488 results on '"Iacobelli, Simona"'
Search Results
152. Comparison between Anti-Thymocyte Globulin and Alemtuzumab and the Possible Impact of KIR-Ligand Mismatch in Melphalan/Fludarabine Dose-Reduced Conditioning Followed by HLA-Matched and Mismatched Unrelated Stem Cell Transplantation in Patients with Multiple Myeloma.
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Kroeger, Nicolaus, primary, Shaw, Brownen, additional, Iacobelli, Simona, additional, Zabelina, Tatjana, additional, Peggs, Karl, additional, Shimoni, Avichai, additional, Nagler, Arnon, additional, Binder, Thomas, additional, Schwerdtfeger, Rainer, additional, Kiehl, Michael, additional, Sayer, Herbert G., additional, Ayuk, Francis, additional, Eiermann, Thomas, additional, and Marks, David, additional
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- 2004
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153. Low tumor burden is associated with early B-cell reconstitution and is a predictor of favorable outcome after non-myeloablative stem cell transplant for chronic lymphocytic leukemia.
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Hebenstreit, Karin, Iacobelli, Simona, Leiblein, Sabine, Eisfeld, Ann-Kathrin, Pfrepper, Christian, Heyn, Simone, Vucinic, Vladan, Franke, Georg-Nikolaus, Krahl, Rainer, Fricke, Stephan, Becker, Cornelia, Pönisch, Wolfram, Behre, Gerhard, Niederwieser, Dietger, and Lange, Thoralf
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HEALTH outcome assessment , *STEM cell transplantation research , *CHRONIC lymphocytic leukemia treatment , *B cells , *GRAFT versus host disease , *LYMPHOPROLIFERATIVE disorders , *CYCLOSPORINE , *IMMUNOSUPPRESSIVE agents - Abstract
Reconstitution, engraftment kinetics and tumor cell clearance were analyzed after reduced intensity conditioning hematopoietic cell transplant (RIC-HCT) in patients with chronic lymphocytic leukemia (CLL). Patients were transplanted from unrelated ( n = 40) or related ( n = 10) donors after fludarabine and 2 Gy total body irradiation followed by cyclosporine and mycophenolate mofetil. The vast majority of patients (96%) engrafted with absolute neutrophil count (ANC) > 0.5 × 109/L at day + 22. CLL cells decreased (median 2%, range 0-69%) within 28 days, but disappeared by day + 180 after HCT. Donor T-cell chimerism increased to > 95% at day 56 and donor B-cell chimerism to 94% at day + 360. Overall survival was 51 ± 8%, incidence of progression 37 ± 7% and non-relapse related mortality (NRM) 30 ± 7% at 4 years. The most common causes of NRM were graft-versus-host disease (GvHD) (14%) and sepsis (6%). Disease status at HCT was significantly associated with early B-cell reconstitution ( p = 0.04) and with increased risk of relapse/progression in univariate and multivariate analysis ( p = 0.022). Tumor cells were undetectable by day + 180, although B-cell reconstitution did not occur until 1.5 years after RIC-HCT. The best predictors for progression-free survival (PFS) and overall survival (OS) were complete response (CR) or first partial response (PR1) and the absence of bulky disease at transplant, respectively. [ABSTRACT FROM AUTHOR]
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- 2014
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154. Reduced-intensity conditioning for myeloma: lower nonrelapse mortality but higher relapse rates compared with myeloablative conditioning
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Crawley, Charles, Iacobelli, Simona, Björkstrand, Bo, Apperley, Jane F., Niederwieser, Dietger, and Gahrton, Gösta
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Despite the widespread adoption of reduced-intensity conditioning (RIC) for myeloma, there are few data comparing outcomes with RIC with myeloablative conditioning (MAC). We report the outcomes of patients undergoing allogeneic transplantations for myeloma and reported to the EBMT. A minimum data set was available on 320 RIC and 196 MAC allografts performed between 1998 and 2002. The RIC patients were older (51 vs 45 years) with more progressive disease (28% vs 21%) and more had received a prior transplant (76% vs 11%). In addition, there was a longer time to transplantation and an increased use of peripheral blood and T-cell depletion. For RIC and MAC, respectively, the nonrelapse mortality (NRM) at 2 years was 24% and 37% (P = .002); overall survival, 38.1% and 50.8% (not significant [ns]); and progression-free survival (PFS), 18.9% and 34.5% (P = .001). On multivariate analysis, RIC was associated with a reduction in NRM (HR, 0.5), but this was offset by an increase in relapse risk (HR, 2.0), and the conditioning intensity did not impact on overall survival or retain significance for PFS. These data suggest that there is a continuing need to investigate dose intensity in the conditioning for myeloma allografts.
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- 2007
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155. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes
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Martino, Rodrigo, Iacobelli, Simona, Brand, Ronald, Jansen, Thekla, van Biezen, Anja, Finke, Jürgen, Bacigalupo, Andrea, Beelen, Dietrich, Reiffers, Jossy, Devergie, Agnes, Alessandrino, Emilie, Mufti, Ghulam J., Barge, Renée, Sierra, Jorge, Ruutu, Tapani, Boogaerts, Marc, Falda, Michele, Jouet, Jean-Pierre, Niederwieser, Dieter, and de Witte, Theo
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In this multicenter retrospective study, the outcomes of 836 patients with myelodysplastic syndrome (MDS) who underwent transplantation with a human leukocyte antigen (HLA)–identical sibling donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In multivariate analysis, the 3-year relapse rate was significantly increased after RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.2-2.2; P= .001), but the 3-year nonrelapse mortality (NRM) rate was decreased in the RIC group (HR, 0.61; 95% CI, 0.41-0.91; P= .015). The 3-year probabilities of progression-free and overall survivals were similar in both groups (39% after SMC vs 33% in RIC; multivariate P= .9; and 45% vs 41%, respectively; P= .8). In conclusion, the lower 3-year NRM after RIC is encouraging, since these patients were older (age > 50 years in 73% RIC vs 28% in SMC, P< .001) and had more adverse pretransplantation variables. However, based on the higher risk of relapse, patients with no contraindications for SMC should not receive RIC outside of prospective randomized trials, which are needed to establish the position of RIC-based transplantation in the treatment of patients with MDS.
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- 2006
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156. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation
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Schönland, Stefan O., Lokhorst, Henk, Buzyn, Agnes, Leblond, Veronique, Hegenbart, Ute, Bandini, Giuseppe, Campbell, Andrew, Carreras, Enric, Ferrant, Augustin, Grommisch, Leanthe, Jacobs, Peter, Kröger, Nicolaus, La Nasa, Giorgio, Russell, Nigel, Zachee, Pierre, Goldschmidt, Hartmut, Iacobelli, Simona, Niederwieser, Dietger, and Gahrton, Gösta
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Using the European Group for Blood and Marrow Transplantation (EBMT) registry, we retrospectively studied 19 patients with AL (amyloid light-chain) amyloidosis who underwent allogeneic (allo; n = 15) or syngeneic (syn; n = 4) hematopoietic stem cell transplantation (SCT) between 1991 and 2003. For allo-SCT, full-intensity conditioning was used in 7 patients and reduced-intensity conditioning (RIC) in 8 patients. Engraftment was durable in 12 of those 15 patients. The median follow-up time is 19 months. Kaplan-Meier probabilities of overall and progression-free survival were 60% and 53% at 1 year, respectively. Overall, 40% of patients died of transplant-related mortality (TRM). Best hematologic response after SCT was complete remission (CR) and partial remission (PR) in 8 and 2 patients, respectively, leading to an organ response in 8 of these patients. Seven of the 10 patients in remission are long-term survivors. In 5 of 7 evaluable patients in CR, chronic graft-versus-host disease (GvHD) was observed, indicating the contribution of immune effects to disease control. The main clinical problem was cardiac failure in patients with poor performance status due to amyloidosis or in combination with severe infections. These data suggest that allo-SCT might be a promising and potentially curative treatment modality for selected patients with AL amyloidosis. (Blood. 2005;107:2578-2584)
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- 2006
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157. Impact of Relapse after Allogeneic Hematopoietic Stem Cell Transplant on Subsequent Outcome in Patients with Chronic Myeloid Leukemia: A Better Understanding through Multi-State Modeling.
