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  • 1
    Language: English
    In: American journal of transplantation, 2016-07, Vol.16 (7), p.2106-2116
    Description: Alloantibody‐mediated graft injury is a major cause of kidney dysfunction and loss. The complement‐binding ability of de novo donor‐specific antibodies (dnDSAs) has been suggested as a prognostic tool to stratify patients for clinical risk. In this study, we analyzed posttransplant kinetics of complement‐fixing dnDSAs and their role in antibody‐mediated rejection development and graft loss. A total of 114 pediatric nonsensitized recipients of first kidney allograft were periodically monitored for dnDSAs using flow bead assays, followed by C3d and C1q assay in case of positivity. Overall, 39 patients developed dnDSAs, which were C1q+ and C3d+ in 25 and nine patients, respectively. At follow‐up, progressive acquisition over time of dnDSA C1q and C3d binding ability, within the same antigenic specificity, was observed, paralleled by an increase in mean fluorescence intensity that correlated with clinical outcome. C3d‐fixing dnDSAs were better fit to stratify graft loss risk when the different dnDSA categories were evaluated in combined models because the 10‐year graft survival probability was lower in patients with C3d‐binding dnDSA than in those without dnDSAs or with C1q+/C3d− or non‐complement‐binding dnDSAs (40% vs. 94%, 100%, and 100%, respectively). Based on the kinetics profile, we favor dnDSA removal or modulation at first confirmed positivity, with treatment intensification guided by dnDSA biological characteristics. In this longitudinal study of renal transplant recipients, the authors demonstrate that patients with de novo donor‐specific HLA antibodies capable of C3d binding are more likely to develop antibody‐mediated rejection and graft loss, and describe the dynamic and progressive phenomenon of complement‐binding ability acquisition.
    Subject(s): immunosuppression/immune modulation ; rejection: antibody‐mediated (ABMR) ; clinical research/practice ; kidney transplantation/nephrology ; alloantibody ; kidney (allograft) function/dysfunction ; immunobiology ; monitoring: immune ; Prognosis ; Follow-Up Studies ; Complement C3d - immunology ; Humans ; Middle Aged ; Child, Preschool ; Graft Rejection - metabolism ; Infant ; Male ; Kidney Function Tests ; Complement C3d - metabolism ; Young Adult ; Adult ; Female ; Retrospective Studies ; Child ; Isoantibodies - metabolism ; Glomerular Filtration Rate ; Kidney Failure, Chronic - surgery ; Histocompatibility Testing ; Risk Factors ; HLA Antigens - immunology ; Graft Rejection - etiology ; Graft Survival ; Graft Rejection - diagnosis ; Adolescent ; Isoantibodies - immunology ; Tissue Donors ; Longitudinal Studies ; Kidney Transplantation - adverse effects ; Analysis ; Kidney diseases ; Chemical properties ; Index Medicus
    ISSN: 1600-6135
    E-ISSN: 1600-6143
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Annals of oncology, 2018-12, Vol.29, p.x11-x11
    ISSN: 0923-7534
    E-ISSN: 1569-8041
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: EBSCOhost EJS
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  • 3
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2016-04, Vol.51 (4), p.536-541
    Description: Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients 〈18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88 ± 1% and 81 ± 1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91 ± 1% and 83 ± 1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90-96% and an EFS of 83-93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.
    Subject(s): Thalassemia - therapy ; Thalassemia - mortality ; Europe ; Humans ; Middle Aged ; Hematopoietic Stem Cell Transplantation ; Male ; Survival Rate ; Disease-Free Survival ; Societies, Medical ; Adolescent ; Adult ; Female ; Registries ; Bone marrow ; Thalassemia ; Care and treatment ; Transplantation ; Research ; Health aspects ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Leukemia, 2015-02, Vol.29 (2), p.396-405
    Description: Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.
    Subject(s): Busulfan - analogs & derivatives ; Neutrophils - cytology ; Prospective Studies ; Humans ; Immunosuppressive Agents - therapeutic use ; Middle Aged ; Male ; Graft vs Host Disease - immunology ; T-Lymphocytes, Regulatory - immunology ; Young Adult ; Blood Platelets - cytology ; Antilymphocyte Serum - therapeutic use ; Adult ; Female ; Child ; Sirolimus - therapeutic use ; Busulfan - therapeutic use ; Administration, Oral ; HLA Antigens - immunology ; Rituximab ; Treatment Outcome ; Vidarabine - analogs & derivatives ; Vidarabine - therapeutic use ; Mycophenolic Acid - analogs & derivatives ; Mycophenolic Acid - therapeutic use ; Adolescent ; Graft vs Host Disease - prevention & control ; T-Lymphocytes - immunology ; Aged ; Tissue Donors ; Transplantation Conditioning ; Peripheral Blood Stem Cell Transplantation ; Antibodies, Monoclonal, Murine-Derived - therapeutic use ; Prevention ; Complications and side effects ; Care and treatment ; Graft versus host reaction ; Transplantation ; T cells ; Blood diseases ; Health aspects ; Hematopoietic stem cells ; Research ; Drug therapy ; Risk factors ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2017-09, Vol.52 (9), p.1326-1329
    Subject(s): Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2011, Vol.46 (2), p.200-207
    Description: When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.
