45 results on '"di Grazia, C."'
Search Results
2. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome
- Author
-
Mikulska, M., Nicolini, L., Signori, A., Rivoli, G., Del Bono, V., Raiola, A.M., Di Grazia, C., Dominietto, A., Varaldo, R., Ghiso, A., Bacigalupo, A., and Viscoli, C.
- Published
- 2014
- Full Text
- View/download PDF
3. DLI after haploidentical BMT with post-transplant CY
- Author
-
Ghiso, A, Raiola, A M, Gualandi, F, Dominietto, A, Varaldo, R, Van Lint, M T, Bregante, S, Di Grazia, C, Lamparelli, T, Galaverna, F, Stasia, A, Luchetti, S, Geroldi, S, Grasso, R, Colombo, N, and Bacigalupo, A
- Published
- 2015
- Full Text
- View/download PDF
4. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update
- Author
-
Bacigalupo, A, Dominietto, A, Ghiso, A, Di Grazia, C, Lamparelli, T, Gualandi, F, Bregante, S, Van Lint, M T, Geroldi, S, Luchetti, S, Grasso, R, Pozzi, S, Colombo, N, Tedone, E, Varaldo, R, and Raiola, A M
- Published
- 2015
- Full Text
- View/download PDF
5. Assessment of orbital volume and morphological changes after rapid maxillary expansion performed with tooth-bone and bone-borne devices. A retrospective study using surface-to surface matching technique
- Author
-
Nicotra, C, Ronsivalle, V, Casella, F, Di Grazia, C, Isola, G, and Lo Giudice, A
- Published
- 2020
6. Enhancing the diagnosis of maxillary transverse discrepancy through 3-D technology and surface-to-surface superimposition. Description of the digital workflow with a documented case report
- Author
-
Lo Giudice, A, Nucera, R, Ronsivalle, V, Di Grazia, C, Rugeri, M, and Quinzi, V
- Subjects
Palatal Expansion Technique ,Surface-to-surface superimposition ,Maxilla ,Humans ,Female ,Digital work-flow ,Maxillary transverse discrepancy ,3-D technology ,Child ,Workflow ,Malocclusion - Abstract
Maxillary transverse discrepancy is often diagnosed in childhood. The evaluation of morphological characteristics of the maxilla is crucial for appropriate treatment of this condition, however conventional diagnostic method is based on visual inspection and transversal linear parameters. In this paper, we described a user-friendly diagnostic digital workflow based on the surface-to-surface analysis. We also described a case report.A 6-year-old female patient presenting mild transversal maxillary deficiency associated with functional posterior crossbite was treated by using maxillary removable appliance. In this respect, the appliance was designed in accordance to the morphological characteristics of the maxilla obtained by using the diagnostic digital work-flow and the maxillary surface-to-surface analysis.The present user-friendly diagnostic digital workflow based on surface-to-surface analysis helps clinicians to detect specific morphological characteristics of the maxilla, such as shape and area of asymmetry, in order to reach a comprehensive diagnosis and choose the correct biomechanics for treating the condition.
- Published
- 2020
7. S1624 A DAY 100 LAB-SCORE PREDICTS EXTENSIVE CGVHD, OVERALL SURVIVAL AND TRANSPLANT-RELATED MORTALITY AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: FINAL ANALYSIS
- Author
-
Metafuni, E., primary, Cavattoni, I., additional, Lamparellli, T., additional, Raiola, A.M., additional, Ghiso, A., additional, Galaverna, F., additional, Gualandi, F., additional, Di Grazia, C., additional, Dominietto, A., additional, Varaldo, R., additional, Van Lint, M.T., additional, Angelucci, E., additional, and Bacigalupo, A., additional
- Published
- 2019
- Full Text
- View/download PDF
8. Serial monitoring of isavuconazole blood levels during prolonged antifungal therapy
- Author
-
Furfaro, E, primary, Signori, A, additional, Di Grazia, C, additional, Dominietto, A, additional, Raiola, A M, additional, Aquino, S, additional, Ghiggi, C, additional, Ghiso, A, additional, Ungaro, R, additional, Angelucci, E, additional, Viscoli, C, additional, and Mikulska, M, additional
- Published
- 2019
- Full Text
- View/download PDF
9. DLI after haploidentical BMT with post-transplant CY
- Author
-
Ghiso, A, primary, Raiola, A M, additional, Gualandi, F, additional, Dominietto, A, additional, Varaldo, R, additional, Van Lint, M T, additional, Bregante, S, additional, Di Grazia, C, additional, Lamparelli, T, additional, Galaverna, F, additional, Stasia, A, additional, Luchetti, S, additional, Geroldi, S, additional, Grasso, R, additional, Colombo, N, additional, and Bacigalupo, A, additional
- Published
- 2014
- Full Text
- View/download PDF
10. Small bowel intussussception due to metastatic melanoma of unknown primary site. Case report.
- Author
-
STAGNITTI, F., ORSINI, S., MARTELLUCCI, A., TUDISCO, A., AVALLONE, M., AIUTI, F., DI GIROLAMO, V., STEFANELLI, F., DE ANGELIS, F., COSTANTINO, A., DI GRAZIA, C., NAPOLEONI, A., NICODEMI, S., CIPRIANI, B., CECI, F., MOSILLO, R., CORELLI, S., CASCIARO, G., and SPAZIANI, E.
- Published
- 2014
11. Biliodigestive fistulae and gallstone ileus: diagnostic and therapeutic considerations. Our experience.
- Author
-
STAGNITTI, F., TUDISCO, A., CECI, F., NICODEMI, S., ORSINI, S., AVALLONE, M., DI GIROLAMO, V., STEFANELLI, F., DE ANGELIS, F., DI GRAZIA, C., CIPRIANI, B., AIUTI, F., NAPOLEONI, A., MOSILLO, R., CORELLI, S., CASCIARO, G., COSTANTINO, A., MARTELLUCCI, A., and SPAZIANI, E.
