59 results on '"Boccadoro M."'
Search Results
2. The bone marrow of myeloma patients is steadily inhabited by a normal-sized pool of functional regulatory T cells irrespectiveof the disease status
- Author
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Foglietta, M., primary, Castella, B., additional, Mariani, S., additional, Coscia, M., additional, Godio, L., additional, Ferracini, R., additional, Ruggeri, M., additional, Muccio, V., additional, Omede, P., additional, Palumbo, A., additional, Boccadoro, M., additional, and Massaia, M., additional
- Published
- 2014
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3. Bortezomib cumulative dose, efficacy, and tolerability with three different bortezomib-melphalan-prednisone regimens in previously untreated myeloma patients ineligible for high-dose therapy
- Author
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Mateos, M.-V., primary, Bringhen, S., additional, Richardson, P. G., additional, Lahuerta, J. J., additional, Larocca, A., additional, Oriol, A., additional, Boccadoro, M., additional, Garcia-Sanz, R., additional, Di Raimondo, F., additional, Esseltine, D.-L., additional, van de Velde, H., additional, Desai, A., additional, Londhe, A., additional, San Miguel, J. F., additional, and Palumbo, A., additional
- Published
- 2014
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4. High XBP1 expression is a marker of better outcome in multiple myeloma patients treated with bortezomib
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Gambella, M., primary, Rocci, A., additional, Passera, R., additional, Gay, F., additional, Omede, P., additional, Crippa, C., additional, Corradini, P., additional, Romano, A., additional, Rossi, D., additional, Ladetto, M., additional, Boccadoro, M., additional, and Palumbo, A., additional
- Published
- 2014
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5. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials
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Bringhen, S., primary, Mateos, M. V., additional, Zweegman, S., additional, Larocca, A., additional, Falcone, A. P., additional, Oriol, A., additional, Rossi, D., additional, Cavalli, M., additional, Wijermans, P., additional, Ria, R., additional, Offidani, M., additional, Lahuerta, J. J., additional, Liberati, A. M., additional, Mina, R., additional, Callea, V., additional, Schaafsma, M., additional, Cerrato, C., additional, Marasca, R., additional, Franceschini, L., additional, Evangelista, A., additional, Teruel, A.-I., additional, van der Holt, B., additional, Montefusco, V., additional, Ciccone, G., additional, Boccadoro, M., additional, Miguel, J. S., additional, Sonneveld, P., additional, and Palumbo, A., additional
- Published
- 2013
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6. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials
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Palumbo, A., primary, Waage, A., additional, Hulin, C., additional, Beksac, M., additional, Zweegman, S., additional, Gay, F., additional, Gimsing, P., additional, Leleu, X., additional, Wijermans, P., additional, Sucak, G., additional, Pezzatti, S., additional, Juliusson, G., additional, Pegourie, B., additional, Schaafsma, M., additional, Galli, M., additional, Turesson, I., additional, Kolb, B., additional, van der Holt, B., additional, Baldi, I., additional, Rolke, J., additional, Ciccone, G., additional, Wetterwald, M., additional, Lokhorst, H., additional, Boccadoro, M., additional, Rodon, P., additional, and Sonneveld, P., additional
- Published
- 2012
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7. Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes
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Ferrero, S., primary, Capello, D., additional, Svaldi, M., additional, Boi, M., additional, Gatti, D., additional, Drandi, D., additional, Rossi, D., additional, Barbiero, S., additional, Mantoan, B., additional, Mantella, E., additional, Zanni, M., additional, Ghione, P., additional, Larocca, A., additional, Passera, R., additional, Bertoni, F., additional, Gattei, V., additional, Forconi, F., additional, Laurenti, L., additional, Del Poeta, G., additional, Marasca, R., additional, Cortelazzo, S., additional, Gaidano, G., additional, Palumbo, A., additional, Boccadoro, M., additional, and Ladetto, M., additional
- Published
- 2011
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8. [Prognostic factors in multiple myeloma]
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Boccadoro M, Bianchi A, Dianzani U, Frieri R, Gallone G, Massimo MASSAIA, Omede P, Palumbo A, and Pileri A
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Drug Resistance ,Immunologic Deficiency Syndromes ,Antineoplastic Agents ,Oncogenes ,Prognosis ,Thymidine Kinase ,Neoplasm Proteins ,Myeloma Proteins ,Neoplastic Stem Cells ,Humans ,Kidney Failure, Chronic ,Multiple Myeloma ,beta 2-Microglobulin ,Cell Division - Published
- 1989
9. B lymphocytes receptors: a new biological approach for immunofluorescence studies
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PIERFRANCO CONTE, Boccadoro, M., and Pileri, A.
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immunology ,B-Lymphocytes ,Myeloproliferative Disorders ,immunology, Fluorescent Antibody Technique, Multiple Myeloma ,immunology, Myeloproliferative Disorders ,Fluorescent Antibody Technique ,Multiple Myeloma - Published
- 1977
10. A prospective, multicenter study on hematopoietic stemcell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and 'on-demand' plerixafor in multiple myeloma patients treated with novel agents.
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Mina R, Petrucci MT, Bonello F, Bongarzoni V, Saccardi R, Bertuglia G, Mengarelli A, Spadaro A, Lisi C, Curci P, Lemoli RM, Ballanti S, Floris R, Cupelli L, Tosi P, Olivieri A, Rota-Scalabrini D, Cangialosi C, Nozzoli C, Anaclerico B, Fazio F, Bruno B, Mancuso K, Corradini P, Milone G, and Boccadoro M
- Subjects
- Humans, Middle Aged, Male, Female, Aged, Prospective Studies, Adult, Hematopoietic Stem Cell Transplantation methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Transplantation, Autologous, Treatment Outcome, Multiple Myeloma therapy, Hematopoietic Stem Cell Mobilization methods, Cyclams administration & dosage, Cyclams therapeutic use, Benzylamines, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte Colony-Stimulating Factor therapeutic use, Heterocyclic Compounds administration & dosage, Heterocyclic Compounds therapeutic use
- Abstract
High-dose melphalan plus autologous stem cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem cell (HSC) collection is crucial to ensure hematologic recovery after ASCT. In this prospective, observational study we evaluated HSC mobilization with granulocyte colony-stimulating factor (G-CSF), cyclophosphamide, and 'on-demand' plerixafor (in patients with <20×106 CD34+ cells/L after at least 4 days of G-CSF or failing to collect ≥1×106 CD34+ cells/kg after the first apheresis) in NDMM patients treated with novel agent-based induction therapy. The primary endpoint was the rate of poor mobilizers (patients collecting <2×106 CD34+ cells/kg or requiring plerixafor rescue to reach an adequate HSC harvest). Secondary endpoints included the rate of patients collecting ≥2×106 CD34+ cells/kg after plerixafor administration and the identification of factors predicting mobilization failure or plerixafor need. Overall, 301 patients (median age 60 years) were enrolled. Two hundred and eighty-seven of 301 (95%) and 274 of 301 (93%) patients collected ≥2×106 and ≥4×106 CD34+ cells/kg, respectively, with a median of 9.9×106 CD34+ cells/kg collected. Poor mobilizers were 48 of 301 (16%): 34 of 301 (11%) required plerixafor rescue, and 14 of 301 (5%) failed HSC collection regardless of plerixafor. Thirty-four of 38 (90%) patients receiving plerixafor collected ≥2×106 CD34+ cells/kg. Bone marrow plasmacytosis at diagnosis >60% (odds ratio [OR]=4.14), lenalidomide use (OR=4.45), and grade 3-4 hematologic toxicities during induction (OR=3.53) were independently associated with a higher risk of mobilization failure or plerixafor need. Cyclophosphamide plus G-CSF and 'on-demand' plerixafor is an effective strategy in NDMM patients treated with novel agents, resulting in a high rate of HSC collection and high HSC yield (clinicaltrials gov. identifier: NCT03406091).
- Published
- 2024
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11. 2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde.