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Guglielmi, Cesare, Fiocco, Marta, Brand, Ronald, Olavarria, Eduardo, Iacobelli, Simona, Putter, Hein, Niederwieser, Dietger W., de Witte, T.M., and Gratwohl, Alois
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- 2006
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158. The role of renal impairment at diagnosis in multiple myeloma undergoing autologous transplantation. A retrospective analysis of the CMWP
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Scheid, Christof, Hoek, Jennifer, Russell, Nigel H., Didier Blaise, Mayer, Jiri, Ljungman, Per, Lenhoff, Stig, Kobbe, Guido, Iacobelli, Simona, Isaksson, Cecilia, Schaap, Nicolaas, Basak, Grzegorz, Hayden, Patrick, Gonzalez Muniz, Soledad, Apperley, Jane, Rambaldi, Alessandro, Wilson, Keith M. O., Parody Porras, Rocio, Jantunen, Esa, Anagnostopoulos, Achilles, Schoenland, Stefan, Yakoub-Agha, Ibrahim, Kroeger, Nicolaus, Morris, Curly, and Garderet, Laurent
159. Pre-engraftment and post-engraftment Gram=negative rods bacteremia in HSCT patients: Risk factors and association with mortality
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Averbuch, Diana, Tridello, Gloria, Hoek, Jennifer, Mikulska, Malgorzata, Pabst, Thomas, Yanez San Segundo, Lucrecia, Akan, Hamdi, Ozcelik, Tulay, Donnini, Irene, Klyasova, Galina, Sousa, Aida Botelho, Zuckerman, Tsila, Wu, Depei, Tecchio, Cristina, La Camara, Rafael, Sahika Zeynep Aki, Ljungman, Per, Gulbas, Zafer, Nicolas, Emmanuelle, Calore, Elisabetta, Perruccio, Katia, Ram, Ron, Annaloro, Claudio, Martino, Rodrigo, Avni, Batia, Shaw, Peter, Gil, Lidia, Iacobelli, Simona, Styczynski, Jan, Engelhard, Dan, and Cesaro, Simone
160. Bortezomib(Velcade (R))-Thalidomide-Dexamethasone (VTD) Is Superior to Thalidomide-Dexamethasone (TD) In Patients with Multiple Myeloma (MM) Progressing or Relapsing After Autologous Transplantation
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Garderet, Laurent, Iacobelli, Simona, Moreau, Philippe, Dib, Mamoun, Caillot, Denis, Niederwieser, Dietger W., Masszi, Tamas, Fontan, Jean, Michallet, Mauricette, Gratwohl, Alois, Milone, Giuseppe, Doyen, Chantal, Pegourie, Brigitte, Roman Hajek, Casassus, Philippe, Kolb, Brigitte, Chaleteix, Carine, Hertenstein, Bernd, Onida, Francesco, Ludwig, Heinz, Vekemans, Marie Christiane, Ketterer, Nicolas, Daguenel, Anne, Gorin, Norbert C., Harousseau, Jean Luc, Witte, Theo, Morris, Curly, and Gahrton, Gosta
161. External validation of scores predicting non-relapse mortality in patients with myelodysplastic syndrome: a study from MDS subcommittee of the CMWP EBMT
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Carre, Martin, Porcher, Raphael, Finke, Juergen, Ehninger, Gerhard, Koster, Linda, Beelen, Dietrich, Ganser, Arnold, Volin, Liisa, Lozano, Sara, Sengeloev, Henrik, Michallet, Mauricette, Tischer, Johanna, Olavarria, Eduardo, Pascual Cascon, Maria Jesus, Iacobelli, Simona, Koc, Yener, Jindra, Pavel, Mutlu Arat, Witte, Theo, Kroeger, Nicolaus, and Robin, Marie
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Medizin
162. Protective Environment for Hematopoietic Cell Transplant (HSCT) Recipients: The Infectious Diseases Working Party EBMT Analysis of Global Recommendations on Health-Care Facilities
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Styczynski, Jan, Iacobelli, Simona, Donnelly, Peter, Tridello, Gloria, Hoek, Jennifer, Mikulska, Malgorzata, and Cesaro, Simone
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- 2017
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163. Bortezomib(Velcade®)-Thalidomide-Dexamethasone (VTD) Is Superior to Thalidomide-Dexamethasone (TD) In Patients with Multiple Myeloma (MM) Progressing or Relapsing After Autologous Transplantation
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Garderet, Laurent, Iacobelli, Simona, Moreau, Philippe, Dib, Mamoun, Caillot, Denis, Niederwieser, Dietger W, Masszi, Tamas, Fontan, Jean, Michallet, Mauricette, Gratwohl, Alois, Milone, Giuseppe, Doyen, Chantal, Pegourie, Brigitte, Hajek, Roman, Casassus, Philippe, Kolb, Brigitte, Chaleteix, Carine, Hertenstein, Bernd, Onida, Francesco, Ludwig, Heinz, Vekemans, marie Christiane, Ketterer, Nicolas, Daguenel, Anne, Gorin, Norbert C., Harousseau, jean Luc, de Witte, Theo, Morris, Curly, and Gahrton, Gosta
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The Thalidomide-Dexamethasone (TD) regimen has provided encouraging results in relapsed MM. To improve results, bortezomib (Velcade) has been added to the combination in previous phase II studies, the so called VTD regimen. In January 2006, the European Group for Blood and Marrow Transplantation (EBMT) and the Intergroupe Francophone du Myélome (IFM) initiated a prospective, randomized, parallel-group, open-label phase III, multicenter study, comparing VTD (arm A) with TD (arm B) for MM patients progressing or relapsing after autologous transplantation.Inclusion criteria: patients in first progression or relapse after at least one autologous transplantation, including those who had received bortezomib or thalidomide before transplant. Exclusion criteria: subjects with neuropathy above grade 1 or non secretory MM. Primary study end point was time to progression (TTP). Secondary end points included safety, response rate, progression-free survival (PFS) and overall survival (OS). Treatment was scheduled as follows: bortezomib 1.3 mg/m2 was given as an i.v bolus on Days 1, 4, 8 and 11 followed by a 10-Day rest period (days 12 to 21) for 8 cycles (6 months) and then on Days 1, 8, 15, 22 followed by a 20-Day rest period (days 23 to 42) for 4 cycles (6 months). In both arms, thalidomide was scheduled at 200 mg/Day orally for one year and dexamethasone 40 mg/Day orally four days every three weeks for one year. Patients reaching remission could proceed to a new stem cell harvest. However, transplantation, either autologous or allogeneic, could only be performed in patients who completed the planned one year treatment period. Response was assessed by EBMT criteria, with additional category of near complete remission (nCR). Adverse events were graded by the NCI-CTCAE, Version 3.0.The trial was based on a group sequential design, with 4 planned interim analyses and one final analysis that allowed stopping for efficacy as well as futility. The overall alpha and power were set equal to 0.025 and 0.90 respectively. The test for decision making was based on the comparison in terms of the ratio of the cause-specific hazards of relapse/progression, estimated in a Cox model stratified on the number of previous autologous transplantations. Relapse/progression cumulative incidence was estimated using the proper nonparametric estimator, the comparison was done by the Gray test. PFS and OS probabilities were estimated by the Kaplan-Meier curves, the comparison was performed by the Log-Rank test. An interim safety analysis was performed when the first hundred patients had been included. The safety committee recommended to continue the trial.As of 1st July 2010, 269 patients had been enrolled in the study, 139 in France (IFM 2005-04 study), 21 in Italy, 38 in Germany, 19 in Switzerland (a SAKK study), 23 in Belgium, 8 in Austria, 8 in the Czech republic, 11 in Hungary, 1 in the UK and 1 in Israel. One hundred and sixty nine patients were males and 100 females; the median age was 61 yrs (range 29–76). One hundred and thirty six patients were randomized to receive VTD and 133 to receive TD. The current analysis is based on 246 patients (124 in arm A, 122 in arm B) included in the second interim analysis, carried out when 134 events were observed. Following this analysis, the trial was stopped because of significant superiority of VTD over TD. The remaining patients were too premature to contribute to the analysis. The number of previous autologous transplants was one in 63 vs 60 and two or more in 61 vs 62 patients in arm A vs B respectively. The median follow-up was 25 months. The median TTP was 20 months vs 15 months respectively in arm A and B, with cumulative incidence of relapse/progression at 2 years equal to 52% (95% CI: 42%-64%) vs 70% (95% CI: 61%-81%) (p=0.0004, Gray test). The same superiority of arm A was also observed when stratifying on the number of previous autologous transplantations. At 2 years, PFS was 39% (95% CI: 30%-51%) vs 23% (95% CI: 16%-34%) (A vs B, p=0.0006, Log-Rank test). OS in the first two years was comparable in the two groups.VTD resulted in significantly longer TTP and PFS in patients relapsing after ASCT. Analysis of response and safety data are on going and results will be presented at the meeting. Protocol EU-DRACT number: 2005-001628-35.Niederwieser: Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau.
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- 2010
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164. Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplant: May We Predict Graft vs Leukemia without Graft vs Host Disease?.
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Guglielmi, Cesare, Bergantini, Stefania, Iacobelli, Simona, van Biezen, Anja, Olavarria, Eduardo, Gratwohl, Alois, Schattenberg, Antonius V.M.B., Verdonck, Leo F., Niederwieser, Dietger W., and de Witte, T.M.
