzner B., Espigado I., Tilly H., Schroyens W., Favre C., Russo D., Gastl G., Bay J. -O., Alessandrino E. P., Majolino I., Bosi A., Zuckerman T., Aljurf M., Thomson J., Pioltelli P., Anagnostopoulos A., Schouten H., Tholouli E., Gurman G., Vural F., Zver S., Muniz S. G., Afanasyev B., Pohlreich D., Hellmann A., Rosler W., Martin S., Apperley J., Finnegan D., Renaud M., Nemet D., Culligan D., Castagna L., Cascavilla N., Koh M., Chacon M. J., Ozdogu H., Spencer A., Llamas C. V., Grasso M., Lopez S. G., Benedetti F., Deeren D., De Revel T., Musso M., Halaburda K., Sureda A., Angelucci E., Diez-Martin J. L., Hunter H., Koc Y., Bordessoule D., Fouillard L., Di Bartolomeo P., Mazza P., Novitzky N., Peschel C., Lopez J. L. B., Cascon M. J. P., Romeril K. R., Schots R., Brussel H., Koistinen P., Arcese W., Aktan M., Rodeghiero F., Butler A., Pizzuti M., Melpignano A., Carella A. M., Valcarcel D., De Toledo Codina J. S., Galieni P., Bader P., Cavanna L., Sucak G., Broom A. J. M., Garcia P. G., Nicolas-Virelizier E., Rizzoli V., Witz F., Collin M., Ringhoffer M., Kansu E., Martin H., Moraleda J., Pranger D., Greil R., Bazarbachi A., Ozturk M., Fagioli F., Jantunen E., Yeshurun M., Altuntas F., Bassan R., Rohrlich P. -S., Jimenez S., Glaisner S., Vinante O., Clausen J., Lopez-Jimenez J., Theunissen K., Specchia G., Pavone V., Krauter J., Edwards D., Rifon J., Everaus H., Da Prada G. A., Wattad M., Milone G., Walewski J., Thieblemont C., Nasa G. L., Duchosal M., Ferrara F., Devidas A., Delmer A., Degos L., Van Gelder, M, De Wreede, L, Bornhauser, M, Niederwieser, D, Karas, M, Anderson, N, Gramatzki, M, Dreger, P, Michallet, M, Petersen, E, Bunjes, D, Potter, M, Beelen, D, Cornelissen, J, Yakoub-Agha, I, Russell, N, Finke, J, Schoemans, H, Vitek, A, Urbano-Ispizua, A, Blaise, D, Volin, L, Chevallier, P, Caballero, D, Putter, H, Van Biezen, A, Henseler, A, Schonland, S, Kroger, N, Schetelig, J, Ehninger, G, Jindra, P, Sengeloev, H, Ispizua, A, Arnold, R, Veelken, J, Mufti, G, Milpied, N, Benedetto, B, Schaap, M, Leblond, V, Nikolousis, M, Hallek, M, Passweg, J, Ljungman, P, Masszi, T, Stelljes, M, Browne, P, Glass, B, Espiga, C, Bourhis, J, Roussy, G, Gribben, J, Foa, R, Sierra, J, Mayer, J, Thomson, K, Meijer, E, Blau, W, Holler, E, Bacigalupo, A, Guilhot, F, Carlson, K, Zachee, P, Ifrah, N, Marin, J, Socie, G, Mcquaker, G, Cortelezzi, A, Lenhoff, S, Tischer, J, Irrera, G, Fanin, R, Beguin, Y, Nagler, A, Mackinnon, S, Itala-Remes, M, Deconinck, E, Wulf, G, Corradini, P, Gilleece, M, Wing, B, Peniket, A, Ganser, A, Stuhler, G, Faber, E, Komarnicki, M, Kanz, L, Brune, M, Lamy, T, Sanz, M, Kyrcz-Krzemien, S, Orchard, K, Hunter, A, Sandstedt, A, Fegueux, N, Bandini, G, Robinson, S, Craddock, C, Crawley, C, Griskevicius, L, Bloor, A, Reman, O, Hilgendorf, I, Cannell, P, Ciceri, F, Kalhs, P, Sica, S, Greinix, H, Scime, R, Selleslag, D, Kruger, W, Huynh, A, Einsele, H, Bittenbring, J, Olivieri, A, Hermine, O, Gedde-Dahl, T, Zsiros, J, Guyotat, D, Cordonnier, C, Campos, A, Casini, M, Martinelli, G, Muller, L, Van Imhoff, G, Neubauer, A, Lioure, B, Hamladji, R, Noens, L, Theobald, M, Salvi, F, Ram, R, Poire, X, Or, R, Chalandon, Y, Solano, C, Wilson, K, Santasusana, J, Karakasis, D, Schafer-Eckart, K, Wahlin, A, Mohty, M, Velardi, A, Bron, D, Alegre, A, Cairoli, R, Marotta, G, Lange, A, Narni, F, Fauser, A, Rambaldi, A, Guillerm, G, Heras, I, Snowden, J, Wiktor-Jedrzejczak, W, Schanz, U, Cahn, J, Abecasis, M, Kobbe, G, Salim, R, Junghanss, C, Segel, E, Clement, L, Zak, P, Metzner, B, Espigado, I, Tilly, H, Schroyens, W, Favre, C, Russo, D, Gastl, G, Bay, J, Alessandrino, E, Majolino, I, Bosi, A, Zuckerman, T, Aljurf, M, Thomson, J, Pioltelli, P, Anagnostopoulos, A, Schouten, H, Tholouli, E, Gurman, G, Vural, F, Zver, S, Muniz, S, Afanasyev, B, Pohlreich, D, Hellmann, A, Rosler, W, Martin, S, Apperley, J, Finnegan, D, Renaud, M, Nemet, D, Culligan, D, Castagna, L, Cascavilla, N, Koh, M, Chacon, M, Ozdogu, H, Spencer, A, Llamas, C, Grasso, M, Lopez, S, Benedetti, F, Deeren, D, De Revel, T, Musso, M, Halaburda, K, Sureda, A, Angelucci, E, Diez-Martin, J, Hunter, H, Koc, Y, Bordessoule, D, Fouillard, L, Di Bartolomeo, P, Mazza, P, Novitzky, N, Peschel, C, Lopez, J, Cascon, M, Romeril, K, Schots, R, Brussel, H, Koistinen, P, Arcese, W, Aktan, M, Rodeghiero, F, Butler, A, Pizzuti, M, Melpignano, A, Carella, A, Valcarcel, D, De