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Musto P, Engelhardt M, Caers J, Bolli N, Kaiser M, Van de Donk N, Terpos E, Broijl A, De Larrea CF, Gay F, Goldschmidt H, Hajek R, Vangsted AJ, Zamagni E, Zweegman S, Cavo M, Dimopoulos M, Einsele H, Ludwig H, Barosi G, Boccadoro M, Mateos MV, Sonneveld P, and Miguel JS
- Subjects
- Disease Progression, Humans, Prospective Studies, Risk Factors, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance therapy, Multiple Myeloma drug therapy, Multiple Myeloma therapy, Smoldering Multiple Myeloma diagnosis, Smoldering Multiple Myeloma therapy
- Abstract
According to the updated International Myeloma Working Group criteria, smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by an M-component >3 g/dL, bone marrow plasma cell infiltration >10% and <60%, and absence of any myeloma-defining event. Active multiple myeloma is preceded by SMM, with a median time to progression of approximately 5 years. Cases of SMM range from the extremes of "monoclonal gammopathy of undetermined significance-like", in which patients never progress during their lifetimes, to "early multiple myeloma", in which transformation into symptomatic disease, based on genomic evolution, may be rapid and devastating. Such a "split personality" makes the prognosis and management of individual patients challenging, particularly with regard to the identification and possible early treatment of high-risk SMM. Outside of clinical trials, the conventional approach to SMM generally remains close observation until progression to active multiple myeloma. However, two prospective, randomized trials have recently demonstrated a significant clinical benefit in terms of time to progression, and of overall survival in one of the two studies, for some patients with higher-risk SMM treated with lenalidomide ± dexamethasone, raising the question of whether such an approach should be considered a new standard of care. In this paper, experts from the European Myeloma Network describe current biological and clinical knowledge on SMM, focusing on novel insights into its molecular pathogenesis, new prognostic scoring systems proposed to identify SMM patients at higher risk of early transformation, and updated results of completed or ongoing clinical trials. Finally, some practical recommendations for the real-life management of these patients, based on Delphi consensus methodology, are provided.
- Published
- 2021
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12. European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma.
- Author
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Bruno B, Wäsch R, Engelhardt M, Gay F, Giaccone L, D'Agostino M, Rodríguez-Lobato LG, Danhof S, Gagelmann N, Kröger N, Popat R, Van de Donk NWCJ, Terpos E, Dimopoulos MA, Sonneveld P, Einsele H, and Boccadoro M
- Subjects
- B-Cell Maturation Antigen, Humans, Immunotherapy, Adoptive, Receptors, Antigen, T-Cell genetics, Multiple Myeloma therapy, Receptors, Chimeric Antigen genetics
- Abstract
Chimeric antigen receptor (CAR) T cells (CAR-T) have dramatically changed the treatment landscape of B-cell malignancies, providing a potential cure for relapsed/refractory patients. Long-term responses in patients with acute lymphoblastic leukemia and non Hodgkin lymphomas have encouraged further development in myeloma. In particular, B-cell maturation antigen (BCMA)-targeted CAR-T have established very promising results in heavily pre-treated patients. Moreover, CAR-T targeting other antigens (i.e., SLAMF7 and CD44v6) are currently under investigation. However, none of these current autologous therapies have been approved, and despite high overall response rates across studies, main issues such as long-term outcome, toxicities, treatment resistance, and management of complications limit as yet their widespread use. Here, we critically review the most important pre-clinical and clinical findings, recent advances in CAR-T against myeloma, as well as discoveries in the biology of a still incurable disease, that, all together, will further improve safety and efficacy in relapsed/refractory patients, urgently in need of novel treatment options.
- Published
- 2021
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13. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies.
- Author
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Mina R, Bonello F, Petrucci MT, Liberati AM, Conticello C, Ballanti S, Musto P, Olivieri A, Benevolo G, Capra A, Gilestro M, Galieni P, Cavo M, Siniscalchi A, Palumbo A, Montefusco V, Gaidano G, Omedé P, Boccadoro M, and Bringhen S
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Dexamethasone therapeutic use, Humans, In Situ Hybridization, Fluorescence, Oligopeptides, Treatment Outcome, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
- Abstract
Despite remarkable advances in the treatment of multiple myeloma in the last decades, the prognosis of patients harboring high-risk cytogenetic abnormalities remains dismal as compared to that of standard-risk patients. Proteasome inhibitors demonstrated to partially ameliorate the prognosis of high-risk patients. We pooled together data from two phase I/II trials on transplant-ineligible patients with multiple myeloma receiving upfront carfilzomib cyclophosphamide and dexamethasone followed by carfilzomib maintenance. The aim of this analysis was to compare treatment outcomes in patients with standard- versus high-risk cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH) analysis. High risk was defined by the presence of at least one chromosomal abnormality, including t(4;14), del17p and t(14;16). Overall, 94 patients were included in the analysis: 57 (61%) in the standard-risk and 37 (39%) in the high-risk group. Median follow-up was 38 months. In standard- vs. high-risk patients, we observed similar progression-free survival (3-year PFS: 52% vs. 43%, respectively; p=0.50), overall survival (3-year OS: 78% vs. 73%; p=0.38), and overall response rate (88% vs 95%; p=0.47), with no statistical differences between the two groups. No difference in terms of progression-free survival was observed between patients with or without del17p. Carfilzomib, used both as induction and maintenance agent for transplant-ineligible newly diagnosed multiple myeloma patients, mitigated the poor prognosis carried by high-risk cytogenetics and resulted into similar progression-free survival and overall survival, as compared to standard-risk patients. ClinicalTrials.gov IDs: NCT01857115 (IST-CAR-561) and NCT01346787 (IST-CAR-506).
- Published
- 2021
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14. Elotuzumab, lenalidomide, and dexamethasone as salvage therapy for patients with multiple myeloma: Italian, multicenter, retrospective clinical experience with 300 cases outside of controlled clinical trials.
- Author
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Gentile M, Specchia G, Derudas D, Galli M, Botta C, Rocco S, Conticello C, Califano C, Giuliani N, Mangiacavalli S, Attingenti E, Lombardo A, Brunori M, Rossi E, Antonioli E, Ria R, Zambello R, Di Renzo N, Mele G, Marcacci G, Musto P, Capalbo S, Cascavilla N, Cerchione C, Belotti A, Criscuolo C, Uccello G, Curci P, Vigna E, Fraticelli V, Vincelli D, Bonalumi A, Siniscalchi A, Stocchi R, Martino M, Ballanti S, Gangemi D, Gagliardi A, Gamberi B, Pompa A, Recchia AG, Tripepi G, Pitino A, Frigeri F, Consoli U, Bringhen S, Zamagni E, Patriarca F, De Stefano V, Di Raimondo F, Palmieri S, Petrucci MT, Offidani M, Boccadoro M, Cavo M, and Morabito F
- Subjects
- Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dexamethasone therapeutic use, Humans, Italy epidemiology, Lenalidomide therapeutic use, Retrospective Studies, Salvage Therapy, Multiple Myeloma drug therapy
- Published
- 2021
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15. Standardization of flow cytometric minimal residual disease assessment in international clinical trials - a feasibility study from the European Myeloma Network.
- Author
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Hofste op Bruinink D, Oliva S, Rihova L, Schmitz A, Gilestro M, Te Marvelde J, Kralova R, Høholt H, Broijl A, Johnsen HE, Hajek R, Boccadoro M, Sonneveld P, Omedè P, and Van der Velden VHJ
- Subjects
- Feasibility Studies, Flow Cytometry, Humans, Neoplasm, Residual, Reference Standards, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Published
- 2020
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16. Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial.
