120 results on '"Longoni, D"'
Search Results
2. The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome
- Author
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Minelli, A, Maserati, E, Nicolis, E, Zecca, M, Sainati, L, Longoni, D, Lo Curto, F, Menna, G, Poli, F, De Paoli, E, Cipolli, M, Locatelli, F, Pasquali, F, and Danesino, C
- Published
- 2009
- Full Text
- View/download PDF
3. Purified autologous grafting in childhood acute lymphoblastic leukemia in second remission: evidence for long-term clinical and molecular remissions
- Author
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Balduzzi, A, Gaipa, G, Bonanomi, S, Dassi, M, Perseghin, P, Buscemi, F, D'Aniello, E, Rovelli, A, Schirò, R, Longoni, D, Rambaldi, A, Uderzo, C, and Biondi, A
- Published
- 2001
- Full Text
- View/download PDF
4. Aberrant GM-CSF signal transduction pathway in juvenile myelomonocytic leukemia assayed by flow cytometric intracellular STAT5 phosphorylation measurement
- Author
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Gaipa, G, Bugarin, C, Longoni, D, Cesana, S, Molteni, C, Faini, A, Timeus, F, Zecca, M, and Biondi, A
- Published
- 2009
- Full Text
- View/download PDF
5. EVI-1 gene expression in myeloid clonogenic cells from juvenile myelomonocytic leukemia (JMML)
- Author
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Privitera, E, Longoni, D, Brambillasca, F, and Biondi, A
- Published
- 1997
- Full Text
- View/download PDF
6. Risk of seizures in children receiving busulphan-containing regimens for stem cell transplantation
- Author
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Caselli D, Rosati A, Faraci M, Podda M, Ripaldi M, Longoni D, Cesaro S, Lo Nigro L, Paolicchi O, Maximova N, Menconi MC, Ziino O, Cicalese MP, Santarone S, Nesi F, Aricò M, Locatelli F, Prete A, Bone Marrow Transplantation Working Group of the Associazione Italiana Ematologia Oncologia Pediatrica., Caselli, D, Rosati, A, Faraci, M, Podda, M, Ripaldi, M, Longoni, D, Cesaro, S, Lo Nigro, L, Paolicchi, O, Maximova, N, Menconi, Mc, Ziino, O, Cicalese, Mp, Santarone, S, Nesi, F, Aricò, M, Locatelli, F, Prete, A, and Bone Marrow Transplantation Working Group of the Associazione Italiana Ematologia Oncologia, Pediatrica.
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Busulphan ,stem cell transplantation ,Conditioning regimen ,Epilepsy ,Young Adult ,Seizures ,Medicine ,Humans ,Risk factor ,HEMATOPOIETIC STEM CELL TRASPLANTATION ,pediatric ,Child ,Antineoplastic Agents, Alkylating ,Busulfan ,Transplantation ,business.industry ,Prophylaxis ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,seizure prophylaxis ,Infant ,Hematology ,medicine.disease ,Regimen ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Child, Preschool ,Brain lesions ,Female ,Stem cell ,business - Abstract
Busulphan (BU) is associated with neurotoxicity and risk of seizures. Hence, seizure prophylaxis is routinely utilized during BU administration for stem cell transplantation (SCT). We collected data on the incidence of seizures among children undergoing SCT in Italy. Fourteen pediatric transplantation centers agreed to report unselected data on children receiving BU as part of the conditioning regimen for SCT between 2005 and 2012. Data on 954 pediatric transplantation procedures were collected; of them, 66% of the patients received BU orally, and the remaining 34%, i.v. All the patients received prophylaxis of seizures, according to local protocols, consisting of different schedules and drugs. A total of 13 patients (1.3%) developed seizures; of them, 3 had a history of epilepsy (or other seizure-related pre-existing condition); 3 had documented brain lesions potentially causing seizures per se; 1 had febrile seizures, 1 severe hypo-osmolality. In the remaining 5 patients, seizures were considered not explained and, thus, potentially related to BU administration. The incidence of seizures in children receiving BU-containing regimen was very low (1.3%); furthermore, most of them had at least 1—either pre-existing or concurrent—associated risk factor for seizures.
- Published
- 2013
7. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes
- Author
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de Latour, R. Peffault, Peters, C., Gibsons, B., Strahm, B., Lankester, A., de Heredia, C. D., Longoni, D., Fioredda, F., Locatelli, F., Yaniv, I., Wachowiak, J., Donadieu, J., Lawitschka, A., Bierings, M., Wlodarski, M., Corbacioglu, S., Bonanomi, S., Samarasinghe, S., Leblanc, T., Dufour, C., Dalle, J-H, Pediat Working Party PDWP, and European Grp Blood Marrow
- Subjects
Male ,medicine.medical_specialty ,Transplantation Conditioning ,BLOOD ,Adolescent ,SEVERE APLASTIC-ANEMIA ,medicine.medical_treatment ,Hemoglobinuria, Paroxysmal ,DYSKERATOSIS-CONGENITA ,Hematopoietic stem cell transplantation ,ACUTE MYELOID-LEUKEMIA ,Fanconi anemia ,medicine ,Humans ,Progenitor cell ,Intensive care medicine ,Child ,Bone Marrow Diseases ,MYELODYSPLASTIC SYNDROME ,Transplantation ,Shwachman–Diamond syndrome ,EUROPEAN GROUP ,business.industry ,Hematopoietic Stem Cell Transplantation ,Anemia, Aplastic ,Infant ,SEVERE CONGENITAL NEUTROPENIA ,Hematology ,Bone Marrow Failure Disorders ,COLONY-STIMULATING FACTOR ,medicine.disease ,Allografts ,Surgery ,Graft-versus-host disease ,surgical procedures, operative ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Child, Preschool ,HSCT ,FANCONI-ANEMIA ,Female ,SHWACHMAN-DIAMOND-SYNDROME ,Stem cell ,business - Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.
- Published
- 2015
- Full Text
- View/download PDF
8. Molecular Genetic Testing of Fanconi Anemia: Experience of the Italian Research Group on Fanconi Anemia
- Author
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Savoia, A., Criscuolo, M., Bottega, R., Borriello, A., Pillon, M., Longoni, D., Farruggia, P., Misuraca, A., Dufur, C., Savoia, A, Criscuolo, M, Bottega, R, Borriello, Adriana, Pillon, M, Longoni, D, P., Farruggia P, Misuraca, A, C., Dufur, '-', Savoia, Anna, M., Criscuolo, Bottega, Roberta, A., Borriello, M., Pillon, D., Longoni, P., Farruggia, and A., Misuraca
- Subjects
Fanconi anemia Mutations Italian research group Molecular testing Genetic testing - Published
- 2010
9. Mild pre-transplant cardiomyopathy may not impair long-term quality of life after bone marrow transplantation
- Author
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Nicolini, B, Balduzzi, A, Tagliabue, A, Longoni, D, Uderzo, C, Galli, M, Nicolini B, Balduzzi A, Tagliabue A, Longoni D, Uderzo C, Galli MA, Nicolini, B, Balduzzi, A, Tagliabue, A, Longoni, D, Uderzo, C, Galli, M, Nicolini B, Balduzzi A, Tagliabue A, Longoni D, Uderzo C, and Galli MA
- Abstract
An 8-year-old child with acute myeloid leukemia (AML), underwent an allogeneic bone marrow transplant (BMT) from his HLA matched sister in spite of having a mild cardiomyopathy. We followed the patient with periodic electrocardiograms (ECG) and echocardiograms which have not worsened, and the patient's quality of life is not compromised 14 years after BMT.
- Published
- 2000
10. Molecular genetic testing of Fanconi anemia: experience of the Italian Research Group on Fanconi Anemia
- Author
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De Rocco, D., Faleschini, M., Bottega, R., Cappelli, E., Svahn, J., Farruggia, P., Longoni, D., Poggi, V., Pillon, M., Dufour, C., Savoia, A., '-', DE ROCCO, Daniela, Faleschini, Michela, Bottega, Roberta, E., Cappelli, J., Svahn, P., Farruggia, D., Longoni, V., Poggi, M., Pillon, C., Dufour, and Savoia, Anna
- Subjects
Fanconi anemia ,screening ,patients ,mutation ,patient - Published
- 2013
11. Epidemiology of infections in children with acquired aplastic anaemia: a retrospective multicenter study in Italy
- Author
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Quarello, P, Saracco, P, Giacchino, M, Caselli, D, Caviglia, I, Longoni, D, Varotto, S, Rana, I, Amendola, A, Misuraca, A, Licciardello, M, Paolucci, Paolo, Ladogana, S, Rivetti, E, Dufour, C, and Castagnola, E.