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Donor lymphocyte infusions (DLI) have radically changed the prognosis of patients relapsing after allogeneic hematopoietic stem cell transplant (SCT) for chronic myeloid leukemia (CML). Major obstacles to success with DLI are represented by leukemia resistance and by secondary GvHD (GvHD2). The best result of is when a patient treated with DLI achieve a durable molecular remission without experiencing GvHD2. It is unclear which factors may predict for such a favourable outcome when CML patients are treated with DLI. We retrospectively identified 500 patients (59% males, median age 39 years, range 4–64), treated with DLI for CML relapse (81 molecular [16%], 150 cytogenetic [30%], 211 hematological chronic [42%], and 58 hematological accelerated [12%]) at 68 EBMT centers before 2004 with adequate information collected on disease response, GvHD2 and survival after DLI. Donor was an HLA-identical sibling in 73%, unrelated in 27%. DLI started with a cell dose <2×107 CD3+ cells/Kg in 62% of the cases; 208 patients (42%) received 2 or more additional infusions of donor cells. Cumulative cell dose ranged from 1×105 CD3+ cells/Kg to 1.4×109 (median 7×107). Molecular remission and/or cytogenetic complete remission was achieved in 340 patients (68%) in a median of 7.5 months (95% within 41 months). GvHD2 occurred in 60% of patients at a median of 3 months from 1st transfusion of donor lymphocytes (95% within 24 months). Sixteen recurred at a median of 19 months (range 3–48). Actuarial probability of being alive and responsive to DLI without experiencing any GvHD2 was 29% (95% confidence interval [95CI]: 27–31%) and 27% (95CI: 24–30%) at 5 and 10 years after DLI, respectively. We studied the prognostic effect of following factors: patient age at DLI, donor type, donor sex, sex mismatch with the donor, phase at SCT, stem cell source, T-depletion, total body irradiation in the conditioning regimen, GvHD prior to DLI, interval from SCT to DLI, type of relapse. Multivariate analysis with a Cox model adjusted for the period of DLI (=1997 vs >1997), showed that chronic GvHD after transplant and prior to relapse (hazard ratio [HR]: 1.5, 95CI: 1.2–1.9, p<0.001), an interval from SCT to DLI <1 year (HR: 1.7, 95CI: 1.3–2.2, p<0.001), and hematological relapse (HR: 1.6, 95CI: 1.2–2.0, p<0.001), were adverse features. 94 patients (20%), 222 (48%), 133 (28%), and 17 (4%) had 0, 1, 2, and 3 adverse features, respectively. Survival in remission without experiencing GvHD2 at 5 years improved from 14%, 30%, to 56% in patients with 2–3, 1, and 0 adverse features, respectively. We conclude that:“pure” GvL effect (ie. durable remission without GvHD2) was observed in more than 25% of patients treated with DLI for CML relapsing after allogeneic SCT;occurrence of chronic GvHD prior to relapse, the interval from SCT to DLI, and the type of relapse are the main factors associated with the chance of a “pure” GvL effect;patients treated with DLI beyond 1 year from SCT for a molecular/cytogenetic relapse that was not preceded by chronic GvHD have more than 50% chance of exploiting the “pure” GvL effect.
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- 2006
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165. Complications of Autologous Stem Cell Transplantation in Multiple Myeloma: Results from the CALM Study.
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Waszczuk-Gajda, Anna, Penack, Olaf, Sbianchi, Giulia, Koster, Linda, Blaise, Didier, Reményi, Péter, Russell, Nigel, Ljungman, Per, Trneny, Marek, Mayer, Jiri, Iacobelli, Simona, Kobbe, Guido, Scheid, Christof, Apperley, Jane, Touzeau, Cyrille, Lenhoff, Stig, Jantunen, Esa, Anagnostopoulos, Achilles, Paris, Laura, and Browne, Paul
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STEM cell transplantation , *MULTIPLE myeloma , *AUTOGRAFTS , *MONOCLONAL gammopathies , *TREATMENT effectiveness , *BACTERIAL diseases - Abstract
Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies. [ABSTRACT FROM AUTHOR]
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- 2022
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166. Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
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Carré, Martin, Porcher, Raphaël, Finke, Jürgen, Ehninger, Gerhard, Koster, Linda, Beelen, Dietrich, Ganser, Arnold, Volin, Liisa, Lozano, Sara, Friis, Lone, Michallet, Mauricette, Tischer, Johanna, Olavarria, Eduardo, Cascon, Maria Jesús Pascual, Iacobelli, Simona, Koc, Yener, Jindra, Pavel, Arat, Mutlu, de Witte, Theo, and Yakoub Agha, Ibrahim
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BLOOD groups , *HEMATOPOIETIC stem cell transplantation , *COMORBIDITY , *STEM cell transplantation , *ALEMTUZUMAB , *KARNOFSKY Performance Status , *BONE marrow - Abstract
• Allotransplant for myelodysplastic syndrome is limited by high nonrelapse mortality. • Comorbidities assessed by the original Sorror score impact mortality negatively. • Chronological age also continues to play an independent prognostic role on mortality. • Both age and comorbidities should be integrated in the allotransplant decision process. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P =.016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P =.022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P <.0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs. [ABSTRACT FROM AUTHOR]
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- 2020
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167. Pollen variability in Quercus L. species and relative systematic implications.
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Di Marco, Gabriele, D'Agostino, Alessia, Braglia, Roberto, Redi, Enrico Luigi, Iacobelli, Simona, Gismondi, Angelo, and Canini, Antonella
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POLLEN , *OAK , *PALYNOLOGY , *STATISTICAL correlation , *PLANT metabolites , *PLANT proteins , *HONEY , *CAROTENOIDS - Abstract
This study aims to address one of the challenges related to the complexity of the Quercus L. genus, that is the identification of structural elements favouring the systematic identification of the oak pollen. Thus, in this contribution, we explored the variation of morphometric and chemical parameters in pollen samples collected from 47 different Quercus species and hybrids. Several qualitative (e.g., outline in polar view, class, aperture structures) and quantitative (e.g., diameter, exine and sporoderm thickness, autofluorescence, content in proteins and plant metabolites) features were evaluated by optic microscopy and spectrophotometric assays. Statistical analyses were also carried out to assess significant correlations and clustering effects among the studied taxa, based on phenotypical and biochemical data, to identify the parameters which could be useful for taxonomic discrimination at inter- and intra-specific level. Only few morphological traits showed the potentiality to be diagnostic, such as pollen diameter and outline in polar view. The intensity of pollen autofluorescence varied among the samples but it did not seem to correlate with protein, carotenoid, phenolic and flavonoid content. However, differences in protein and carotenoid levels were detected, suggesting them as possible taxonomic discriminants for oak pollen. Thus, our work represents a step forward in understanding morphology and biochemistry of oak pollen, constitutes an experimental set-up applicable in future systematic studies on other genera, and opens new perspectives for further molecular investigations on Quercus species. • Analysis of pollen collected from 47 different Quercus species and hybrids. • Identification of structural elements for the systematic identification of the oak pollen. • Pollen diameter and outline in polar view showed the potentiality to be diagnostic. • Differences in protein and carotenoid level were discriminant elements for oak pollen. • Statistical correlations were used to taxonomically discriminate inter- and intra-specific level. [ABSTRACT FROM AUTHOR]
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- 2023
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168. Outcome of a Salvage Third Autologous Stem Cell Transplantation in Multiple Myeloma.
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Garderet, Laurent, Blaise, Didier, Koenecke, Christian, Peschel, Christian, Radocha, Jakub, Metzner, Bernd, Lenain, Pascal, Schäfer-Eckart, Kerstin, Pohlreich, David, Grasso, Mariella, Caillot, Denis, Iacobelli, Simona, Einsele, Herman, Ladetto, Marco, Kröger, Nicolaus, Koster, Linda, Goldschmidt, Hartmut, Schönland, Stefan, Johansson, Jan-Erik, and Bourhis, Jean Henri
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STEM cell transplantation , *MULTIPLE myeloma treatment , *AUTOTRANSPLANTATION , *HEALTH outcome assessment , *DISEASE relapse , *MULTIVARIATE analysis - Abstract
To evaluate the outcomes of salvage third autologous stem cell transplantation (ASCT) in patients with relapsed multiple myeloma. We analyzed 570 patients who had undergone a third ASCT between 1997 and 2010 (European Society for Blood and Marrow Transplantation data), of whom 482 patients underwent tandem ASCT and a third ASCT at first relapse (AARA group) and 88 patients underwent an upfront ASCT with second and third transplantations after subsequent relapses (ARARA group). With a median follow-up after salvage third ASCT of 61 months in the AARA group and 48 months in the ARARA group, the day +100 nonrelapse mortality in the 2 groups was 4% and 7%, the incidence of second primary malignancy was 6% and 7%, the median progression-free survival was 13 and 8 months, and median overall survival (OS) was 33 and 15 months. In the AARA group, according to the relapse-free interval (RFI) from the second ASCT, the median OS after the third ASCT was 17 months if the RFI was <18 months, 37 months if the RFI was between 18 and 36 months, and 64 months if the RFI was ≥36 months ( P < .001). In the ARARA group, the median OS after the third ASCT was 7 months if the RFI was <6 months, 13 months if the RFI was between 6 and 18 months, and 27 months if the RFI was ≥18 months ( P < .001). In a multivariate analysis of the AARA group, the favorable prognostic factor was an RFI after second ASCT of ≥18 months. Progressive disease and a Karnofsky Performance Status score of <70 at third ASCT were unfavorable factors. A salvage third ASCT is of value for patients with relapsed myeloma, particularly for those with a long duration of response and chemosensitive disease at the time of transplantation. [ABSTRACT FROM AUTHOR]
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- 2018
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169. Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a 5q Deletion.
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Garderet, Laurent, Ziagkos, Dimitris, van Biezen, Anja, Iacobelli, Simona, Finke, Jürgen, Maertens, Johan, Volin, Liisa, Ljungman, Per, Chevallier, Patrice, Passweg, Jakob, Schaap, Nicolaas, Beelen, Dietrich, Nagler, Arnon, Blaise, Didier, Poiré, Xavier, Yakoub-Agha, Ibrahim, Lenhoff, Stig, Craddock, Charles, Schots, Rik, and Rambaldi, Alessandro
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HEMATOPOIETIC stem cell transplantation , *MYELODYSPLASTIC syndromes treatment , *HOMOGRAFTS , *DELETION mutation , *DISEASE incidence , *SURVIVAL analysis (Biometry) - Abstract
The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [5q]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+ . A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46% (95% CI, 38 to 54), whereas the estimated 4 year survival, relapse-free and overall, was 25% (95% CI, 18 to 33) and 30% (95% CI, 23 to 38), respectively. In a multivariate analysis patients with del (5q) and a blast excess displayed poorer survival (hazard ratio, 2.38; 95% CI, 1.44 to 3.93; P < .001), whereas female recipient sex resulted in improved survival (hazard ratio, .61; 95% CI, .41 to .90; P = .01). We conclude that allogeneic HCT can cure a subset of patients with MDS and a del (5q) abnormality. [ABSTRACT FROM AUTHOR]
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- 2018
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170. Partially anaortic clampless off-pump coronary artery bypass prevents neurologic injury compared to on-pump coronary surgery: a propensity score-matched study on 286 patients.