- Author
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Bringhen S, D'Agostino M, Paris L, Ballanti S, Pescosta N, Spada S, Pezzatti S, Grasso M, Rota-Scalabrini D, De Rosa L, Pavone V, Gazzera G, Aquino S, Poggiu M, Santoro A, Gentile M, Baldini L, Petrucci MT, Tosi P, Marasca R, Cellini C, Palumbo A, Falco P, Hájek R, Boccadoro M, and Larocca A
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dexamethasone therapeutic use, Disease-Free Survival, Humans, Maintenance Chemotherapy, Melphalan therapeutic use, Prednisone therapeutic use, Progression-Free Survival, Treatment Outcome, Lenalidomide therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
- Abstract
n the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction therapy was prospectively evaluated in transplant-ineligible patients with multiple myeloma. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. The analysis presented here (median follow-up of 71 months) is focused on maintenance treatment and on subgroup analyses defined according to the International Myeloma Working Group Frailty Score. Of the 654 evaluable patients, 217 were in the lenalidomide-dexamethasone arm, 217 in the melphalan-prednisone-lenalidomide arm and 220 in the cyclophosphamide-prednisone-lenalidomide arm. With regards to the Frailty Score, 284 (43%) patients were fit, 205 (31%) were intermediate-fit and 165 (25%) were frail. After induction, 402 patients were eligible for maintenance therapy (lenalidomide arm, n=204; lenalidomide-prednisone arm, n=198). After a median duration of maintenance of 22.0 months, progression-free survival from the start of maintenance was 22.2 months with lenalidomide-prednisone vs 18.6 months with lenalidomide (hazard ratio 0.85, P =0.14), with no differences across frailty subgroups. The most frequent grade ≥3 toxicity was neutropenia (10% of lenalidomide-prednisone and 21% of lenalidomide patients; P =0.001). Grade ≥3 non-hematologic adverse events were rare (<15%). In fit patients, melphalan-prednisone-lenalidomide significantly prolonged progression-free survival compared to cyclophosphamide-prednisone-lenalidomide (hazard ratio 0.72, P =0.05) and lenalidomide-dexamethasone (hazard ratio 0.72, P =0.04). Likewise, a trend towards a better overall survival was noted for patients treated with melphalan-prednisone-lenalidomide or cyclophosphamide-prednisone-lenalidomide, as compared to lenalidomide-dexamethasone. No differences were observed in intermediate-fit and frail patients. This analysis showed positive outcomes of maintenance with lenalidomide-based regimens, with a good safety profile. For the first time, we showed that fit patients benefit from a full-dose triplet regimen, while intermediate-fit and frail patients benefit from gentler regimens. ClinicalTrials.gov registration number: NCT01093196., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
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17. First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials.
- Author
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Larocca A, Mina R, Offidani M, Liberati AM, Ledda A, Patriarca F, Evangelista A, Spada S, Benevolo G, Oddolo D, Innao V, Cangiolosi C, Bernardini A, Musto P, Amico V, Fraticelli V, Paris L, Giuliani N, Falcone AP, Zambello R, De Paoli L, Romano A, Palumbo A, Montefusco V, Hájek R, Boccadoro M, and Bringhen S
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Treatment Outcome, Bortezomib therapeutic use, Dexamethasone therapeutic use, Lenalidomide therapeutic use, Melphalan therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Prednisone therapeutic use
- Abstract
Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196)., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
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18. HIF-1α is over-expressed in leukemic cells from TP53 -disrupted patients and is a promising therapeutic target in chronic lymphocytic leukemia.
- Author
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Griggio V, Vitale C, Todaro M, Riganti C, Kopecka J, Salvetti C, Bomben R, Bo MD, Magliulo D, Rossi D, Pozzato G, Bonello L, Marchetti M, Omedè P, Kodipad AA, Laurenti L, Del Poeta G, Mauro FR, Bernardi R, Zenz T, Gattei V, Gaidano G, Foà R, Massaia M, Boccadoro M, and Coscia M
- Subjects
- Animals, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Mice, Phosphatidylinositol 3-Kinases genetics, Tumor Microenvironment, Tumor Suppressor Protein p53 genetics, Von Hippel-Lindau Tumor Suppressor Protein, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
In chronic lymphocytic leukemia (CLL), the hypoxia-inducible factor 1 (HIF-1) regulates the response of tumor cells to hypoxia and their protective interactions with the leukemic microenvironment. In this study, we demonstrate that CLL cells from TP53 -disrupted ( TP53
dis ) patients have constitutively higher expression levels of the α-subunit of HIF-1 (HIF-1α) and increased HIF-1 transcriptional activity compared to the wild-type counterpart. In the TP53dis subset, HIF-1α upregulation is due to reduced expression of the HIF-1α ubiquitin ligase von Hippel-Lindau protein (pVHL). Hypoxia and stromal cells further enhance HIF-1α accumulation, independently of TP53 status. Hypoxia acts through the downmodulation of pVHL and the activation of the PI3K/AKT and RAS/ERK1-2 pathways, whereas stromal cells induce an increased activity of the RAS/ERK1-2, RHOA/RHOA kinase and PI3K/AKT pathways, without affecting pVHL expression. Interestingly, we observed that higher levels of HIF-1A mRNA correlate with a lower susceptibility of leukemic cells to spontaneous apoptosis, and associate with the fludarabine resistance that mainly characterizes TP53dis tumor cells. The HIF-1α inhibitor BAY87-2243 exerts cytotoxic effects toward leukemic cells, regardless of the TP53 status, and has anti-tumor activity in Em-TCL1 mice. BAY87-2243 also overcomes the constitutive fludarabine resistance of TP53dis leukemic cells and elicits a strongly synergistic cytotoxic effect in combination with ibrutinib, thus providing preclinical evidence to stimulate further investigation into use as a potential new drug in CLL., (Copyright© 2020 Ferrata Storti Foundation.)- Published
- 2020
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19. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs.
- Author
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Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, and Boccadoro M
- Subjects
- Humans, Lenalidomide therapeutic use, Progression-Free Survival, Proportional Hazards Models, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Pharmaceutical Preparations
- Abstract
Extramedullary disease is relatively frequent in multiple myeloma, but our knowledge on the subject is limited and mainly relies on small case series or single center experiences. Little is known regarding the role of new drugs in this setting. We performed a meta-analysis of eight trials focused on the description of extramedullary disease characteristics, clinical outcome, and response to new drugs. A total of 2,332 newly diagnosed myeloma patients have been included; 267 (11.4%) had extramedullary disease, defined as paraosseous in 243 (10.4%), extramedullary plasmocytoma in 12 (0.5%), and not classified in 12 (0.5%) patients. Median progression-free survival was 25.3 months and 25.2 in extramedullary disease and non-extramedullary disease patients, respectively. In multivariate analysis the presence of extramedullary disease did not impact on progression-free survival (hazard ratio 1.15, P =0.06), while other known prognostic factors retained their significance. Patients treated with immunomodulatory drugs, mainly lenalidomide, or proteasome inhibitors had similar progression-free survival and progression-free survival-2 regardless of extramedullary disease presence. Median overall survival was 63.5 months and 79.9 months ( P =0.01) in extramedullary and non-extramedullary disease patients, respectively, and in multivariate analysis the presence of extramedullary disease was associated with a reduced overall survival (hazard ratio 1.41, P <0.001), in line with other prognostic factors. With the limits of the use of low sensitivity imaging techniques, that lead to an underestimation of extramedullary disease, we conclude that in patients treated with new drugs the detrimental effect of extramedullary disease at diagnosis is limited, that lenalidomide is effective as are proteasome inhibitors, and that these patients tend to acquire a more aggressive disease in later stages. (EUDRACT2005-004714-32, NCT01063179 NCT00551928, NCT01091831, NCT01093196, NCT01190787, NCT01346787, NCT01857115)., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
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20. Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network.
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Moreau P, Sonneveld P, Boccadoro M, Cook G, Mateos MV, Nahi H, Goldschmidt H, Dimopoulos MA, Lucio P, Bladé J, Delforge M, Hajek R, Ludwig H, Facon T, Miguel JFS, and Einsele H
- Subjects
- Consensus, Europe, Humans, Societies, Medical, Immunotherapy, Adoptive methods, Multiple Myeloma therapy, Practice Guidelines as Topic standards
- Abstract
Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development., (Copyright© 2019 Ferrata Storti Foundation.)
- Published
- 2019
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21. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies.