- Published
- 2014
12. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes
- Author
-
Elisabetta Sauta, Marie Robin, Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Lin-Pierre Zhao, Juan Carlos Caballero Berrocal, Claudia Sala, Giulia Maggioni, Massimo Bernardi, Carmen Di Grazia, Luca Vago, Giulia Rivoli, Lorenza Borin, Saverio D'Amico, Cristina Astrid Tentori, Marta Ubezio, Alessia Campagna, Antonio Russo, Daniele Mannina, Luca Lanino, Patrizia Chiusolo, Luisa Giaccone, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Olivier Nibourel, Marilena Bicchieri, Niccolo’ Bolli, Alessandro Rambaldi, Francesco Passamonti, Victor Savevski, Armando Santoro, Ulrich Germing, Shahram Kordasti, Valeria Santini, Maria Diez-Campelo, Guillermo Sanz, Francesc Sole, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Matteo Giovanni Della Porta, Sauta, E, Robin, M, Bersanelli, M, Travaglino, E, Meggendorfer, M, Zhao, L, Caballero Berrocal, J, Sala, C, Maggioni, G, Bernardi, M, Di Grazia, C, Vago, L, Rivoli, G, Borin, L, D'Amico, S, Tentori, C, Ubezio, M, Campagna, A, Russo, A, Mannina, D, Lanino, L, Chiusolo, P, Giaccone, L, Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Nibourel, O, Bicchieri, M, Bolli, N, Rambaldi, A, Passamonti, F, Savevski, V, Santoro, A, Germing, U, Kordasti, S, Santini, V, Diez-Campelo, M, Sanz, G, Sole, F, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, and Della Porta, M
- Subjects
Cancer Research ,Oncology ,Myelodysplastic Syndrome ,MDS ,IPSS-M ,Hematology ,Settore MED/15 - Abstract
PURPOSE Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. METHODS A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. RESULTS IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively). In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk. Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. CONCLUSION IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.
- Published
- 2023
13. Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody-Begelomab
- Author
-
Edoardo Benedetti, Carlo Borghero, Francesca Gualandi, Anna Paola Iori, Mattia Algeri, Carmen Di Grazia, Patrizia Chiusolo, Maurizio Musso, Carmine Selleri, Antonio M. Risitano, Anna Maria Raiola, Francesca Bonifazi, Massimo Martino, Alice Bertaina, Francesco Onida, Emanuele Angelucci, Alessandro Rambaldi, Riccardo Varaldo, Andrea Bacigalupo, Simona Sica, Franco Locatelli, Francesco Zallio, Fabio Ciceri, Lucia Prezioso, Matteo Parma, Bacigalupo, A., Angelucci, E., Raiola, A. M., Varaldo, R., Di Grazia, C., Gualandi, F., Benedetti, E., Risitano, A., Musso, M., Zallio, F., Ciceri, F., Chiusolo, P., Sica, S., Rambaldi, A., Bonifazi, F., Parma, M., Martino, M., Onida, F., Iori, A. P., Selleri, C., Borghero, C., Bertaina, A., Prezioso, L., Algeri, M., and Locatelli, F.
- Subjects
Adult ,medicine.medical_specialty ,medicine.drug_class ,Graft vs Host Disease ,Monoclonal antibody ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Acute graft versus host disease ,medicine ,Humans ,Prospective Studies ,Treatment of steroid resistant acute graft versus ,Stage (cooking) ,Adverse effect ,Prospective cohort study ,Transplantation ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Compassionate Use ,Antibodies, Monoclonal ,Hematology ,Steroid resistant ,Settore MED/15 - MALATTIE DEL SANGUE ,begelomab ,methylprednisolone ,acute respiratory failure ,030220 oncology & carcinogenesis ,Acute Disease ,biology.protein ,Steroids ,Antibody ,business ,treatment of steroid resistant acute graft versus host disease with an anti cd26 monoclonal antibody begelomab ,030215 immunology - Abstract
We have treated 69 patients with steroid refractory acute graft versus host disease (SR-aGvHD), with an anti-CD26 monoclonal antibody (Begelomab): 28 patients in two prospective studies (EudraCT No. 2007-005809-21; EudraCT No. 2012-001353-19), and 41 patients on a compassionate use study. The median age of patients was 42 and 44 years; the severity of GvHD was as follows: grade II in 8 patients, grade III in 33, and grade IV in 28 patients. There were no adverse events directly attributable to the antibody. Day 28 response was 75% in the prospective studies and 61% in the compassionate use patients, with complete response rates of 11 and 12%. Response for grade III GvHD was 83 and 73% in the two groups; response in grade IV GvHD was 66 and 56% in the two groups. Non relapse mortality (NRM) at 6 months was 28 and 38%. Overall there were 64, 56, 68% responses for skin, liver, and gut stage 3-4 GvHD. The overall survival at 1 year was 50% for the prospective studies and 33% for the compassionate use patients. In conclusion, Begelomab induces over 60% responses in SR-aGvHD, including patients with severe gut and liver GvHD, having failed one or more lines of treatment.
- Published
- 2020
14. Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial.
- Author
-
Cavallaro G, Grassi A, Pavoni C, Micò MC, Busca A, Cavattoni IM, Santarone S, Borghero C, Olivieri A, Milone G, Chiusolo P, Musto P, Saccardi R, Patriarca F, Pane F, Saporiti G, Rivela P, Terruzzi E, Cerretti R, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Bernasconi P, Iori AP, Castagna L, Mordini N, Oldani E, Di Grazia C, Bacigalupo A, and Rambaldi A
- Subjects
- Humans, Middle Aged, Adult, Female, Male, Aged, Follow-Up Studies, Busulfan administration & dosage, Busulfan therapeutic use, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute drug therapy, Vidarabine analogs & derivatives, Vidarabine administration & dosage, Vidarabine therapeutic use, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Transplantation, Homologous
- Abstract
We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
15. Haploidentical bone marrow transplantation for AML in remission after TBF conditioning: a long-term follow-up.
- Author
-
Raiola AM, Di Grazia C, Dominietto A, Bregante S, Giammarco S, Varaldo R, Sorà F, Metafuni E, Limongiello MA, Laudisi A, Passannante M, Galli E, Gambella M, Sica S, Bacigalupo A, Angelucci E, and Chiusolo P
- Subjects
- Humans, Bone Marrow Transplantation, Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Published
- 2024
- Full Text
- View/download PDF
16. Lower blood levels of isavuconazole in critically ill patients compared with other populations: possible need for therapeutic drug monitoring.