- Subjects
Male ,Adolescent ,Incidence ,Anemia, Aplastic ,Bacteremia ,Infections ,Fever of Unknown Origin ,Cohort Studies ,Italy ,Risk Factors ,aplastic anaemia ,infection ,children ,Child, Preschool ,Humans ,Female ,Child ,Retrospective Studies - Abstract
Infection is a significant cause of death in patients with aplastic anaemia (AA). However, few studies have examined the characteristics of infections in patients with AA, especially in children. The aim of this retrospective study was to evaluate the incidence and types of infections in a large cohort of paediatric patients with AA referred to eight AIEOP (Italian Association of Paediatric Oncology and Haematology) centres in Italy. The study included 78 patients, 45 boys and 33 girls, median age 9.29 yrs (1st-3rd quartile 3.59-13.09) diagnosed with AA. During the study period, 111 infectious episodes were observed in 42 (54%) patients. Fifty-one (46%) episodes were fever of unknown origin and 60 (54%) were documented infections (DI). In this group, microbiologically documented infection (MDI) with bacteremia accounted for 23 (38%) episodes, MDI without bacteremia for 7 (12%), clinically documented infection for 25 (42%) and invasive fungal diseases for 5 (8%). The rate (episodes/1000 d at risk) was similar in severe aplastic anemia and very severe aplastic anemia both before and after day 120. During the first 120 d from diagnosis, the cumulative risk of a DI was 21% (95% CI 12-29) with the last episode at day 117, but the 50% of episodes were observed in the first 24 d. After day 120, the cumulative risk of DI was again 21% (95% CI 12-29), with the last episode at day 445 of follow-up, with 50% of episodes observed in the first 120 d of observation (240 d from the diagnosis of AA). We found a statistically significant association between the grade of aplasia at diagnosis and the incidence of IEs (P = 0.0002). No association was found between gender, age at diagnosis, response at day +120 and at day +180, use of G-CSF and occurrence of IEs. The actuarial overall survival at 5 yrs was 90% ± 3.6. The mortality rate attributable to infection complication was 9%. This is a large paediatric cohort study reporting the epidemiology of infectious complications in children with AA and that allow us to compare the epidemiological data in this diseases with that of the most recent studies in neutropenic children with cancer. Our findings confirm that infections represent the main cause of death in patients with AA and they are important for the design of management strategies of febrile neutropenia in these patients.
- Published
- 2012
12. The Italian Registry of paediatric acquired aplastic anaemia: a retrospective survey
- Author
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Saracco, P, Lorenzati, A, Oneto, R, Iori, Ap, Pillon, M, Russo, G, Nardi, G, Martire, B, Cesaro, S, Farruggia, P, Longoni, D, Tucci, F, Ladogana, S, Zecca, M, Misuraca, A, Onofrillo, D, Locasciulli, A, and Dufour, C
- Published
- 2011
13. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes
- Author
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Haematologie, Child Health, Regenerative Medicine and Stem Cells, de Latour, R. Peffault, Peters, C., Gibsons, B., Strahm, B., Lankester, A., de Heredia, C. D., Longoni, D., Fioredda, F., Locatelli, F., Yaniv, I., Wachowiak, J., Donadieu, J., Lawitschka, A., Bierings, M., Wlodarski, M., Corbacioglu, S., Bonanomi, S., Samarasinghe, S., Leblanc, T., Dufour, C., Dalle, J-H, Pediat Working Party PDWP, European Grp Blood Marrow, Haematologie, Child Health, Regenerative Medicine and Stem Cells, de Latour, R. Peffault, Peters, C., Gibsons, B., Strahm, B., Lankester, A., de Heredia, C. D., Longoni, D., Fioredda, F., Locatelli, F., Yaniv, I., Wachowiak, J., Donadieu, J., Lawitschka, A., Bierings, M., Wlodarski, M., Corbacioglu, S., Bonanomi, S., Samarasinghe, S., Leblanc, T., Dufour, C., Dalle, J-H, Pediat Working Party PDWP, and European Grp Blood Marrow
- Published
- 2015
14. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes
- Author
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Peffault De Latour, R., Peters, C., Gibson, B., Strahm, B., Lankester, A., De Heredia, C. D., Longoni, D., Fioredda, F., Locatelli, Franco, Yaniv, I., Wachowiak, J., Donadieu, J., Lawitschka, A., Bierings, M., Wlodarski, M., Corbacioglu, S., Bonanomi, S., Samarasinghe, S., Leblanc, T., Dufour, C., Dalle, J. -H., Locatelli F. (ORCID:0000-0002-7976-3654), Peffault De Latour, R., Peters, C., Gibson, B., Strahm, B., Lankester, A., De Heredia, C. D., Longoni, D., Fioredda, F., Locatelli, Franco, Yaniv, I., Wachowiak, J., Donadieu, J., Lawitschka, A., Bierings, M., Wlodarski, M., Corbacioglu, S., Bonanomi, S., Samarasinghe, S., Leblanc, T., Dufour, C., Dalle, J. -H., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.
- Published
- 2015
15. Changes in cytokine profile pre- and post-immunosuppression in acquired aplastic anemia
- Author
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Dufour, C, Ferretti, E, Bagnasco, F, Burlando, O, Lanciotti, M, Ramenghi, Ugo, Saracco, P, Van Lint MT, Longoni, D, Torelli, Gf, Pillon, M, Locasciulli, A, Misuraca, A, La Spina, M, Bacigalupo, A, Pistoia, V, Corcione, A, Svahn, J, and Marrow Failure Study Group of the AIEOP
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,CD3 Complex ,aplastic anemia ,medicine.medical_treatment ,TNF-a ,Bone Marrow Cells ,Interferon-gamma ,Young Adult ,IFN-g ,Internal medicine ,medicine ,Humans ,Interferon gamma ,Aplastic anemia ,Child ,Cells, Cultured ,Interleukin 4 ,Cell Proliferation ,Immunosuppression Therapy ,Hematology ,immunosuppression ,Tumor Necrosis Factor-alpha ,business.industry ,Bone marrow failure ,Anemia, Aplastic ,Immunosuppression ,Middle Aged ,IL4 ,Flow Cytometry ,medicine.disease ,Cytokine ,Child, Preschool ,Immunology ,Brief Reports ,Female ,Tumor necrosis factor alpha ,Interleukin-4 ,business ,medicine.drug - Abstract
Cytokine expression assessed by flow cytometry in 53 acquired aplastic anemia patients before and after combined immunosuppression (EBMT WPSAA protocols) showed that CD3(+) marrow cells containing TNF-alpha, IFN-gamma and IL4 were similar in subjects with disease at onset (DO) and responsive to treatment who had more CD3(+)/TNF-alpha(+) and CD 3(+)/IFN-gamma(+) cells than normal controls. In vitro block of TNF-alpha and/or IFN-gamma significantly increased BFU-e over baseline in 28 patients. In responsive to treatment patients only TNF-alpha block significantly incremented colonies over normal controls. Absolute marrow CD3(+)/TNF-alpha(+) and CD3(+)/IFN-gamma(+) cells prospectively tested in a group of 21 subjects declined significantly more in Responders than in Non Responders to immunosuppression at Response Evaluation Time respect to Diagnosis. Both in Responders and in Non Responders these cells remained higher than in normal controls. This study suggests that immunosuppression does not fully clear excess TNF-alpha and IFN-gamma from marrow of patients with good outcome and raises the hypothesis that additional cytokine blockade might be useful in immunosuppression for acquired aplastic anemia.
- Published
- 2009
16. IL-10 prevents the generation of dendritic cells from CD14+ blood monocytes, promotes the differentiation to mature macrophages and stimulates endocytosis of FITC-dextran
- Author
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Allavena P, Longoni D, Bernasconi S, Stoppacciaro A, Ruco L, Mantovani A., PIEMONTI , LORENZO, Allavena, P, Piemonti, L, Longoni, D, Bernasconi, S, Stoppacciaro, A, Ruco, L, Mantovani, A, RicciardiCastagnoli, P, Piemonti, Lorenzo, and Mantovani, A.