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Bringhen S, Mina R, Petrucci MT, Gaidano G, Ballanti S, Musto P, Offidani M, Spada S, Benevolo G, Ponticelli E, Galieni P, Cavo M, Di Toritto TC, Di Raimondo F, Montefusco V, Palumbo A, Boccadoro M, and Larocca A
- Subjects
- Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug Administration Schedule, Female, Humans, Induction Chemotherapy, Maintenance Chemotherapy, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma etiology, Multiple Myeloma mortality, Oligopeptides adverse effects, Prognosis, Survival Analysis, Treatment Outcome, Antineoplastic Agents administration & dosage, Multiple Myeloma drug therapy, Oligopeptides administration & dosage
- Abstract
Twice-weekly carfilzomib is approved at 27 and 56 mg/m
2 to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m2 carfilzomib, without adding significant toxicity. Data were pooled from two phase I/II studies of newly diagnosed multiple myeloma patients who received nine induction cycles of carfilzomib (either 70 mg/m2 once-weekly or 36 mg/m2 twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analyzed (once-weekly, n=63; twice-weekly, n=58). We found no significant difference in median progression-free survival [35.7 months (95%CI: 23.7-not reached, NR) vs 35.5 months (95%CI: 24.3-NR); HR: 1.39; P =0.26] and 3-year overall survival [70% [95%CI: 59%-84%) vs 72% (95%CI: 60%-85%); HR: 1.27; P =0.5] between once-weekly and twice-weekly carfilzomib. From the start of maintenance, 3-year progression-free survival [47% (95%CI: 33%-68%) vs 51% (95%CI: 38%-70%); HR: 1.04; P =0.92] and overall survival [72% (95%CI: 58%-89%) vs 73% (95%CI: 59%-90%); HR: 0.82; P =0.71] were similar in the once- versus twice-weekly carfilzomib. The rate of grade 3-5 hematologic (24% vs 30%; P =0.82) and non-hematologic (38% vs 41%; P =0.83) adverse events was similar in the two groups. Once-weekly 70 mg/m2 carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m2 carfilzomib and provided a more convenient schedule. The trials are registered at clinicaltrials.gov identifiers : 01857115 (IST-CAR-561 ) and 01346787 ( IST-CAR-506)., (Copyright© 2019 Ferrata Storti Foundation.)- Published
- 2019
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22. European Myeloma Network recommendations on tools for the diagnosis and monitoring of multiple myeloma: what to use and when.
- Author
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Caers J, Garderet L, Kortüm KM, O'Dwyer ME, van de Donk NWCJ, Binder M, Dold SM, Gay F, Corre J, Beguin Y, Ludwig H, Larocca A, Driessen C, Dimopoulos MA, Boccadoro M, Gramatzki M, Zweegman S, Einsele H, Cavo M, Goldschmidt H, Sonneveld P, Delforge M, Auner HW, Terpos E, and Engelhardt M
- Subjects
- Multiple Myeloma pathology, Practice Guidelines as Topic, Multiple Myeloma blood, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve prognostic purposes and are useful for follow-up of myeloma patients. Molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches provides additional prognostic information on patients' long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group updated their guidelines on different diagnostic recommendations, which should be of value to enable appropriate use of the recommendations both at diagnosis and during follow-up., (Copyright© 2018 Ferrata Storti Foundation.)
- Published
- 2018
- Full Text
- View/download PDF
23. Cardiovascular adverse events in modern myeloma therapy - Incidence and risks. A review from the European Myeloma Network (EMN) and Italian Society of Arterial Hypertension (SIIA).
- Author
-
Bringhen S, Milan A, Ferri C, Wäsch R, Gay F, Larocca A, Salvini M, Terpos E, Goldschmidt H, Cavo M, Petrucci MT, Ludwig H, Auner HW, Caers J, Gramatzki M, Boccadoro M, Einsele H, Sonneveld P, and Engelhardt M
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cardiotoxicity, Europe, Humans, Incidence, Italy, Molecular Targeted Therapy adverse effects, Molecular Targeted Therapy methods, Multiple Myeloma therapy, Public Health Surveillance, Risk, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Multiple Myeloma complications, Multiple Myeloma epidemiology
- Abstract
Cardiovascular disease in patients with multiple myeloma may derive from factors unrelated to the disease (age, diabetes, dyslipidemia, obesity, prior cardiovascular diseases), related to the disease (cardiac AL-amyloidosis, hyperviscosity, high-output failure, arteriovenous shunting, anemia, renal dysfunction) and/or related to anti-myeloma treatment (anthracyclines, corticosteroids, alkylating agents, immunomodulatory drugs, proteasome inhibitors). Good knowledge of cardiovascular events, effective dose reductions, prevention and management of early and late cardiovascular side effects of chemotherapeutic agents are essential in current clinical practice. Myeloma experts are obliged to carefully balance the efficacy and toxicity of drugs for each individual patient. This review summarizes current data and novel insights into cardiovascular adverse events of today's anti-myeloma treatment, focusing on carfilzomib, as a starting point for developing consensus recommendations on preventing and managing cardiovascular side effects in patients with multiple myeloma., (Copyright© 2018 Ferrata Storti Foundation.)
- Published
- 2018
- Full Text
- View/download PDF
24. Highly sensitive MYD88 L265P mutation detection by droplet digital polymerase chain reaction in Waldenström macroglobulinemia.
- Author
-
Drandi D, Genuardi E, Dogliotti I, Ferrante M, Jiménez C, Guerrini F, Schirico ML, Mantoan B, Muccio V, Lia G, Zaccaria GM, Omedè P, Passera R, Orsucci L, Benevolo G, Cavallo F, Galimberti S, Sanz RG, Boccadoro M, Ladetto M, and Ferrero S
- Subjects
- Amino Acid Substitution, Biomarkers, Tumor, Case-Control Studies, Circulating Tumor DNA, Combined Modality Therapy, Diagnosis, Differential, Humans, Neoplasm, Residual, Polymerase Chain Reaction methods, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Waldenstrom Macroglobulinemia therapy, Alleles, Mutation, Myeloid Differentiation Factor 88 genetics, Waldenstrom Macroglobulinemia diagnosis, Waldenstrom Macroglobulinemia genetics
- Abstract
We here describe a novel method for MYD88
L265P mutation detection and minimal residual disease monitoring in Waldenström macroglobulinemia, by droplet digital polymerase chain reaction, in bone marrow and peripheral blood cells, as well as in circulating cell-free DNA. Our method shows a sensitivity of 5.00×10-5 , which is far superior to the widely used allele-specific polymerase chain reaction (1.00×10-3 ). Overall, 291 unsorted samples from 148 patients (133 with Waldenström macroglobulinemia, 11 with IgG lymphoplasmacytic lymphoma and 4 with IgM monoclonal gammopathy of undetermined significance) were analyzed: 194 were baseline samples and 97 were followup samples. One hundred and twenty-two of 128 (95.3%) bone marrow and 47/66 (71.2%) baseline peripheral blood samples scored positive for MYD88L265P To investigate whether MYD88L265P detection by droplet digital polymerase chain reaction could be used for minimal residual disease monitoring, mutation levels were compared with IGH -based minimal residual disease analysis in 10 patients, and was found to be as informative as the classical, standardized, but not yet validated in Waldenström macroglobulinemia, IGH -based minimal residual disease assay (r2 =0.64). Finally, MYD88L265P detection by droplet digital polymerase chain reaction on plasma circulating tumor DNA from 60 patients showed a good correlation with bone marrow findings (bone marrow median mutational value 1.92×10-2 , plasma circulating tumor DNA value: 1.4×10-2 , peripheral blood value: 1.03×10-3 ). This study indicates that droplet digital polymerase chain reaction assay of MYD88L265P is a feasible and sensitive tool for mutation screening and minimal residual disease monitoring in Waldenström macroglobulinemia. Both unsorted bone marrow and peripheral blood samples can be reliably tested, as can circulating tumor DNA, which represents an attractive, less invasive alternative to bone marrow for MYD88L265P detection., (Copyright © 2018 Ferrata Storti Foundation.)- Published
- 2018
- Full Text
- View/download PDF
25. From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives.
- Author
-
Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW, Caers J, Gramatzki M, van de Donk N, Oliva S, Zamagni E, Garderet L, Straka C, Hajek R, Ludwig H, Einsele H, Dimopoulos M, Boccadoro M, Kröger N, Cavo M, Goldschmidt H, Bruno B, and Sonneveld P
- Subjects
- Europe, Humans, Practice Guidelines as Topic, Salvage Therapy instrumentation, Salvage Therapy methods, Transplantation, Autologous methods, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Immunotherapy, Adoptive methods, Multiple Myeloma therapy
- Abstract
Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival. In the light of these findings, novel agent-based induction followed by autologous transplantation is considered the standard upfront treatment for eligible patients (level of evidence: 1A). Post-transplant consolidation and maintenance treatment can further improve patient outcome (1A). The availability of several novel agents has led to the development of multiple combination regimens such as salvage treatment options. In this context, the role of salvage autologous transplantation and allotransplant has not been extensively evaluated. In the case of prolonged remission after upfront autologous transplantation, another autologous transplantation at relapse can be considered (2B). Patients who experience early relapse and/or have high-risk features have a poor prognosis and may be considered as candidates for clinical trials that, in young and fit patients, may also include an allograft in combination with novel agents (2B). Ongoing studies are evaluating the role of novel cellular therapies, such as inclusion of antibody-based triplets and quadruplets, and chimeric antigen receptor-T cells. Despite encouraging preliminary results, longer follow up and larger patient numbers are needed before the clinical use of these novel therapies can be widely recommended., (Copyright© 2018 Ferrata Storti Foundation.)