- Author
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Bassano, Carlo, Bovio, Emanuele, Uva, Floriano, Iacobelli, Simona, Iasevoli, Nicola, Farinaccio, Andrea, and Ruvolo, Giovanni
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CORONARY artery bypass , *CORONARY artery surgery , *NERVOUS system injuries , *REVASCULARIZATION (Surgery) , *PREVENTION , *PATIENTS - Abstract
Anaortic coronary artery bypass proved to prevent early neurologic injury compared to on-pump CABG. The Cardica PAS-Port is a fully automated device that might be able to perform proximal aorto-venous anastomoses without an increased embolic risk. We evaluated early post-operative neurologic outcome in a matched population following clampless OPCAB (CCAB: either 'all-arterial' or with automatically anastomosed venous grafts) or on-pump CABG. 366 consecutive patients were submitted to isolated coronary bypass by a single surgeon experienced in both off and on-pump procedures between January 2009 and December 2013. Of these patients, 223 underwent a clampless off-pump revascularization. After propensity score matching, 143 pairs were selected, who received either off-pump or on-pump surgery. In the off-pump group, CCAB was performed with an all-arterial approach ( n = 33) or with automated proximal anastomosis of the venous graft(s) by means of the Cardica PAS-Port connector ( n = 110). Neurologic injury was defined as non-reversible (NRNI: lethal coma or stroke) or reversible (RNI: TIA or delirium). Operative mortality was 2.4 % (CCAB 1.4 %; CABG 3.5 %; p = 0.14). The global rate of early neurologic injury was 5.6 % (CCAB 2.1 vs. CABG 9.1 %; p = 0.006). Incidence was 1.4 % for NRNI (CCAB 0 vs. CABG 2.8 %; p = 0.04) and 4.2 % for RNI (CCAB 2.1 vs. CABG 6.3 %; p = 0.06). No differences were found among other major perioperative outcomes. CCAB prevents both early post-operative RNI and NRNI. This result can be achieved with a totally anaortic strategy and also with the aid of a fully automated device for proximal aorto-venous anastomoses. [ABSTRACT FROM AUTHOR]
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- 2016
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171. 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
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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
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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.
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- 2018
172. Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?
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Radujkovic, Aleksandar, Guglielmi, Cesare, Bergantini, Stefania, Iacobelli, Simona, van Biezen, Anja, Milojkovic, Dragana, Gratwohl, Alois, Schattenberg, Antonius V.M.B., Verdonck, Leo F., Niederwieser, Dietger W., de Witte, Theo, Kröger, Nicolaus, and Olavarria, Eduardo
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LEUKEMIA treatment , *MYELOID leukemia , *STEM cell transplantation , *GRAFT versus host disease , *CANCER relapse , *BLOOD donors , *MEDICAL statistics , *CD30 antigen , *THERAPEUTICS - Abstract
Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD–free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3 + cells ≥ 50 × 10 6 /kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD. [ABSTRACT FROM AUTHOR]
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- 2015
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173. Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita
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Julián Sevilla, Paul Veys, E T Korthof, Régis Peffault de Latour, Dorine Bresters, Tracey A. O'Brien, Marco Zecca, Maura Faraci, Simona Iacobelli, Jean Hugues Dalle, Antonio M. Risitano, Luca Arcuri, Maurizio Miano, Francesca Fioredda, Ardeshir Ghavamzadeh, Reuven Or, Miguel Angel Diaz, Brune Mats, E V Skorobogatova, Josue de la Fuente, Cora Knol, Petr Sedlacek, Franca Fagioli, Cristina Díaz de Heredia, Ayami Yoshimi, Michael Maschan, Jakub Tolar, Owen P. Smith, Carlo Dufour, Mahmoud Aljurf, Maria Teresa Van Lint, Alain Fisher, Anja van Biezen, Fioredda, Francesca, Iacobelli, Simona, Korthof, Elisabeth T., Knol, Cora, van Biezen, Anja, Bresters, Dorine, Veys, Paul, Yoshimi, Ayami, Fagioli, Franca, Mats, Brune, Zecca, Marco, Faraci, Maura, Miano, Maurizio, Arcuri, Luca, Maschan, Michael, O'Brien, Tracey, Diaz, Miguel A., Sevilla, Julian, Smith, Owen, Peffault de Latour, Regi, de la Fuente, Josue, Or, Reuven, Van Lint, Maria T., Tolar, Jakub, Aljurf, Mahmoud, Fisher, Alain, Skorobogatova, Elena V., Diaz de Heredia, Cristina, Risitano, Antonio, Dalle, Jean-Hugue, Sedláček, Petr, Ghavamzadeh, Ardeshir, and Dufour, Carlo
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,Pulmonary Fibrosis ,haematopoietic stem cell transplantation ,Graft vs Host Disease ,Disease ,dyskeratosis congenita ,Settore MED/01 - Statistica Medica ,Young Adult ,bone marrow failure ,Hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Bone Marrow Diseases ,business.industry ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Bone marrow failure ,medicine.disease ,Survival Analysis ,Tissue Donors ,Transplantation ,Haematopoiesis ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Bone marrow ,Stem cell ,business ,Dyskeratosis congenita ,030215 immunology - Abstract
Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n = 94) patients ever studied. Overall survival (OS) and event-free survival (EFS) at 3 years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20 years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non-myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft-versus-host disease and T-B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre-existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.
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- 2018
174. Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: A single-center cohort study
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Biancone, Livia, Zuzzi, Sara, Ranieri, Micaela, Petruzziello, Carmelina, Calabrese, Emma, Onali, Sara, Ascolani, Marta, Zorzi, Francesca, Condino, Giovanna, Iacobelli, Simona, and Pallone, Francesco
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INTESTINAL fistula , *CROHN'S disease , *ULCERATIVE colitis , *CANCER risk factors , *COHORT analysis , *IMMUNOMODULATORS - Abstract
Abstract: Background & Aims: The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. Methods: In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. Results: IBD population included 1222 patients :615 Crohn''s disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000pt/year vs 2.9/1000pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL,1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08–1.45; UC:HR 1.33;95%CI 1.15–1.55 for an increase by 5years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11–5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05–7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). Conclusions: Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer. [Copyright &y& Elsevier]
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- 2012
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175. Association of aplastic anaemia and lymphoma: a report from the severe aplastic anaemia working party of the European Society of Blood and Bone Marrow Transplantation
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Patrice Chevallier, Harry C. Schouten, Peter Dreger, Anita J. Hill, Judith C. W. Marsh, André Tichelli, Sébastien Maury, Antonio M. Risitano, Carlo Dufour, Régis Peffault de Latour, Simona Iacobelli, Michael Medinger, Benedetto Bruno, Edward Kanfer, Austin G. Kulasekararaj, Alicia Rovó, Mickey Koh, Igor Wolfgang Blau, Paola Quarello, Jose M Ribera, Cora Knol, Jakob Passweg, Rovó, Alicia, Kulasekararaj, Austin, Medinger, Michael, Chevallier, Patrice, Ribera, Jose M., Peffault de Latour, Regi, Knol, Cora, Iacobelli, Simona, Kanfer, Edward, Bruno, Benedetto, Maury, Sébastien, Quarello, Paola, Koh, Mickey B. C., Schouten, Harry, Blau, Igor W., Tichelli, André, Hill, Anita, Risitano, Antonio, Passweg, Jakob, Marsh, Judith, Dreger, Peter, and Dufour, Carlo
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Oncology ,medicine.medical_specialty ,lymphoid neoplasms ,Bone marrow transplantation ,business.industry ,lymphoid neoplasm ,haematopoietic stem cell transplantation ,lymphoma ,Hematology ,medicine.disease ,aplastic anaemia ,Lymphoma ,Settore MED/01 - Statistica Medica ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Lymphoid neoplasms ,610 Medicine & health ,business ,030215 immunology - Published