Toledo Codina, J, Galieni, P, Bader, P, Hahn, Cavanna, L, Sucak, G, Broom, A, Garcia, P, Nicolas-Virelizier, E, Rizzoli, V, Witz, F, Collin, M, Ringhoffer, M, Kansu, E, Martin, H, Moraleda, J, Pranger, D, Greil, R, Bazarbachi, A, Ozturk, M, Fagioli, F, Jantunen, E, Yeshurun, M, Altuntas, F, Bassan, R, Rohrlich, P, Jimenez, S, Glaisner, S, Vinante, O, Clausen, J, Lopez-Jimenez, J, Theunissen, K, Specchia, G, Pavone, V, Krauter, J, Edwards, D, Rifon, J, Everaus, H, Da Prada, G, Wattad, M, Milone, G, Walewski, J, Thieblemont, C, Nasa, G, Duchosal, M, Ferrara, F, Devidas, A, Delmer, A, Degos, L, Van Gelder M., De Wreede L. C., Bornhauser M., Niederwieser D., Karas M., Anderson N. S., Gramatzki M., Dreger P., Michallet M., Petersen E., Bunjes D., Potter M., Beelen D., Cornelissen J. J., Yakoub-Agha I., Russell N. H., Finke J., Schoemans H., Vitek A., Urbano-Ispizua A., Blaise D., Volin L., Chevallier P., Caballero D., Putter H., Van Biezen A., Henseler A., Schonland S., Kroger N., Schetelig J., Ehninger G., Jindra P., Sengeloev H., Russell N., Ispizua A. U., Arnold R., Veelken J. H., Mufti G., Milpied N., Benedetto B., Schaap M., Leblond V., Nikolousis M., Hallek M., Passweg J., Ljungman P., Masszi T., Stelljes M., Browne P., Glass B., Espiga C. R., Bourhis J. H., Roussy G., Gribben J., Foa R., Sierra J., Mayer J., Thomson K., Meijer E., Blau W., Holler E., Bacigalupo A., Guilhot F., Carlson K., Zachee P., Ifrah N., Marin J. R. C., Socie G., McQuaker G., Cortelezzi A., Lenhoff S., Tischer J., Irrera G., Fanin R., Beguin Y., Nagler A., Mackinnon S., Itala-Remes M., Deconinck E., Wulf G., Corradini P., Gilleece M., Wing B., Peniket A., Ganser A., Stuhler G., Faber E., Komarnicki M., Kanz L., Brune M., Lamy T., Sanz M., Kyrcz-Krzemien S., Orchard K., Hunter A., Sandstedt A., Fegueux N., Bandini G., Robinson S., Craddock C., Crawley C., Griskevicius L., Bloor A., Reman O., Hilgendorf I., Cannell P., Ciceri F., Kalhs P., Sica S., Greinix H., Scime R., Selleslag D., Kruger W., Huynh A., Einsele H., Bittenbring J., Olivieri A., Hermine O., Gedde-Dahl T., Zsiros J., Guyotat D., Cordonnier C., Campos A., Casini M., Martinelli G., Muller L. P., Van Imhoff G., Neubauer A., Lioure B., Hamladji R. -M., Noens L., Theobald M., Salvi F., Ram R., Poire X., Or R., Chalandon Y., Solano C., Wilson K., Santasusana J. M. R., Karakasis D., Schafer-Eckart K., Wahlin A., Mohty M., Velardi A., Bron D., Alegre A., Cairoli R., Marotta G., Lange A., Narni F., Fauser A., Rambaldi A., Guillerm G., Heras I., Snowden J., Wiktor-Jedrzejczak W., Schanz U., Cahn J. Y., Abecasis M., Kobbe G., Salim R., Junghanss C., Segel E. K., Clement L., Zak P., Metzner B., Espigado I., Tilly H., Schroyens W., Favre C., Russo D., Gastl G., Bay J. -O., Alessandrino E. P., Majolino I., Bosi A., Zuckerman T., Aljurf M., Thomson J., Pioltelli P., Anagnostopoulos A., Schouten H., Tholouli E., Gurman G., Vural F., Zver S., Muniz S. G., Afanasyev B., Pohlreich D., Hellmann A., Rosler W., Martin S., Apperley J., Finnegan D., Renaud M., Nemet D., Culligan D., Castagna L., Cascavilla N., Koh M., Chacon M. J., Ozdogu H., Spencer A., Llamas C. V., Grasso M., Lopez S. G., Benedetti F., Deeren D., De Revel T., Musso M., Halaburda K., Sureda A., Angelucci E., Diez-Martin J. L., Hunter H., Koc Y., Bordessoule D., Fouillard L., Di Bartolomeo P., Mazza P., Novitzky N., Peschel C., Lopez J. L. B., Cascon M. J. P., Romeril K. R., Schots R., Brussel H., Koistinen P., Arcese W., Aktan M., Rodeghiero F., Butler A., Pizzuti M., Melpignano A., Carella A. M., Valcarcel D., De Toledo Codina J. S., Galieni P., Bader P., Cavanna L., Sucak G., Broom A. J. M., Garcia P. G., Nicolas-Virelizier E., Rizzoli V., Witz F., Collin M., Ringhoffer M., Kansu E., Martin H., Moraleda J., Pranger D., Greil R., Bazarbachi A., Ozturk M., Fagioli F., Jantunen E., Yeshurun M., Altuntas F., Bassan R., Rohrlich P. -S., Jimenez S., Glaisner S., Vinante O., Clausen J., Lopez-Jimenez J., Theunissen K., Specchia G., Pavone V., Krauter J., Edwards D., Rifon J., Everaus H., Da Prada G. A., Wattad M., Milone G., Walewski J., Thieblemont C., Nasa G. L., Duchosal M., Ferrara F., Devidas A., Delmer A., and Degos L.