- Published
- 2018
- Full Text
- View/download PDF
26. European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma.
- Author
-
Engelhardt M, Terpos E, Kleber M, Gay F, Wäsch R, Morgan G, Cavo M, van de Donk N, Beilhack A, Bruno B, Johnsen HE, Hajek R, Driessen C, Ludwig H, Beksac M, Boccadoro M, Straka C, Brighen S, Gramatzki M, Larocca A, Lokhorst H, Magarotto V, Morabito F, Dimopoulos MA, Einsele H, Sonneveld P, and Palumbo A
- Subjects
- Autografts, Clinical Trials, Phase III as Topic, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma diagnosis, Multiple Myeloma therapy
- Abstract
Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B).
- Published
- 2014
- Full Text
- View/download PDF
27. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials.
- Author
-
Palumbo A, Waage A, Hulin C, Beksac M, Zweegman S, Gay F, Gimsing P, Leleu X, Wijermans P, Sucak G, Pezzatti S, Juliusson G, Pégourié B, Schaafsma M, Galli M, Turesson I, Kolb B, van der Holt B, Baldi I, Rolke J, Ciccone G, Wetterwald M, Lokhorst H, Boccadoro M, Rodon P, and Sonneveld P
- Subjects
- Aged, Aged, 80 and over, Female, Hematologic Diseases chemically induced, Hematologic Diseases diagnosis, Humans, Male, Multiple Myeloma mortality, Randomized Controlled Trials as Topic, Survival Rate trends, Thalidomide adverse effects, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Thalidomide therapeutic use
- Abstract
Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival.
- Published
- 2013
- Full Text
- View/download PDF
28. Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes.
- Author
-
Ferrero S, Capello D, Svaldi M, Boi M, Gatti D, Drandi D, Rossi D, Barbiero S, Mantoan B, Mantella E, Zanni M, Ghione P, Larocca A, Passera R, Bertoni F, Gattei V, Forconi F, Laurenti L, Del Poeta G, Marasca R, Cortelazzo S, Gaidano G, Palumbo A, Boccadoro M, and Ladetto M
- Subjects
- B-Lymphocytes immunology, B-Lymphocytes pathology, Complementarity Determining Regions chemistry, Complementarity Determining Regions immunology, Data Mining, Databases, Nucleic Acid, Humans, Multigene Family immunology, Multiple Myeloma immunology, Myeloma Proteins chemistry, Myeloma Proteins immunology, Sequence Analysis, DNA, Somatic Hypermutation, Immunoglobulin immunology, Complementarity Determining Regions genetics, Genes, Immunoglobulin Heavy Chain immunology, Multiple Myeloma genetics, Myeloma Proteins genetics
- Abstract
Background: Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive., Design and Methods: To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters., Results: Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets., Conclusions: Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.
- Published
- 2012
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- View/download PDF
29. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.
- Author
-
Palumbo A, Larocca A, Genuardi M, Kotwica K, Gay F, Rossi D, Benevolo G, Magarotto V, Cavallo F, Bringhen S, Rus C, Masini L, Iacobelli M, Gaidano G, Mitsiades C, Anderson K, Boccadoro M, and Richardson P
- Subjects
- Dose-Response Relationship, Drug, Humans, Melphalan administration & dosage, Multiple Myeloma mortality, Multiple Myeloma pathology, Polydeoxyribonucleotides administration & dosage, Prednisone administration & dosage, Salvage Therapy methods, Thalidomide administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Background: Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen., Design and Methods: This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35., Results: Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient., Conclusions: This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.
- Published
- 2010
- Full Text
- View/download PDF
30. Bortezomib with or without dexamethasone in relapsed multiple myeloma following allogeneic hematopoietic cell transplantation.
- Author
-
Bruno B, Patriarca F, Sorasio R, Mattei D, Montefusco V, Peccatori J, Bonifazi F, Petrucci MT, Milone G, Guidi S, Giaccone L, Rotta M, Fanin R, Boccadoro M, and Corradini P
- Subjects
- Bortezomib, Disease-Free Survival, Humans, Multiple Myeloma drug therapy, Recurrence, Retrospective Studies, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Antineoplastic Agents therapeutic use, Boronic Acids therapeutic use, Dexamethasone therapeutic use, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy, Pyrazines therapeutic use
- Abstract
We retrospectively evaluated the efficacy of bortezomib in 23 patients with multiple myeloma who had relapsed after allografting. Bortezomib was given as single agent to 9 patients (39%) and in combination with steroids in the other 14 (61%). Major toxicities were thrombocytopenia (10/23, 43%) and peripheral neuropathy (12/23, 52%). The overall response rate was 61% (14/23), including 22% (5/23) immunofixation-negative complete remissions. No significant differences in toxicity and response rates were seen between patients treated with bortezomib plus steroids and bortezomib alone. After a median follow-up of 6 months, progression free survival was 6 months. Twenty-one patients are alive, two and five in continuous very good partial and complete remissions, respectively.
- Published
- 2006
31. Corticosteroids can reverse severe imatinib-induced hepatotoxicity.
- Author
-
Ferrero D, Pogliani EM, Rege-Cambrin G, Fava C, Mattioli G, Dellacasa C, Campa E, Perfetti P, Fumagalli M, and Boccadoro M
- Subjects
- Benzamides, Humans, Imatinib Mesylate, Liver drug effects, Methylprednisolone therapeutic use, Prednisone therapeutic use, Adrenal Cortex Hormones therapeutic use, Antineoplastic Agents adverse effects, Chemical and Drug Induced Liver Injury, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Liver pathology, Liver Diseases drug therapy, Piperazines adverse effects, Pyrimidines adverse effects
- Abstract
Background: Imatinib can induce severe hepatotoxicity, in 1-5% of CML patients, many of whom need permanent imatinib discontinuation., Design and Results: We report 5 CML patients who developed grade 3-4 hepatotoxicity after 2-8 months in imatinib. Different aetiologies of liver damage were ruled out and toxicity recurred in 2 patients with further attempts at low dose imatinib. In all patients prednisone or methylprednisolone at 25- 40 mg/day resolved hepatotoxicity in 3-8 weeks and allowed imatinib to be resumed at full doses. Corticosteroid were tapered off in 3-5 months without hepatotoxicity recurrence., Conclusions: Corticosteroid may avoid discontinuation for hepatotoxicity of the most effective anti-CML therapy.
- Published
- 2006
32. Correlation between fatigue and hemoglobin level in multiple myeloma patients: results of a cross-sectional study.
- Author
-
Palumbo A, Petrucci MT, Lauta VM, Musto P, Caravita T, Barbui AM, Nunzi M, and Boccadoro M
- Subjects
- Female, Humans, Italy, Male, Multivariate Analysis, Regression Analysis, Remission Induction, Sex Factors, Surveys and Questionnaires, Fatigue, Hemoglobins biosynthesis, Multiple Myeloma blood
- Abstract
This cross-sectional study showed a positive correlation between fatigue-related quality of life, evaluated with the FACT-An questionnaire, and hemoglobin level in 1071 patients with multiple myeloma. Multiple regression analysis adjusting for several covariates was used. Improved FACT-An scores in women and men were associated with hemoglobin increase up to sex-specific normal values.