- 2019
176. Complement C3 vs C5 inhibition in severe COVID-19: Early clinical findings reveal differential biological efficacy.
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Mastellos, Dimitrios C., Pires da Silva, Bruno G.P., Fonseca, Benedito A.L., Fonseca, Natasha P., Auxiliadora-Martins, Maria, Mastaglio, Sara, Ruggeri, Annalisa, Sironi, Marina, Radermacher, Peter, Chrysanthopoulou, Akrivi, Skendros, Panagiotis, Ritis, Konstantinos, Manfra, Ilenia, Iacobelli, Simona, Huber-Lang, Markus, Nilsson, Bo, Yancopoulou, Despina, Connolly, E. Sander, Garlanda, Cecilia, and Ciceri, Fabio
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ECULIZUMAB , *COVID-19 , *ADULT respiratory distress syndrome , *COMPLEMENT inhibition , *PAROXYSMAL hemoglobinuria , *THROMBOTIC thrombocytopenic purpura , *COMPLEMENT activation , *SARS-CoV-2 - Abstract
Growing clinical evidence has implicated complement as a pivotal driver of COVID-19 immunopathology. Deregulated complement activation may fuel cytokine-driven hyper-inflammation, thrombotic microangiopathy and NET-driven immunothrombosis, thereby leading to multi-organ failure. Complement therapeutics have gained traction as candidate drugs for countering the detrimental consequences of SARS-CoV-2 infection. Whether blockade of terminal complement effectors (C5, C5a, or C5aR1) may elicit similar outcomes to upstream intervention at the level of C3 remains debated. Here we compare the efficacy of the C5-targeting monoclonal antibody eculizumab with that of the compstatin-based C3-targeted drug candidate AMY-101 in small independent cohorts of severe COVID-19 patients. Our exploratory study indicates that therapeutic complement inhibition abrogates COVID-19 hyper-inflammation. Both C3 and C5 inhibitors elicit a robust anti-inflammatory response, reflected by a steep decline in C-reactive protein and IL-6 levels, marked lung function improvement, and resolution of SARS-CoV-2-associated acute respiratory distress syndrome (ARDS). C3 inhibition afforded broader therapeutic control in COVID-19 patients by attenuating both C3a and sC5b-9 generation and preventing FB consumption. This broader inhibitory profile was associated with a more robust decline of neutrophil counts, attenuated neutrophil extracellular trap (NET) release, faster serum LDH decline, and more prominent lymphocyte recovery. These early clinical results offer important insights into the differential mechanistic basis and underlying biology of C3 and C5 inhibition in COVID-19 and point to a broader pathogenic involvement of C3-mediated pathways in thromboinflammation. They also support the evaluation of these complement-targeting agents as COVID-19 therapeutics in large prospective trials. • Deregulated complement activation underpins the pathophysiology of severe COVID-19 • Complement inhibition abrogates COVID-19 hyper-inflammation leading to resolution of SARS-CoV-2-associated ARDS • Divergent profiles of C3 vs C5 inhibition point to a broader impact of C3 inhibition on NET-driven thromboinflammation [ABSTRACT FROM AUTHOR]
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- 2020
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177. Stem cell transplantation in severe congenital neutropenia: An analysis from the European Society for Blood and Marrow Transplantation
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Fioredda, F., Iacobelli, S., Biezen, A. van, Gaspar, B., Ancliff, P., Donadieu, J., Aljurf, M., Peters, C., Calvillo, M., Matthes-Martin, S., Morreale, G., van't Veer-Tazelaar, N., Wreede, L. de, Seraihy, A. al, Yesilipek, A., Fischer, A., Bierings, M., Ozturk, G., Smith, O., Veys, P., Ljungman, P., Latour, R.P. de, Codina, J.S.D., Or, R., Ganser, A., Afanasyev, B., Wynn, R., Kalwak, K., Marsh, J., Dufour, C., Pediat Dis Working Parties Europea, Fioredda, Francesca, Iacobelli, Simona, Van Biezen, Anja, Gaspar, Bobby, and Risitano, ANTONIO MARIA
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Male ,Graft Rejection ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Biochemistry ,Allograft ,Retrospective Studie ,Cumulative incidence ,Non-U.S. Gov't ,Child ,Societies, Medical ,Incidence (epidemiology) ,Research Support, Non-U.S. Gov't ,Histocompatibility Testing ,Incidence ,Medicine (all) ,Hematopoietic Stem Cell Transplantation ,Hematology ,Allografts ,Clinical Trial ,Multicenter Study ,Europe ,surgical procedures, operative ,Child, Preschool ,Acute Disease ,Cyclosporine ,Female ,Unrelated Donors ,Kostmann syndrome ,Human ,Adult ,medicine.medical_specialty ,Neutropenia ,Adolescent ,Immunology ,Research Support ,Settore MED/01 - Statistica Medica ,Middle East ,Internal medicine ,Medical ,medicine ,Journal Article ,Humans ,Aplastic anemia ,Congenital Neutropenia ,Preschool ,Retrospective Studies ,business.industry ,Unrelated Donor ,Cell Biology ,medicine.disease ,Surgery ,Transplantation ,Methotrexate ,business ,Societies - Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken.
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- 2015
178. Hematopoietic cell transplantation for older acute myeloid leukemia patients in first complete remission: results of a randomized phase III study.
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Niederwieser D, Hasenclever D, Berdel WE, Biemond BJ, Al-Ali H, Chalandon Y, Van Gelder M, Junghanß C, Gahrton G, Hänel M, Hehlmann R, Heinicke T, Hochhaus A, Iacobelli S, Kooy RVM, Kröger N, Janssen J, Jentzsch M, Breywisch F, Mohty M, Masouridi-Levrat S, Ossenkoppele G, Passweg J, Pönisch W, Schetelig J, Schliemann C, Schwind S, Stelljes M, Verdonck LF, Vucinic V, Löwenberg B, and Cornelissen J
- Abstract
Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/lowdose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to five years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (n=83) or non-HCT (n=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95%CI:18.9-30.1) in the HCT and 15.6 months (95%CI:10.4-20.8) in the non-HCT arm (p=0.022) due to a decrease in cumulative relapse incidence from 91.1 (95%CI:80.7-100.0) after non-HCT to 37.8 (95%CI:27.2-48.4)% after HCT (p.
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- 2024
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179. Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC).
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Niederwieser C, Iacobelli S, Franke GN, Koster L, van Os M, Platzbecker U, Hübel K, Scheid C, Müller LP, Stelljes M, Morozova E, Passweg J, Onida F, Dreger P, Saccardi R, Ladetto M, Salmenniemi U, Bethge W, Poiré X, Kobbe G, McLornan DP, Robin M, and Kröger N
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- Humans, Middle Aged, Adult, Male, Female, Aged, Busulfan therapeutic use, Busulfan administration & dosage, Hematopoietic Stem Cell Transplantation methods, Adolescent, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine administration & dosage, Cyclophosphamide therapeutic use, Myeloablative Agonists therapeutic use, Young Adult, Follow-Up Studies, Prospective Studies, Transplantation Conditioning methods, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality
- Abstract
Short-term outcome of myeloablative (MAC) and reduced intensity (RIC) conditioning in the prospective randomized international EBMT RICMAC study in patients with myelodyplastic syndrome (MDS) was comparable but longer follow up is lacking. Patients with MDS aged 18-65 years were randomized to receive MAC (N = 64) with busulfan/cyclophosphamide or RIC (n = 65) with busulfan/fludarabine followed by stem cell transplantation -(HCT) from HLA matched or mismatched donor. After a median follow-up of 6.2 (0.4-12.5) years, 10-year OS and RFS were 54.0% and 43.9% for RIC and 44.4% and 44.2% for MAC (p = 0.15 and p = 0.78), respectively. Since the first report, 6 patients died on NRM, 4 after RIC, and 2 after MAC. Similarly, 8 patients relapsed (4 in each arm), increasing the number of relapsed patients to 28. The second HCT was performed in 18 pts, 8 in the MAC, and 10 in the RIC arm. In a multivariate analysis, ECOG status and chemotherapy prior to HCT were independent risk factors for OS and RFS, ECOG and low cytogenetic risk for NRM and chemotherapy prior to HCT for RI. Patients with low cytogenetic risk had better OS [p = 0.002], RFS [p = 0.02], and NRM (p = 0.015) after RIC as compared to MAC., (© 2024. The Author(s).)
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- 2024
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180. Correction: Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.
- Author
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Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, Salmenniemi U, Dreger P, von dem Borne P, Snowden JA, Robinson S, Finazzi MC, Schroeder T, Collin M, Eder M, Forcade E, Loschi M, Bramanti S, Pérez-Simón JA, Czerw T, Polverelli N, Drozd-Sokolowska J, Raj K, Hernández-Boluda JC, and McLornan DP
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- 2024
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181. Treosulfan compared to busulfan in allogeneic haematopoietic stem cell transplantation for myelofibrosis: a registry-based study from the Chronic Malignancies Working Party of the EBMT.
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Robin M, Iacobelli S, Koster L, Passweg J, Avenoso D, Wilson KMO, Salmenniemi U, Dreger P, von dem Borne P, Snowden JA, Robinson S, Finazzi MC, Schroeder T, Collin M, Eder M, Forcade E, Loschi M, Bramanti S, Pérez-Simón JA, Czerw T, Polverelli N, Drozd-Sokolowska J, Raj K, Hernández-Boluda JC, and McLornan DP
- Subjects
- Humans, Middle Aged, Male, Female, Adult, Aged, Transplantation Conditioning methods, Transplantation, Homologous methods, Graft vs Host Disease mortality, Busulfan analogs & derivatives, Busulfan therapeutic use, Primary Myelofibrosis therapy, Primary Myelofibrosis mortality, Hematopoietic Stem Cell Transplantation methods, Registries
- Abstract
We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.4 mg/kg in 323 considered higher dose (HD)). Groups were compared using adjusted Cox models. Cumulative incidences of engraftment and acute GVHD were similar across the 3 groups. The TREO group had significantly better OS than BU-HD (HR:0.61, 95% CI: 0.39-0.93) and a trend towards better OS over BU-RIC (HR: 0.66, 95% CI: 0.41-1.05). Moreover, the TREO cohort had a significantly better Progression-Free-Survival (PFS) than both the BU-HD (HR: 0.57, 95% CI: 0.38-0.84) and BU-RIC (HR: 0.60, 95% CI: 0.39-0.91) cohorts, which had similar PFS estimates. Non-relapse mortality (NRM) was reduced in the TREO and BU-RIC cohorts (HR: 0.44, 95% CI: 0.24-0.80 TREO vs BU-HD; HR: 0.54, 95% CI: 0.28-1.04 TREO vs BU-RIC). Of note, relapse risk did not significantly differ across the three groups. In summary, within the limits of a registry-based study, TREO conditioning may improve PFS in MF HSCT and have lower NRM than BU-HD with a similar relapse risk to BU-RIC. Prospective studies are needed to confirm these findings., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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182. Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients - A clinical trial to registry data comparison.