Abstract

Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

Published
2017

8. Clinician Concepts of Cure in Adult Relapsed and Refractory Philadelphia-Negative B Cell Precursor Acute Lymphoblastic Leukemia: A Delphi Study

Author

Bassan, R, Hoelzer, D, Thomas, X, Montesinos, P, Pavlu, J, McKendrick, J, Kudlac, A, Barlev, A, Barber, B, Cong, Z, Bassan, R, Hoelzer, D, Thomas, X, Montesinos, P, Pavlu, J, McKendrick, J, Kudlac, A, Barlev, A, Barber, B, and Cong, Z

Abstract

Introduction Despite the poor prognosis for adults with relapsed or refractory (RR) Philadelphia chromosome (Ph)-negative B cell precursor acute lymphoblastic leukemia (ALL), long-term survival is possible and may even be considered as “cure”. Methods This study used a Delphi panel approach to explore concepts of cure in RR Ph-negative B cell precursor ALL. Ten European experts in this disease area participated in a survey and face-to-face panel meeting. Results Findings showed that clinicians conceptualize “cure” as a combination of three broad treatment outcomes that vary depending on the treatment stage: complete remission early in treatment (1–3 months) indicates initial success; eradicating cancer cells (minimal residual disease negative status) consolidates the early clinical response; leukemia-free survival is required in the long term. Conclusions Although such terminology remains contested, clinicians would begin considering “cure” as early as 2 years provided the patient is off therapy, with most considering the term applicable by the third year.

Published
2019

9. Clinician Concepts of Cure in Adult Relapsed and Refractory Philadelphia-Negative B Cell Precursor Acute Lymphoblastic Leukemia: A Delphi Study

Author

Bassan, R, Hoelzer, D, Thomas, X, Montesinos, P, Pavlu, J, McKendrick, J, Kudlac, A, Barlev, A, Barber, B, Cong, Z, Bassan, R, Hoelzer, D, Thomas, X, Montesinos, P, Pavlu, J, McKendrick, J, Kudlac, A, Barlev, A, Barber, B, and Cong, Z

Abstract

Introduction Despite the poor prognosis for adults with relapsed or refractory (RR) Philadelphia chromosome (Ph)-negative B cell precursor acute lymphoblastic leukemia (ALL), long-term survival is possible and may even be considered as “cure”. Methods This study used a Delphi panel approach to explore concepts of cure in RR Ph-negative B cell precursor ALL. Ten European experts in this disease area participated in a survey and face-to-face panel meeting. Results Findings showed that clinicians conceptualize “cure” as a combination of three broad treatment outcomes that vary depending on the treatment stage: complete remission early in treatment (1–3 months) indicates initial success; eradicating cancer cells (minimal residual disease negative status) consolidates the early clinical response; leukemia-free survival is required in the long term. Conclusions Although such terminology remains contested, clinicians would begin considering “cure” as early as 2 years provided the patient is off therapy, with most considering the term applicable by the third year.

Published
2019

10. Autologous stem cell transplantation (ASCT) or whole-brain radiotherapy (WBRT) as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with newly diagnosed primary cns lymphoma (PCNSL): results of the IELSG32 randomized Phase II Trial

Author

Ferreri, A. J. M., Cwynarski, K., Pulczynski, E., Fox, C. P., Schorb, E., La Rosee, P., Binder, M., Fabbri, A., Torri, V., Minacapelli, E., Falautano, M., Ilariucci, F., Ambrosetti, A., Roth, A., Hemmaway, C., Johnson, P., Linton, K. M., Pukrop, T., Gorlov, J. S., Balzarotti, M., Hess, G., Keller, U., Stilgenbauer, S., Panse, J., Tucci, A., Orsucci, L., Pisani, F., Levis, A., Krause, S., Schmoll, H. J., Hertenstein, B., Zaccaria, A., Guarini, A., Atta, J., Bassan, R., Cervetti, J., Elter, T., Enggaard, L., Haenel, M., Kneba, M., Liberati, M., Martelli, M., Martens, U., Morra, E., Pinto, A., Zaja, F., Ponzoni, M., Deckert, M., Politi, L. S., Finke, J., Reni, M., Cavalli, F., Zucca, E., Illerhaus, G., Ferreri, A. J. M., Cwynarski, K., Pulczynski, E., Fox, C. P., Schorb, E., La Rosee, P., Binder, M., Fabbri, A., Torri, V., Minacapelli, E., Falautano, M., Ilariucci, F., Ambrosetti, A., Roth, A., Hemmaway, C., Johnson, P., Linton, K. M., Pukrop, T., Gorlov, J. S., Balzarotti, M., Hess, G., Keller, U., Stilgenbauer, S., Panse, J., Tucci, A., Orsucci, L., Pisani, F., Levis, A., Krause, S., Schmoll, H. J., Hertenstein, B., Zaccaria, A., Guarini, A., Atta, J., Bassan, R., Cervetti, J., Elter, T., Enggaard, L., Haenel, M., Kneba, M., Liberati, M., Martelli, M., Martens, U., Morra, E., Pinto, A., Zaja, F., Ponzoni, M., Deckert, M., Politi, L. S., Finke, J., Reni, M., Cavalli, F., Zucca, E., and Illerhaus, G.

