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1. ELTROMBOPAG ADDED TO STANDARD IMMUNOSUPPRESSION IMPROVES RESPONSE RATE IN SEVERE APLASTIC ANEMIA: RESULTS OF THE MULTICENTER PHASE III PROSPECTIVE RANDOMIZED RACE TRIAL

Author

Risitano, AM, Kulasekararaj, A, Iacobelli, S, Terwel, S, Hill, A, Halkes, CJM, Recher, C, Barraco, F, Forcade, E, Llamas, JCV, Drexler, B, Mear, JB, Van Lint, MT, Raymakers, RAP, De Groot, MR, Daguindau, E, Nur, E, Barcellini, W, Russell, NH, Terriou, L, Iori, AP, Sanchez-Ortega, I, Xicoy, B, Jarque, I, Cavenagh, J, De Fontbrune, FS, Marotta, S, Munir, T, Tjon, JML, Tavitian, S, Praire, A, Clement, L, Rabian, F, Smith, AE, Cook, R, Marano, L, Griffin, M, Palmisani, E, Muus, P, Cacace, F, Frieri, C, Passweg, JR, Marsh, JCW, Socie, G, Mufti, GJ, Dufour, C, and de Latour, RP

Published
2021

2. Impact of T-cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party

Author

Samarasinghe, S, Clesham, K, Iacobelli, S, Sbianchi, G, Knol, C, Hamladji, R-M, Socié, G, Aljurf, M, Koh, M, Sengeloev, H, Dalle, J-H, Robinson, S, Van Lint, MT, Halkes, CJ, Beelen, D, Mufti, GJ, Snowden, J, Blaise, D, Peffault de Latour, R, Marsh, J, Dufour, C, Risitano, AM, Severe Aplastic Anaemia Working Party of the EBMT, Samarasinghe, Sujith, Clesham, Katherine, Iacobelli, Simona, Sbianchi, Giulia, Knol, Cora, Hamladji, Rose-Marie, Socié, Gerard, Aljurf, Mahmoud, Koh, Mickey, Sengeloev, Henrik, Dalle, Jean-Hugue, Robinson, Stephen, Van Lint, Maria Teresa, Halkes, Constantijn J. M., Beelen, Dietrich, Mufti, Ghulam J., Snowden, John, Blaise, Didier, de Latour, Regis Peffault, Marsh, Judith, Dufour, Carlo, and Risitano, Antonio M

Subjects
Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Anemia, T-Lymphocytes, medicine.medical_treatment, Medizin, Graft vs Host Disease, Hematopoietic stem cell transplantation, Lower risk, Gastroenterology, Lymphocyte Depletion, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Living Donors, medicine, Humans, Young adult, Child, Alemtuzumab, Aged, Antilymphocyte Serum, Retrospective Studies, Transplant Conditioning, business.industry, Hematopoietic Stem Cell Transplantation, Immunization, Passive, Anemia, Aplastic, Infant, Hematology, Middle Aged, Settore MED/15, medicine.disease, Transplantation, Settore MED/01, Treatment Outcome, surgical procedures, operative, Child, Preschool, 030220 oncology & carcinogenesis, Female, business, 030215 immunology, medicine.drug
Abstract

We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.

Published
2018
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13. Results of the Ebmt Saawp Phase III Prospective Randomized Multicenter Race Study of Horse Atg and Ciclosporin with or Without Eltrombopag in Naive Saa Patients

Author

de Latour, RP, Marsh, J, Iacobelli, S, Terwel, S, Hill, A, Halkes, CJM, Recher, C, Barraco, F, Forcade, E, Llamas, JCV, Dresler, B, Mear, JB, Van Lint, MT, Raymakers, RAP, De Groot, MR, Daguindau, E, Nur, E, Barcellini, W, Russell, NH, Terriou, L, Iori, AP, Sanchez-Ortega, I, Xicoy, B, Jarque, I, Cavenagh, J, de Fontbrune, FS, Kulasekararaj, A, Marotta, S, Munir, T, Tjon, JML, Tavitian, S, Praire, A, Clement, L, Rabian, F, Smith, AE, Cook, R, Marano, L, Griffin, M, Palmisani, E, Muus, P, Cacace, F, Passweg, JR, Socie, G, Mufti, GJ, Dufour, C, and Risitano, A

