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Article ; Online: Blinatumomab Redirects Donor Lymphocytes against CD19

Mancusi, Antonella / Zorutti, Francesco / Ruggeri, Loredana / Bonato, Samanta / Tricarico, Sara / Zei, Tiziana / Iacucci Ostini, Roberta / Viglione, Valerio / Sembenico, Rebecca / Sciabolacci, Sofia / Cardinali, Valeria / Martelli, Massimo Fabrizio / Mecucci, Cristina / Carotti, Alessandra / Martelli, Maria Paola / Velardi, Andrea / Pierini, Antonio

International journal of molecular sciences

2023 Volume 24, Issue 22

Abstract: Blinatumomab alone or with donor leukocyte infusions (DLI) has been used after allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage therapy in relapsing patients with ... ...

Abstract	Blinatumomab alone or with donor leukocyte infusions (DLI) has been used after allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage therapy in relapsing patients with CD19
MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation/adverse effects ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; T-Lymphocytes/pathology
Chemical Substances	blinatumomab (4FR53SIF3A)
Language	English
Publishing date	2023-11-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242216105
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Article ; Online: T cell depletion and no post transplant immune suppression allow separation of graft versus leukemia from graft versus host disease.

Pierini, Antonio / Ruggeri, Loredana / Mancusi, Antonella / Carotti, Alessandra / Falzetti, Franca / Terenzi, Adelmo / Martelli, Massimo Fabrizio / Velardi, Andrea

Bone marrow transplantation

2019 Volume 54, Issue Suppl 2, Page(s) 775–779

Abstract: Allogeneic hematopoietic cell transplantation from a human leukocyte antigen (HLA) haplotype mismatched donor (haploidentical transplantation) was not feasible for the treatment of hematologic malignancies until the early 1990s, due to the high risk of ... ...

Abstract	Allogeneic hematopoietic cell transplantation from a human leukocyte antigen (HLA) haplotype mismatched donor (haploidentical transplantation) was not feasible for the treatment of hematologic malignancies until the early 1990s, due to the high risk of rejection and graft-versus-host disease (GVHD). The first successful protocol of haploidentical transplantation was based on a highly myeloablative and immunosuppressive conditioning regimen and the infusion of a "mega-dose" of T-cell-depleted hematopoietic stem cells. More than 90% of patients engrafted and <10% developed GVHD. The protocol did not include post-transplant immunosuppression, which favored the graft-versus-tumor effect mediated by alloreactive NK cells and residual alloreactive T cells. However, donor post-transplant immune reconstitution was slow with a high risk of infection-related mortality. More recently, T-cell-depleted haploidentical transplantation has become the platform for innovative cell therapies that aim to enhance T-cell immunity while preventing adverse reactions against host tissues. One strategy is adoptive immunotherapy with conventional T cells and regulatory T cells. Preclinical studies and clinical trials have proven that regulatory T cells control GVHD caused by co-infused conventional T cells while the graft-versus-tumor effect is retained. The use of regulatory T cells in the absence of any other form of immune suppression allowed for a conventional T cell-mediated full eradication of disease in the vast majority of high-risk acute leukemia patients.
MeSH term(s)	Graft vs Host Disease/physiopathology ; Graft vs Leukemia Effect/physiology ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Lymphocyte Depletion/methods ; Transplantation Conditioning/methods ; Transplantation, Homologous/methods
Language	English
Publishing date	2019-08-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-019-0597-y
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Zs.A 2168: Show issues

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Article ; Online: A pro-inflammatory environment in bone marrow of Treg transplanted patients matches with graft-versus-leukemia effect.