Published
2017

11. Autologous stem cell transplantation (ASCT) or whole-brain radiotherapy (WBRT) as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with newly diagnosed primary cns lymphoma (PCNSL): results of the IELSG32 randomized Phase II Trial

Author

Ferreri, A. J. M., Cwynarski, K., Pulczynski, E., Fox, C. P., Schorb, E., La Rosee, P., Binder, M., Fabbri, A., Torri, V., Minacapelli, E., Falautano, M., Ilariucci, F., Ambrosetti, A., Roth, A., Hemmaway, C., Johnson, P., Linton, K. M., Pukrop, T., Gorlov, J. S., Balzarotti, M., Hess, G., Keller, U., Stilgenbauer, S., Panse, J., Tucci, A., Orsucci, L., Pisani, F., Levis, A., Krause, S., Schmoll, H. J., Hertenstein, B., Zaccaria, A., Guarini, A., Atta, J., Bassan, R., Cervetti, J., Elter, T., Enggaard, L., Haenel, M., Kneba, M., Liberati, M., Martelli, M., Martens, U., Morra, E., Pinto, A., Zaja, F., Ponzoni, M., Deckert, M., Politi, L. S., Finke, J., Reni, M., Cavalli, F., Zucca, E., Illerhaus, G., Ferreri, A. J. M., Cwynarski, K., Pulczynski, E., Fox, C. P., Schorb, E., La Rosee, P., Binder, M., Fabbri, A., Torri, V., Minacapelli, E., Falautano, M., Ilariucci, F., Ambrosetti, A., Roth, A., Hemmaway, C., Johnson, P., Linton, K. M., Pukrop, T., Gorlov, J. S., Balzarotti, M., Hess, G., Keller, U., Stilgenbauer, S., Panse, J., Tucci, A., Orsucci, L., Pisani, F., Levis, A., Krause, S., Schmoll, H. J., Hertenstein, B., Zaccaria, A., Guarini, A., Atta, J., Bassan, R., Cervetti, J., Elter, T., Enggaard, L., Haenel, M., Kneba, M., Liberati, M., Martelli, M., Martens, U., Morra, E., Pinto, A., Zaja, F., Ponzoni, M., Deckert, M., Politi, L. S., Finke, J., Reni, M., Cavalli, F., Zucca, E., and Illerhaus, G.

Published
2017

12. CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease

Author

Mannelli, F, Gianfaldoni, G, Intermesoli, T, Cattaneo, C, Borlenghi, E, Cortelazzo, S, Cavattoni, I, Pogliani, E, Fumagalli, M, Angelucci, E, Romani, C, Ciceri, F, Corti, C, Scattolin, A, Cortelezzi, A, Mattei, D, Audisio, E, Spinelli, O, Oldani, E, Bosi, A, Rambaldi, A, Bassan, R, Bassan, R., INTERMESOLI, TAMARA, POGLIANI, ENRICO MARIA, FUMAGALLI, MONICA, Mannelli, F, Gianfaldoni, G, Intermesoli, T, Cattaneo, C, Borlenghi, E, Cortelazzo, S, Cavattoni, I, Pogliani, E, Fumagalli, M, Angelucci, E, Romani, C, Ciceri, F, Corti, C, Scattolin, A, Cortelezzi, A, Mattei, D, Audisio, E, Spinelli, O, Oldani, E, Bosi, A, Rambaldi, A, Bassan, R, Bassan, R., INTERMESOLI, TAMARA, POGLIANI, ENRICO MARIA, and FUMAGALLI, MONICA

Abstract

The prognostic significance of CD20 expression in acute lymphoblastic leukemia has been investigated in children and adults and is still under debate. The aim of our study was to correlate CD20 expression with clinical-biological characteristics and outcome in 172 Philadelphia-negative patients prospectively treated in a multicenter trial introducing the molecular evaluation of minimal residual disease for therapeutic purposes. We considered 20% as the threshold for CD20 positivity. Complete remission rate, minimal residual disease negativity rate at weeks 10, 16 and 22, and disease-free and overall survival were similar among CD20 positive and negative patients, even considering minimal residual disease results and related therapeutic choices. Our study failed to demonstrate any prognostic significance for CD20 expression in Philadelphia-negative acute lymphoblastic leukemia. This conclusion is supported for the first time by a comparable minimal residual disease response rate among CD20 negative and positive patients. ClinicalTrials.gov ID, NCT00358072., The prognostic significance of CD20 expression in acute lymphoblastic leukemia has been investigated in children and adults but is still a subject of debate. The aim of our study was to correlate CD20 expression with clinical-biological characteristics and outcome in 172 Philadelphia chromosome negative patients prospectively treated in a multicenter trial introducing the molecular evaluation of minimal residual disease for therapeutic purposes. We considered 20% as the threshold for CD20 positivity. Complete remission rate, minimal residual disease negativity rate at weeks 10, 16 and 22, and disease-free and overall survival were similar among CD20-positive and -negative patients, even considering minimal residual disease results and related therapeutic choices. Our study failed to demonstrate any prognostic significance for CD20 expression in Philadelphia chromosome negative acute lymphoblastic leukemia. This conclusion is supported for the first time by a comparable minimal residual disease response rate among CD20-positive and -negative and positive patients.