- Author
-
Mikulska M, Melchio M, Signori A, Ullah N, Miletich F, Sepulcri C, Limongelli A, Giacobbe DR, Balletto E, Russo C, Magnasco L, Vena A, Di Grazia C, Raiola AM, Portunato F, Dentone C, Battaglini D, Ball L, Robba C, Angelucci E, Brunetti I, and Bassetti M
- Subjects
- Humans, Aged, Retrospective Studies, Triazoles, Drug Monitoring methods, Critical Illness, Nitriles, Pyridines
- Abstract
Background: Isavuconazole is first-line treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) is deemed not necessary, since most patients reached therapeutic levels (>1 mg/L) in large studies. Low levels were reported in some critically ill patients admitted to the ICU. The aim was to compare isavuconazole levels between critically ill and non-critically ill patients., Materials and Methods: Retrospective analysis of data from all patients treated with standard-dose isavuconazole between 1 January 2019 and 26 October 2022 was performed. The following data were collected: TDM results from the first 30 days of therapy; ward of admission; demographic and clinical characteristics; continuous renal replacement therapy; extracorporeal membrane oxygenation; and co-administered drugs., Results: Seventy-two patients (median age 65 years) and 188 TDM measurements (mean number of samples per patient 2.6 ± 1.7) were included; 33 (45.8%) were ICU patients (3 also had haematological disorders); 39 (54.2%) were non-ICU patients, of whom 31 had haematological disorders. In all patients, the mean isavuconazole blood level was 3.33 ± 2.26 mg/L. Significantly lower levels were observed in the ICU versus the non-ICU population: mean 2.02 ± 1.22 versus 4.15 ± 2.31 mg/L (P < 0.001). Significantly higher rates of subtherapeutic levels were observed in ICU patients compared with the non-ICU population: all determinations <2 mg/L in 33.3% versus 7.7%, and all determinations <1 mg/L in 12.1% versus 0%, respectively. Predictors of lower isavuconazole levels were admission to the ICU, BMI > 25 kg/m2, bilirubin > 1.2 mg/dL and the absence of haematological disorder., Conclusions: ICU patients had significantly lower isavuconazole blood levels compared to non-ICU population. The TDM of isavuconazole for efficacy should be performed in ICU., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
17. Acute graft versus host disease 1976-2020: reduced incidence and predictive factors.
- Author
-
Di Francesco A, Raiola AM, Dominietto A, Di Grazia C, Gualandi F, Van Lint MT, Bregante S, Chiusolo P, Laurenti L, Sora F, Giammarco S, Metafuni E, Fresa A, Sica S, Angelucci E, and Bacigalupo A
- Abstract
We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years ( p < 0.00001). The median day of onset of GvHD in the three periods was day +14, day +16, and day +30, respectively ( p < 0.0001). The cumulative incidence (CI) of GvHD grades II-IV in the three periods was 47, 24, and 16%, respectively ( p < 0.00001). The CI of GvHD grades III-IV was 13, 5, and 4% ( p < 0.001). In multivariate analysis, significant predictive factors for GvHD II-IV, on top of year of transplant, were anti-thymocyte globulin (ATG) (RR 0.67, p > 0.001); post-transplant cyclophosphamide (PTCY) (RR 0.41, p < 0.001), a family mismatched donor (RR 1.31, p = 0.03) a matched unrelated donor (RR 2.1, p < 0.001), an unrelated mismatched donor (RR1.8, p = 0.001), donor age above 40 years (RR 1.27, p < 0.001), hematological malignancy-as compared to aplastic anemia (RR 2.3, p < 0.001). When selecting only GvHD grade II, in a multivariate analysis, there was a significant reduction of transplant-related mortality (TRM) for patients grafted in 2001-2010 (RR 0.62, p < 0.0001) and for patients grafted in 2011-2020 (RR 0.35, p < 0.0001) as compared to grafts before the year 2000. A similar reduction in time was seen for patients with GvHD grades III-IV. The overall TRM in the three periods was 30, 22, and 16% ( p < 0.0001) and survival was 47, 51, and 58% ( p < 0.0001). Relapse risk was unchanged. In conclusion, we showed improved prevention of acute GvHD with time, together with a significant delay in the onset of the disease. Treatment of GvHD has also improved over time, as suggested by both reduced TRM and improved survival in more recent transplant periods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Di Francesco, Raiola, Dominietto, Di Grazia, Gualandi, Van Lint, Bregante, Chiusolo, Laurenti, Sora, Giammarco, Metafuni, Fresa, Sica, Angelucci and Bacigalupo.)
- Published
- 2024
- Full Text
- View/download PDF
18. Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients.
- Author
-
Mikulska M, Sepulcri C, Dentone C, Magne F, Balletto E, Baldi F, Labate L, Russo C, Mirabella M, Magnasco L, Di Grazia C, Ghiggi C, Raiola AM, Giacobbe DR, Vena A, Beltramini S, Bruzzone B, Lemoli RM, Angelucci E, and Bassetti M
- Subjects
- Drug Therapy, Combination, Recurrence, Humans, Male, Female, Middle Aged, Aged, Drug Combinations, Treatment Outcome, Immunocompromised Host, Antiviral Agents therapeutic use, Antibodies, Monoclonal therapeutic use, COVID-19, COVID-19 Drug Treatment adverse effects, COVID-19 Drug Treatment methods, Antibodies, Neutralizing therapeutic use
- Abstract
Background: Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients., Methods: We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up., Results: Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction)., Conclusions: Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19., Competing Interests: Potential conflicts of interest. E. A. reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Vertex Pharmaceuticals and Celgene (Bristol-Myers Squibb), Vifor Pharma, Novartis, Blue Bird Bio, Menarini Stemline, Glaxo, Regeneron, Gilead, and Novartis. M. B. reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Bayer, bioMérieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, and Shionogi. D. R. G. reports research grants and/or personal fees for advisor/consultant and/or speaker/chairman from Gilead, Shionogi, Pfizer, and Tillotts Pharma. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
- View/download PDF
19. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes.
- Author
-
Sauta E, Robin M, Bersanelli M, Travaglino E, Meggendorfer M, Zhao LP, Caballero Berrocal JC, Sala C, Maggioni G, Bernardi M, Di Grazia C, Vago L, Rivoli G, Borin L, D'Amico S, Tentori CA, Ubezio M, Campagna A, Russo A, Mannina D, Lanino L, Chiusolo P, Giaccone L, Voso MT, Riva M, Oliva EN, Zampini M, Riva E, Nibourel O, Bicchieri M, Bolli N, Rambaldi A, Passamonti F, Savevski V, Santoro A, Germing U, Kordasti S, Santini V, Diez-Campelo M, Sanz G, Sole F, Kern W, Platzbecker U, Ades L, Fenaux P, Haferlach T, Castellani G, and Della Porta MG
- Subjects
- Humans, Prognosis, Retrospective Studies, Risk Factors, Neoplasm Recurrence, Local, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes therapy
- Abstract
Purpose: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M., Methods: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed., Results: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score., Conclusion: IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.