Guardalupi, Francesco / Sorrentino, Carlo / Corradi, Giulia / Giancola, Raffaella / Baldoni, Stefano / Ulbar, Francesca / Fabi, Bianca / Andres Ejarque, Rosa / Timms, Jessica / Restuccia, Francesco / Santarone, Stella / Accorsi, Patrizia / Sportoletti, Paolo / De Falco, Filomena / Rosati, Emanuela / Carotti, Alessandra / Falzetti, Franca / Velardi, Andrea / Martelli, Massimo Fabrizio /

Kordasti, Shahram / Pierini, Antonio / Ruggeri, Loredana / Di Ianni, Mauro

Leukemia

2023 Volume 37, Issue 7, Page(s) 1572–1575

MeSH term(s)	Humans ; Bone Marrow ; T-Lymphocytes, Regulatory ; Bone Marrow Transplantation ; Transplantation, Homologous ; Leukemia ; Graft vs Host Disease/etiology
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Research Support, Non-U.S. Gov't ; Letter
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-01932-x
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Zs.A 2295: Show issues

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Article ; Online: Rifaximin use favoured micafungin-resistant Candida spp. infections in recipients of allogeneic hematopoietic cell transplantation.

Marzuttini, Francesca / Mancusi, Antonella / Bonato, Samanta / Griselli, Mario / Tricarico, Sara / Casarola, Genni / Paradiso, Matteo / Ruggeri, Loredana / Terenzi, Adelmo / Merluzzi, Mara / Prigitano, Anna / Tortorano, Anna Maria / Pitzurra, Lucia / Falini, Brunangelo / Carotti, Alessandra / Velardi, Andrea / Pierini, Antonio

Annals of hematology

2021 Volume 100, Issue 9, Page(s) 2375–2380

Abstract: Damage to gut mucosa following conditioning regimens may favour bacterial infections that can trigger graft versus host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Rifaximin, an oral and non-absorbable ...

Abstract	Damage to gut mucosa following conditioning regimens may favour bacterial infections that can trigger graft versus host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Rifaximin, an oral and non-absorbable antibiotic, has been recently proposed as effective prophylaxis to reduce bacterial infections in the gut and consequently acute GvHD in this setting. The present study evaluated safety and outcomes of HSCT patients that were treated with rifaximin prophylaxis at Perugia University Hospital. Rifaximin prophylaxis was introduced as standard of care in HSCT patients in May 2018. We retrieved data from 118 consecutive transplants, and we compared the outcomes of rifaximin-treated patients with historical controls that did not receive antibiotic prophylaxis. While incidences of neutropenic fever, documented bacterial infections, and aGvHD were similar in the two groups, we found an increased frequency of invasive candidiasis and clinically relevant Candida spp. infections in rifaximin-treated patients (5 patients vs 1 patient, 25% [± 0.99%] vs 1% [± 0.01%], p < .0001). Three rifaximin-treated patients experienced life-threating candidemia (2 C. krusei, 1 C. orthopsilosis). Rifaximin was the only factor that increased the risk of Candida spp. infections. Rifaximin could have contributed to microbiome disruption which favoured an outbreak of life-threatening Candida infections. This important complication forced us to halt its use. Larger, prospective studies are needed to assess the impact of rifaximin prophylaxis on incidence of bacterial infections, aGvHD, and survival of HSCT patients.
MeSH term(s)	Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/therapeutic use ; Antifungal Agents/therapeutic use ; Candida/drug effects ; Candidiasis/drug therapy ; Drug Resistance, Fungal ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Micafungin/therapeutic use ; Middle Aged ; Retrospective Studies ; Rifaximin/adverse effects ; Rifaximin/therapeutic use ; Risk Factors ; Transplantation, Homologous/adverse effects
Chemical Substances	Anti-Bacterial Agents ; Antifungal Agents ; Rifaximin (L36O5T016N) ; Micafungin (R10H71BSWG)
Language	English
Publishing date	2021-06-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-021-04569-x
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Article ; Online: The "ultimate" haploidentical transplantation for the elderly with high-risk acute myeloid leukemia.

Pierini, Antonio / Ruggeri, Loredana / Carotti, Alessandra / Falzetti, Franca / Piccinelli, Sara / Saldi, Simonetta / Lancellotta, Valentina / Aristei, Cynthia / Velardi, Andrea / Martelli, Massimo Fabrizio

Bone marrow transplantation

2019 Volume 54, Issue Suppl 2, Page(s) 803–805

MeSH term(s)	Adult ; Female ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Transplantation Conditioning/methods ; Transplantation, Haploidentical/methods
Language	English
Publishing date	2019-08-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632854-4
ISSN	1476-5365 ; 0268-3369 ; 0951-3078
ISSN (online)	1476-5365
ISSN	0268-3369 ; 0951-3078
DOI	10.1038/s41409-019-0618-x
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Zs.A 2168: Show issues

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Article ; Online: Haploidentical age-adapted myeloablative transplant and regulatory and effector T cells for acute myeloid leukemia.