Published
2020

18. Outcomes of haploidentical stem cell transplantation for chronic lymphocytic leukemia: a retrospective study on behalf of the chronic malignancies working party of the EBMT

Author

van Gorkom G, van Gelder M, Eikema DJ, Blok HJ, van Lint MT, Koc Y, Ciceri F, Beelen D, Chevallier P, Selleslag D, Blaise D, Foá R, Corradini P, Castagna L, Moreno C, Solano C, Müller LP, Tischer J, Hilgendorf I, Hallek M, Bittenbring J, Theobald M, Schetelig J, Kröger N, CLL subcommittee, and Chronic Malignancies Working Party of the EBMT

Published
2018

19. Haploidentical transplantation outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) study

Author

Li, Zhuoyan, primary, Labopin, Myriam, additional, Ciceri, Fabio, additional, Blaise, Didier, additional, Tischer, Johanna, additional, Ehninger, Gerhard, additional, Van Lint, MT, additional, Koc, Yener, additional, Santarone, Stella, additional, Forcade, Edouard, additional, Castagna, Luca, additional, Polge, Emmanuelle, additional, Mailhol, Audrey, additional, Ruggeri, Annalisa, additional, Mohty, Mohamad, additional, Savani, Bipin N., additional, and Nagler, Arnon, additional

Published
2018
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20. Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved?

Author

Giammarco, S, de Latour, Rp, Sica, Simona, Dufour, C, Socie, G, Passweg, J, Kroger, N, Petersen, E, Van Lint, Mt, Oneto, R, Signori, A, Bacigalupo, Andrea, Sica, S (ORCID:0000-0003-2426-3465), Bacigalupo, A (ORCID:0000-0002-9119-567X), Giammarco, S, de Latour, Rp, Sica, Simona, Dufour, C, Socie, G, Passweg, J, Kroger, N, Petersen, E, Van Lint, Mt, Oneto, R, Signori, A, Bacigalupo, Andrea, Sica, S (ORCID:0000-0003-2426-3465), and Bacigalupo, A (ORCID:0000-0002-9119-567X)

Abstract

N/A

Published
2018

21. First line treatment of aplastic anemia with thymoglobuline in Europe and Asia: Outcome of 955 patients treated 2001-2012

Author

Bacigalupo, Andrea, Oneto, R, Schrezenmeier, H, Hochsmann, B, Dufour, C, Kojima, S, Zhu, X, Chen, X, Issaragrisil, S, Chuncharunee, S, Jeong, Dc, Giammarco, Sabrina, Van Lint, Mt, Zheng, Y, Vallejo, C, Bacigalupo Andrea (ORCID:0000-0002-9119-567X), Giammarco S, Bacigalupo, Andrea, Oneto, R, Schrezenmeier, H, Hochsmann, B, Dufour, C, Kojima, S, Zhu, X, Chen, X, Issaragrisil, S, Chuncharunee, S, Jeong, Dc, Giammarco, Sabrina, Van Lint, Mt, Zheng, Y, Vallejo, C, Bacigalupo Andrea (ORCID:0000-0002-9119-567X), and Giammarco S

Abstract

The aim of this study was to assess the outcome of patients with aplastic anemia (AA), receiving rabbit anti-thymocyte globulin (Thymoglobulin, SANOFI) and cyclosporin, as first line treatment. Eligible were 955 patients with AA, treated first line with Thymoglobulin, between 2001 and 2008 (n = 492), or between 2009 and 2012 (n = 463). The median age of the patients was 21 years (range 1-84). Mortality within 90 days was 5.7% and 2.4%, respectively in the two time periods (P = .007).The actuarial 10-year survival for the entire population was 70%; transplant free survival was 64%. Predictors of survival in multivariate analysis, were severity of the disease, patients age and the interval between diagnosis and treatment. Survival was 87% vs 61% for responders at 6 months versus nonresponders (P < .0001). The 10-year survival of nonresponders at 6 months, undergoing a subsequent transplant (n = 110), was 64%, vs 60% for patient not transplantated (n = 266) (P = .1). The cumulative incidence of response was 37%, 52%, 65% respectively, at 90, 180, and 365 days. In multivariate analysis, negative predictors of response at 6 months, were older age, longer interval diagnosis treatment, and greater severity of the disease. In conclusion, early mortality is low after first line treatment of AA with Thymoglobulin, and has been further reduced after year 2008. Patients age, together with interval diagnosis-treament and severity of the disease, remain strong predictors of response and survival