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Beelen DW, Iacobelli S, Koster L, Eikema DJ, van Biezen A, Stölzel F, Ciceri F, Bethge W, Dreger P, Wagner-Drouet EM, Reményi P, Stelljes M, Markiewicz M, McLornan DP, Yakoub-Agha I, and Mohty M
- Subjects
- Humans, Aged, Middle Aged, Female, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Hematopoietic Stem Cell Transplantation methods, Busulfan analogs & derivatives, Busulfan therapeutic use, Busulfan administration & dosage, Busulfan pharmacology, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine pharmacology, Vidarabine administration & dosage, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes drug therapy, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Cyclophosphamide pharmacology, Transplantation Conditioning methods, Registries, Melphalan therapeutic use, Melphalan administration & dosage, Melphalan pharmacology
- Abstract
A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients., (© 2024. The Author(s).)
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- 2024
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183. Plain language summary of RACE study results: addition of eltrombopag to standard treatment of severe aplastic anemia.
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de Latour RP, Kulasekararaj A, Iacobelli S, Griffin M, Halkes CJ, Dufour C, and Risitano AM
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- Humans, Antilymphocyte Serum therapeutic use, Cyclosporine therapeutic use, Benzoates therapeutic use, Immunosuppressive Agents therapeutic use, Treatment Outcome, Anemia, Aplastic drug therapy
- Abstract
What Is This Summary About?: Severe aplastic anemia (SAA) and very severe aplastic anemia (vSAA) are blood diseases of the bone marrow. If a suitable donor for bone marrow transplant as initial treatment is unavailable, standard immunosuppression is used. Standard immunosuppression treatment includes horse antithymocyte globulin (hATG) and cyclosporin A (CsA). This summary investigated the results of standard immunosuppression treatment (Group A) versus standard immunosuppression treatment with a medication called eltrombopag (Group B) in participants with SAA and vSAA. Eltrombopag is a medicine that improves the blood platelet level and is taken by mouth (orally)., What Were the Results of the Study?: Compared to Group A, more participants in Group B showed increased blood cell level to a normal range without SAA or vSAA and faster treatment response. Side effects were similar in both groups even with the addition of eltrombopag for Group B. Participants in both groups reported feeling well after 6, 12 and 24 months. Differences in the participant-reported scores (overall health, physical, emotional, and social) between Group A and Group B were minimal., What Do the Results of the Study Mean?: Immunosuppression treatment (hATG plus CsA) with eltrombopag benefited participants with SAA and vSAA and could be the new standard for SAA in persons who cannot undergo bone marrow transplant. At this time, eltrombopag is only approved in specific countries to treat the condition under study that is discussed in this summary. Clinical Trial Registration: NCT02099747 (RACE study).
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- 2024
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184. Correction: An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.
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Beksac M, Iacobelli S, Koster L, Cornelissen J, Griskevicius L, Rabin NK, Stoppa AM, Meijer E, Mear JB, Zeerleder S, Mayer J, Fenk R, Fegueux N, Chevallier P, Konirova E, Snowden JA, Engelhardt M, Orchard K, Hulin C, Schaap N, Sossa C, Elmaagacli A, McLornan DP, Hayden PJ, Schönland S, and Yakoub-Agha I
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- 2023
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185. An early post-transplant relapse prediction score in multiple myeloma: a large cohort study from the chronic malignancies working party of EBMT.
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Beksac M, Iacobelli S, Koster L, Cornelissen J, Griskevicius L, Rabin NK, Stoppa AM, Meijer E, Mear JB, Zeerleder S, Mayer J, Fenk R, Fegueux N, Chevallier P, Konirova E, Snowden JA, Engelhardt M, Orchard K, Hulin C, Schaap N, Sossa C, Elmaagacli A, McLornan DP, Hayden PJ, Schönland S, and Yakoub-Agha I
- Subjects
- Humans, Cohort Studies, Neoplasm Recurrence, Local, Transplantation Conditioning, Melphalan, Transplantation, Autologous, Multiple Myeloma therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Early relapse (ER) following Autologous Hematopoietic Cell Transplantation (AHCT) confers a poor prognosis. We therefore developed a novel scoring system to predict ER. A total of 14,367 AHCT-1 patients were transplanted between 2014 and 2019, and were conditioned with Melphalan 200 mg/m
2 (Mel200) (n = 7228; 2014-2017) (training cohort); Mel200 (n = 5616; 2018-2019) or Mel140 (n = 1523; 2018-2019) (validation cohorts). PFS-12 and the Cumulative Incidence of Relapse at 12 months were 84.1% and 14.7% (training Mel200), 87.2% and 11.6% (validation Mel200), and 80.3% and 16.9% (validation Mel140), respectively. The points in the risk score were: 0, 1,2 for ISS stages I, II, and III; Disease status: 0 (CR/VGPR); 1 (PR); 2 (SD/MR); 4 (Relapse/Progression); and 1 for Karnofsky ≤ 70. The distribution of scores: 0 (24%), 1 (33.9%), 2 (29.6 %), 3 (9.5%), and ≥4 (2.7%). The score separated PFS-12, with the lowest risk group (n = 1752) having a PFS-12 of 91.7% and the highest risk group (n = 195) 57.1%. This also applied in cytogenetically high-risk patients. If the pre-score baseline risks are 15% (standard risk) and 25% (high-risk), a score of ≥4 confers calculated risks of 38% and 54%, respectively. This novel EBMT ER score, therefore, allows for the identification of five discrete prognostic groups., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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186. Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modeling.
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Lawless S, Iacobelli S, Knelange NS, Chevallier P, Blaise D, Milpied N, Foà R, Cornelissen JJ, Lioure B, Benjamin R, Poiré X, Minnema MC, Collin M, Lenhoff S, Snowden JA, Santarone S, Wilson KMO, Trigo F, Dreger P, Böhmer LH, Putter H, Garderet L, Kröger N, Yaukoub-Agha I, Schönland S, and Morris C
- Subjects
- Humans, Retrospective Studies, Transplantation, Homologous, Disease-Free Survival, Transplantation, Autologous, Recurrence, Leukemia, Plasma Cell diagnosis, Leukemia, Plasma Cell therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR]=0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.
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- 2023
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187. Complement C3 inhibition in severe COVID-19 using compstatin AMY-101.
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Skendros P, Germanidis G, Mastellos DC, Antoniadou C, Gavriilidis E, Kalopitas G, Samakidou A, Liontos A, Chrysanthopoulou A, Ntinopoulou M, Kogias D, Karanika I, Smyrlis A, Cepaityte D, Fotiadou I, Zioga N, Mitroulis I, Gatselis NK, Papagoras C, Metallidis S, Milionis H, Dalekos GN, Willems L, Persson B, Manivel VA, Nilsson B, Connolly ES, Iacobelli S, Papadopoulos V, Calado RT, Huber-Lang M, Risitano AM, Yancopoulou D, Ritis K, and Lambris JD
- Abstract
Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 ( n = 16) or placebo ( n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81.3%) were free of supplemental oxygen at day 14. Three nonresponders and two placebo-treated patients succumbed to disease-related complications. AMY-101 significantly reduced CRP and ferritin and restrained thrombin and NET generation. Complete and sustained C3 inhibition was observed in all responders. Residual C3 activity in the three nonresponders suggested the presence of a convertase-independent C3 activation pathway overriding the drug's inhibitory activity. These findings support the design of larger trials exploring the potential of C3-based inhibition in COVID-19 or other complement-mediated diseases.
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- 2022
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188. Prognostic value of a new clinically-based classification system in patients with CMML undergoing allogeneic HCT: a retrospective analysis of the EBMT-CMWP.
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Onida F, Sbianchi G, Radujkovic A, Sockel K, Kröger N, Sierra J, Socié G, Cornelissen J, Poiré X, Raida L, Bourhis JH, Finke J, Passweg J, Salmenniemi U, Schouten HC, Beguin Y, Martin S, Deconinck E, Ganser A, Zver S, Lioure B, Rohini R, Koster L, Hayden P, Iacobelli S, Robin M, and Yakoub-Agha I
- Subjects
- Humans, Prognosis, Retrospective Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myelomonocytic, Chronic
- Abstract
Recently a new three-group clinical classification was reported by an International Consortium to stratify CMML patients with regard to prognosis. The groups were defined as follows: (1) Myelodysplastic (MD)-CMML: WBC ≤ 10 × 10
9 /l, circulating immature myeloid cells (IMC) = 0, no splenomegaly; (2) MD/MP (overlap)-CMML: WBC 10-20 × 109 /l or WBC ≤ 10 × 109 /l but IMC > 0 and/or splenomegaly; (3) Myeloproliferative (MP)-CMML: WBC > 20 × 109 /l. By analysing EBMT Registry patients who underwent allo-HCT for CMML between 1997 and 2016, we aimed to determine the impact of this classification on transplantation outcome and to make a comparison with the conventional WHO classification (CMML-0/CMML-1/CMML-2). Patient grouping was based on the data registered at time of transplantation, with IMC replaced by peripheral blasts. Among 151 patients included in the analysis, 38% were classified as MD-CMML, 42% as MD/MP-CMML and 20% as MP-CMML. With a median survival of 17 months in the whole series, MD-CMML patients were distinguished as a low-risk group with higher CR rate at transplant and a longer post-transplant 2-year progression-free survival in comparison to others (44.5% vs 33.5%, respectively), whereas the WHO classification was superior in identifying high-risk patients (CMML-2) with inferior survival outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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189. Analyzing differences between restricted mean survival time curves using pseudo-values.