Published
2012

13. Results of a lymphoblastic leukemia-like chemotherapy program with risk-adapted mediastinal irradiation and stem cell transplantation for adult patients with lymphoblastic lymphoma

Author

Cortelazzo, S, Intermesoli, T, Oldani, E, Ciceri, F, Rossi, G, Pogliani, E, Mattei, D, Romani, C, Cortelezzi, A, Borlenghi, E, Corti, C, Peruta, B, Spinelli, O, Rambaldi, A, Bassan, R, Bassan, R., INTERMESOLI, TAMARA, POGLIANI, ENRICO MARIA, Cortelazzo, S, Intermesoli, T, Oldani, E, Ciceri, F, Rossi, G, Pogliani, E, Mattei, D, Romani, C, Cortelezzi, A, Borlenghi, E, Corti, C, Peruta, B, Spinelli, O, Rambaldi, A, Bassan, R, Bassan, R., INTERMESOLI, TAMARA, and POGLIANI, ENRICO MARIA

Abstract

The therapeutic role of mediastinal radiotherapy and stem cell transplantation (SCT) in lymphoblastic lymphoma (LL) remains controversial. In a risk-oriented design, we adopted a flexible treatment program in which (1) patients with persistent mediastinal abnormality, evaluated by post-induction computed chest tomography, received mediastinal irradiation; and (2) those with persistence of minimal residual disease (MRD), evaluated by MRD analysis of the bone marrow, underwent SCT. Twenty-eight out of 30 patients (T-lineage, n = 24; B-lineage, n = 6) achieved a complete response. Of 21 patients with mediastinal mass, 13 (62%) achieved a complete response after chemotherapy alone, while 6 (28.5%) required additional irradiation. Eleven patients were evaluated for MRD: 6 were negative and 5 positive. On the basis of MRD findings and clinical risk characteristics, 14 patients underwent SCT, 13 received maintenance chemotherapy, and 1 had local radiotherapy. Five patients relapsed. Among the 14 non-irradiated patients with T-LL, the mediastinal recurrence rate was only 7%. After a median follow-up of 3.9 years, 21 patients who responded were alive without recurrence (75%). The projected 5-year survival, disease-free survival, and relapse rate were 72%, 77%, and 18%, respectively. This program induced high remission and survival rates, indicating the feasibility and the benefits potentially associated with a selective, response-oriented policy of mediastinal irradiation and a concurrent MRD-based strategy to assign adult LL patients to SCT

Published
2012

14. Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

Author

Gökbuget, N, Gökbuget, N, Kelsh, M, Chia, V, Advani, A, Bassan, R, Dombret, H, Doubek, M, Fielding, AK, Giebel, S, Haddad, V, Hoelzer, D, Holland, C, Ifrah, N, Katz, A, Maniar, T, Martinelli, G, Morgades, M, O'Brien, S, Ribera, J-M, Rowe, JM, Stein, A, Topp, M, Wadleigh, M, Kantarjian, H, Gökbuget, N, Gökbuget, N, Kelsh, M, Chia, V, Advani, A, Bassan, R, Dombret, H, Doubek, M, Fielding, AK, Giebel, S, Haddad, V, Hoelzer, D, Holland, C, Ifrah, N, Katz, A, Maniar, T, Martinelli, G, Morgades, M, O'Brien, S, Ribera, J-M, Rowe, JM, Stein, A, Topp, M, Wadleigh, M, and Kantarjian, H

Abstract

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

Published
2016

15. Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

Author

Gökbuget, N, Gökbuget, N, Kelsh, M, Chia, V, Advani, A, Bassan, R, Dombret, H, Doubek, M, Fielding, AK, Giebel, S, Haddad, V, Hoelzer, D, Holland, C, Ifrah, N, Katz, A, Maniar, T, Martinelli, G, Morgades, M, O'Brien, S, Ribera, J-M, Rowe, JM, Stein, A, Topp, M, Wadleigh, M, Kantarjian, H, Gökbuget, N, Gökbuget, N, Kelsh, M, Chia, V, Advani, A, Bassan, R, Dombret, H, Doubek, M, Fielding, AK, Giebel, S, Haddad, V, Hoelzer, D, Holland, C, Ifrah, N, Katz, A, Maniar, T, Martinelli, G, Morgades, M, O'Brien, S, Ribera, J-M, Rowe, JM, Stein, A, Topp, M, Wadleigh, M, and Kantarjian, H