Published
2018

24. Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants

Author

Bacigalupo, A, Lamparelli, T, Milone, G, Sormani, MARIA PIA, Ciceri, F, Peccatori, J, Locasciulli, A, Majolino, I, DI BARTOLOMEO, P, Mazza, F, Sacchi, N, Pollicheni, S, Pinto, V, VAN LINT MT, GRUPPO ITALIANO TRAPIANTO MIDOLLO OSSEO GITMO, Bacigalupo, A, Lamparelli, T, Milone, G, Sormani, Mp, Ciceri, Fabio, Peccatori, J, Locasciulli, A, Majolino, I, Di Bartolomeo, P, Mazza, F, Sacchi, N, Pollicheni, S, Pinto, V, and Van Lint, Mt

Subjects
Adult, Risk, medicine.medical_specialty, Randomization, Graft vs Host Disease, Gastroenterology, Recurrence, Multicenter trial, Internal medicine, Immunopathology, Cause of Death, medicine, Animals, Humans, Antilymphocyte Serum, Transplantation, Acute leukemia, Hematology, business.industry, Hematopoietic Stem Cell Transplantation, medicine.disease, Anti-thymocyte globulin, surgical procedures, operative, Graft-versus-host disease, medicine.anatomical_structure, Immunology, Multivariate Analysis, Bone marrow, Rabbits, business
Abstract

We have previously shown that hemopoietic stem cell transplant (HSCT) recipients can be stratified on day+7 as having low, intermediate or a high risk of transplant-related mortality (TRM). With the aim of reducing TRM and GVHD, intermediate and high-risk patients (n = 170) were randomized to receive anti-thymocyte globulin (ATG, thymoglobuline) on day+7 (n = 84) or no treatment (n = 86) (controls). There was a reduction of TRM from 35% in controls to 29% in ATG patients (P = 0.3), of acute GVHD III-IV from 15 to 5% (P = 0.02) and of chronic GVHD from 26 to 11% (P = 0.03); survival was comparable. The predictive value of the day+7 score on TRM was confirmed for controls (19 vs 42% for intermediate vs high risk, respectively, P = 0.03), whereas ATG abrogated this predictive effect (29 vs 29%). ATG reduced GVHD (P = 0.006) in high-risk patients, but not in patients with an intermediate risk. In conclusion, we confirm that TRM can be predicted on the basis of day+7 laboratory values, after alternative donor HSCT; in high-, but not intermediate-risk patients, the administration of ATG on day+7 reduces GVHD. These results may represent a platform for risk-adapted post transplant immune modulation. Bone Marrow Transplantation (2010) 45, 385-391; doi:10.1038/bmt.2009.151; published online 6 July 2009

Published
2009

26. Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome

Author

Alessandrino, Ep, Porta, Mg, Malcovati, L, Jackson, Ch, Pascutto, C, Bacigalupo, A, Teresa van Lint, M, Falda, M, Bernardi, M, Onida, F, Guidi, S, Iori, Ap, Cerretti, R, Marenco, P, Pioltelli, P, Angelucci, E, Oneto, R, Ripamonti, F, Rambaldi, A, Bosi, A, Cazzola, M, Gruppo Italiano Trapianto di Midollo Osseo Levis, A, Bandini, G, Casini, M, Rossi, G, Baronciani, D, La Nasa, G, Milone, G, Mordini, N, Van Lint MT, Corradini, P, Milani, R, Morra, E, Lambertenghi Deliliers, G, Ciceri, F, Castagna, L, Narni, F, Selleri, C, Scime, R, Iannitto, E, Musso, M, Locatelli, F, Zecca, M, Martelli, F, Visani, G, Di Bartolomeo, P, Cavanna, L, Papineschi, Federico, Messina, G, Merli, F, Foa, R, Locasciulli, A, Majolino, I, Chiusolo, P, Leone, G, Arcese, W, Carella, Am, Cascavilla, N, Mazza, P, Bruno, B, Boccadoro, M, Fanin, R, Cerno, M, Bortolo, S, and Author information, Raimondi R.