Pierini, Antonio / Ruggeri, Loredana / Carotti, Alessandra / Falzetti, Franca / Saldi, Simonetta / Terenzi, Adelmo / Zucchetti, Claudio / Ingrosso, Gianluca / Zei, Tiziana / Iacucci Ostini, Roberta / Piccinelli, Sara / Bonato, Samanta / Tricarico, Sara / Mancusi, Antonella / Ciardelli, Sara / Limongello, Roberto / Merluzzi, Mara / Di Ianni, Mauro / Tognellini, Rita /

Minelli, Olivia / Mecucci, Cristina / Martelli, Maria Paola / Falini, Brunangelo / Martelli, Massimo Fabrizio / Aristei, Cynthia / Velardi, Andrea

Blood advances

2021 Volume 5, Issue 5, Page(s) 1199–1208

Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment in eradicating high-risk acute myeloid leukemia (AML). Here, we present data from a novel HLA-haploidentical HSCT protocol that addressed the 2 remaining major ... ...

Abstract	Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment in eradicating high-risk acute myeloid leukemia (AML). Here, we present data from a novel HLA-haploidentical HSCT protocol that addressed the 2 remaining major unmet medical needs: leukemia relapse and chronic graft-versus-host disease (cGVHD). Fifty AML patients were enrolled in the study. The conditioning regimen included total body irradiation for patients up to age 50 years and total marrow/lymphoid irradiation for patients age 51 to 65 years. Irradiation was followed by thiotepa, fludarabine, and cyclophosphamide. Patients received an infusion of 2 × 106/kg donor regulatory T cells on day -4 followed by 1 × 106/kg donor conventional T cells on day -1 and a mean of 10.7 × 106 ± 3.4 × 106/kgpurified CD34+ hematopoietic progenitor cells on day 0. No pharmacological GVHD prophylaxis was administered posttransplantation. Patients achieved full donor-type engraftment. Fifteen patients developed grade ≥2 acute GVHD (aGVHD). Twelve of the 15 patients with aGVHD were alive and no longer receiving immunosuppressive therapy. Moderate/severe cGVHD occurred in only 1 patient. Nonrelapse mortality occurred in 10 patients. Only 2 patients relapsed. Consequently, at a median follow-up of 29 months, the probability of moderate/severe cGVHD/relapse-free survival was 75% (95% confidence interval, 71%-78%). A novel HLA-haploidentical HSCT strategy that combines an age-adapted myeloablative conditioning regimen with regulatory and conventional T-cell adoptive immunotherapy resulted in an unprecedented cGVHD/relapse-free survival rate in 50 AML patients with a median age of 53 years. This trial was registered with the Umbria Region Institutional Review Board Public Registry as identification code 02/14 and public registry #2384/14 and at www.clinicaltrials.gov as #NCT03977103.
MeSH term(s)	Aged ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy ; Middle Aged ; Transplantation Conditioning ; Whole-Body Irradiation
Language	English
Publishing date	2021-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2020003739
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Article ; Online: Gene Abnormalities in Transplant Associated-Thrombotic Microangiopathy: Comparison between Recipient and Donor's DNA.

Rodrigues, Evangeline Millicent / Ardissino, Gianluigi / Pintarelli, Giulia / Capone, Valentina / Mariotti, Jacopo / Verna, Marta / Bernardo, Maria Ester / Faraci, Maura / Tozzi, Monica / Bucalossi, Alessandro / Schiavello, Elisabetta / Biassoni, Veronica / Guidetti, Anna / Carotti, Alessandra / Facchini, Luca / Terruzzi, Elisabetta / Giglio, Fabio / Zecca, Marco / Onida, Francesco /

Caroti, Leonardo / Cesaro, Simone / Consonni, Dario / Cugno, Massimo / Porcaro, Luigi

Thrombosis and haemostasis

2021 Volume 122, Issue 7, Page(s) 1247–1250

MeSH term(s)	DNA ; Humans ; Thrombotic Microangiopathies/diagnosis ; Thrombotic Microangiopathies/genetics
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2021-12-29
Publishing country	Germany
Document type	Letter ; Comment
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0041-1740498
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Article ; Online: The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell-Depleted Hematopoietic Stem Cell Transplantation.