- Published
- 2023
- Full Text
- View/download PDF
20. Outcome of early treatment of SARS-CoV-2 infection in patients with haematological disorders.
- Author
-
Mikulska M, Testi D, Russo C, Balletto E, Sepulcri C, Bussini L, Dentone C, Magne F, Policarpo S, Campoli C, Miselli F, Cilli A, Ghiggi C, Aquino S, Di Grazia C, Giannella M, Giacobbe DR, Vena A, Raiola AM, Bonifazi F, Zinzani P, Cavo M, Lemoli R, Angelucci E, Viale P, Bassetti M, and Bartoletti M
- Subjects
- Humans, Retrospective Studies, SARS-CoV-2, Antibodies, Monoclonal, Antiviral Agents therapeutic use, COVID-19, Hematologic Diseases, Hematologic Neoplasms complications, Hematologic Neoplasms therapy
- Abstract
Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n = 120, 37%; sotrovimab, n = 73) or antivirals (n = 208, 63%; nirmatrelvir/ritonavir, n = 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n = 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p < 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n = 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
21. Comparison of outcomes for HLA-matched sibling and haplo-identical donors in Myelodysplastic syndromes: report from the chronic malignancies working party of EBMT.
- Author
-
Raj K, Eikema DJ, Sheth V, Koster L, de Wreede LC, Blaise D, Di Grazia C, Koc Y, Potter V, Chevallier P, Lopez-Corral L, Wu D, Mielke S, Maertens J, Meijer E, Huynh A, Passweg J, Luft T, Pérez-Simón JA, Ciceri F, Piekarska A, Hayri Ozsan G, Kröger N, Robin M, and Yakoub-Agha I
- Subjects
- Adult, Cyclophosphamide therapeutic use, Humans, Middle Aged, Recurrence, Retrospective Studies, Siblings, Transplantation Conditioning, Unrelated Donors, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation, Myelodysplastic Syndromes drug therapy, Neoplasms drug therapy
- Abstract
Myelodysplastic syndromes (MDS) are the second common indication for an Allo-HCT. We compared the outcomes of 1414 matched sibling (MSD) with 415 haplo-identical donors (HD) transplanted with post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis between 2014 and 2017. The median age at transplant with MSD was 58 and 61 years for HD. The median time to neutrophil engraftment was longer for HD being 20 vs 16 days for MSD (p < 0.001). Two-year overall survival (OS) and PFS (progression free survival) with MSD were significantly better at 58% compared with 50%, p ≤ 0.001, and 51% vs 47%, p = 0.029, with a HD. Relapse at 2 years was lower with a HD 23% than with MSD 29% (p = 0.016). Non relapse mortality (NRM) was higher with HD in the first 6 months post-transplant [HR 2.59 (1.5-4.48) p < 0.001] and was also higher at 2 years being 30% for HD and 20% for MSD, p ≤ 0.001. The incidence of acute GVHD grade II-IV and III-IV at 100 days was comparable for MSD and HD, however, chronic GVHD at 2 years was significantly higher with MSD being 44% vs 32% for HD (p < 0.001). After multivariable analysis, OS and primary graft failure were significantly worse for HD particularly before 6 months [HR 1.93(1.24-3.0)], and HR [3.5(1.5-8.1)]. The median age of HD 37 (IQR 30-47) years was significantly lower than sibling donors 56 (IQR 49-62 years) p < 0.001. However, there was no effect on NRM, relapse or PFS. This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it's use when no better donor is available., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
22. Predicting the outcome for patients with myelofibrosis undergoing an allogeneic hemopoietic stem cell transplant.
- Author
-
Sora F, Giammarco S, Raiola AM, Di Grazia C, Bregante S, Gualandi F, Varaldo R, Chiusolo P, Sica S, Laurenti L, Innocenti I, Autore F, Metafuni E, Galli E, Bacigalupo A, and Angelucci E
- Subjects
- Humans, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation adverse effects, Primary Myelofibrosis diagnosis, Primary Myelofibrosis etiology, Primary Myelofibrosis therapy
- Published
- 2022
- Full Text
- View/download PDF
23. Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01.
- Author
-
Bonifazi F, Pavoni C, Peccatori J, Giglio F, Arpinati M, Busca A, Bernasconi P, Grassi A, Iori AP, Patriarca F, Brunello L, Di Grazia C, Carella AM, Cilloni D, Picardi A, Proia A, Santarone S, Sorasio R, Carluccio P, Chiusolo P, Cupri A, Luppi M, Nozzoli C, Baronciani D, Casini M, Grillo G, Musso M, Onida F, Palazzo G, Parma M, Tringali S, Vacca A, Vallisa D, Sacchi N, Oldani E, Masciulli A, Gheorghiu A, Girmenia C, Martino M, Bruno B, Rambaldi A, and Ciceri F
- Subjects
- Busulfan therapeutic use, Humans, Prospective Studies, Recurrence, Thiotepa therapeutic use, Transplantation Conditioning methods, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Leukemia therapy
- Abstract
The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
24. The day 100 score predicts moderate to severe cGVHD, transplant mortality, and survival after hematopoietic cell transplantation.
- Author
-
Metafuni E, Cavattoni IM, Lamparelli T, Raiola AM, Ghiso A, Galaverna F, Gualandi F, Di Grazia C, Dominietto A, Varaldo R, Signori A, Chiusolo P, Sora' F, Giammarco S, Laurenti L, Sica S, Angelucci E, and Bacigalupo A
- Subjects
- Humans, Incidence, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGVHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified 4 independent predictors of moderate-severe cGVHD: gamma-glutamyl transferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l, and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0 to 1), intermediate (2 to 3), and high (4) score. The cumulative incidence of moderate-severe cGVHD was 12%, 20%, and 52% (P < .0001) in the training cohort, and 13%, 24%, and 33% (P = .002) in the validation cohort, respectively. The 5-year cumulative incidence of transplant-related mortality (TRM) was 5%, 14%, 27% (P < .0001) and 5%, 16%, 31% (P < .0001), respectively. The 5-year survival was 64%, 57%, 54% (P = .009) and 70%, 59%, 42% (P = .0008) in the 2 cohorts, respectively. In conclusion, Day100 score predicts cGVHD, TRM, and survival and, if validated in a separate group of patients, could be considered for trials of preemptive therapy., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
25. Pre-transplant minimal residual disease assessment and transplant-related factors predict the outcome of acute myeloid leukemia patients undergoing allogeneic stem cell transplantation.