Subjects
Oncology, Adolescent, Adult, Aged, Aged, 80 and over, Child, Cohort Studies, Female, Humans, Male, Markov Chains, Middle Aged, Myelodysplastic Syndromes, Risk, Survival Analysis, Time Factors, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation, Hematology, Homologous, medicine.medical_specialty, Allogeneic transplantation, medicine.medical_treatment, Hematopoietic stem cell transplantation, Natural history of disease, Internal medicine, medicine, 80 and over, Survival analysis, Transplantation, business.industry, Myelodysplastic syndromes, Original Articles, medicine.disease, Settore MED/15, Surgery, allogeneic transplantation, International Prognostic Scoring System, Risk assessment, business
Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Registry studies have shown that advanced disease stage at transplantation is associated with inferior overall survival. To define the optimal timing of allogeneic HSCT, we carried out a decision analysis by studying 660 patients who received best supportive care and 449 subjects who underwent transplantation. Risk assessment was based on both the International Prognostic Scoring System (IPSS) and the World Health Organization classification-based Prognostic Scoring System (WPSS). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of allogeneic HSCT on survival. This model estimated life expectancy from diagnosis according to treatment policy at different risk stages. Relative to supportive care, estimated life expectancy increased when transplantation was delayed from the initial stages until progression to intermediate-1 IPSS-risk or to intermediate WPSS-risk stage, and then decreased for higher risks. Modeling decision analysis on WPSS versus IPSS allowed better estimation of the optimal timing of transplantation. These observations indicate that allogeneic HSCT offers optimal survival benefits when the procedure is performed before MDS patients progress to advanced disease stages. Am. J. Hematol. 88:581–588, 2013. © 2013 Wiley Periodicals, Inc.

Published
2013

28. Fludarabine, cyclophosphamide, anti-thymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia (SAA): a retrospective study from the EBMT-SAA Working Party

Author

Bacigalupo, A, Socie', G, Lanino, E, Prete, A, Locatelli, F, Locasciulli, A, Cesaro, Simone, Shimoni, A, Marsh, J, Brune, M, van Lint MT, Oneto, R, and Passweg, J.

Subjects
Thymocyte globulin, alternative donor transplants, severe aplastic anemia
Published
2010

30. Outcome of allogeneic stem cell transplantation following reduced-intensity conditioninig regimen in patients with idiopathic myelofibrosis: the g.I.T.m.o. Experience

Author

Patriarca, Francesca, Bacigalupo, A, Sperotto, A, Isola, Miriam, Bruno, B, van Lint MT, Iori, Ap, Di Bartolomeo, P, Musso, M, Pioltelli, P, Visani, G, Iacopino, P, Fanin, Renato, and Bosi, A.

Subjects
surgical procedures, operative, hemic and lymphatic diseases, MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
Published
2010

31. Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation

Author

Crocchiolo, R, Zino, E, Vago, L, Oneto, R, Bruno, B, Pollichieni, S, Sacchi, N, Sormani, Mp, Marcon, J, Lamparelli, T, Fanin, R, Garbarino, L, Miotti, V, Bandini, G, Bosi, A, Ciceri, F, Bacigalupo, A, Fleischhauer, K, Gruppo Italiano Trapianto di Midollo Osseo, Terapia Cellulare, Cellule Staminale Ematopoietiche e., Italian Bone Marrow Donor Registry, Scalari, P, Bontempelli, M, Prinoth, O, Carcassi, C, Marcenò, R, Porfirio, Rombolà, G, Lombardo, Ferrioli, G, Poli, F, Scalamogna, M, Mazzi, B, Rossi, F, Mascaretti, L, Albergoni, Salvaneschi, L, Martinetti, M, Valentini, Renzo, Nesci, S, Papola, F, Scatena, Mariotti, Perrone, Laurenti, Grammatico, P, Mariani, M, Favoino, B, Guizzardi, Pontiero, Leoni, P, Rambaldi, A, Casini, M, Angelucci, E, Baronciani, D, La Nasa, G, Milone, G, Guidi, S, Van Lint MT, Dini, G, Corradini, P, Milani, R, Morra, E, Marenco, P, Lambretenghi Deliliers, G, Onida, F, Marcatti, M, Castagna, L, Pioltelli, P, Selleri, C, Zanesco, L, Scimè, R, Musso, M, Alessandrino, Ep, Locatelli, F, Visani, G, Di Bartolomeo, P, Papineschi, Federico, Favre, C, Iori, Ap, Foà, R, Locasciulli, A, Majolino, I, Majolino, P, Leone, G, Arcese, W, Cerretti, R, Carella, Am, Cascavilla, N, Lauria, F, Mazza, P, Cerno, M, and Benedetti, F.