- Published
- 1997
17. Studio prospettico di una popolazione italiana con sindrome di Shwachman-Diamond: sorveglianza ematologica e genetica
- Author
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Sainati, L, Longoni, D, Basso, G, Biondi, A, Fenu, S, Locatelli, F, Spinelli, M, Testi, Anna Maria, Zecca, M, Bugarin, C, Cipolli, M, Minelli, A, Di Meglio AM, Tridello, G, Leszl, A, Mastella, G, Pasquali, F, Petaros, P, Poli, F, and Varotto, S.
- Published
- 2005
18. Treatment of Graft versus Host Disease with Mesenchymal Stromal Cells: A Phase I Study on 40 Adult and Pediatric Patients
- Author
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Introna, M, Lucchini, G, Dander, E, Galimberti, S, Rovelli, A, Balduzzi, A, Longoni, D, Pavan, F, Masciocchi, F, Algarotti, A, Micò, C, Grassi, A, Deola, S, Cavattoni, I, Gaipa, G, Belotti, D, Perseghin, P, Parma, M, Pogliani, E, Golay, J, Pedrini, O, Capelli, C, Cortelazzo, S, D'Amico, G, Biondi, A, Rambaldi, A, Biagi, E, DANDER, ERICA, GALIMBERTI, STEFANIA, PAVAN, FABIO, MASCIOCCHI, FRANCESCA, GRASSI, ALICE, DEOLA, SARA, GAIPA, GIUSEPPE, BELOTTI, DANIELA, POGLIANI, ENRICO MARIA, BIONDI, ANDREA, BIAGI, ETTORE, Introna, M, Lucchini, G, Dander, E, Galimberti, S, Rovelli, A, Balduzzi, A, Longoni, D, Pavan, F, Masciocchi, F, Algarotti, A, Micò, C, Grassi, A, Deola, S, Cavattoni, I, Gaipa, G, Belotti, D, Perseghin, P, Parma, M, Pogliani, E, Golay, J, Pedrini, O, Capelli, C, Cortelazzo, S, D'Amico, G, Biondi, A, Rambaldi, A, Biagi, E, DANDER, ERICA, GALIMBERTI, STEFANIA, PAVAN, FABIO, MASCIOCCHI, FRANCESCA, GRASSI, ALICE, DEOLA, SARA, GAIPA, GIUSEPPE, BELOTTI, DANIELA, POGLIANI, ENRICO MARIA, BIONDI, ANDREA, and BIAGI, ETTORE
- Abstract
This phase I multicenter study was aimed at assessing the feasibility and safety of intravenous administration of third party bone marrow-derived mesenchymal stromal cells (MSC) expanded in platelet lysate in 40 patients (15 children and 25 adults), experiencing steroid-resistant grade II to IV graft-versus-host disease (GVHD). Patients received a median of 3 MSC infusions after having failed conventional immunosuppressive therapy. A median cell dose of 1.5 × 10(6)/kg per infusion was administered. No acute toxicity was reported. Overall, 86 adverse events and serious adverse events were reported in the study, most of which (72.1%) were of infectious nature. Overall response rate, measured at 28 days after the last MSC injection, was 67.5%, with 27.5% complete response. The latter was significantly more frequent in patients exhibiting grade II GVHD as compared with higher grades (61.5% versus 11.1%, P = .002) and was borderline significant in children as compared with adults (46.7 versus 16.0%, P = .065). Overall survival at 1 and 2 years from the first MSC administration was 50.0% and 38.6%, with a median survival time of 1.1 years. In conclusion, MSC can be safely administered on top of conventional immunosuppression for steroid resistant GVHD treatment. Eudract Number 2008-007869-23, NCT01764100
- Published
- 2014
19. Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia
- Author
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Hasegawa, D, Bugarin, C, Giordan, M, Bresolin, S, Longoni, D, Micalizzi, C, Ramenghi, U, Bertaina, A, Basso, G, Locatelli, Franco, Biondi, Alberto, Te Kronnie, G, Gaipa, G, Locatelli, F (ORCID:0000-0002-7976-3654), Biondi, A (ORCID:0000-0002-2470-7858), Hasegawa, D, Bugarin, C, Giordan, M, Bresolin, S, Longoni, D, Micalizzi, C, Ramenghi, U, Bertaina, A, Basso, G, Locatelli, Franco, Biondi, Alberto, Te Kronnie, G, Gaipa, G, Locatelli, F (ORCID:0000-0002-7976-3654), and Biondi, A (ORCID:0000-0002-2470-7858)
- Abstract
To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59-100%) and a specificity of 87% (CI 70-96%). Positive and negative predictive values were 71% (CI 42-92%) and 96% (CI 82-100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.
- Published
- 2013
20. Safe and Effective Treatment of Graft Versus Host Disease with Platelet Lysate-Expanded Human Mesenchymal Stromal Cells: A Phase 1 Study On 47 Adult and Pediatric Patients
- Author
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Introna, M, Lucchini, G, Dander, E, Rovelli, A, Balduzzi, A, Longoni, D, Pavan, F, Masciochi, F, Algarotti, A, Micò, C, Grassi, A, Cavattoni, I, Deola, S, Gaipa, G, Belotti, D, Perseghin, P, Parma, M, Pogliani, E, Golay, J, Gotti, E, Capelli, C, Cortelazzo, S, D'Amico, G, Biondi, A, Rambaldi, A, Biagi, E, DANDER, ERICA, PAVAN, FABIO, DEOLA, SARA, GAIPA, GIUSEPPE, BELOTTI, DANIELA, POGLIANI, ENRICO MARIA, BIONDI, ANDREA, BIAGI, ETTORE, Introna, M, Lucchini, G, Dander, E, Rovelli, A, Balduzzi, A, Longoni, D, Pavan, F, Masciochi, F, Algarotti, A, Micò, C, Grassi, A, Cavattoni, I, Deola, S, Gaipa, G, Belotti, D, Perseghin, P, Parma, M, Pogliani, E, Golay, J, Gotti, E, Capelli, C, Cortelazzo, S, D'Amico, G, Biondi, A, Rambaldi, A, Biagi, E, DANDER, ERICA, PAVAN, FABIO, DEOLA, SARA, GAIPA, GIUSEPPE, BELOTTI, DANIELA, POGLIANI, ENRICO MARIA, BIONDI, ANDREA, and BIAGI, ETTORE
- Published
- 2012
21. Mesenchymal stem cells from Shwachman-Diamond syndrome patients display normal functions and do not contribute to hematological defects
- Author
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André, V, Longoni, D, Bresolin, S, Cappuzzello, C, Dander, E, Galbiati, M, Bugarin, C, Di Meglio, A, Nicolis, E, Maserati, E, Serafini, M, Warren, A, Te Kronnie, G, Cazzaniga, G, Sainati, L, Cipolli, M, Biondi, A, D'Amico, G, CAPPUZZELLO, CLAUDIA, DANDER, ERICA, Warren, AJ, BIONDI, ANDREA, D'Amico, G., André, V, Longoni, D, Bresolin, S, Cappuzzello, C, Dander, E, Galbiati, M, Bugarin, C, Di Meglio, A, Nicolis, E, Maserati, E, Serafini, M, Warren, A, Te Kronnie, G, Cazzaniga, G, Sainati, L, Cipolli, M, Biondi, A, D'Amico, G, CAPPUZZELLO, CLAUDIA, DANDER, ERICA, Warren, AJ, BIONDI, ANDREA, and D'Amico, G.
- Abstract
Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by bone marrow (BM) dysfunction and exocrine pancreatic insufficiency. SDS patients have an increased risk for myelodisplastic syndrome and acute myeloid leukemia. Mesenchymal stem cells (MSCs) are the key component of the hematopoietic microenvironment and are relevant in inducing genetic mutations leading to leukemia. However, their role in SDS is still unexplored. We demonstrated that morphology, growth kinetics and expression of surface markers of MSCs from SDS patients (SDS-MSCs) were similar to normal MSCs. Moreover, SDS-MSCs were able to differentiate into mesengenic lineages and to inhibit the proliferation of mitogen-activated lymphocytes. We demonstrated in an in vitro coculture system that SDS-MSCs, significantly inhibited neutrophil apoptosis probably through interleukin-6 production. In a long-term coculture with CD34+-sorted cells, SDS-MSCs were able to sustain CD34+ cells survival and to preserve their stemness. Finally, SDS-MSCs had normal karyotype and did not show any chromosomal abnormality observed in the hematological components of the BM of SDS patients. Despite their pivotal role in the hematopoietic stem cell niche, our data suggest that MSC themselves do not seem to be responsible for the hematological defects typical of SDS patients. © 2012 Macmillan Publishers Limited All rights reserved.