- Published
- 2005
33. Management of multiple myeloma and related-disorders: guidelines from the Italian Society of Hematology (SIE), Italian Society of Experimental Hematology (SIES) and Italian Group for Bone Marrow Transplantation (GITMO).
- Author
-
Barosi G, Boccadoro M, Cavo M, Corradini P, Marchetti M, Massaia M, Merlini G, Tosi P, and Tura S
- Subjects
- Combined Modality Therapy, Disease Management, Evidence-Based Medicine, Humans, Italy, Multiple Myeloma complications, Societies, Medical, Multiple Myeloma therapy
- Abstract
Objectives: Perceiving the need for rigorous recommendations to facilitate decisions concerning the management of patients with multiple myeloma (MM), the Italian Society of Hematology (SIE) and the two affiliate societies (SIES and GITMO) commissioned a project to develop guidelines for the therapy of MM using evidence-based knowledge and consensus formation techniques., Methods: After a comprehensive systematic review of 1,450 papers, an Expert Panel formulated and graded sixty recommendations according to the supporting evidence. Evidence gaps were filled with twenty-two consensus-based statements. High grade recommendations (grade A) are reported below., Results: Treatment should be immediately initiated in MM patients with related organ damage: those patients aged below 65 years who do not have severe co-morbidities should receive autologous stem cell transplantation, while patients not candidates for autologous stem cell transplantation should receive oral melphalan and prednisone. Interferon-a should not be associated with conventional chemotherapy, but it can be offered with or without steroids as a maintenance therapy to patients who have reached a plateau phase. High-dose dexamethasone-containing regimens or high-dose dexamethasone alone are recommended as a first-line therapy when cytoreduction is urgently required (i.e., MM with spinal cord compression or with rapidly progressive renal failure). MM patients with moderate-to-severe anemia should receive erythropoietin, while patients with bone disease or osteopenia should receive long-term bisphophonates. Recommendations for the management of the clinical manifestations caused by the monoclonal protein (i.e. hyperviscosity, cast nephropathy, AL amyloidosis) and of solitary bone and extramedullary plasmacytoma were also elaborated., Conclusions: A substantial proportion of clinical care for MM can be guided by evidence-based treatment recommendations.
- Published
- 2004
34. Differentiating agents + low-dose chemotherapy in the management of old/poor prognosis patients with acute myeloid leukemia or myelodysplastic syndrome.
- Author
-
Ferrero D, Campa E, Dellacasa C, Campana S, Foli C, and Boccadoro M
- Subjects
- Acute Disease, Adult, Aged, Aged, 80 and over, Calcitriol administration & dosage, Cytarabine administration & dosage, Disease Progression, Female, Humans, Isotretinoin administration & dosage, Male, Middle Aged, Thioguanine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Myeloid drug therapy, Myelodysplastic Syndromes drug therapy
- Abstract
13-cis retinoic acid + (OH)2 vitamin D3 + low-dose 6-thioguanine and cytarabine were tested in 26 patients with acute myeloid leukemia (AML) and in 4 patients with myelodysplastic syndrome (MDS) (median age 72.5), ineligible for standard chemotherapy. The response rate was 50%, with 27% complete remission. The median survival of the whole group and responders was 7.5 (1-47+) and 16.5 months (3.5-47+), respectively.
- Published
- 2004
35. Oral melphalan at diagnosis hampers adequate collection of peripheral blood progenitor cells in multiple myeloma.
- Author
-
Boccadoro M, Palumbo A, Bringhen S, Merletti F, Ciccone G, Richiardi L, Rus C, Bertola A, Giaccone L, Omedè P, and Musto P
- Subjects
- Administration, Oral, Adult, Aged, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Blood Cell Count, Combined Modality Therapy, Contraindications, Cyclophosphamide pharmacology, Dexamethasone administration & dosage, Doxorubicin administration & dosage, Female, Humans, Male, Melphalan administration & dosage, Middle Aged, Multiple Myeloma blood, Multiple Myeloma therapy, Odds Ratio, Retrospective Studies, Salvage Therapy, Stem Cell Transplantation, Vincristine administration & dosage, Antineoplastic Agents, Alkylating pharmacology, Hematopoietic Stem Cell Mobilization methods, Hematopoietic Stem Cells drug effects, Melphalan pharmacology, Multiple Myeloma drug therapy
- Abstract
Background and Objectives: Since optimal collection of peripheral blood progenitor cells (PBPC) remains crucial for high-dose therapy in patients with multiple myeloma (MM) in relapse phase or refractory to chemotherapy, we evaluated several variables that may influence mobilization., Design and Methods: Eighty-nine patients who underwent a standard mobilization procedure with cyclophosphamide (3 g/m2) and growth factors entered the study. A composite collection totalling at least 2x106 CD34+/kg was defined as a sufficient yield: 59 patients achieved an adequate collection. A reliable factor to predict adequate yields was prior therapy: an adequate collection was obtained in 92% of patients treated with conventional non-alkylating therapy (VAD-based regimens), in 56% treated with oral melphalan and in 23% who had received intravenous melphalan., Results: The three groups were similar for most clinical features. After adjustment for several potential confounders, the probability of an adequate PBPC collection remained higher in the group treated with non-alkylating agents, with an odds ratio (OR) of 6.14 (95% confidence interval, CI=1.34, 28.13) and lower in those treated with intravenous melphalan (OR=0.08; CI=0.01-0.61), when compared to the group treated with oral melphalan. Among the other prognostic factors (stage, percentage of bone marrow plasma cells, b2-microglobulin, labeling index, isotype, monoclonal component, Bence-Jones proteinuria) evaluated at diagnosis, there was no clear association with progenitor cell yield., Interpretation and Conclusions: In conclusion, patients who are potential candidates for high-dose therapy with PBPC support should not receive conventional alkylating therapy, even orally. Alternatively, progenitor cells should be collected early in the course of MM.
- Published
- 2002
36. Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma.
- Author
-
Palumbo A, Giaccone L, Bertola A, Pregno P, Bringhen S, Rus C, Triolo S, Gallo E, Pileri A, and Boccadoro M
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols toxicity, Dexamethasone toxicity, Humans, Middle Aged, Multiple Myeloma complications, Multiple Myeloma mortality, Salvage Therapy, Thalidomide toxicity, Treatment Outcome, Dexamethasone administration & dosage, Multiple Myeloma drug therapy, Thalidomide administration & dosage
- Abstract
Background and Objectives: The immunomodulatory drug thalidomide can inhibit angiogenesis and induce apoptosis in experimental models. It can also induce marked and durable response in advanced myeloma patients. Thalidomide has been used at doses ranging from 200 to 800 mg with significant toxicity. No data are available on the impact of low-dose thalidomide plus dexamethasone as salvage therapy for relapsed patients., Design and Methods: To address this issue, myeloma patients were treated with 100 mg/day thalidomide continuously and dexamethasone 40 mg, days 1-4, every month. Between June 1999 and August 2000, 77 patients (median age 65 years) who had relapsed or were refractory to chemotherapy were treated with thalidomide plus dexamethasone., Results: After a minimum of 3 months of treatment, 14 patients (18%) showed a myeloma protein reduction of 75%-100%, 18 patients (23%) showed a response of 50-75%, 19 patients (25%) a response of 25-50% and 26 patients (34%) a response of < 25% or disease progression. After a median follow-up of 8 months, median progression-free survival was 12 months. Thalidomide was well tolerated. Constipation (12%) and sedation (6%) were mild. Tingling or numbness were present in 17% of patients, discontinuation of treatment was required in 10% of patients., Interpretation and Conclusions: The association of low-dose thalidomide plus dexamethasone is active against advanced myeloma. A significant proportion of patients benefit from this treatment as a salvage therapy postponing the delivery of chemotherapy.
- Published
- 2001
37. Dose-intensive melphalan with stem cell support (CM regimen) is effective and well tolerated in elderly myeloma patients.