- Author
-
Guolo F, Di Grazia C, Minetto P, Raiola AM, Clavio M, Miglino M, Tedone E, Contini P, Mangerini R, Kunkl A, Colombo N, Pugliese G, Carminati E, Marcolin R, Passannante M, Bagnasco S, Galaverna F, Lamparelli T, Ballerini F, Cagnetta A, Cea M, Gobbi M, Bacigalupo A, Lemoli RM, and Angelucci E
- Subjects
- Female, Humans, Male, Middle Aged, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Neoplasm, Residual
- Abstract
We studied pretransplant minimal residual disease (MRD) in 224 patients (median age 44 years; range 17-65) with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplant (HSCT) in complete remission. MRD was evaluated on marrow samples using multicolor flow cytometry and assessment of WT1 gene expression. Both methods showed a strong prognostic value and their combination allowed the identification of three groups of patients with different risk of relapse. In multivariate analysis, combined MRD was the only predictor of cumulative incidence of relapse, regardless of donor type, conditioning regimen, first or second CR at HSCT, HSCT year, and ELN risk group. Multivariate regression model showed that only negative combined MRD status (P < .001) and myeloablative conditioning (P = .004) were independently associated with better OS. Among MRD-positive patients, a reduced incidence of relapse was observed in patients receiving haplo transplant (P < .05) and in patients who showed grade II-IV aGVHD (P < .03). In patients with negative combined MRD, the intensity of conditioning regimen did not affect the overall favorable outcome. We suggest that pretransplant MRD evaluation combined with transplant-related factors can identify AML patients at higher risk for relapse and might help in defining the overall transplant strategy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
26. Second haploidentical stem cell transplantation for primary graft failure.
- Author
-
Giammarco S, Raiola AM, Di Grazia C, Bregante S, Gualandi F, Varaldo R, Chiusolo P, Sora F, Sica S, Laurenti L, Metafuni E, Innocenti I, Autore F, Murgia B, Bacigalupo A, and Angelucci E
- Subjects
- Busulfan, Cyclophosphamide, Humans, Middle Aged, Thiotepa, Transplantation Conditioning, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation
- Abstract
We report the outcome of 19 patients who experienced primary graft failure (PrGF) after a haploidentical (HAPLO), unmanipulated bone marrow transplant. The median age of patients was 52 years; the conditioning regimen of the first HAPLO transplant was either full dose total body irradiation (TBI) or fludarabine, busulfan, and thiotepa (TBF); PTCY was given to all patients together with cyclosporine and mycophenolate. All 19 patients with PrGF received a second HAPLO graft, at a median interval of 42 days (34-82) after HSCT, using the Baltimore protocol and G-CSF mobilized PB from the same (n = 13) or another HAPLO family donor (n = 6). GvHD prophylaxis was again PTCY-based; 14/19 patients had trilineage recovery (74%) and 1-year survival was 66%. Engraftment at second HAPLO was seen in 7/8 patient with, and in 5/7 patients without donor-specific antibodies (DSA). In a multivariate logistic regression analysis on the original group of 503 patients, there was a trend for a reduced dose of busulfan, to increase the risk of PrGF (p = 0.1). In conclusion, patients with PrGF following a HAPLO transplant, can be rescued with a second early HAPLO transplant, using the same or a different donor.
- Published
- 2021
- Full Text
- View/download PDF
27. Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen.
- Author
-
Chiusolo P, Bregante S, Giammarco S, Lamparelli T, Casarino L, Dominietto A, Raiola AM, Metafuni E, Di Grazia C, Gualandi F, Sora F, Laurenti L, Sica S, Barosi G, Guolo F, Rossi M, Rossi E, Vannucchi A, Signori A, De Stefano V, Bacigalupo A, and Angelucci E
- Subjects
- Adult, Aged, Allografts, Busulfan administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Melphalan administration & dosage, Middle Aged, Splenectomy, Survival Rate, Thiotepa administration & dosage, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy, Transplantation Chimera, Transplantation Conditioning
- Abstract
The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival., (© 2020 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
28. Enhancing the diagnosis of maxillary transverse discrepancy through 3-D technology and surface-to-surface superimposition. Description of the digital workflow with a documented case report.
- Author
-
Lo Giudice A, Nucera R, Ronsivalle V, Di Grazia C, Rugeri M, and Quinzi V
- Subjects
- Child, Female, Humans, Palatal Expansion Technique, Workflow, Malocclusion, Maxilla
- Abstract
Background: Maxillary transverse discrepancy is often diagnosed in childhood. The evaluation of morphological characteristics of the maxilla is crucial for appropriate treatment of this condition, however conventional diagnostic method is based on visual inspection and transversal linear parameters. In this paper, we described a user-friendly diagnostic digital workflow based on the surface-to-surface analysis. We also described a case report., Case Report: A 6-year-old female patient presenting mild transversal maxillary deficiency associated with functional posterior crossbite was treated by using maxillary removable appliance. In this respect, the appliance was designed in accordance to the morphological characteristics of the maxilla obtained by using the diagnostic digital work-flow and the maxillary surface-to-surface analysis., Conclusion: The present user-friendly diagnostic digital workflow based on surface-to-surface analysis helps clinicians to detect specific morphological characteristics of the maxilla, such as shape and area of asymmetry, in order to reach a comprehensive diagnosis and choose the correct biomechanics for treating the condition.
- Published
- 2020
- Full Text
- View/download PDF
29. Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody-Begelomab.