- Published
- 2012
22. Phenotypical And Functional Characterization Of Mesenchymal Stem Cells Derived From Patients Affected By Schwachman-Diamond Syndrome
- Author
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André, V, Longoni, D, Cipolli, M, Biondi, A, D'Amico, G, ANDRÉ, VALENTINA ISABELLA, BIONDI, ANDREA, D'Amico, G., André, V, Longoni, D, Cipolli, M, Biondi, A, D'Amico, G, ANDRÉ, VALENTINA ISABELLA, BIONDI, ANDREA, and D'Amico, G.
- Published
- 2011
23. Agranulocytosis due to deferiprone: a case report with cytomorphological and functional bone marrow examination.
- Author
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Masera, N, Tavecchia, L, Longoni, D, Maglia, O, Biondi, A, Masera, G, Longoni, DV, BIONDI, ANDREA, Masera, G., Masera, N, Tavecchia, L, Longoni, D, Maglia, O, Biondi, A, Masera, G, Longoni, DV, BIONDI, ANDREA, and Masera, G.
- Published
- 2011
24. Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation
- Author
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Dander, E, Balduzzi, A, Zappa, G, Lucchini, G, Perseghin, P, André, V, Todisco, E, Rahal, D, Migliavacca, M, Longoni, D, Solinas, G, Villa, A, Berti, E, Mina, P, Parma, M, Allavena, P, Biagi, E, Rovelli, A, Biondi, A, D'Amico, G, DANDER, ERICA, LUCCHINI, GIOVANNA, ANDRÉ, VALENTINA ISABELLA, MIGLIAVACCA, MADDALENA, VILLA, ANTONELLO, BERTI, EMILIO, Mina, PD, BIAGI, ETTORE, BIONDI, ANDREA, D'Amico, G., Dander, E, Balduzzi, A, Zappa, G, Lucchini, G, Perseghin, P, André, V, Todisco, E, Rahal, D, Migliavacca, M, Longoni, D, Solinas, G, Villa, A, Berti, E, Mina, P, Parma, M, Allavena, P, Biagi, E, Rovelli, A, Biondi, A, D'Amico, G, DANDER, ERICA, LUCCHINI, GIOVANNA, ANDRÉ, VALENTINA ISABELLA, MIGLIAVACCA, MADDALENA, VILLA, ANTONELLO, BERTI, EMILIO, Mina, PD, BIAGI, ETTORE, BIONDI, ANDREA, and D'Amico, G.
- Abstract
Objectives. Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients. Methods. Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA. Results. An increased TH-17 population (up to 4.8% of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4%) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17(+)/interferon (IFN)-gamma(-) and IL-17(+)/IFN-gamma(+) subsets and expressed IL-23 receptor. Interestingly, IFN-gamma(+)TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD. Conclusions. These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.
- Published
- 2009
25. Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia
- Author
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Hasegawa, D, primary, Bugarin, C, additional, Giordan, M, additional, Bresolin, S, additional, Longoni, D, additional, Micalizzi, C, additional, Ramenghi, U, additional, Bertaina, A, additional, Basso, G, additional, Locatelli, F, additional, Biondi, A, additional, te Kronnie, G, additional, and Gaipa, G, additional
- Published
- 2013
- Full Text
- View/download PDF
26. Reconstitution of lymphocyte subpopulations in children with inherited metabolic storage diseases after haematopoietic cell transplantation
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Corti, P, Peters, C, Balduzzi, A, Bertagnolio, B, Biondi, A, Bugarin, C, Dassi, M, Furlan, F, Gaipa, G, Longoni, D, Maglia, O, Parini, R, Perseghin, P, Uderzo, C, Uziel, G, Masera, G, Rovelli, A, BIONDI, ANDREA, MASERA, GIUSEPPE, Rovelli, A., Corti, P, Peters, C, Balduzzi, A, Bertagnolio, B, Biondi, A, Bugarin, C, Dassi, M, Furlan, F, Gaipa, G, Longoni, D, Maglia, O, Parini, R, Perseghin, P, Uderzo, C, Uziel, G, Masera, G, Rovelli, A, BIONDI, ANDREA, MASERA, GIUSEPPE, and Rovelli, A.
- Abstract
We prospectively evaluated the reconstitution of lymphocyte subpopulations in nine children with lysosomal diseases who underwent 11 allogeneic haematopoietic cell transplants (HCTs) following CD34(+) immunomagnetic enrichment, limited T-cell addback and in vivo B-cell depletion. Absolute lymphocyte count recovery was slow to cross the 5th percentile, occurring at a median of 10 months after HCT in patients with full chimaerism. Natural killer cells represented up to 90% of the total lymphoid population during the first 3 months. CD4(+) lymphocyte recovery occurred 9-18 months after HCT. In most patients, CD8(+) lymphocyte recovery was slow and comparable with that of CD4(+) lymphocytes. The CD4(+)/CD8(+) ratio normalised by 3-7 months after HCT in 50% of the patients. CD8(+) lymphocyte recovery was enhanced in patients with viral reactivation. Reconstitution of B-lymphocytes was particularly delayed in patients treated with rituximab. Declining chimaerism, rejection and viral reactivation were the most common problems in our series. Because of the unique graft manipulation, the pace of lymphocyte reconstitution was particularly slow, suggesting that these patients are at a significantly increased risk of infections for up to 2 years after HCT.
- Published
- 2005
27. Mesenchymal stem cells from Shwachman–Diamond syndrome patients display normal functions and do not contribute to hematological defects
- Author
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André, V, primary, Longoni, D, additional, Bresolin, S, additional, Cappuzzello, C, additional, Dander, E, additional, Galbiati, M, additional, Bugarin, C, additional, Di Meglio, A, additional, Nicolis, E, additional, Maserati, E, additional, Serafini, M, additional, Warren, A J, additional, te Kronnie, G, additional, Cazzaniga, G, additional, Sainati, L, additional, Cipolli, M, additional, Biondi, A, additional, and D'Amico, G, additional
- Published
- 2012
- Full Text
- View/download PDF
28. Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome
- Author
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Necchi, V., primary, Minelli, A., additional, Sommi, P., additional, Vitali, A., additional, Caruso, R., additional, Longoni, D., additional, Frau, M. R., additional, Nasi, C., additional, De Gregorio, F., additional, Zecca, M., additional, Ricci, V., additional, Danesino, C., additional, and Solcia, E., additional
- Published
- 2012
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29. Phenotypical and Functional Characterization of Mesenchymal Stem Cells Derived From Patients Affected by Schwachman-Diamond Syndrome
- Author
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André, V., primary, Longoni, D., additional, Cipolli, M., additional, Biondi, A., additional, and D'Amico, G., additional
- Published
- 2011
- Full Text
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30. Diamond-Blackfan anemia: genotype-phenotype correlations in Italian patients with RPL5 and RPL11 mutations
- Author
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Quarello, P., primary, Garelli, E., additional, Carando, A., additional, Brusco, A., additional, Calabrese, R., additional, Dufour, C., additional, Longoni, D., additional, Misuraca, A., additional, Vinti, L., additional, Aspesi, A., additional, Biondini, L., additional, Loreni, F., additional, Dianzani, I., additional, and Ramenghi, U., additional
- Published
- 2009
- Full Text
- View/download PDF
31. Aberrant GM-CSF signal transduction pathway in juvenile myelomonocytic leukemia assayed by flow cytometric intracellular STAT5 phosphorylation measurement
- Author
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Gaipa, G, primary, Bugarin, C, additional, Longoni, D, additional, Cesana, S, additional, Molteni, C, additional, Faini, A, additional, Timeus, F, additional, Zecca, M, additional, and Biondi, A, additional
- Published
- 2008
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32. Severe disseminated toxoplasmosis after unrelated bone marrow transplantation: a case report
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Longoni, D, Fumagalli, R, Fumagalli, M, Cappellini, A, Uderzo, C, Longoni, D, Fumagalli, R, Fumagalli, M, Cappellini, A, and Uderzo, C
- Abstract
We report on a case of disseminated toxoplasmosis that occurred 39 days after unrelated bone marrow transplantation in a patient in good clinical and hematologic condition. The clinical course was characterized by presentation of septic shock and the evolution of sudden and rapidly overwhelming respiratory failure which was unresponsive to emergency and anti-shock therapy. Disseminated toxoplasmosis was diagnosed at autopsy
- Published
- 2000
33. Bone marrow transplantation for childhood hematological disorders: a global pediatric approach in a twelve year single center experience
- Author
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Uderzo, C, Biagi, E, Rovelli, A, Balduzzi, A, Schirò, R, Longoni, D, Arrigo, C, Nicolini, B, Placa, L, Da Prada, A, Mascaretti, L, Giltri, G, Galimberti, S, Valsecchi, M, Locasciulli, A, Masera, G, GALIMBERTI, STEFANIA, VALSECCHI, MARIA GRAZIA, Masera, G., Uderzo, C, Biagi, E, Rovelli, A, Balduzzi, A, Schirò, R, Longoni, D, Arrigo, C, Nicolini, B, Placa, L, Da Prada, A, Mascaretti, L, Giltri, G, Galimberti, S, Valsecchi, M, Locasciulli, A, Masera, G, GALIMBERTI, STEFANIA, VALSECCHI, MARIA GRAZIA, and Masera, G.