Abstract

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

Published
2016

16. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL

Author

Rousselot, P, Coudé, M, Gokbuget, N, Gambacorti Passerini, C, Hayette, S, Cayuela, J, Huguet, F, Leguay, T, Chevallier, P, Salanoubat, C, Bonmati, C, Alexis, M, Hunault, M, Glaisner, S, Agape, P, Berthou, C, Jourdan, E, Fernandes, J, Sutton, L, Banos, A, Reman, O, Lioure, B, Thomas, X, Ifrah, N, Lafage-Pochitaloff, M, Bornand, A, Morisset, L, Robin, V, Pfeifer, H, Delannoy, A, Ribera, J, Bassan, R, Delord, M, Hoelzer, D, Dombret, H, Ottmann, O, Rousselot, P, Coudé, M, Gokbuget, N, Gambacorti Passerini, C, Hayette, S, Cayuela, J, Huguet, F, Leguay, T, Chevallier, P, Salanoubat, C, Bonmati, C, Alexis, M, Hunault, M, Glaisner, S, Agape, P, Berthou, C, Jourdan, E, Fernandes, J, Sutton, L, Banos, A, Reman, O, Lioure, B, Thomas, X, Ifrah, N, Lafage-Pochitaloff, M, Bornand, A, Morisset, L, Robin, V, Pfeifer, H, Delannoy, A, Ribera, J, Bassan, R, Delord, M, Hoelzer, D, Dombret, H, and Ottmann, O

Abstract

Prognosis of Philadelphia-positive (Ph1) acutelymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL(EWALL) study number 01 for Ph+ ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18months followed by dasatinib until relapse or death. Seventy-one patients with amedian age of 69 years were enrolled; 77% had a high comorbidity score.Complete remission ratewas 96% and 65% of patients achieved a3-logreduction inBCR-ABL1transcript levelsduringconsolidation.Only7patientsunderwent allogeneic hematopoietic stemcell transplantation. At 5 years, overall survivalwas 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24were tested formutation bySanger sequencing, and 75%were T315I-positive.BCR-ABL1T315Iwastested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph+ ALL. Monitoring of BCRABL1T315I from diagnosis identified patientswith at high risk of early relapse and may help to personalize therapy.

Published
2016

17. Abnormally expanded pro-B hematogones associated with congenital cytomegalovirus infection

Author

Intermesoli, T, Mangili, G, Salvi, A, Biondi, A, Bassan, R, Bassan, R., BIONDI, ANDREA, Intermesoli, T, Mangili, G, Salvi, A, Biondi, A, Bassan, R, Bassan, R., and BIONDI, ANDREA

Abstract

Hematogones are nonleukemic immature lymphocytes that display a B-precursor phenotype and populate the pediatric bone marrow. We present the case of a newborn with an atypical, marked expansion of hematogones similar to the pro-B cells of infant acute lymphoblastic leukemia, which demonstrated their nonleukemic nature through gene rearrangement analysis and were associated with a congenital cytomegalovirus infection.

Published
2007

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

Author

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

Abstract

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

Published
2005

19. The European LeukemiaNet: achievements and perspectives

Author

Hehlmann, R., Grimwade, D., Simonsson, B., Apperley, J., Baccarani, M., Barbui, T., Barosi, G., Bassan, R., Bene, M.C., Berger, U., Buchner, T., Burnett, A., Cross, N.C., Witte, T.J. de, Dohner, H., Dombret, H., Einsele, H., Engelich, G., Foa, R., Fonatsch, C., Gokbuget, N., Gluckman, E., Gratwohl, A., Guilhot, F., Haferlach, C., Haferlach, T., Hallek, M., Hasford, J., Hochhaus, A., Hoelzer, D., Kiladjian, J.J., Labar, B., Ljungman, P., Mansmann, U., Niederwieser, D., Ossenkoppele, G., Ribera, J.M., Rieder, H., Serve, H., Schrotz-King, P., Sanz, M.A., Saussele, S., Hehlmann, R., Grimwade, D., Simonsson, B., Apperley, J., Baccarani, M., Barbui, T., Barosi, G., Bassan, R., Bene, M.C., Berger, U., Buchner, T., Burnett, A., Cross, N.C., Witte, T.J. de, Dohner, H., Dombret, H., Einsele, H., Engelich, G., Foa, R., Fonatsch, C., Gokbuget, N., Gluckman, E., Gratwohl, A., Guilhot, F., Haferlach, C., Haferlach, T., Hallek, M., Hasford, J., Hochhaus, A., Hoelzer, D., Kiladjian, J.J., Labar, B., Ljungman, P., Mansmann, U., Niederwieser, D., Ossenkoppele, G., Ribera, J.M., Rieder, H., Serve, H., Schrotz-King, P., Sanz, M.A., and Saussele, S.

Abstract

Contains fulltext : 96402.pdf (publisher's version ) (Open Access), The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.

Published
2011

20. The European LeukemiaNet: achievements and perspectives

Author

Hehlmann, R., Grimwade, D., Simonsson, B., Apperley, J., Baccarani, M., Barbui, T., Barosi, G., Bassan, R., Bene, M.C., Berger, U., Buchner, T., Burnett, A., Cross, N.C., Witte, T.J. de, Dohner, H., Dombret, H., Einsele, H., Engelich, G., Foa, R., Fonatsch, C., Gokbuget, N., Gluckman, E., Gratwohl, A., Guilhot, F., Haferlach, C., Haferlach, T., Hallek, M., Hasford, J., Hochhaus, A., Hoelzer, D., Kiladjian, J.J., Labar, B., Ljungman, P., Mansmann, U., Niederwieser, D., Ossenkoppele, G., Ribera, J.M., Rieder, H., Serve, H., Schrotz-King, P., Sanz, M.A., Saussele, S., Hehlmann, R., Grimwade, D., Simonsson, B., Apperley, J., Baccarani, M., Barbui, T., Barosi, G., Bassan, R., Bene, M.C., Berger, U., Buchner, T., Burnett, A., Cross, N.C., Witte, T.J. de, Dohner, H., Dombret, H., Einsele, H., Engelich, G., Foa, R., Fonatsch, C., Gokbuget, N., Gluckman, E., Gratwohl, A., Guilhot, F., Haferlach, C., Haferlach, T., Hallek, M., Hasford, J., Hochhaus, A., Hoelzer, D., Kiladjian, J.J., Labar, B., Ljungman, P., Mansmann, U., Niederwieser, D., Ossenkoppele, G., Ribera, J.M., Rieder, H., Serve, H., Schrotz-King, P., Sanz, M.A., and Saussele, S.