Published
2009

32. Changes in cytokine profile pre- and post-immunosuppression in acquired aplastic anemia

Author

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

33. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome : a study from the Gruppo Italiano Trapianto di Midollo Osseo(GITMO)

Author

Alessandrino, Ep, Della Porta MG, Bacigalupo, A, Van Lint MT, Falda, M, Onida, F, Bernardi, M, Iori, Ap, Rambaldi, A, Cerretti, R, Marenco, P, Pioltelli, P, Malcovati, L, Pascutto, C, Oneto, R, Fanin, R, Bosi, A, Collaboratori Levis, A, Bandini, G, Casini, M, Rossi, G, Angelucci, E, Baronciani, D, La Nasa, G, Milone, G, Mordini, N, Guidi, S, Corradini, P, Milani, R, Morra, E, Lambretenghi Deliliers, G, Ciceri, F, Castagna, L, Narni, F, Selleri, C, Scimè, R, Iannitto, E, Musso, M, Locatelli, F, Martelli, F, Visani, G, Di Bartolomeo, P, Cavanna, L, Papineschi, F, Messina, G, Gugliotta, L, Foà, R, Locasciulli, A, Majolino, I, Chiusolo, P, Leone, G, Arcese, W, Carella, Am, Cascavilla, N, Mazza, P, Bruno, Benedetto, Boccadoro, Mario, Cerno, M, and Raimondi, R.

Subjects
Adult, Male, medicine.medical_specialty, Blood transfusion, Adolescent, medicine.medical_treatment, Immunology, World Health Organization, Biochemistry, Gastroenterology, Humans, Myelodysplastic Syndromes, Prognosis, Aged, Recurrence, Survival Rate, Classification, Blood Transfusion, Hematopoietic Stem Cell Transplantation, Middle Aged, Female, Refractory, hemic and lymphatic diseases, Internal medicine, medicine, Survival rate, Acute leukemia, Hematology, business.industry, Cancer, Cell Biology, medicine.disease, Surgery, Transplantation, Who classification, business, Settore MED/15 - Malattie del Sangue
Abstract

We evaluated the impact of World Health Organization (WHO) classification and WHO classification–based Prognostic Scoring System (WPSS) on the outcome of patients with myelodysplastic syndrome (MDS) who underwent allogeneic stem cell transplantation (allo-SCT) between 1990 and 2006. Five-year overall survival (OS) was 80% in refractory anemias, 57% in refractory cytopenias, 51% in refractory anemia with excess blasts 1 (RAEB-1), 28% in RAEB-2, and 25% in acute leukemia from MDS (P = .001). Five-year probability of relapse was 9%, 22%, 24%, 56%, and 53%, respectively (P < .001). Five-year transplant-related mortality (TRM) was 14%, 39%, 38%, 34%, and 44%, respectively (P = .24). In multivariate analysis, WHO classification showed a significant effect on OS (P = .017) and probability of relapse (P = .01); transfusion dependency was associated with a reduced OS (P = .01) and increased TRM (P = .037), whereas WPSS showed a prognostic significance on both OS (P = .001) and probability of relapse (P < .001). In patients without excess blasts, multilineage dysplasia and transfusion dependency affected OS (P = .001 and P = .009, respectively), and were associated with an increased TRM (P = .013 and P = .031, respectively). In these patients, WPSS identified 2 groups with different OS and TRM. These data suggest that WHO classification and WPSS have a relevant prognostic value in posttransplantation outcome of MDS patients.