- Abstract
One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out., One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out.
- Published
- 2000
34. The outcome of children with Fanconi anemia given hematopoietic stem cell transplantation and the influence of fludarabine in the conditioning regimen: a report from the Italian pediatric group
- Author
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Locatelli, F., primary, Zecca, M., additional, Pession, A., additional, Morreale, G., additional, Longoni, D., additional, Di Bartolomeo, P., additional, Porta, F., additional, Fagioli, F., additional, Nobili, B., additional, Bernardo, M. E., additional, and Messina, C., additional
- Published
- 2007
- Full Text
- View/download PDF
35. Morbidity and mortality due to liver disease in children undergoing allogeneic bone marrow transplantation: a 10-year prospective study
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Locasciulli, A, Testa, M, Valsecchi, M, Vecchi, L, Longoni, D, Sparano, P, Rovelli, A, Uderzo, C, Masera, G, Alberti, A, Valsecchi, MG, Locasciulli, A, Testa, M, Valsecchi, M, Vecchi, L, Longoni, D, Sparano, P, Rovelli, A, Uderzo, C, Masera, G, Alberti, A, and Valsecchi, MG
- Abstract
We have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3. 6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.
- Published
- 1997
36. Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia
- Author
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Privitera, E, primary, Schiro, R, additional, Longoni, D, additional, Ronchi, A, additional, Rambaldi, A, additional, Bernasconi, S, additional, Ottolenghi, S, additional, Masera, G, additional, and Biondi, A, additional
- Published
- 1995
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- View/download PDF
37. Suppression of juvenile chronic myelogenous leukemia colony growth by interleukin-1 receptor antagonist [see comments]
- Author
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Schiro, R, primary, Longoni, D, additional, Rossi, V, additional, Maglia, O, additional, Doni, A, additional, Arsura, M, additional, Carrara, G, additional, Masera, G, additional, Vannier, E, additional, and Dinarello, CA, additional
- Published
- 1994
- Full Text
- View/download PDF
38. Constitutive Expression of GATA-1, EPOR, α-Globin, and γ-Globin Genes in Myeloid Clonogenic Cells From Juvenile Chronic Myelocytic Leukemia
- Author
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Privitera, E., Schiro, R., Longoni, D., Ronchi, A., Rambaldi, A., Bernasconi, S., Ottolenghi, S., Masera, G., and Biondi, A.
- Abstract
Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously in the absence of growth factors. To better understand the relationship between the erythroid abnormalities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation—GATA-1, EPOR, α-globin, β-globin, and γ-glo-bin genes—in JCML peripheral blood (PB) cells and in vitro-derived colonies. Northern blot analysis of PB cells from five JCML patients indicated levels of GATA-1 transcripts much higher than those usually found in other types of leukemic cells, and S1 nuclease protection assay detected significantly increased expression of γ-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-forming unit (CFU-GM) colonies, obtained in vitro in the absence of added growth factors from four JCML patients, detected GATA-1, EPOR, and globin (α and γ) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were positive only for GATA-1. Single JCML colonies were tested for the presence of two different transcripts; whereas α- and γ-globin genes appeared mostly coexpressed, β-globin mRNA was detected only in a minority of the γ-globin-positive colonies, indicating that the leukemic pattern of hemoglobin synthesis is mainly fetal. In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identified in bone marrow cells at diagnosis and an expression pattern superimposable to that of the JCML colonies, consistently displaying a high γ-globin:β-globin mRNA ratio. The expression of erythroid markers within populations of leukemic cells, both in vivo and in vitro, supports the hypothesis that abnormal JCML erythroid cells may originate from the same mutated progenitor that sustains the growth of the leukemic cells.
- Published
- 1995
- Full Text
- View/download PDF
39. Molecular basis of Diamond-Blackfan anemia: New findings from the Italian registry and a review of the literature
- Author
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Campagnoli, M. F., Garelli, E., Quarello, P., Carando, A., Varotto, S., Nobili, B., Longoni, D., Vanna Pecile, Zecca, M., Dufour, C., Ramenghi, U., Dianzani, I., Campagnoli, Mf, Garelli, E, Quarello, P, Carando, A, Varotto, S, Nobili, Bruno, Longoni, D, Pecile, V, Zecca, M, Dufour, C, Ramenghi, U, and Dianzan, I.
- Subjects
Molecular Epidemiology ,Diamond-Blackfan anemia ,erythropoiesis ,RPS19 ,mutation ,Phenotype ,Italy ,Codon, Initiator ,Humans ,Translocation, Genetic ,Anemia, Diamond-Blackfan - Abstract
Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress.We present clinical and molecular data from 97 Italian DBA patients and a review of the literature.We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases.Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.
40. Bone marrow transplantation for childhood hematological disorders: a global pediatric approach in a twelve year single center experience
- Author
-
Uderzo, C., Biagi, E., Rovelli, A., Adriana Cristina Balduzzi, Schirò, R., Longoni, D., Arrigo, C., Nicolini, B., Placa, L., Da Prada, A., Mascaretti, L., Giltri, G., Galimberti, S., Valsecchi, M. G., Locasciulli, A., Masera, G., Uderzo, C, Biagi, E, Rovelli, A, Balduzzi, A, Schirò, R, Longoni, D, Arrigo, C, Nicolini, B, Placa, L, Da Prada, A, Mascaretti, L, Giltri, G, Galimberti, S, Valsecchi, M, Locasciulli, A, and Masera, G
- Subjects
Adult ,Male ,Time Factors ,Time Factor ,Adolescent ,Graft vs Host Disease ,Infant ,Hematologic Diseases ,Follow-Up Studie ,Child, Preschool ,Humans ,Female ,Child ,Human ,Bone Marrow Transplantation ,Follow-Up Studies - Abstract
One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out. One hundred and 43 consecutive pediatric patients (June 1985-December 1996) with at least 18 months of follow-up, were considered: most of the patients (111/143, 77.6%) underwent allogeneic BMT. The median follow-up was 5.7 years. Overall survival and 5 years EFS were 48.6% and 46.9%, respectively. For patients who underwent allogeneic BMT from HLA-identical siblings, the 5 years EFS for ALL was 75% in 1st CR, 60.4% in 2nd CR, 22.3% in > 2nd CR and 86.7% for AML in 1st CR. The EFS for Allo-BMT in "good" and "poor" prognosis patients was 68.6% and 21.8%, respectively (p value = 0.001). Early mortality in Allo-BMT patients was 17.7% between 1985-1990 and 10.3% between 1991-1996. Early treatment-related organ complications occurred mostly in patients who underwent BMT from an unrelated or a mismatched family donor. Late toxicity was evaluated in 57 patients (median follow-up of 82 months): none of the patients complained of significant late cardiac or respiratory dysfunction. With regards to growth, 18/57 patients (31.6%) lost more than two height centile channels. Three cases of thyroid neoplasms were observed. Evaluation of psychosocial functioning, studied in 39 patients who had at least 2 years of follow-up in CR, did not reveal any evident quality of life impairment. The possibility of curing childhood hematological malignancies is based on a global pediatric and multidisciplinary approach. A continuous need to improve results in terms of EFS and quality of life suggests that further multicenter prospective studies should be carried out.