Abstract

Contains fulltext : 96402.pdf (publisher's version ) (Open Access), The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.

Published
2011

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

Author

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

Abstract

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

Published
2010

22. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008

Author

Brüggemann, M, Schrauder, A, Raff, T, Pfeifer, H, Dworzak, M, Ottmann, O G, Asnafi, V, Baruchel, A, Bassan, R, Benoit, Y, Biondi, A, Cavé, H, Dombret, H, Fielding, A K, Foà, R, Gökbuget, N, Goldstone, A H, Goulden, N, Henze, G, Hoelzer, D, Janka-Schaub, G E, Macintyre, E A, Pieters, R, Rambaldi, A, Ribera, J-M, Schmiegelow, K, Spinelli, O, Stary, J, von Stackelberg, A, Kneba, M, Schrappe, M, van Dongen, J J M, Brüggemann, M, Schrauder, A, Raff, T, Pfeifer, H, Dworzak, M, Ottmann, O G, Asnafi, V, Baruchel, A, Bassan, R, Benoit, Y, Biondi, A, Cavé, H, Dombret, H, Fielding, A K, Foà, R, Gökbuget, N, Goldstone, A H, Goulden, N, Henze, G, Hoelzer, D, Janka-Schaub, G E, Macintyre, E A, Pieters, R, Rambaldi, A, Ribera, J-M, Schmiegelow, K, Spinelli, O, Stary, J, von Stackelberg, A, Kneba, M, Schrappe, M, and van Dongen, J J M

Abstract

Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR- and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols.

Published
2010

23. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008

Author

Brüggemann, M, Schrauder, A, Raff, T, Pfeifer, H, Dworzak, M, Ottmann, O G, Asnafi, V, Baruchel, A, Bassan, R, Benoit, Y, Biondi, A, Cavé, H, Dombret, H, Fielding, A K, Foà, R, Gökbuget, N, Goldstone, A H, Goulden, N, Henze, G, Hoelzer, D, Janka-Schaub, G E, Macintyre, E A, Pieters, R, Rambaldi, A, Ribera, J-M, Schmiegelow, K, Spinelli, O, Stary, J, von Stackelberg, A, Kneba, M, Schrappe, M, van Dongen, J J M, Brüggemann, M, Schrauder, A, Raff, T, Pfeifer, H, Dworzak, M, Ottmann, O G, Asnafi, V, Baruchel, A, Bassan, R, Benoit, Y, Biondi, A, Cavé, H, Dombret, H, Fielding, A K, Foà, R, Gökbuget, N, Goldstone, A H, Goulden, N, Henze, G, Hoelzer, D, Janka-Schaub, G E, Macintyre, E A, Pieters, R, Rambaldi, A, Ribera, J-M, Schmiegelow, K, Spinelli, O, Stary, J, von Stackelberg, A, Kneba, M, Schrappe, M, and van Dongen, J J M

Abstract

Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR- and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols.

Published
2010

24. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008.

Author

Brüggemann, M, Schrauder, A, Raff, T, Pfeifer, H, Dworzak, M, Ottmann, O, Asnafi, V, Baruchel, A, Bassan, R, Benoit, Y, Biondi, A, Cavé, H, Dombret, H, Fielding, A, Foà, R, Gökbuget, N, Goldstone, A, Goulden, N, Henze, G, Hoelzer, D, Janka Schaub, G, Macintyre, E, Pieters, R, Rambaldi, A, Ribera, J, Schmiegelow, K, Spinelli, O, Stary, J, von Stackelberg, A, Kneba, M, Schrappe, M, van Dongen, J, Ottmann, OG, BIONDI, ANDREA, Fielding, AK, Goldstone, AH, Janka Schaub, GE, Macintyre, EA, Ribera, JM, van Dongen, JJ, Brüggemann, M, Schrauder, A, Raff, T, Pfeifer, H, Dworzak, M, Ottmann, O, Asnafi, V, Baruchel, A, Bassan, R, Benoit, Y, Biondi, A, Cavé, H, Dombret, H, Fielding, A, Foà, R, Gökbuget, N, Goldstone, A, Goulden, N, Henze, G, Hoelzer, D, Janka Schaub, G, Macintyre, E, Pieters, R, Rambaldi, A, Ribera, J, Schmiegelow, K, Spinelli, O, Stary, J, von Stackelberg, A, Kneba, M, Schrappe, M, van Dongen, J, Ottmann, OG, BIONDI, ANDREA, Fielding, AK, Goldstone, AH, Janka Schaub, GE, Macintyre, EA, Ribera, JM, and van Dongen, JJ

Abstract

Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR- and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols

Published
2010

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

Author

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

Abstract

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

Published
2009

26. The sensitivity of acute lymphoblastic leukemia cells carrying the t(12;21) translocation to campath-1H-mediated cell lysis