Published
2008

34. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Author

Patriarca, F, Bacigalupo, A, Sperotto, A, Isola, M, Soldano, F, Bruno, B, van Lint MT, Iori, Ap, Santarone, S, Porretto, F, Pioltelli, P, Visani, G, Iacopino, P, Fanin, R, Bosi, A, Milone, G, Montanari, M, La Nasa, G, Dessalvi, P, Bonifazi, F., Servida, P, Lambertenghi, G, Corradini, P, Falda, M, Mazza, P, Benedetti, F, Raimondi, R, Selleri, Carmine, Locasciulli, A, Alessandrino, P, Narni, F, and Papineschi, F.

Published
2008

35. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

Author

Alessandrino, Ep, Della Porta MG, Bacigalupo, A, Van Lint MT, Falda, M, Onida, F, Bernardi, M, Iori, Ap, Rambaldi, A, Cerretti, R, Marenco, P, Pioltelli, P, Malcovati, L, Pascutto, C, Oneto, R, Fanin, R, Bosi, A, Gruppo Italiano Trapianto di Midollo Osseo, Levis, A, Bandini, G, Casini, M, Rossi, G, Angelucci, E, Baronciani, D, La Nasa, G, Milone, G, Mordini, N, Guidi, S, Corradini, P, Milani, R, Morra, E, Lambretenghi Deliliers, G, Ciceri, F, Castagna, L, Narni, F, Selleri, C, Scimè, R, Iannitto, E, Musso, M, Locatelli, F, Martelli, F, Visani, G, Di Bartolomeo, P, Cavanna, L, Papineschi, Federico, Messina, G, Gugliotta, L, Foà, R, Locasciulli, A, Majolino, I, Chiusolo, P, Leone, G, Arcese, W, Carella, Am, Cascavilla, N, Mazza, P, Bruno, B, Boccadoro, M, Cerno, M, and Raimondi, R.

Published
2008

37. Hematopoietic Stem-Cell Transplantation for Advanced Systemic Mastocytosis

Author

Ustun, C, Reiter, A, Scott, Bl, Nakamura, R, Damaj, G, Kreil, S, Shanley, R, Hogan, Wj, Perales, M, Shore, T, Baurmann, H, Stuart, R, Gruhn, B, Doubek, M, Hsu, Jw, Tholouli, E, Gromke, T, Godley, La, Pagano, Livio, Gilman, A, Wagner, Em, Shwayder, T, Bornhauser, M, Papadopoulos, Eb, Bohm, A, Vercellotti, G, Van Lint, Mt, Schmid, C, Rabitsch, W, Pullarkat, V, Legrand, F, Yakoub Agha, I, Saber, W, Barrett, J, Hermine, O, Hagglund, H, Sperr, Wr, Popat, U, Alyea, Ep, Devine, S, Deeg, Hj, Weisdorf, D, Akin, C, Valent, P., Pagano, Livio (ORCID:0000-0001-8287-928X), Ustun, C, Reiter, A, Scott, Bl, Nakamura, R, Damaj, G, Kreil, S, Shanley, R, Hogan, Wj, Perales, M, Shore, T, Baurmann, H, Stuart, R, Gruhn, B, Doubek, M, Hsu, Jw, Tholouli, E, Gromke, T, Godley, La, Pagano, Livio, Gilman, A, Wagner, Em, Shwayder, T, Bornhauser, M, Papadopoulos, Eb, Bohm, A, Vercellotti, G, Van Lint, Mt, Schmid, C, Rabitsch, W, Pullarkat, V, Legrand, F, Yakoub Agha, I, Saber, W, Barrett, J, Hermine, O, Hagglund, H, Sperr, Wr, Popat, U, Alyea, Ep, Devine, S, Deeg, Hj, Weisdorf, D, Akin, C, Valent, P., and Pagano, Livio (ORCID:0000-0001-8287-928X)

Abstract

PURPOSE: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. PATIENTS AND METHODS: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). RESULTS: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. CONCLUSION: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.