- Author
-
Palumbo A, Triolo S, Baldini L, Callea V, Capaldi A, De Stefano V, Grasso M, Liberati M, Lotesoriere C, Marcenò R, Marmont F, Musto P, Petrucci MT, Spriano M, Pileri A, and Boccadoro M
- Subjects
- Aged, Antigens, CD34 blood, Antigens, CD34 drug effects, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating pharmacology, Antineoplastic Agents, Alkylating toxicity, Cyclophosphamide administration & dosage, Cyclophosphamide toxicity, Drug Evaluation, Graft Survival drug effects, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation standards, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents toxicity, Melphalan pharmacology, Middle Aged, Multiple Myeloma complications, Transplantation, Autologous, Melphalan administration & dosage, Melphalan toxicity, Multiple Myeloma drug therapy
- Abstract
Background and Objective: Multiple myeloma (MM) typically afflicts elderly patients. High-dose therapy has recently been shown to lead to a better outcome than standard treatment, mainly in younger patients. The extent to which older subjects can benefit from intensified approaches without excessive toxicity is examined in this study., Design and Methods: Between December 1994 and May 1997, 12 Italian Multiple Myeloma Study Group institutions entered 68 patients at diagnosis (median age 65) into an intensified chemotherapy regimen: cyclophosphamide (CY) 3 g/m(2) plus melphalan 60 mg/m(2) followed by peripheral blood progenitor cells (PBPC) and G-CSF (CM regimen). CY (day 0) and G-CSF were used to mobilize PBPC harvested by a single leukapheresis on day 10. Melphalan was infused on day 11. PBPC were kept unprocessed at 4 degrees C for 48 hours and reinfused on day 12. Three CM regimens were delivered at 6-month intervals., Results: Sufficient PBPC to support the first CM cycle were available (median CD34(+) harvest: 4.9x10(6)/kg), but dropped significantly after the second (median CD34(+) harvest: 2x10(6)/kg) and the third (median CD34(+) harvest: 0.9x10(6)/kg). The median durations of severe neutropenia (absolute neutrophil count < 500 microL) were 3, 4, and 3 days, and those of severe thrombocytopenia (platelets < 25,000/microL) were 2.5, 2, and 1 days, after the first, second and third courses, respectively. The frequency of extramedullary toxicities was low. Treatment-related mortality (TRM) was 3% after the first CM, only. Complete remission (CR) was 14% after the first, 16% after the second and 27% after the third CM. After a median follow-up of 34 months (range 19-49 months), median event-free survival was 35.6 months., Interpretation and Conclusions: These results indicate that dose-intensity of melphalan can be increased by reinfusing PBPC with acceptable low toxicity. The combination of CY and melphalan followed by PBPC is an effective chemotherapy for elderly myeloma patients. Repeated melphalan infusion hampered subsequent CD34(+) harvests.
- Published
- 2000
38. An analysis of which subgroups of multiple myeloma patients, divided according to b(2)-microglobulin and plasma cell labeling index, benefit from high dose vs conventional chemotherapy.
- Author
-
Boccadoro M, Tarella C, Palumbo A, Argentino C, Triolo S, Dominietto A, Callea V, Lauta VM, Molica S, Musto P, Marmont F, Gianni AM, and Pileri A
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cell Count, Disease-Free Survival, Dose-Response Relationship, Drug, Follow-Up Studies, Humans, Longitudinal Studies, Middle Aged, Severity of Illness Index, Survival Rate, Treatment Outcome, Antineoplastic Agents administration & dosage, Multiple Myeloma therapy, Plasma Cells pathology, beta 2-Microglobulin blood
- Abstract
Background and Objective: The clinical advantage of high-dose therapy (HDT) over standard treatment for multiple myeloma (MM) patients has been recently assessed. Which patient subgroups benefit most from this approach is unclear., Design and Methods: To address this issue, the outcome of 54 patients under 55 years old treated with HDT was compared with that of 101 age-matched controls selected from 390 patients who received standard melphalan and prednisone (MP) chemotherapy in a national multi-center trial (M90 protocol)., Results: The complete response (CR) rate was 50% in the HDT group compared to 5% in the MP group. Event-free survival (EFS) was three times longer for the HDT patients (median 34.5 vs 12.2 months, p<0. 0001), though the controls enjoyed a prolonged survival after relapse, and hence there was no statistically significant difference in OS. Overall survival (OS) was analyzed in relation to to two major prognostic factors: b(2)-microglobulin (b(2)-M) and bone marrow plasma cell labeling index (LI). HDT significantly improved OS in poor prognosis patients with a high LI (>1.2%), (median 49.5 vs 32.5 months, p<0.03), whereas it did not prolong OS in poor prognosis patients with high b(2 )-M (> 3 mg/L)., Interpretation and Conclusions: In conclusion, HDT has a major impact on CR and EFS, and is the treatment of choice for patients with a high LI. Alternative strategies should be adopted in poor prognosis patients with high b(2 )-M.
- Published
- 1999
39. Current therapeutic options for multiple myeloma.
- Author
-
Pileri A, Palumbo A, and Boccadoro M
- Subjects
- Humans, Multiple Myeloma therapy
- Published
- 1996
40. Cyclophosphamide (3.6 g/m2) therapy with G-CSF support for resistant myeloma.
- Author
-
Palumbo A, Boccadoro M, Bruno B, Triolo S, and Pileri A
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Dexamethasone, Doxorubicin administration & dosage, Drug Resistance, Female, Heart Diseases chemically induced, Hematuria chemically induced, Herpes Zoster etiology, Humans, Male, Mesna administration & dosage, Middle Aged, Multiple Myeloma mortality, Neutropenia chemically induced, Neutropenia therapy, Prednisone administration & dosage, Remission Induction, Survival Analysis, Treatment Outcome, Vincristine administration & dosage, Cyclophosphamide therapeutic use, Granulocyte Colony-Stimulating Factor therapeutic use, Immunologic Factors therapeutic use, Multiple Myeloma drug therapy, Neutropenia prevention & control, Salvage Therapy
- Abstract
Background: In myeloma patients resistance to both melphalan- and doxorubicin-containing regimens has been related to very short survival (approximately 6 months). The development of effective regimens combined with a low toxicity rate is mandatory in this patient subgroup., Methods: Fourteen resistant myeloma patients were treated with cyclophosphamide (a total of 3.6 g/m2 was delivered in 2 doses on days 1 and 3) and prednisone (2 mg/kg, days 1-4) every month for 4 cycles. G-CSF support was administered to reduce myelosuppression., Results: This combination was well tolerated. Granulocyte levels fell below 0.1 x 10(9)/L in all patients after a median of 9 days (range 8-11), followed by recovery to 0.5 x 10(9)/L after a median of 12 days from the start of treatment (range 10-13 days). Platelets never fell below 50 x 10(9)/L. All patients were treated on an outpatient basis and only 2 required hospitalization for major complications (pneumonia and heart failure). Response to cyclophosphamide was observed in 6/14 patients: 2 achieved complete remission, 4 showed a 50% or greater reduction of the M-component. Five patients are still in remission after 2, 6, 7, 9 and 10 months; 1 relapsed after 10 months. All patients except one are alive 4-16 months from the start of treatment., Conclusions: This schedule may represent a new approach for resistant myeloma, and its very low toxicity allows it to be delivered on an outpatient basis.
- Published
- 1994
41. Phenotypic and functional analysis of peripheral blood lymphocytes during interferon-alpha 2b therapy in multiple myeloma patients with low tumor mass.
- Author
-
Bianchi A, Omedé P, Attisano C, Camponi A, Dianzani U, Boccadoro M, Pileri A, and Massaia M
- Subjects
- Antigens, CD analysis, Antigens, Neoplasm analysis, HLA-DR Antigens analysis, Immunity, Cellular, Immunophenotyping, Interferon alpha-2, Killer Cells, Lymphokine-Activated pathology, Killer Cells, Natural pathology, Leukocyte Count, Multiple Myeloma blood, Multiple Myeloma immunology, Multiple Myeloma pathology, Neoplastic Stem Cells pathology, Recombinant Proteins, T-Lymphocyte Subsets drug effects, Time Factors, Immunologic Factors therapeutic use, Interferon-alpha therapeutic use, Multiple Myeloma therapy, T-Lymphocyte Subsets pathology
- Abstract
Background: IFN-alpha has recently been shown to prolong the remission phase in MM patients with low tumor mass. So far, it is not known whether IFN-alpha exerts its effect directly on the myeloma cells or is mediated by modulation of the host response., Methods: The immune status of 12 multiple myeloma patients with low tumor mass (10 in remission phase, 2 with stage IA disease) was investigated by phenotypic and functional analyses before, after 3, and after 6 months of recombinant interferon-alpha 2b (IFN-alpha) therapy., Results: Phenotyping of peripheral blood lymphocytes (PBL) revealed a significant decrease of HLA-DR+ (P = 0.01) and CD20+ (P = 0.04) cells after 6 months of therapy. Two-color phenotyping of purified T cell populations (PBT) showed a significant increase of CD4+ CD11b+ cells (P = 0.01) after 6 months of therapy. Functional analyses were carried out on PBL (NK cell-mediated cytotoxicity) and PBT (alloreactive cytotoxicity, CTL; IL2-induced cytotoxicity, LAK activity). NK and CTL activities were poorly influenced by IFN-alpha treatment, whereas LAK activity showed a significant increase (P = 0.007). Any significant association between these immunological changes and the disease status was questioned by the lack of differences between MM in relapse and MM with stable disease at the sixth month of IFN-alpha therapy., Conclusions: i) IFN-alpha in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-alpha therapy.