- Author
-
Bacigalupo A, Angelucci E, Raiola AM, Varaldo R, Di Grazia C, Gualandi F, Benedetti E, Risitano A, Musso M, Zallio F, Ciceri F, Chiusolo P, Sica S, Rambaldi A, Bonifazi F, Parma M, Martino M, Onida F, Iori AP, Selleri C, Borghero C, Bertaina A, Prezioso L, Algeri M, and Locatelli F
- Subjects
- Acute Disease, Adult, Antibodies, Monoclonal therapeutic use, Humans, Prospective Studies, Steroids, Graft vs Host Disease drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
We have treated 69 patients with steroid refractory acute graft versus host disease (SR-aGvHD), with an anti-CD26 monoclonal antibody (Begelomab): 28 patients in two prospective studies (EudraCT No. 2007-005809-21; EudraCT No. 2012-001353-19), and 41 patients on a compassionate use study. The median age of patients was 42 and 44 years; the severity of GvHD was as follows: grade II in 8 patients, grade III in 33, and grade IV in 28 patients. There were no adverse events directly attributable to the antibody. Day 28 response was 75% in the prospective studies and 61% in the compassionate use patients, with complete response rates of 11 and 12%. Response for grade III GvHD was 83 and 73% in the two groups; response in grade IV GvHD was 66 and 56% in the two groups. Non relapse mortality (NRM) at 6 months was 28 and 38%. Overall there were 64, 56, 68% responses for skin, liver, and gut stage 3-4 GvHD. The overall survival at 1 year was 50% for the prospective studies and 33% for the compassionate use patients. In conclusion, Begelomab induces over 60% responses in SR-aGvHD, including patients with severe gut and liver GvHD, having failed one or more lines of treatment.
- Published
- 2020
- Full Text
- View/download PDF
30. Hepatitis E Virus Infection in an Italian Cohort of Hematopoietic Stem Cell Transplantation Recipients: Seroprevalence and Infection.
- Author
-
Furfaro E, Nicolini L, Della Vecchia A, Di Grazia C, Raiola AM, Varaldo R, Ferrando F, Barisione G, Bruzzone B, Angelucci E, Viscoli C, and Mikulska M
- Subjects
- Aged, Humans, Italy epidemiology, Prospective Studies, RNA, Viral, Retrospective Studies, Seroepidemiologic Studies, Hematopoietic Stem Cell Transplantation adverse effects, Hepatitis E diagnosis, Hepatitis E epidemiology, Hepatitis E etiology, Hepatitis E virus genetics
- Abstract
Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
- Full Text
- View/download PDF
31. Graft versus host disease in unmanipulated haploidentical marrow transplantation with a modified post-transplant cyclophosphamide (PT-CY) regimen: an update on 425 patients.
- Author
-
Bacigalupo A, Maria Raiola A, Dominietto A, Di Grazia C, Gualandi F, Lint MTV, Chiusolo P, Laurenti L, Sora F, Giammarco S, and Angelucci E
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Young Adult, Cyclophosphamide therapeutic use, Graft vs Host Disease therapy, Transplantation, Haploidentical methods
- Abstract
This is an update on acute and chronic graft-versus-host disease (GvHD) in 425 patients with hematologic malignancies, undergoing an unmanipulated haploidentical (HAPLO) graft from related donors, with a modified post-transplant cyclophosphamide (PT-CY) regimen. All patients received a myeloablative conditioning regimen, either based on thiotepa busulfan fludarabine (TBF), or on full-dose total body irradiation (TBI). The cumulative incidence of acute GvHD-grade II-IV was 29%, and the CI of GvHD-grade III-IV was 4%. We found older donors and older patients to have higher rates of grade II-IV acute GvHD; female donors, diagnosis, disease phase, year of transplant, and the conditioning regimen had no predictive effect on acute GvHD. There was no impact of grade II GvHD, but a significant impact of grade III-IV acute GvHD, on overall survival. The CI of moderate-severe chronic GvHD was 18%: the major predictor was a previous acute GvHD, followed by combined donor and recipients age. In conclusion, PT-CY given on days+3 + 5 results in a relatively low, but not insignificant risk of acute and chronic GvHD, in patients grafted from the related HAPLO donors. The use of young donors appears to reduce this risk.
- Published
- 2019
- Full Text
- View/download PDF
32. Efficacy of lamivudine prophylaxis in preventing hepatitis B virus reactivation in patients with resolved infection undergoing allogeneic SCT and receiving rituximab.
- Author
-
Zappulo E, Nicolini LA, Di Grazia C, Dominietto A, Lamparelli T, Gualandi F, Caligiuri P, Bruzzone B, Angelucci E, Viscoli C, and Mikulska M
- Subjects
- Adult, Aged, Female, Hematologic Neoplasms etiology, Hepatitis B prevention & control, Hepatitis B virus drug effects, Humans, Italy, Male, Middle Aged, Young Adult, Antibiotic Prophylaxis, Antiviral Agents therapeutic use, Hepatitis B drug therapy, Lamivudine therapeutic use, Rituximab therapeutic use, Stem Cell Transplantation statistics & numerical data, Virus Activation drug effects
- Abstract
Purpose: Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains. The aim of this study was to investigate the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients with a resolved HBV infection., Methods: Patients who received first allogeneic SCT in years 2009-2016 were evaluated. Sixty-three patients with resolved infection received LAM prophylaxis and were included in the study. Baseline and post-SCT characteristics were recorded, including rituximab exposure, length of LAM prophylaxis, and time from transplant to the last clinical and virological follow-up., Results: Overall, 39 patients (62%) were male, 39 (62%) had acute myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29 (53%) received myeloablative conditioning, and 15 (24%) received rituximab post-transplant. Median clinical follow-up was 24 months after SCT (range 0.3-97); median virological follow-up 16 months (range 0.3-78), and median length of LAM prophylaxis of 14.5 months (range 0.3-78). No patient experienced HBV reactivation while on LAM prophylaxis. One patient experienced reactivation 8 months after discontinuing prophylaxis., Conclusions: In this high-risk population, LAM prophylaxis was effective in preventing HBV reactivation in patients with resolved infection. It should be considered a reasonable first-line prophylactic agent to be administered in this setting.
- Published
- 2019
- Full Text
- View/download PDF
33. Early minimal residual disease assessment after AML induction with fludarabine, cytarabine and idarubicin (FLAI) provides the most useful prognostic information.
- Author
-
Minetto P, Guolo F, Clavio M, Kunkl A, Colombo N, Carminati E, Fugazza G, Matarese S, Guardo D, Ballerini F, Di Grazia C, Raiola AM, Cagnetta A, Cea M, Miglino M, Lemoli RM, and Gobbi M
- Subjects
- Adolescent, Adult, Aged, Cytarabine administration & dosage, Disease-Free Survival, Female, Humans, Idarubicin administration & dosage, Male, Middle Aged, Neoplasm, Residual, Survival Rate, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Leukemia, Myeloid, Acute blood, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality
- Published
- 2019
- Full Text
- View/download PDF
34. A Modified Post-Transplant Cyclophosphamide Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: A Multicenter Study.