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Ambrogi F, Iacobelli S, and Andersen PK
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- Humans, Proportional Hazards Models, Survival Analysis, Survival Rate, Research Design, Software
- Abstract
Hazard ratios are ubiquitously used in time to event analysis to quantify treatment effects. Although hazard ratios are invaluable for hypothesis testing, other measures of association, both relative and absolute, may be used to fully elucidate study results. Restricted mean survival time (RMST) differences between groups have been advocated as useful measures of association. Recent work focused on model-free estimates of the difference in restricted mean survival through follow-up times, instead of focusing on a single time horizon. The resulting curve can be used to quantify the association in time units with a simultaneous confidence band. In this work a model-based estimate of the curve is proposed using pseudo-values allowing for possible covariate adjustment. The method is easily implementable with available software and makes possible to compute a simultaneous confidence region for the curve. The pseudo-values regression using multiple restriction times is in good agreement with the estimates obtained by standard direct regression models fixing a single restriction time. Moreover, the proposed method is flexible enough to reproduce the results of the non-parametric approach when no covariates are considered. Examples where it is important to adjust for baseline covariates will be used to illustrate the different methods together with some simulations., (© 2022. The Author(s).)
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- 2022
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190. Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT.
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Czerw T, Iacobelli S, Malpassuti V, Koster L, Kröger N, Robin M, Maertens J, Chevallier P, Watz E, Poiré X, Snowden JA, Kuball J, Kinsella F, Blaise D, Reményi P, Mear JB, Cammenga J, Rubio MT, Maury S, Daguindau E, Finnegan D, Hayden P, Hernández-Boluda JC, McLornan D, and Yakoub-Agha I
- Subjects
- Adult, Aged, Humans, Middle Aged, Retrospective Studies, Transplantation Conditioning, Unrelated Donors, Young Adult, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms etiology, Primary Myelofibrosis therapy
- Abstract
The optimal CD34 + cell dose in the setting of RIC allo-HCT for myelofibrosis (MF) remains unknown. We retrospectively analyzed 657 patients with primary or secondary MF transplanted with use of peripheral blood (PB) stem cells after fludarabine/melphalan or fludarabine/busulfan RIC regimen. Median patient age was 58 (range, 22-76) years. Donors were HLA-identical sibling (MSD) or unrelated (UD). Median follow-up was 46 (2-194) months. Patients transplanted with higher doses of CD34 + cells (>7.0 × 10
6 /kg), had an increased chance of achievement of both neutrophil (hazard ratio (HR), 1.46; P < 0.001) and platelet engraftment (HR, 1.43; P < 0.001). In a model with interaction, for patients transplanted from a MSD, higher CD34 + dose was associated with improved overall survival (HR, 0.63; P = 0.04) and relapse-free survival (HR, 0.61; P = 0.02), lower risk of non-relapse mortality (HR, 0.57; P = 0.04) and higher rate of platelet engraftment. The combined effect of higher cell dose and UD was apparent only for higher neutrophil and platelet recovery rate. We did not document any detrimental effect of high CD34 + dose on transplant outcomes. More bulky splenomegaly was an adverse factor for survival, engraftment and NRM. Our analysis suggests a potential benefit for MF patients undergoing RIC PB-allo-HCT receiving more than 7.0 × 106 /kg CD34 + cells., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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191. Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia.
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Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, Halkes CJM, Recher C, Barraco F, Forcade E, Vallejo JC, Drexler B, Mear JB, Smith AE, Angelucci E, Raymakers RAP, de Groot MR, Daguindau E, Nur E, Barcellini W, Russell NH, Terriou L, Iori AP, La Rocca U, Sureda A, Sánchez-Ortega I, Xicoy B, Jarque I, Cavenagh J, Sicre de Fontbrune F, Marotta S, Munir T, Tjon JML, Tavitian S, Praire A, Clement L, Rabian F, Marano L, Hill A, Palmisani E, Muus P, Cacace F, Frieri C, van Lint MT, Passweg JR, Marsh JCW, Socié G, Mufti GJ, Dufour C, and Risitano AM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Anemia, Aplastic drug therapy, Anemia, Aplastic genetics, Antilymphocyte Serum adverse effects, Benzoates adverse effects, Cyclosporine adverse effects, Drug Therapy, Combination, Female, Humans, Hydrazines adverse effects, Immunosuppressive Agents adverse effects, Male, Middle Aged, Progression-Free Survival, Prospective Studies, Pyrazoles adverse effects, Receptors, Thrombopoietin agonists, Remission Induction, Young Adult, Anemia, Aplastic therapy, Antilymphocyte Serum therapeutic use, Benzoates therapeutic use, Cyclosporine therapeutic use, Hydrazines therapeutic use, Immunosuppression Therapy, Immunosuppressive Agents therapeutic use, Pyrazoles therapeutic use
- Abstract
Background: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia., Methods: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months., Results: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome., Conclusions: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.)., (Copyright © 2022 Massachusetts Medical Society.)
- Published
- 2022
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192. Outcomes and toxicity of allogeneic hematopoietic cell transplantation in chronic myeloid leukemia patients previously treated with second-generation tyrosine kinase inhibitors: a prospective non-interventional study from the Chronic Malignancy Working Party of the EBMT.
- Author
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Masouridi-Levrat S, Olavarria E, Iacobelli S, Aljurf M, Morozova E, Niittyvuopio R, Sengeloev H, Reményi P, Helbig G, Browne P, Ganser A, Nagler A, Snowden JA, Robin M, Passweg J, Van Gorkom G, Wallet HL, Hoek J, Blok HJ, De Witte T, Kroeger N, Hayden P, Chalandon Y, and Agha IY
- Subjects
- Dasatinib adverse effects, Humans, Imatinib Mesylate adverse effects, Middle Aged, Prospective Studies, Protein Kinase Inhibitors adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
- Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients., (© 2021. The Author(s).)
- Published
- 2022
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193. IgD Subtype But Not IgM or Non-Secretory Is a Prognostic Marker for Poor Survival Following Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. Results From the EBMT CALM (Collaboration to Collect Autologous Transplant Outcomes in Lymphomas and Myeloma) Study.
- Author
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Lawless S, Sbianchi G, Morris C, Iacobelli S, Bosman P, Blaise D, Reményi P, Byrne JL, Mayer J, Apperley J, Lund J, Kobbe G, Schaap N, Isaksson C, Lenhoff S, Basak G, Touzeau C, Wilson KMO, González Muñiz S, Scheid C, Browne P, Anagnostopoulos A, Rambaldi A, Jantunen E, Kröger N, Schönland S, Yakoub-Agha I, and Garderet L
- Subjects
- Adult, Aged, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Multiple Myeloma, Progression-Free Survival, Survival Analysis, Transplantation Conditioning mortality, Transplantation, Autologous mortality, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation methods, Immunoglobulin D metabolism, Transplantation Conditioning methods, Transplantation, Autologous methods
- Abstract
Background: The Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study has provided an opportunity to evaluate the real-world outcomes of patients with myeloma. The aim of this study was to compare the outcome according to the different subtypes of myeloma using CALM data., Patients: This study compared overall survival (OS), progression-free survival (PFS), and complete remission (CR) and the impact of novel versus non-novel drug containing induction regimens prior to autologous hematopoietic cell transplantation (HCT) of 2802 patients with "usual" and "rare" myelomas., Results: Our data suggest that IgM and non-secretory myeloma have superior PFS and OS compared with IgD myeloma and outcomes comparable to those for usual myeloma. Patients who received novel agent induction had higher rates of CR prior to transplant. Non-novel induction regimens were associated with inferior PFS but no difference in OS. Although not the primary focus of this study, we show that poor mobilization status is associated with reduced PFS and OS, but these differences disappear in multivariate analysis suggesting that poor mobilization status is a surrogate for other indicators of poor prognosis., Conclusion: We confirm that IgD myeloma is associated with the worst prognosis and inferior outcomes compared with the other isotypes., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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194. Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT.
- Author
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Gagelmann N, Eikema DJ, de Wreede LC, Rambaldi A, Iacobelli S, Koster L, Caillot D, Blaise D, Remémyi P, Bulabois CE, Passweg J, Leleu X, Zver S, Kobbe G, Ljungman P, Chevallier P, Ringhoffer M, Martin M, Salmenniemi U, Poiré X, Lenhoff S, Pioltelli P, Mordini N, Delforge M, Garderet L, Schönland S, Yakoub-Agha I, and Kröger N
- Subjects
- Disease-Free Survival, Humans, Neoplasm Recurrence, Local, Stem Cell Transplantation, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Abstract
We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).
- Published
- 2021
- Full Text
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195. Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation.