Published
2014

39. Bone marrow or peripheral blood as a source of stem cells for allogeneic transplants

Author

Almalina Bacigalupo, Francesco Frassoni, and Van Lint Mt

Subjects
Pathology, medicine.medical_specialty, business.industry, medicine.medical_treatment, CD34, Hematopoietic Stem Cell Transplantation, Hematology, Disease, Hematopoietic stem cell transplantation, Tissue Donors, Haematopoiesis, surgical procedures, operative, medicine.anatomical_structure, medicine, Humans, Transplantation, Homologous, Bone marrow, Prospective Studies, Stem cell, business, Prospective cohort study, Stem cell transplantation for articular cartilage repair, Bone Marrow Transplantation, Retrospective Studies
Abstract

Peripheral blood stem cell transplants are being increasingly used in the allogeneic setting and are often preferred to the conventional bone marrow source. The aim of this report is to review available data on peripheral blood versus bone marrow hematopoietic stem cell transplantation. The discussion is restricted to HLA-identical sibling transplants receiving unmanipulated grafts. This is because data with appropriate follow-up are available only for this type of comparison: we have preliminary data on the use of peripheral blood from unrelated donors, and on the use of T-cell depletion/CD34+ selection methods. The latter are evolving rapidly and it may be difficult to find a concurrent group of patients receiving T-cell-depleted or CD34-selected marrow. The results of retrospective and prospective studies are similar: hematologic and immune recovery are faster after peripheral blood grafts, acute graft-versus-host disease is comparable, whereas chronic graft-versus-host disease is increased in recipients of peripheral blood transplants. Transplant-related mortality is similar in the two groups, whereas disease recurrence is lower after peripheral blood grafts. The general opinion is that peripheral blood grafts are indicated for patients with advanced disease, whereas for patients with early-phase disease the two sources may give comparable results.

Published
2000

41. Mast cell leukemia: A report of ten cases

Author

Valentini, C, Rondoni, M, Pogliani, E, Van Lint, M, Cattaneo, C, Marbello, L, Pulsoni, A, Giona, F, Martinelli, G, Leone, G, Pagano, L, Valentini, CG, Van Lint, MT, Pagano, L., POGLIANI, ENRICO MARIA, Valentini, C, Rondoni, M, Pogliani, E, Van Lint, M, Cattaneo, C, Marbello, L, Pulsoni, A, Giona, F, Martinelli, G, Leone, G, Pagano, L, Valentini, CG, Van Lint, MT, Pagano, L., and POGLIANI, ENRICO MARIA

Published
2008

42. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD

Author

Perfetti, P, Carlier, P, Strada, P, Gualandi, F, Occhini, D, Van Lint, M, Ibatici, A, Lamparelli, T, Bruno, B, Raiola, A, Dominietto, A, Di Grazia, C, Bregante, S, Zia, S, Ferrari, G, Stura, P, Pogliani, E, Bacigalupo, A, Van Lint, MT, Raiola, AM, Ferrari, GM, Bacigalupo, A., POGLIANI, ENRICO MARIA, Perfetti, P, Carlier, P, Strada, P, Gualandi, F, Occhini, D, Van Lint, M, Ibatici, A, Lamparelli, T, Bruno, B, Raiola, A, Dominietto, A, Di Grazia, C, Bregante, S, Zia, S, Ferrari, G, Stura, P, Pogliani, E, Bacigalupo, A, Van Lint, MT, Raiola, AM, Ferrari, GM, Bacigalupo, A., and POGLIANI, ENRICO MARIA

Abstract

Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.