- Author
-
Chiusolo P, Bug G, Olivieri A, Brune M, Mordini N, Alessandrino PE, Dominietto A, Raiola AM, Di Grazia C, Gualandi F, Van Lint MT, Ferrara F, Finizio O, Angelucci E, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Cyclosporine therapeutic use, Drug Administration Schedule, Graft Survival, Graft vs Host Disease, Humans, Leukemia, Myeloid, Acute mortality, Middle Aged, Multivariate Analysis, Myeloablative Agonists administration & dosage, Predictive Value of Tests, Survival Analysis, Young Adult, Bone Marrow Transplantation methods, Cyclophosphamide therapeutic use, Leukemia, Myeloid, Acute therapy, Transplantation, Haploidentical methods
- Abstract
We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg on days +3 and +5. The median age was 51 (range, 17-74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
- Full Text
- View/download PDF
35. High vs low dose cyclosporine-a, after allogeneic marrow transplantation in leukemia: Long term follow up of a randomized study.
- Author
-
Bacigalupo A, Van Lint MT, Sica S, Laurenti L, Rosales MB, Dominietto A, di Grazia C, and Angelucci E
- Published
- 2018
- Full Text
- View/download PDF
36. Impact of HLA Disparity in Haploidentical Bone Marrow Transplantation Followed by High-Dose Cyclophosphamide.
- Author
-
Raiola AM, Risitano A, Sacchi N, Giannoni L, Signori A, Aquino S, Bregante S, Di Grazia C, Dominietto A, Geroldi S, Ghiso A, Gualandi F, Lamparelli T, Tedone E, Van Lint MT, Varaldo R, Ibatici A, Marani C, Marotta S, Guolo F, Avenoso D, Garbarino L, Pane F, Bacigalupo A, and Angelucci E
- Subjects
- Bone Marrow Transplantation mortality, Graft Rejection immunology, Graft vs Host Disease prevention & control, Humans, Survival Analysis, Transplantation, Haploidentical mortality, Bone Marrow Transplantation adverse effects, Cyclophosphamide therapeutic use, HLA Antigens immunology, Histocompatibility immunology, Transplantation, Haploidentical adverse effects
- Abstract
We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
37. Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia.
- Author
-
Guolo F, Minetto P, Clavio M, Miglino M, Galaverna F, Raiola AM, Di Grazia C, Colombo N, Pozzi S, Ibatici A, Bagnasco S, Guardo D, Kunkl A, Ballerini F, Ghiggi C, Lemoli RM, Gobbi M, and Bacigalupo A
- Subjects
- Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Prognosis, Recurrence, Retrospective Studies, Survival Analysis, Flow Cytometry methods, Leukemia, Myeloid, Acute diagnosis, Neoplasm, Residual diagnosis, WT1 Proteins analysis
- Published
- 2017
- Full Text
- View/download PDF
38. Haploidentical bone marrow transplantation in patients with advanced myelodysplastic syndrome.
- Author
-
Varaldo R, Raiola AM, Di Grazia C, Aquino S, Beltrami G, Bregante S, Cruciani F, Dominietto A, Ghiso A, Giannoni L, Gualandi F, Ibatici A, Lamparelli T, Marani C, Van Lint MT, Santini V, Bacigalupo A, and Angelucci E
- Subjects
- Adult, Aged, Allografts, Disease-Free Survival, Female, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myelodysplastic Syndromes mortality, Time-to-Treatment, Transplantation Conditioning, Treatment Outcome, Bone Marrow Transplantation, Hematopoietic Stem Cell Transplantation, Histocompatibility, Living Donors, Myelodysplastic Syndromes therapy
- Published
- 2017
- Full Text
- View/download PDF
39. Menstrual patterns, fertility and main pregnancy outcomes after allogeneic haematopoietic stem cell transplantation.
- Author
-
Chiodi S, Spinelli S, Bruzzi P, Anserini P, Di Grazia C, and Bacigalupo A
- Subjects
- Adult, Age Factors, Estradiol blood, Female, Follicle Stimulating Hormone blood, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Humans, Infertility etiology, Menstruation Disturbances blood, Pregnancy, Pregnancy Outcome, Retrospective Studies, Transplantation Conditioning methods, Fertility, Hematopoietic Stem Cell Transplantation adverse effects, Menstrual Cycle, Menstruation Disturbances etiology, Transplantation Conditioning adverse effects
- Abstract
Two-hundred and sixty-nine females aged ≤42 and undergoing an allogeneic stem cell transplant were retrospectively studied to assess the effect of age, conditioning regimen and chronic graft-versus-host disease (cGVHD) on resumption of stable menstrual cyclicity. Overall, a stable menstrual cyclicity was observed in 22% of cases. The cumulative probability of menses resumption was significantly age and conditioning regimen related. A statistically significant inverse correlation between cGVHD severity and menses resumption was observed only in univariate analysis. In patients with residual ovarian function, infertility was found in 43% and early menopause in 45%. An increased incidence of prematurity and low birth weight (LBW) was observed among the single spontaneous pregnancies. Follicle-stimulating hormone (FSH) and 17 beta-oestradiol levels were found to be inadequate to detect both early signs of menses resumption and menstrual stability. Our study confirms the crucial role of full dose total body irradiation (TBI) and age on menses recovery and fertility after haematopoietic stem cell transplantation (HSCT). The impact of severe cGVHD remains unclear.
- Published
- 2016
- Full Text
- View/download PDF
40. High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk-oriented consolidation: A critical review of a 10-year, single-center experience in younger, non M3 AML patients.
- Author
-
Guolo F, Minetto P, Clavio M, Miglino M, Di Grazia C, Ballerini F, Pastori G, Guardo D, Colombo N, Kunkl A, Fugazza G, Rebesco B, Sessarego M, Lemoli RM, Bacigalupo A, and Gobbi M
- Subjects
- Adolescent, Adult, Aged, Aminoglycosides therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Child, Cytarabine administration & dosage, Female, Gemtuzumab, Humans, Idarubicin administration & dosage, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Retrospective Studies, Survival Analysis, Survival Rate, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Vidarabine toxicity, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Consolidation Chemotherapy methods, Induction Chemotherapy methods, Leukemia, Myeloid, Acute drug therapy
- Abstract
About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m(2) (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m(2) per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher anti-leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C + Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755-762, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
- Full Text
- View/download PDF
41. Wilms Tumor 1 Expression and Pre-emptive Immunotherapy in Patients with Acute Myeloid Leukemia Undergoing an Allogeneic Hemopoietic Stem Cell Transplantation.