- Published
- 1991
42. [Multiple myeloma. Mechanisms of proliferation and neoplastic progression and their clinical implications].
- Author
-
Boccadoro M, Battaglio S, Dianzani U, Frieri R, Gallone G, Massaia M, Omedè P, Palumbo A, and Pileri A
- Subjects
- Animals, C-Reactive Protein metabolism, Cell Division, Gene Expression Regulation, Neoplastic, Humans, Interleukin-6 metabolism, Lymphocyte Subsets, Mice, Multiple Myeloma genetics, Multiple Myeloma immunology, Mutation, Neoplasm Proteins metabolism, Plasma Cells pathology, Prognosis, Proto-Oncogenes, beta 2-Microglobulin metabolism, Multiple Myeloma pathology
- Published
- 1991
43. Consolidation treatment with dexamethasone and alpha-2B recombinant interferon further reduces the M-component level in multiple myeloma patients responding to conventional induction chemotherapy.
- Author
-
Palumbo AP, Garino AL, Frieri R, Gallone G, Boccadoro M, and Pileri A
- Subjects
- Combined Modality Therapy, Humans, Interferon alpha-2, Melphalan administration & dosage, Multiple Myeloma blood, Multiple Myeloma drug therapy, Prednisone administration & dosage, Recombinant Proteins, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dexamethasone therapeutic use, Immunologic Factors therapeutic use, Interferon-alpha therapeutic use, Multiple Myeloma therapy, Myeloma Proteins analysis
- Abstract
Three patients with symptomatic multiple myeloma who had achieved an objective response after conventional induction chemotherapy were treated with alpha-2b-interferon plus intermittent high-dose dexamethasone as consolidation therapy. This treatment included three mega units of alpha-2b-interferon three times a week, plus 4 days pulsed high-dose dexamethasone every 28 days for 6 months. Toxicity was limited to a mild flu-like syndrome. A further and significant M-component reduction (50%), obtained after conventional chemotherapy, suggests the value of intermittent high-dose dexamethasone plus interferon as consolidation therapy.
- Published
- 1990
44. Analysis of the breakpoint cluster region in essential thrombocythemia.
- Author
-
Corradini P, Palumbo AP, Battaglio S, Ponzio G, Boccadoro M, and Pileri A
- Subjects
- Chromosomes, Human, Pair 15 ultrastructure, Chromosomes, Human, Pair 9 ultrastructure, Female, Humans, Male, Megakaryocytes ultrastructure, Oncogenes, Prognosis, Translocation, Genetic, Philadelphia Chromosome, Thrombocythemia, Essential genetics
- Abstract
Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by a platelet count higher than 1000 x 10(9)/l. Bone marrow karyotype aberrations are occasionally observed. The presence of cytogenetic and molecular markers of chronic myeloid leukemia (CML) was assessed in 25 patients with the clinical features of ET. One displayed a complex translocation (9; 15; 22) (q34.1 or q34.3; q26.1; q11), and another a Philadelphia chromosome with standard translocation (9; 22) (q34; q11). Southern blot analysis revealed a rearranged breakpoint cluster region (bcr) in each case. Both patients experienced a stormy disease course without a leukemic transformation. These data indicate that the Philadelphia chromosome rarely occurs in ET and strongly influences patient outcome.
- Published
- 1990
45. Multiple myeloma: altered CD4/CD8 ratio in bone marrow.
- Author
-
Redoglia V, Boccadoro M, Battaglio S, Dianzani U, Massaia M, and Pileri A
- Subjects
- CD8 Antigens, Humans, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, Bone Marrow immunology, CD4 Antigens metabolism, Multiple Myeloma immunology
- Abstract
The expression of CD3, CD4 and CD8 antigens was simultaneously evaluated in peripheral blood and bone marrow lymphocytes from 22 multiple myeloma (MM) patients. The coexpression of CD11b and HLA-DR antigens was also analyzed within the CD4+ and CD8+ subpopulations in 4 MM patients. In peripheral blood the percentage of CD3+ and CD8+ cells was in the normal range, and the percentage of CD4+ was slightly reduced, leading to an altered CD4/CD8 ratio (less than 1) in only 7 patients. On the contrary, in bone marrow the percentage of CD4+ was profoundly reduced, leading to an altered CD4/CD8 ratio in all MM patients. As we previously reported in peripheral blood, an expansion of the CD11b+ and HLA-DR+ lymphocytes was observed within the CD4+ and CD8+ bone marrow T-cell subpopulations. A T-lymphocyte subset imbalance is more evident in bone marrow than in peripheral blood, and it is not due to a different lymphocyte distribution within the hematological compartments.
- Published
- 1990
46. GM-CSF-exposed peripheral blood progenitors as sole source of stem cells for autologous transplantation in two patients with multiple myeloma.
- Author
-
Pileri A, Tarella C, Bregni M, Boccadoro M, Siena S, Caracciolo D, Bonadonna G, and Gianni AM
- Subjects
- Adult, Female, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells drug effects, Humans, Male, Middle Aged, Blood Transfusion, Autologous methods, Colony-Stimulating Factors therapeutic use, Growth Substances therapeutic use, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Abstract
Two patients (aged 52 and 44) received high-dose sequential chemotherapy followed by myeloablative therapy and autotransplantation as first line treatment of a stage III multiple myeloma with high plasmacell labelling index. Autograft was performed with peripheral blood cells collected after high-dose etoposide followed by rhGM-CSF continuous infusion. During this period very high numbers of circulating hemopoietic progenitors were detected in both patients. Prompt, complete and durable hematological recovery was observed after autograft with peripheral blood stem cells. Thus, we conclude that massively released progenitors after high-dose chemotherapy and rhGM-CSF include stem cells capable of marrow reconstitution.
- Published
- 1990
47. B lymphocytes receptors: a new biological approach for immunofluorescence studies.
- Author
-
Conte PF, Boccadoro M, and Pileri A
- Subjects
- B-Lymphocytes immunology, Fluorescent Antibody Technique, Multiple Myeloma immunology, Myeloproliferative Disorders immunology
- Published
- 1977
48. [Monoclonal gammopathy of uncertain significance].
- Author
-
Boccadoro M, Gavarotti P, and Pileri A
- Subjects
- Diagnosis, Differential, Humans, Multiple Myeloma diagnosis, Plasmacytoma diagnosis
- Published
- 1984
49. Breakdown of RNA and protein synthesis template stability in proliferating and non proliferating human myeloma cells.
- Author
-
Pileri A, Conte PF, Boccadoro M, and Hulin N
- Subjects
- Cell Division, Cells, Cultured, Humans, Multiple Myeloma metabolism, Myeloma Proteins biosynthesis, RNA, Neoplasm biosynthesis
- Published
- 1977
50. Multiple myeloma: biological and clinical significance of bone marrow plasma cell labelling index.
- Author
-
Boccadoro M, Massaia M, Dianzani U, and Pileri A
- Subjects
- Cell Transformation, Neoplastic, Humans, Kinetics, Multiple Myeloma diagnosis, Plasma Cells metabolism, Prognosis, Tritium, Bone Marrow Cells, Multiple Myeloma pathology, Thymidine metabolism
- Published
- 1987
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