- Author
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Hernández-Boluda JC, Pereira A, Kröger N, Beelen D, Robin M, Bornhäuser M, Angelucci E, Vitek A, Blau IW, Niittyvuopio R, Finke J, Cornelissen JJ, Passweg J, Dreger P, Petersen E, Kanz L, Sanz J, Zuckerman T, Zinger N, Iacobelli S, Hayden P, Czerw T, McLornan D, and Yakoub-Agha I
- Subjects
- Europe, Female, Graft vs Host Disease etiology, Humans, Kaplan-Meier Estimate, Male, Primary Myelofibrosis diagnosis, Primary Myelofibrosis epidemiology, Prognosis, Proportional Hazards Models, Recurrence, Registries, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy
- Abstract
We aimed to evaluate the determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) and to describe factors predicting the main post-HCT complications. This retrospective study by the European Society for Blood and Marrow Transplantation included 2916 myelofibrosis patients who underwent first allo-HCT from an HLA-identical sibling or unrelated donor between 2000 and 2016. After a median follow-up of 4.7 years from transplant, projected median survival of the series was 5.3 years. Factors independently associated with increased mortality were age ≥ 60 years and Karnofsky Performance Status <90% at transplant, and occurrence of graft failure, grades III-IV acute graft-vs.-host disease (aGVHD), and disease progression/relapse during follow-up. The opposing effects of chronic graft-vs.-host disease (GVHD) on non-relapse mortality and relapse incidence resulted in a neutral influence on survival. Graft failure increased in unrelated donor recipients and decreased with myeloablative conditioning (MAC) and negative donor/recipient cytomegalovirus serostatus. Risk of grades III-IV aGVHD was higher with unrelated donors and decreased with MAC. Relapse incidence tended to be higher in patients with intermediate-2/high-risk DIPSS categories and to decrease in CALR-mutated patients. Acute and chronic GVHD reduced the subsequent risk of relapse. This information has potential implications for patient counseling and clinical decision-making.
- Published
- 2021
- Full Text
- View/download PDF
196. Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation.
- Author
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Costa LJ, Iacobelli S, Pasquini MC, Modi R, Giaccone L, Blade J, Schonland S, Evangelista A, Perez-Simon JA, Hari P, Brown EE, Giralt SA, Patriarca F, Stadtmauer EA, Rosinol L, Krishnan AY, Gahrton G, and Bruno B
- Subjects
- Disease-Free Survival, Humans, Neoplasm Recurrence, Local, Transplantation Conditioning, Transplantation, Autologous, Transplantation, Homologous, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation
- Abstract
Contrary to tandem autologous transplant (auto-auto), autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers graft-versus-myeloma (GVM) effect but with higher toxicity. Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological randomization) and yielded conflicting results. A pooled analysis of multiple trials with extended follow up provides an opportunity to compare these strategies. We obtained individual patient data from participants of four trials comparing auto-auto vs. auto-allo after induction therapy. There were 899 patients in auto-auto and 439 in auto-allo. Median follow up of survivors was 118.5 months. Median overall survival (OS) was 78.0 months in auto-auto and 98.3 months in auto-allo (HR = 0.84, P = 0.02). OS was 36.4% vs. 44.1% at 10 years (P = 0.01) for auto-auto and auto-allo, respectively. Progression-free survival was also improved in auto-allo (HR = 0.84, P = 0.004). Risk of non-relapse mortality was higher in auto-allo (10 year 8.3% vs. 19.7%, P < 0.001), while risk of disease progression was higher in auto-auto (10 year 77.2% vs. 61.6%, P < 0.001). Median post relapse survival was 41.5 months in auto-auto and 62.3 months in auto-allo (HR = 0.71, P < 0.001). This supports the existence of durable GVM effect enhancing myeloma control with subsequent therapies.
- Published
- 2020
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197. Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor.
- Author
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Morris C, Chabannon C, Masszi T, Russell N, Nahi H, Kobbe G, Krejci M, Auner HW, Pohlreich D, Hayden P, Basak GW, Lenhoff S, Schaap N, van Biezen A, Knol C, Iacobelli S, Liu Q, Celanovic M, Garderet L, and Kröger N
- Subjects
- Benzylamines, Cyclams, Hematopoietic Stem Cell Mobilization, Humans, Neoplasm Recurrence, Local, Registries, Heterocyclic Compounds, Multiple Myeloma therapy
- Abstract
Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of hematopoietic stem cells (HSCs) for collection and subsequent autologous hematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM). This international, multicenter, noninterventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF + plerixafor (G-CSF + P) versus G-CSF-; G-CSF + P versus G-CSF + chemotherapy (G-CSF + C); and G-CSF + P + C versus G-CSF + C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF + P versus G-CSF cohorts, 129 versus 129 in the G-CSF + P versus G-CSF + C cohorts, and 117 versus 117 in the G-CSF + P + C versus G-CSF + C cohorts were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded prespecified boundaries; noninferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF + P remains an option for the mobilization of HSCs in poor mobilizers with MM with no substantial differences in PFS, OS, and CIR in comparison with other regimens.
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- 2020
- Full Text
- View/download PDF
198. Autoimmune cytopenias (AIC) following allogeneic haematopoietic stem cell transplant for acquired aplastic anaemia: a joint study of the Autoimmune Diseases and Severe Aplastic Anaemia Working Parties (ADWP/SAAWP) of the European Society for Blood and Marrow Transplantation (EBMT).
- Author
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Miller PDE, Snowden JA, De Latour RP, Iacobelli S, Eikema DJ, Knol C, Marsh JCW, Rice C, Koh M, Fagioli F, Chaganti S, Finke J, Duarte RF, Bader P, Farge D, Passweg JR, Madrigal JA, and Dufour C
- Subjects
- Adult, Bone Marrow, Child, Humans, Retrospective Studies, Transplantation Conditioning adverse effects, Treatment Outcome, Anemia, Aplastic therapy, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
This retrospective study explored the incidence of autoimmune cytopenia (AIC) in 530 paediatric and adult patients with acquired aplastic anaemia (aAA) who underwent first allogeneic HSCT between 2002 and 2012. AIC was a rare complication with a cumulative incidence of AIC at 1, 3, 5 and 10 years post HSCT of 2.5% (1.2-3.9 95% CI), 4.4% (2.6-6.2 95% CI), 4.6% (2.8-6.5 95% CI) and 5.1% (3.1-7.2 95% CI). Overall survival at 5 years after diagnosis of AIC was 85.9% (71-100 95% CI). Twenty-five patients were diagnosed with AIC at a median of 10.6 (2.6-91.5) months post HSCT. Eight (32%) patients were diagnosed with immune thrombocytopenia (ITP), seven (28%) with autoimmune haemolytic anaemia (AIHA), seven (24%) with Evans syndrome and four (16%) with autoimmune neutropenia (AIN). Treatment strategies were heterogeneous. Complete responses were seen in 12 of 25 patients, with death in three patients. In multivariable Cox analysis of a subgroup of 475 patients, peripheral blood stem cell (PBSC) transplant was associated with higher risk of AIC compared with bone marrow (BM) when conditioning regimens contained fludarabine and/or alemtuzumab (2.81 [1.06-7.49 95% CI]; p = 0.038), or anti-thymocyte globulin (ATG) (2.86 [1.11-7.37 95% CI]; p = 0.029). Myeloablative conditioning was associated with a lower risk of AIC compared with reduced intensity conditioning (RIC) in fludarabine and/or alemtuzumab (0.34 [0.12-0.98 95% CI]; p = 0.046) and ATG containing regimens (0.34 [0.12-0.95 95% CI]; p = 0.04). These findings provide clinically useful information regarding the incidence of a rare and potentially life-threatening complication of allogeneic HSCT for aAA, and further support for BM as the preferred stem cell source for transplant of patients with aAA.
- Published
- 2020
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199. Statistical Methods in HSCT and Cellular Therapies
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Iacobelli S, de Wreede LC, Carreras E, Dufour C, Mohty M, and Kröger N
- Abstract
The analysis of data describing the outcomes of patients who have received an HSCT is not only fundamental to assessing the effectiveness of the treatment but can provide invaluable information on the prognostic role of disease and patient factors. Thus, the appropriate analysis and understanding of such data are of paramount importance. This document provides an overview of the main and well-established statistical methods, as well as a brief introduction of more novel techniques. More insight is provided in the EBMT Statistical Guidelines (Iacobelli 2013)., (Copyright 2019, EBMT and the Author(s).)
- Published
- 2019
- Full Text
- View/download PDF
200. Protective environment for hematopoietic cell transplant (HSCT) recipients: The Infectious Diseases Working Party EBMT analysis of global recommendations on health-care facilities.
- Author
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Styczynski J, Tridello G, Donnelly JP, Iacobelli S, Hoek J, Mikulska M, Aljurf M, Gil L, and Cesaro S
- Subjects
- Air Filters standards, Humans, Infection Control, Surveys and Questionnaires, Guideline Adherence statistics & numerical data, Hematopoietic Stem Cell Transplantation standards, Patients' Rooms standards, Practice Guidelines as Topic standards
- Abstract
International guidelines on protective environment for HSCT recipients proposed a set of 10 global recommendations in 2009 on protective environment (GRPE) concerning hospital room design and ventilation. The EBMT Infectious Diseases Working Party undertook a survey on the status on protective environment for HSCT recipients with the aim of surveying current practices and their agreement with GRPE recommendations. The questionnaire consisted of 37 questions divided into 5 sections about filtration, air changes, maintenance, and the protective environment in rooms and the surrounding unit. Overall, 177 centres (response rate 33%) from 36 countries responded, indicating that 99.4% of patient rooms were equipped with HEPA filters, but only 48.6% of the centre's staff were aware of, and could confirm, regular replacement of filters based on manufacturers' recommendations. Well-sealed rooms were used in terms of windows (70.6%), ceilings (35%), and plumbing pipes (51.4%). The sensor monitors in the patient room used to determine when the HEPA filters require changing were installed only in 18.1% of centres. Only 1 centre fulfilled all 10 GRPE recommendations, while 62 centres fulfilled the 3 level "A" recommendations. In conclusion, HEPA-filtered rooms are available in almost all centres, while fewer centres fulfilled other requirements. Knowledge on the details and maintenance of protective environments in the HSCT setting was inadequate, reflecting a lack of communication between the health personnel involved, hospital infection control and the hospital maintenance services.
- Published
- 2018
- Full Text
- View/download PDF
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