41. IL-10 prevents the generation of dendritic cells from CD14+ blood monocytes, promotes the differentiation to mature macrophages and stimulates endocytosis of FITC-dextran
- Author
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Allavena, P., Lorenzo Piemonti, Longoni, D., Bernasconi, S., Stoppacciaro, A., Ruco, L., and Mantovani, A.
- Subjects
Tumor Necrosis Factor-alpha ,Macrophages ,Infant, Newborn ,Lipopolysaccharide Receptors ,Cell Differentiation ,Dextrans ,Dendritic Cells ,In Vitro Techniques ,Fetal Blood ,Endocytosis ,Monocytes ,Interleukin-10 ,Humans ,Fluorescein-5-isothiocyanate
42. The outcome of children with Fanconi anemia given hematopoietic stem cell transplantation and the influence of fludarabine in the conditioning regimen: a report from the Italian Pediatric Group
- Author
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Daniela Longoni, Giuseppe Morreale, Maria Ester Bernardo, Franca Fagioli, Paolo Bartolomeo, Fulvio Porta, Andrea Pession, Chiara Messina, Franco Locatelli, Bruno Nobili, Marco Zecca, Locatelli F, Zecca M, Pession A, Morreale G, Longoni D, Di Bartolomeo P, Porta F, Fagioli F, Nobili B, Bernardo ME, Messina C., Franco, Locatelli, Marco, Zecca, Andrea, Pession, Giuseppe, Morreale, Daniela, Longoni, PAOLO DI, Bartolomeo, Fulvio, Porta, Franca, Fagioli, Nobili, Bruno, MARIA ESTER, Bernardo, Chiara, Messina, Locatelli, F., Zecca, M., Pession, A., Morreale, G., Longoni, D., Di Bartolomeo, P., Porta, F., Fagioli, F., Nobili, B., Bernardo, M. E., and Messina, C.
- Subjects
Adult ,Male ,medicine.medical_specialty ,Unrelated donor ,Myeloid ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Fanconi anemia ,Fludarabine ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Sibling ,Child ,Preschool ,Survival rate ,Probability ,Hematology ,business.industry ,Hematopoietic Stem Cell Transplantation ,medicine.disease ,Surgery ,Survival Rate ,surgical procedures, operative ,medicine.anatomical_structure ,Fanconi Anemia ,Treatment Outcome ,Italy ,Child, Preschool ,Female ,Vidarabine ,business ,medicine.drug - Abstract
Background and Objectives: Hematopoietic stem cell transplantation (HSCT) still represents the only treatment potentially able to prevent/rescue the development of marrow failure and myeloid malignancies in patients with Fanconi anemia (FA). While in the past HSCT from an HLA-identical sibling was proven to cure many patients, a higher incidence of treatment failure has been reported in recipients of an unrelated donor (UD) or HLA-partially matched related allograft. Design and Methods: We analyzed the outcome of 64 FA patients (age range, 2-20 years) who underwent HSCT between January 1989 and December 2005. Patients were transplanted from either an HLA-identical sibling (n=31), an UD (n=26), or an HLA-partially matched relative (n=7). T-cell depletion of the graft was performed in patients transplanted from an HLA-disparate relative. Results: The 8-year estimate of overall survival (OS) for the whole cohort was 67%; it was 87%, 40% and 69% when the donor was an HLA-identical sibling, an UD and a mismatched relative, respectively (p
- Published
- 2007
43. The polymorphisms -318C>T in the promoter and 49A>G in exon 1 of CTLA4 and the risk of aplastic anemia in a Caucasian population
- Author
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Marta Pillon, Almalina Bacigalupo, A. P. Iori, C. Pongiglione, Michaela Calvillo, R. Riccardi, Johanna Svahn, Agnese Marrone, Marina Lanciotti, Riccardo Haupt, L. Boschetto, Ugo Ramenghi, Anna Locasciulli, Mario Capasso, Carlo Dufour, Angela Pistorio, Giuseppe Menna, Daniela Longoni, Achille Iolascon, P. Di Michele, Svahn, J., Capasso, Mario, Lanciotti, M., Marrone, A., Haupt, R., Bacigalupo, A., Pongiglione, C., Boschetto, L., Longoni, D., Pillon, M., Pistorio, A., Michele, P. D., Iori, A. P., Calvillo, M., Locasciulli, A., Menna, G., Riccardi, R., Ramenghi, U., Dufour, C., Iolascon, Achille, Svahn, J, Lanciotti, M, Marrone, A, Haupt, R, Bacigalupo, A, Pongiglione, C, Boschetto, L, Longoni, D, Pillon, M, Pistorio, A, Di Michele, P, Iori, Ap, Calvillo, M, Locasciulli, A, Menna, G, Riccardi, R, Ramenghi, U, and Dufour, C
- Subjects
Male ,medicine.medical_treatment ,SUSCEPTIBILITY ,medicine.disease_cause ,THERAPY ,DISEASE ,Autoimmunity ,Immune tolerance ,Exon ,Risk Factors ,CTLA-4 Antigen ,SYSTEMIC-LUPUS-ERYTHEMATOSUS ,Child ,Promoter Regions, Genetic ,GENE-EXPRESSION ,education.field_of_study ,Anemia, Aplastic ,CTLA4 polymorphisms ,Immunosuppression ,MULTIPLE-SCLEROSIS ,ASSOCIATION ,Exons ,Hematology ,Middle Aged ,Child, Preschool ,Female ,Adult ,Adolescent ,aplastic anemia ,BONE-MARROW ,Population ,immunosuppressive therapy ,chemical and pharmacologic phenomena ,Polymorphism, Single Nucleotide ,White People ,Antigens, CD ,medicine ,Humans ,Genetic Predisposition to Disease ,Aplastic anemia ,education ,Transplantation ,INTERFERON-GAMMA ,business.industry ,Case-control study ,Infant ,medicine.disease ,Antigens, Differentiation ,Gene Expression Regulation ,Case-Control Studies ,Immunology ,business ,Rare disease - Abstract
Aplastic anemia (AA) is a rare disease with a major autoimmune pathogenetic component. CTLA4 is a T-lymphocyte surface molecule involved in the maintenance of immune tolerance. Some polymorphisms associated with a reduced expression of CTLA4, and thus presumably with increased tendency to autoimmunity, have been associated with various autoimmune diseases. In this study, we evaluated the distribution of the low expression polymorphisms -318C > T and 49A > G of CTLA4 in a population of 67 patients with acquired AA and in 100 normal controls. There was no difference in the distribution of the tested polymorphism between patients and controls and, within the patient group, between those who responded to immunosuppression vs those who did not respond. This study indicates that the polymorphisms -318C > T and 49A > G of CTLA4 do not affect the risk of developing AA and do not influence the response to immunosuppression.