- Author
-
Di Grazia C, Pozzi S, Geroldi S, Grasso R, Miglino M, Colombo N, Tedone E, Luchetti S, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Raiola AM, Dominietto A, Varaldo R, Galaverna F, Ghiso A, Sica S, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Bone Marrow Cells metabolism, Female, Humans, Immunotherapy, Adoptive, Leukemia, Myeloid, Acute mortality, Lymphocyte Transfusion, Male, Middle Aged, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation methods, Immunotherapy methods, Leukemia, Myeloid, Acute therapy, Premedication methods, WT1 Proteins analysis
- Abstract
Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
42. Improved Outcome of Alternative Donor Transplantations in Patients with Myelofibrosis: From Unrelated to Haploidentical Family Donors.
- Author
-
Bregante S, Dominietto A, Ghiso A, Raiola AM, Gualandi F, Varaldo R, Di Grazia C, Lamparelli T, Luchetti S, Geroldi S, Casarino L, Pozzi S, Tedone E, Van Lint MT, Galaverna F, Barosi G, and Bacigalupo A
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Primary Myelofibrosis mortality, Retrospective Studies, Survival Analysis, Treatment Outcome, Unrelated Donors, Young Adult, Hematopoietic Stem Cell Transplantation methods, Primary Myelofibrosis therapy, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
This is a retrospective analysis of 95 patients with myelofibrosis who were allografted between 2001 and 2014. The aims of the study were to assess whether the outcome of alternative donor grafts has improved with time and how this compares with the outcome of identical sibling grafts. Patients were studied in 2 time intervals: 2000 to 2010 (n = 58) and 2011 to 2014 (n = 37). The Dynamic International Prognostic Scoring System score was comparable in the 2 time periods, but differences in the most recent group included older age (58 versus 53 years, P = .004), more family haploidentical donors (54% versus 5%, P < .0001), and the introduction of the thiotepa-fludarabine-busulfan conditioning regimen (70% of patients versus 2%, P < .0001). Acute and chronic graft-versus-host disease were comparable in the 2 time periods. The 3-year transplantation-related mortality (TRM) in the 2011 to 2014 period versus the 2000 to 2010 period is 16% versus 32% (P = .10), the relapse rate 16% versus 40% (P = .06), and actuarial survival 70% versus 39% (P = .08). Improved survival was most pronounced in alternative donor grafts (69% versus 21%, P = .02), compared with matched sibling grafts (72% versus 45%, P = .40). In conclusion, the outcome of allografts in patients with myelofibrosis has improved in recent years because of a reduction of both TRM and relapse. Improvement is most significant in alternative donor transplantations, with modifications in donor type and conditioning regimen., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
43. Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia.
- Author
-
De Astis E, Clavio M, Raiola AM, Ghiso A, Guolo F, Minetto P, Galaverna F, Miglino M, Di Grazia C, Ballerini F, Marani C, Pastori G, Mitscheunig L, Cruciani F, Lovera D, Varaldo R, Ghiggi C, Lemoli RM, Bacigalupo A, and Gobbi M
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Blood Component Transfusion, Combined Modality Therapy, Consolidation Chemotherapy, Cytarabine administration & dosage, Cytarabine adverse effects, Daunorubicin administration & dosage, Daunorubicin adverse effects, Diarrhea chemically induced, Drug Administration Schedule, Drug Evaluation, Female, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Kaplan-Meier Estimate, Leukemia, Myeloid, Acute therapy, Liposomes, Male, Middle Aged, Neutropenia chemically induced, Neutropenia drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Proportional Hazards Models, Remission Induction, Retrospective Studies, Vidarabine administration & dosage, Vidarabine adverse effects, Vidarabine analogs & derivatives, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Salvage Therapy
- Abstract
Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoietic stem cell transplantation (HSCT), when clinically indicated, between May 2000 and January 2013. Forty-one patients had acute myeloid leukemia (AML), and 38 had acute lymphoblastic leukemia (ALL). Two patients with myeloid blast crises of CML and three with lymphoid blast crises were included in the AML and ALL subgroups, respectively. Median age was 48 years (range 13-77). FLAD was well tolerated with negligible, nonhematological toxicity. Six patients (7.5 %) died before response evaluation. Forty-seven patients achieved hematologic complete response (CR). Complete remission rate was 53 and 65 % among AML and ALL patients, respectively. No CR was recorded among 11 refractory AML patients. Twenty-four patients (30 %) underwent HSCT. Nine patients received stem cells from an HLA identical sibling, and 15 from an alternative donor (3 unrelated matched, 12 haploidentical sibling). Median overall survival in AML and ALL patients receiving FLAD therapy was 9 and 8 months, respectively. A 5-year projected OS for patients receiving the whole program (FLAD + HSCT) was 24 % for AML patients (median survival 43 months), 28 % for ALL patients treated in relapse (median survival 15 months), and 0 % for ALL patients treated for refractory disease. In this paper, we show that FLAD seems to be an effective bridge therapy to HSCT for a part of poor prognosis acute leukemia patients. However, prospective studies are needed to confirm our results.
- Published
- 2014
- Full Text
- View/download PDF
44. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts.
- Author
-
Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Varaldo R, Ghiso A, Gobbi M, Carella AM, Signori A, Galaverna F, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Female, Gene Expression, HLA Antigens genetics, HLA Antigens immunology, Haplotypes, Hematologic Neoplasms genetics, Hematologic Neoplasms immunology, Hematologic Neoplasms mortality, Histocompatibility Testing, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Myeloablative Agonists therapeutic use, Prospective Studies, Recurrence, Siblings, Survival Analysis, Transplantation, Homologous, Unrelated Donors, Cord Blood Stem Cell Transplantation, Graft vs Host Disease prevention & control, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning methods
- Abstract
We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
45. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation.
- Author
-
Stasia A, Ghiso A, Galaverna F, Raiola AM, Gualandi F, Luchetti S, Pozzi S, Varaldo R, Lamparelli T, Bregante S, Van Lint MT, di Grazia C, and Bacigalupo A
- Subjects
- Adolescent, Adult, Antigens, CD34, Female, Humans, Male, Middle Aged, Treatment Outcome, Young Adult, Graft Survival physiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects
- Abstract
Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.