Author

Golay, J, Cortiana, C, Manganini, M, Cazzaniga, G, Salvi, A, Spinelli, O, Bassan, R, Barbui, T, Biondi, A, Rambaldi, A, Introna, M, Introna, M., BIONDI, ANDREA, Golay, J, Cortiana, C, Manganini, M, Cazzaniga, G, Salvi, A, Spinelli, O, Bassan, R, Barbui, T, Biondi, A, Rambaldi, A, Introna, M, Introna, M., and BIONDI, ANDREA

Abstract

Background and Objectives. Campath-1H is used in conditioning regimens and more recently as an anti-leukemic therapy in acute lymphoblastic leukemias (ALL). We therefore investigated CD52 expression and campath-1H-mediated lysis of ALL cells in vitro. Design and Methods. Complement-mediated cytotoxicity assays were performed on freshly isolated neoplastic cells and cell lines using human serum. Anti body-dependent cellular cytotoxicity (ADCC) was performed by calcein-AM release assays. Results. CD52 was expressed in four out of eight ALL cell lines studied. Among 61 freshly isolated ALL samples CD52 was expressed at varying levels in 87% of cases. Whereas ADCC was equivalent in different CD52(+) lines, complement-dependent cytotoxicity (CDC) was variable. The REH cell line bearing the t(12;21) translocation showed 47-60% lysis when treated with 10 mu g/mL campath-1H compared to 0-6% for the other cell lines expressing equivalent amounts of CD52. Furthermore all nine ALL samples with t(12;21) showed very high CDC (mean 97%) compared to the other 24 CD52(+) cases (mean 24%)(p<0.0001). In t(12;21) samples, efficient CDC was obtained with as little as 1 mu g,/mL campath-1H. CDC correlated in part with CD52 levels, suggesting that CD52 expression and other yet undefined factors contribute to the particular sensitivity of t(12;21) cells. The resistance of non t(12;21) ALL cases could be overcome to a limited extent by increasing the concentration of campath-1H, blocking the CD55 and CD59 complement inhibitors, and more effectively by combining campath-1H with fludarabine. Interpretations and Conclusion. We conclude that most ALL samples express CD52 to a variable level and that campath-1H has cytotoxic activity against CD52(+) ALL, alone or in combination with cytotoxic drugs.

Published
2006

27. Gene expression profile unravels significant differences between childhood and adult Ph+ acute lymphoblastic leukemia

Author

Scrideli, C, Cazzaniga, G, Fazio, G, Pirola, L, Callegaro, A, Bassan, R, Rambaldi, A, Lo Nigro, L, Basso, G, Masera, G, Biondi, A, Scrideli, CA, FAZIO, GRAZIA, MASERA, GIUSEPPE, BIONDI, ANDREA, Scrideli, C, Cazzaniga, G, Fazio, G, Pirola, L, Callegaro, A, Bassan, R, Rambaldi, A, Lo Nigro, L, Basso, G, Masera, G, Biondi, A, Scrideli, CA, FAZIO, GRAZIA, MASERA, GIUSEPPE, and BIONDI, ANDREA

Published
2003

28. Translocation (8;21) in two cases of refractory anemia with excess of blasts in transformation

Author

Maserati, E, Casali, M, Pasquali, F, Locatelli, Franco, Giani, S, Prete, L, Zecca, M, Invernizzi, R, Bassan, R, Locatelli, F (ORCID:0000-0002-7976-3654), Maserati, E, Casali, M, Pasquali, F, Locatelli, Franco, Giani, S, Prete, L, Zecca, M, Invernizzi, R, Bassan, R, and Locatelli, F (ORCID:0000-0002-7976-3654)

Abstract

We report two cases of refractory anemia with excess of blasts in transformation (RAEB-T) with the translocation (8;21), which is frequent in ANLL but not in myelodysplastic syndromes (MDS). A review of such cases leads us to conclude that myeloproliferative disorders characterized by the t(8;21) may be preceded by an MDS phase.

Published
1992

29. Induction of cytotoxicity by interleukin-2 in T gamma-lymphoproliferative disorders

Author

Allavena, P, Introna, M, Rambaldi, A, Zanaboni, F, Rossini, S, Villa, A, Bassan, R, Barbui, T, Mantovani, A, Mantovani, A., VILLA, ANTONELLO, Allavena, P, Introna, M, Rambaldi, A, Zanaboni, F, Rossini, S, Villa, A, Bassan, R, Barbui, T, Mantovani, A, Mantovani, A., and VILLA, ANTONELLO

Abstract

We have studied 7 patients with T gamma-lymphoproliferative disorders, in whom 78-88% of circulating nonadherent lymphocytes had the morphology of large granular lymphocytes (LGL) as assessed by light and transmission electron microscopy. The main common features of the membrane phenotype of these LGL expansions included expression of T3, HNK-1 and AB8.28. Other monoclonal antibody-defined surface markers of LGL (OKM1, B73.1, N901) were variably expressed or absent in these patients. Patients' LGL had little or no natural killer (NK) activity but mediated antibody-dependent cellular cytotoxicity (ADCC). Exposure to interferons (type B or gamma) for 20-72 hr resulted in no appreciable induction of cytolytic activity. In contrast, culture in the presence of interleukin-2 (IL-2) for 3 days resulted in the expression of strong cytolytic activity in all the patients tested against an NK-susceptible (K562) and an NK-resistant (Daudi) target. The expression of T3 antigen, the low levels or lack of native NK activity and the induction of consistent cytotoxicity by prolonged exposure to IL-2 led us to suggest that the cells expanding in these subjects are related to the effectors involved in lymphokine-activated killer (LAK) activity.

Published
1986

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