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- 2005
44. Treatment of Graft versus Host Disease with Mesenchymal Stromal Cells: A Phase I Study on 40 Adult and Pediatric Patients
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Francesca Masciocchi, Attilio Rovelli, Giovanna D'Amico, Sergio Cortelazzo, Adriana Balduzzi, Anna Grassi, Ettore Biagi, Martino Introna, Olga Pedrini, Giovanna Lucchini, Paolo Perseghin, Andrea Biondi, Giuseppe Gaipa, Daniela Longoni, Chiara Capelli, Stefania Galimberti, Erica Dander, Enrico Maria Pogliani, Fabio Pavan, Irene Cavattoni, Matteo Parma, Sara Deola, Josée Golay, Alessandra Algarotti, Daniela Belotti, Caterina Micò, Alessandro Rambaldi, Introna, M, Lucchini, G, Dander, E, Galimberti, S, Rovelli, A, Balduzzi, A, Longoni, D, Pavan, F, Masciocchi, F, Algarotti, A, Micò, C, Grassi, A, Deola, S, Cavattoni, I, Gaipa, G, Belotti, D, Perseghin, P, Parma, M, Pogliani, E, Golay, J, Pedrini, O, Capelli, C, Cortelazzo, S, D'Amico, G, Biondi, A, Rambaldi, A, and Biagi, E
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Mesenchymal stromal cells ,Graft vs Host Disease ,Antineoplastic Agents ,Disease ,Mesenchymal Stem Cell Transplantation ,Severity of Illness Index ,Gastroenterology ,Steroid refractory graft-versus-host disease (GVHD) ,Cell therapy ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Child ,Adverse effect ,Aged ,Transplantation ,Mesenchymal stromal cell ,business.industry ,Remission Induction ,Mesenchymal stem cell ,Infant ,Immunosuppression ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Acute toxicity ,Immunosuppressive treatment ,Surgery ,Graft-versus-host disease ,Drug Resistance, Neoplasm ,Child, Preschool ,Hematologic Neoplasms ,Hematopoietic stem cell transplantation (HSCT) ,Female ,Steroids ,Platelet lysate ,business ,Immunosuppressive Agents - Abstract
This phase I multicenter study was aimed at assessing the feasibility and safety of intravenous administration of third party bone marrow–derived mesenchymal stromal cells (MSC) expanded in platelet lysate in 40 patients (15 children and 25 adults), experiencing steroid-resistant grade II to IV graft-versus-host disease (GVHD). Patients received a median of 3 MSC infusions after having failed conventional immunosuppressive therapy. A median cell dose of 1.5 × 106/kg per infusion was administered. No acute toxicity was reported. Overall, 86 adverse events and serious adverse events were reported in the study, most of which (72.1%) were of infectious nature. Overall response rate, measured at 28 days after the last MSC injection, was 67.5%, with 27.5% complete response. The latter was significantly more frequent in patients exhibiting grade II GVHD as compared with higher grades (61.5% versus 11.1%, P = .002) and was borderline significant in children as compared with adults (46.7 versus 16.0%, P = .065). Overall survival at 1 and 2 years from the first MSC administration was 50.0% and 38.6%, with a median survival time of 1.1 years. In conclusion, MSC can be safely administered on top of conventional immunosuppression for steroid resistant GVHD treatment. Eudract Number 2008-007869-23, NCT01764100.
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- 2014
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45. Homozygosis for (12) CA repeats in the first intron of the human IFN-γ gene is significantly associated with the risk of aplastic anaemia in Caucasian population
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Marta Pillon, Carola Pongiglione, Lucia Giordani, Agnese Marrone, Anna Paola Iori, Riccardo Haupt, Achille Iolascon, Daniela Longoni, Marina Lanciotti, Andrea Bacigalupo, Carlo Dufour, Paola Di Michele, Mario Capasso, Angela Pistorio, Johanna Svahn, Dufour, C, Capasso, Mario, Svahn, J, Marrone, A, Haupt, R, Bacigalupo, A, Giordani, L, Longoni, D, Pillon, M, Pistorio, A, Di Michele, P, Iori, Ap, Pongiglione, C, Lanciotti, M, Iolascon, Achille, C., Dufour, J., Svahn, A., Marrone, R., Haupt, A., Bacigalupo, L., Giordani, D., Longoni, M., Pillon, A., Pistorio, P. D., Michele, A. P., Iori, C., Pongiglione, and M., Lanciotti
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Adult ,Male ,Risk ,medicine.medical_specialty ,Adolescent ,Biology ,White People ,Interferon-gamma ,Polymorphism (computer science) ,Internal medicine ,Genotype ,medicine ,Humans ,Interferon gamma ,Allele ,Aplastic anemia ,Child ,Dinucleotide Repeats ,Gene ,Polymorphism, Genetic ,TRANSPLANTATION ,ANTITHYMOCYTE GLOBULIN ,Homozygote ,Intron ,Bone marrow failure ,NECROSIS-FACTOR-ALPHA ,Anemia, Aplastic ,Infant ,Hematology ,medicine.disease ,Introns ,Endocrinology ,Case-Control Studies ,Child, Preschool ,Immunology ,CYCLOSPORINE ,Female ,medicine.drug - Abstract
Interferon-gamma (IFN-gamma) mediates the final damage of the stem cell compartment in Aplastic Anaemia (AA). Normal subjects homozygous for 12 (CA) repeats of polymorphism variable number of dinucleotide (CA) repeat (VNDR) in position 1349 of the IFN-gamma gene (IFNG) were shown to overproduce IFN-gammain vitro. We studied the distribution of polymorphism VNDR 1349 of IFNG in 67 Caucasian AA patients and in normal controls. Genotype (CA)12-12, (homozygosis for allele 2) and the single allele 12 were significantly more frequent (P = 0.005 and 0.004 respectively) in patients versus controls. The polymorphism was equally distributed in AA patients regardless of their response to immunosuppression. Homozygosity for 12 (CA) repeats of polymorphism VNDR 1349 of IFNG is strongly associated with the risk of AA in Caucasian subjects.
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- 2004
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- View/download PDF
46. Aberrant GM-CSF signal transduction pathway in juvenile myelomonocytic leukemia assayed by flow cytometric intracellular STAT5 phosphorylation measurement
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Andrea Biondi, Cristina Bugarin, Marco Zecca, Stefania Cesana, Daniela Longoni, C Molteni, Andrea Faini, Giuseppe Gaipa, Fabio Timeus, Gaipa, G, Bugarin, C, Longoni, D, Cesana, S, Molteni, C, Faini, A, Timeus, F, Zecca, M, and Biondi, A
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Male ,Cancer Research ,Flow cytometry ,Bone Marrow ,hemic and lymphatic diseases ,STAT5 Transcription Factor ,medicine ,Humans ,Phosphorylation ,STAT5 ,medicine.diagnostic_test ,biology ,Juvenile myelomonocytic leukemia ,Granulocyte-Macrophage Colony-Stimulating Factor ,Infant ,Hematology ,Flow Cytometry ,medicine.disease ,Molecular biology ,Leukemia ,Granulocyte macrophage colony-stimulating factor ,Leukemia, Myelomonocytic, Juvenile ,Oncology ,Child, Preschool ,biology.protein ,Cancer research ,Signal transduction ,Intracellular ,Human ,Signal Transduction ,medicine.drug - Abstract
Aberrant GM-CSF signal transduction pathway in juvenile myelomonocytic leukemia assayed by flow cytometric intracellular STAT5 phosphorylation measurement
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- 2008
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47. Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology
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Fabio Corsolini, Roberta Bottega, Federico Verzegnassi, Adriana Borriello, Elena Nicchia, Silverio Perrotta, Simona Cavani, Marta Pillon, Paola Grammatico, Johanna Svahn, Fulvio Della Ragione, Walter Barberi, Chiara Greco, Anna Locasciulli, Maria Criscuolo, Enrico Cappelli, Ugo Ramenghi, Piero Farruggia, Gabriella Casazza, Daniela Longoni, Fabio Tucci, Chiara Cugno, Daniela De Rocco, Cristina Mecucci, Anna Savoia, Helmut Hanenberg, Carlo Dufour, De Rocco, D, Bottega, R, Cappelli, E, Cavani, S, Criscuolo, M, Nicchia, E, Corsolini, F, Greco, C, Borriello, Adriana, Svahn, J, Pillon, M, Mecucci, C, Casazza, G, Verzegnassi, F, Cugno, C, Locasciulli, A, Farruggia, P, Longoni, D, Ramenghi, U, Barberi, W, Tucci, F, Perrotta, Silverio, Grammatico, P, Hanenberg, H, DELLA RAGIONE, Fulvio, Dufour, C, Savoia, A, Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco, Hematology, DE ROCCO, Daniela, Bottega, Roberta, Nicchia, Elena, Borriello, A, Perrotta, S, Della Ragione, F, and Savoia, Anna
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Candidate gene ,gene amplification ,genotype ,cytogenetics and molecular genetics ,genetic analysis ,Bioinformatics ,Western blotting ,hematopoietic stem cell ,bone marrow failure ,fanconi anemia ,Cohort Studies ,genetic heterogeneity ,single nucleotide polymorphism ,FANCG ,Fanconi anemia ,hemic and lymphatic diseases ,Genotype ,genetics ,gene mutation ,DNA extraction ,Genetics ,biology ,pathogenesis ,Fanconi anemia group A protein ,Articles ,bioinformatics ,cell line ,genetic screening ,Hematology ,cohort analysis ,Fanconi Anemia Complementation Group Proteins ,founder effect ,Italy ,nucleic acid database ,Errata Corrige ,Databases, Nucleic Acid ,amino acid substitution ,Fanconi anemia group C protein ,Fanconi anemia group D2 protein ,Fanconi anemia group G protein ,Fanconi anemia proteinarticle ,bone marrow depression ,controlled study ,gene sequence ,human ,human cell ,missense mutation ,molecular diagnosis ,molecular genetics ,protein analysis ,mosaicism ,mutation ,congenital, hereditary, and neonatal diseases and abnormalities ,Biology ,Polymorphism, Single Nucleotide ,FANCD2 ,medicine ,Humans ,Genetic heterogeneity ,Computational Biology ,nutritional and metabolic diseases ,medicine.disease ,FANCA ,FANCB - Abstract
Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes.