    Subject(s): Biological and medical sciences ; Medical sciences ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Bone marrow, stem cells transplantation. Graft versus host reaction ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Acute Disease ; Histocompatibility Testing ; Humans ; Child, Preschool ; Infant ; Male ; Risk ; Antigens, CD34 - blood ; Transplantation, Homologous ; Cord Blood Stem Cell Transplantation - adverse effects ; Adolescent ; Female ; Graft Rejection ; Graft vs Host Disease - prevention & control ; Cord Blood Stem Cell Transplantation - mortality ; Child ; Mesenchymal Stem Cell Transplantation ; Prevention ; Fetal blood ; Stem cells ; Physiological aspects ; Graft versus host reaction ; Transplantation ; Research ; Health aspects ; Index Medicus ; Medicin och hälsovetenskap
    ISSN: 0268-3369
    ISSN: 1476-5365
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2015-02, Vol.50 (2), p.181-188
    Description: We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.
    Subject(s): Autografts ; Follow-Up Studies ; Leukemia, Myeloid, Acute - pathology ; Humans ; Child, Preschool ; Hematopoietic Stem Cell Transplantation ; Infant ; Male ; Survival Rate ; Abnormal Karyotype ; Cord Blood Stem Cell Transplantation ; Leukemia, Myeloid, Acute - mortality ; fms-Like Tyrosine Kinase 3 - genetics ; Disease-Free Survival ; Allografts ; Adolescent ; Myeloablative Agonists - administration & dosage ; Female ; Transplantation Conditioning - methods ; Child ; Leukemia, Myeloid, Acute - therapy ; Leukemia, Myeloid, Acute - genetics ; Transplantation ; Health aspects ; Patient outcomes ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2017-07, Vol.52 (7), p.1071-1073
    Subject(s): Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Leukemia, 2008-12, Vol.22 (12), p.2193-2200
    Description: The aim of the study was to analyze the impact of minimal residual disease (MRD) after reinduction therapy on the outcome of children with relapsed 'high-risk' acute lymphoblastic leukemia (ALL). Sixty patients with isolated or combined marrow relapse were studied. All patients belonged to the S3 or S4 groups, as defined by the Berlin-Frankfurt-Münster stratification for relapsed ALL. MRD was studied by real-time quantitative PCR after the first, second and third chemotherapy course (time points 1 (TP1), 2 (TP2) and 3 (TP3), respectively). MRD results, not used for treatment refinement, were categorized as negative (NEG MRD), positive not-quantifiable (POS-NQ MRD) when MRD level was below quantitative range (a level 〈10(-4)) or positive within quantitative range (POS MRD) when MRD level was 〉or=10(-4). With a median observation time of 15 months, overall 3-year event-free survival (EFS) was 27%. The 3-year EFS was 73, 45 and 19% for patients with NEG-MRD, POS NQ-MRD and POS-MRD at TP1, respectively (P〈0.05). The prognostic predictive value of MRD was statistically confirmed in multivariate analysis. MRD quantitation early and efficiently differentiates patients who benefit from conventional treatment, including allogeneic hematopoietic stem cell transplantation, from those needing innovative, experimental therapies.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Multivariate Analysis ; Predictive Value of Tests ; Recurrence ; Prognosis ; Prospective Studies ; Cytarabine - therapeutic use ; Humans ; Child, Preschool ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Methotrexate - therapeutic use ; Cyclophosphamide - therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Mercaptopurine - therapeutic use ; Female ; Neoplasm, Residual - mortality ; Asparaginase - therapeutic use ; Child ; Daunorubicin - therapeutic use ; Risk Factors ; Hematopoietic Stem Cell Transplantation ; Treatment Outcome ; Combined Modality Therapy ; Reverse Transcriptase Polymerase Chain Reaction ; Neoplasm, Residual - genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Disease-Free Survival ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Adolescent ; Neoplasm, Residual - drug therapy ; Survival Analysis ; Vincristine - therapeutic use ; Prednisone - therapeutic use ; Care and treatment ; Chemotherapy ; Leukemia in children ; Lymphocytic leukemia in children ; Stem cells ; Transplantation ; Diagnosis ; Acute lymphocytic leukemia ; Lymphoblastic leukemia in children ; Health aspects ; Cancer
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 10
    Language: English
    In: Leukemia, 2011-03, Vol.25 (3), p.455-462
    Description: We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.
    Subject(s): Hematologic and hematopoietic diseases ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Biological and medical sciences ; Medical sciences ; Recurrence ; Humans ; Child, Preschool ; Infant ; Male ; Hematopoietic Stem Cell Transplantation - mortality ; Disease-Free Survival ; Graft vs Host Disease - mortality ; Adolescent ; Myelodysplastic Syndromes - mortality ; Adult ; Female ; Child ; Myelodysplastic Syndromes - surgery ; Care and treatment ; Anemia ; Genetic aspects ; Transplantation ; Research ; Health aspects ; Risk factors ; Myelodysplastic syndromes ; Hematopoietic stem cells ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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