Aristei, Cynthia / Carotti, Alessandra / Palazzari, Elisa / Amico, Lucia / Ruggeri, Loredana / Perrucci, Elisabetta / Falcinelli, Lorenzo / Lancellotta, Valentina / Palumbo, Isabella / Falzetti, Franca / Aversa, Franco / Merluzzi, Mara / Velardi, Andrea / Martelli, Massimo Fabrizio

International journal of radiation oncology, biology, physics

2016 Volume 96, Issue 4, Page(s) 832–839

Abstract: Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA identical ... ...

Abstract	Purpose: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. Methods and materials: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day -12 to day -9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day -9) was given to 26 patients. Results: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). Conclusions: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell-depleted hematopoietic stem cell transplantation, thus affecting DFS.
MeSH term(s)	Adult ; Aged ; Cause of Death ; Disease-Free Survival ; Dose Fractionation ; Female ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation/mortality ; Histocompatibility ; Humans ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/therapy ; Lymphocyte Depletion ; Male ; Middle Aged ; Multivariate Analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Recurrence ; Remission Induction ; Secondary Prevention/methods ; Siblings ; T-Lymphocytes ; Time Factors ; Transplantation Conditioning/methods ; Treatment Outcome ; Whole-Body Irradiation/methods ; Young Adult
Language	English
Publishing date	2016-11-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2016.07.025
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Article: Gene Abnormalities in Transplant Associated-Thrombotic Microangiopathy: Comparison between Recipient and Donor's DNA

Caroti, Leonardo / Cesaro, Simone / Consonni, Dario / Cugno, Massimo / Porcaro, Luigi

Thrombosis and Haemostasis

2021 Volume 122, Issue 07, Page(s) 1247–1250

Language	English
Publishing date	2021-12-29
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0041-1740498
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Article ; Online: Genetic Polymorphisms Affecting IDO1 or IDO2 Activity Differently Associate With Aspergillosis in Humans.

Napolioni, Valerio / Pariano, Marilena / Borghi, Monica / Oikonomou, Vasilis / Galosi, Claudia / De Luca, Antonella / Stincardini, Claudia / Vacca, Carmine / Renga, Giorgia / Lucidi, Vincenzina / Colombo, Carla / Fiscarelli, Ersilia / Lass-Flörl, Cornelia / Carotti, Alessandra / D'Amico, Lucia / Majo, Fabio / Russo, Maria Chiara / Ellemunter, Helmut / Spolzino, Angelica /

Mosci, Paolo / Brancorsini, Stefano / Aversa, Franco / Velardi, Andrea / Romani, Luigina / Costantini, Claudio

Frontiers in immunology

2019 Volume 10, Page(s) 890

Abstract: ... ...

Abstract	Aspergillus
MeSH term(s)	Adolescent ; Adult ; Animals ; Aspergillosis/enzymology ; Aspergillosis/genetics ; Aspergillosis/microbiology ; Aspergillus/physiology ; Child ; Child, Preschool ; Cystic Fibrosis/enzymology ; Cystic Fibrosis/genetics ; Cystic Fibrosis/microbiology ; Epithelial Cells/metabolism ; Epithelial Cells/microbiology ; Female ; Genetic Predisposition to Disease/genetics ; Hematopoietic Stem Cell Transplantation/statistics & numerical data ; Host-Pathogen Interactions ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/microbiology ; Male ; Mice ; Polymorphism, Genetic ; Young Adult
Chemical Substances	IDO1 protein, human ; IDO2 protein, human ; Indoleamine-Pyrrole 2,3,-Dioxygenase
Language	English
Publishing date	2019-05-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.00890
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