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- 2014
48. Morbidity and Mortality Due to Liver Disease in Children Undergoing Allogeneic Bone Marrow Transplantation: A 10-Year Prospective Study
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Marina Testa, Attilio Rovelli, Anna Locasciulli, Giuseppe Masera, Paola Sparano, Laura Vecchi, Maria Grazia Valsecchi, Cornelio Uderzo, Alfredo Alberti, Daniela Longoni, Locasciulli, A, Testa, M, Valsecchi, M, Vecchi, L, Longoni, D, Sparano, P, Rovelli, A, Uderzo, C, Masera, G, and Alberti, A
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Male ,HBsAg ,medicine.medical_specialty ,Cirrhosis ,Adolescent ,Immunology ,Chronic liver disease ,Biochemistry ,Gastroenterology ,Follow-Up Studie ,Liver disease ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Child ,Bone Marrow Transplantation ,Hepatitis ,business.industry ,Liver Diseases ,Liver Disease ,Infant ,Cell Biology ,Hematology ,Hepatitis C ,Hepatitis B ,medicine.disease ,digestive system diseases ,Surgery ,Prospective Studie ,Child, Preschool ,Elevated transaminases ,Female ,Morbidity ,business ,Follow-Up Studies - Abstract
We have conducted a long-term prospective study of children undergoing bone marrow transplantation (BMT) to assess morbidity and mortality for liver disease. One hundred eleven consecutive children were enrolled between June 1985 and June 1995 and were followed-up for a median of 5.5 years after BMT. Before transplant 48/111 children (43%) had abnormal alanine aminotransferase (ALT), none were HBsAg+ and 4/111 were anti-HCV+. After BMT 4/111 patients (3.6%) died of liver failure. No relationship was found between pretransplant hepatitis B (HBV) or C (HCV) infection or elevated transaminases and development of severe liver damage. Eighty-two out of one hundred and eleven patients (74%) had abnormalities of ALT after BMT, transient (n = 54) or persistent (n = 28). None developed clinical signs or symptoms of end stage liver disease or of cirrhosis during follow-up. No significant difference in prevalence of liver disease, was found between children with normal or abnormal ALT at BMT (relative risk [RR] = 1.04). HCV infection could be implicated in the etiology of chronic liver disease in 14/28 patients; 2 other patients were found infected by HBV alone (1 case) or combined with HCV (1 case). In the remaining 12 the etiology of chronic liver disease could not be defined. Posttransplant hepatitis B occurred in 4/111 children (3.6%), including a recipient from a donor who had been previously vaccinated against HBV, while no patient who had been vaccinated developed hepatitis B. The rate of posttransplant seroconversion to anti-HCV was 15%.
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- 1997
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49. Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia
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Marco Giordan, Ugo Ramenghi, Giuseppe Gaipa, Andrea Biondi, G te Kronnie, Concetta Micalizzi, Giuseppe Basso, Alice Bertaina, Silvia Bresolin, Daniela Longoni, Daisuke Hasegawa, Cristina Bugarin, Francesco Locatelli, Hasegawa, D, Bugarin, C, Giordan, M, Bresolin, S, Longoni, D, Micalizzi, C, Ramenghi, U, Bertaina, A, Basso, G, Locatelli, F, Biondi, A, Te Kronnie, G, and Gaipa, G
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medicine.medical_specialty ,CD33 ,CD34 ,juvenile myelomonocytic leukemia, phospho-specific flow cytometry, phospho-STAT5, GM-CSF ,Gastroenterology ,Flow cytometry ,GM-CSF ,Juvenile myelomonocytic leukemia ,Phospho-specific flow cytometry ,Phospho-STAT5 ,Internal medicine ,Positive predicative value ,Medicine ,phospho-specific flow cytometry ,STAT5 ,phospho-STAT5 ,medicine.diagnostic_test ,biology ,business.industry ,Hematology ,medicine.disease ,juvenile myelomonocytic leukemia ,Confidence interval ,Cytomegalovirus infection ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Oncology ,Immunology ,biology.protein ,Original Article ,business - Abstract
To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59-100%) and a specificity of 87% (CI 70-96%). Positive and negative predictive values were 71% (CI 42-92%) and 96% (CI 82-100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria. © 2013 Macmillan Publishers Limited. All rights reserved.
- Published
- 2013
50. Mesenchymal stem cells from Shwachman-Diamond syndrome patients display normal functions and do not contribute to hematological defects
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Marta Galbiati, Alan J. Warren, C Cappuzzello, Erica Dander, Giovanna D'Amico, G te Kronnie, A Di Meglio, Valentina Andre, Emanuela Maserati, Marco Cipolli, Andrea Biondi, Cristina Bugarin, Laura Sainati, Giovanni Cazzaniga, Daniela Longoni, M Serafini, Elena Nicolis, Silvia Bresolin, André, V, Longoni, D, Bresolin, S, Cappuzzello, C, Dander, E, Galbiati, M, Bugarin, C, Di Meglio, A, Nicolis, E, Maserati, E, Serafini, M, Warren, A, Te Kronnie, G, Cazzaniga, G, Sainati, L, Cipolli, M, Biondi, A, D'Amico, G, Warren, Alan [0000-0001-9277-4553], and Apollo - University of Cambridge Repository
- Subjects
Hematopoietic stem cell niche ,CD34 ,Keywords: Shwachman–Diamond syndrome ,Mesenchymal stem cells, Shwachman-Diamond syndrome, hematological defects ,medicine ,SBDS ,Keywords: Shwachman–Diamond syndrome, mesenchymal stem cells, bone marrow failure, SBDS ,Shwachman–Diamond syndrome ,mesenchymal stem cells ,business.industry ,Shwachman-Diamond syndrome ,Mesenchymal stem cell ,Hematology ,medicine.disease ,Leukemia ,Haematopoiesis ,medicine.anatomical_structure ,Oncology ,bone marrow failure ,Immunology ,Cancer research ,Original Article ,Bone marrow ,Stem cell ,business - Abstract
Shwachman-Diamond syndrome (SDS) is a rare inherited disorder characterized by bone marrow (BM) dysfunction and exocrine pancreatic insufficiency. SDS patients have an increased risk for myelodisplastic syndrome and acute myeloid leukemia. Mesenchymal stem cells (MSCs) are the key component of the hematopoietic microenvironment and are relevant in inducing genetic mutations leading to leukemia. However, their role in SDS is still unexplored. We demonstrated that morphology, growth kinetics and expression of surface markers of MSCs from SDS patients (SDS-MSCs) were similar to normal MSCs. Moreover, SDS-MSCs were able to differentiate into mesengenic lineages and to inhibit the proliferation of mitogen-activated lymphocytes. We demonstrated in an in vitro coculture system that SDS-MSCs, significantly inhibited neutrophil apoptosis probably through interleukin-6 production. In a long-term coculture with CD34+-sorted cells, SDS-MSCs were able to sustain CD34+ cells survival and to preserve their stemness. Finally, SDS-MSCs had normal karyotype and did not show any chromosomal abnormality observed in the hematological components of the BM of SDS patients. Despite their pivotal role in the hematopoietic stem cell niche, our data suggest that MSC themselves do not seem to be responsible for the hematological defects typical of SDS patients. © 2012 Macmillan Publishers Limited All rights reserved.
- Published
- 2012
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