Published
2008

43. Advanced mast cell disease: an Italian Hematological Multicenter experience

Author

Pagano, L, Valentini, C, Caira, M, Rondoni, M, Van Lint, M, Candoni, A, Allione, B, Cattaneo, C, Marbello, L, Caramatti, C, Pogliani, E, Iannitto, E, Giona, F, Ferrara, F, Invernizzi, R, Fanci, R, Lunghi, M, Fianchi, L, Sanpaolo, G, Stefani, P, Pulsoni, A, Martinelli, G, Leone, G, Musto, P, Valentini, CG, Van Lint, MT, Stefani, PM, Musto, P., POGLIANI, ENRICO MARIA, Pagano, L, Valentini, C, Caira, M, Rondoni, M, Van Lint, M, Candoni, A, Allione, B, Cattaneo, C, Marbello, L, Caramatti, C, Pogliani, E, Iannitto, E, Giona, F, Ferrara, F, Invernizzi, R, Fanci, R, Lunghi, M, Fianchi, L, Sanpaolo, G, Stefani, P, Pulsoni, A, Martinelli, G, Leone, G, Musto, P, Valentini, CG, Van Lint, MT, Stefani, PM, Musto, P., and POGLIANI, ENRICO MARIA

Abstract

The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.

Published
2008

44. A boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation

Author

Larocca, A, Piaggio, G, Podestà, M, Pitto, A, Bruno, B, Di Grazia, C, Gualandi, F, Occhini, D, Raiola, A, Dominietto, A, Bregante, S, Lamparelli, T, Tedone, E, Oneto, R, Frassoni, F, Van Lint, M, Pogliani, E, Bacigalupo, A, Raiola, AM, Van Lint, MT, POGLIANI, ENRICO MARIA, BACIGALUPO, ANITA, Larocca, A, Piaggio, G, Podestà, M, Pitto, A, Bruno, B, Di Grazia, C, Gualandi, F, Occhini, D, Raiola, A, Dominietto, A, Bregante, S, Lamparelli, T, Tedone, E, Oneto, R, Frassoni, F, Van Lint, M, Pogliani, E, Bacigalupo, A, Raiola, AM, Van Lint, MT, POGLIANI, ENRICO MARIA, and BACIGALUPO, ANITA

Abstract

Background and Objectives. A proportion of patients develop poor graft function (PGF) following an allogeneic hemopoietic stem cell transplant (HSCT). It is uncertain whether a boost of donor marrow or blood cells is beneficial in terms of trilineage recovery and nonrelapse-related mortality (NRM). Design and Methods. The aim of this study was to compare outcomes in patients with PGF and full donor chimerism following an allogeneic HSCT who did or did not receive a boost of donor stem cells. The study included patients with primary PGF - i.e. those failing to achieve sustained graft function- and secondary PGF - i.e. those developing PGF after complete hematologic recovery. We studied 54 patients with PGF: 20 patients received no further donor cell infusion (group A), 14 received a boost of unmanipulated marrow or blood cells from the original donor, without further conditioning (group B), and 20 received donor cells after CD34 selection without conditioning (group C). The three groups were comparable for disease phase, patients' age, donor type, primary or secondary PGF, full donor chimerism and duration of PGF. Results. Trilineage recovery was seen in 40%, 36% and 75% of the patients in, respectively, groups A, B and C (p=0.02). In multivariate Cox analysis trilineage recovery was more frequent in patients with secondary PGF (RR of complete recovery 2.82, p=0.01) and in patients receiving CD34(+)-selected cells (RR of complete recovery 3.0; p=0.007). There was no effect of donor type on hematologic recovery. The rate of NRM was 55%, 64%, 20% in groups A, B and C, respectively (p=0.06) and was highly correlated with trilineage recovery (RR 0.36, p < 0.0001). PGF was the primary cause of death in 30%, 21% and 10% of the patients in the three groups, graft-versus-host disease (GVHD) in 5%, 36%, and 10%. Interpretations and Conclusions. In patients with poor graft function (a) a boost of CD34(+)-selected peripheral blood donor cells is associated with a high chance of

Published
2006

50. 194 Myelodysplastic syndrome or leukemia developing after MDS treated by allogeneic bone marrow transplantation: Outcome of 90 adult patients

Author

Alessandrino, E.P., primary, Astori, C., additional, Van Lint, MT, additional, Bernasconi, P., additional, Arcese, W., additional, Polchi, P., additional, Di Bartolomeo, P., additional, Aversa, F., additional, Izzi, T., additional, Bandini, G., additional, Bosi, A., additional, Lambertenghi, G., additional, Locatelli, F., additional, Falda, M., additional, Iacopino, P., additional, and Bacigalupo, A., additional

Published
1997
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