Publications by authors named "Lucia Savino"

6 Publications

  • Page 1 of 1

Impact of donor age and kinship on clinical outcomes after T-cell-replete haploidentical transplantation with PT-Cy.

Blood Adv 2020 08;4(16):3900-3912

Department of Oncology/Hematology, Azienda Ospedaliera Universitaria (AOU) Città della Salute e della Scienza di Torino, Presidio Molinette, Turin, Italy.

Donor selection contributes to improve clinical outcomes of T-cell-replete haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-Cy). The impact of donor age and other non-HLA donor characteristics remains a matter of debate. We performed a multicenter retrospective analysis on 990 haplo-SCTs with PT-Cy. By multivariable analysis, after adjusting for donor/recipient kinship, increasing donor age and peripheral blood stem cell graft were associated with a higher risk of grade 2 to 4 acute graft-versus-host-disease (aGVHD), whereas 2-year cumulative incidence of moderate-to-severe chronic GVHD was higher for transplants from female donors into male recipients and after myeloablative conditioning. Increasing donor age was associated with a trend for higher nonrelapse mortality (NRM) (hazard ratio [HR], 1.05; P = .057) but with a significant reduced risk of disease relapse (HR, 0.92; P = .001) and improved progression-free survival (PFS) (HR, 0.97; P = .036). Increasing recipient age was a predictor of worse overall survival (OS). Risk of relapse was higher (HR, 1.39; P < .001) in patients aged ≤40 years receiving a transplant from a parent as compared with a sibling. Moreover, OS and PFS were lower when the donor was the mother rather than the father. Pretransplant active disease status was an invariably independent predictor of worse clinical outcomes, while recipient positive cytomegalovirus serostatus and hematopoietic cell transplant comorbidity index >3 were associated with worse OS and PFS. Our results suggest that younger donors may reduce the incidence of aGVHD and NRM, though at higher risk of relapse. A parent donor, particularly the mother, is not recommended in recipients ≤40 years.
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http://dx.doi.org/10.1182/bloodadvances.2020001620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448598PMC
August 2020

DNA methylation dynamic of bone marrow hematopoietic stem cells after allogeneic transplantation.

Stem Cell Res Ther 2019 05 20;10(1):138. Epub 2019 May 20.

Laboratory of Preclinical and Translational Research, IRCCS - Referral Cancer Center of Basilicata (CROB), 85028, Rionero in Vulture, Italy.

Background: Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative therapeutic approach for different hematological malignancies (HMs), and epigenetic modifications, including DNA methylation, play a role in the reconstitution of the hematopoietic system after AHSCT. This study aimed to explore global DNA methylation dynamic of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) from donors and their respective recipients affected by acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and Hodgkin lymphoma (HL) during the first year after transplant.

Methods: We measured DNA methylation profile by Illumina HumanMethylationEPIC in BM HSPC of 10 donors (t0) and their matched recipients at different time points after AHSCT, at day + 30 (t1), + 60 (t2), + 120 (t3), + 180 (t4), and + 365 (t5). Differential methylation analysis was performed by using R software and CRAN/Bioconductor packages. Gene set enrichment analysis was carried out on promoter area of significantly differentially methylated genes by clusterProfiler package and the mSigDB genes sets.

Results: Results show significant differences in the global methylation profile between HL and acute leukemias, and between patients with mixed and complete chimerism, with a strong methylation change, with prevailing hyper-methylation, occurring 30 days after AHSCT. Functional analysis of promoter methylation changes identified genes involved in hematopoietic cell activation, differentiation, shaping, and movement. This could be a consequence of donor cell "adaptation" in recipient BM niche. Interestingly, this epigenetic remodeling was reversible, since methylation returns similar to that of donor HSPCs after 1 year. Only for a pool of genes, mainly involved in dynamic shaping and trafficking, the DNA methylation changes acquired after 30 days were maintained for up to 1 year post-transplant. Finally, preliminary data suggest that the methylation profile could be used as predictor of relapse in ALL.

Conclusions: Overall, these data provide insights into the DNA methylation changes of HSPCs after transplantation and a new framework to investigate epigenetics of AHSCT and its outcomes.
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http://dx.doi.org/10.1186/s13287-019-1245-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528331PMC
May 2019

Timing of clopidogrel loading dose on peripheral blood endothelial progenitor cells, SDF-1α and neointimal hyperplasia in carotid stenting.

Clin Hemorheol Microcirc 2019 ;72(1):23-38

Cardiology Unit, Cardiovascular Department, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy.

Background: Carotid stenting stimulates intimal proliferation through platelet and stem cell activation.

Objective: The aim of this study is to evaluate whether the administration before or after carotid stenting of clopidogrel loading dose may play a role on circulating endothelial progenitor cells, stromal cell-derived factor-1α (SDF-1α) and neointimal hyperplasia.

Methods: We recruited 13 patients (aged 74.52±7.23) with indication of carotid revascularization and in therapy with salicylic acid and statin. We blindly randomized them in two groups: pre-carotid angioplasty with stent (Pre-CAS group) receiving 300 mg of clopidogrel before stenting, and post-carotid angioplasty with stent (Post-CAS group) receiving 300 mg after stenting. At the admission, we valued endothelial progenitor cells, SDF-1α and prospectively we repeated blood samples and measured intima-media thickness to estimate neointimal hyperplasia on the stent at 3, 6 and 12 months.

Results: In the days following the CAS, we found a lower, statistically not significant, trend of endothelial progenitor cells in Pre-CAS group. The SDF-1α concentration tended to be lower at baseline in the pre-CAS group than in the post-CAS group and it did not show an increase in the observed time. On the contrary, in the Post-CAS group we observed a peak at six hours with a significant reduction (p < 0.001) at one day after stenting.The intima-media thickness was significantly lower in the Pre-CAS group than the Post-CAS group both at six months and 12 months after stenting.

Conclusions: Pre-stenting clopidogrel loading dose leaded to short-time modification of endothelial progenitor cells and platelets and to long-term a minor neointimal hyperplasia.
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http://dx.doi.org/10.3233/CH-180429DOI Listing
November 2019

Minimal residual disease after allogeneic stem cell transplant: a comparison among multiparametric flow cytometry, Wilms tumor 1 expression and chimerism status (Complete chimerism versus Low Level Mixed Chimerism) in acute leukemia.

Leuk Lymphoma 2013 Dec 15;54(12):2660-6. Epub 2013 May 15.

Department of Hematology and Stem Cell Transplantation Unit.

Relapse represents the main cause of treatment failure after allogeneic stem cell transplant (allo-SCT). The detection of minimal residual disease (MRD) by multiparametric flow cytometry (MFC), chimerism, cytogenetics and molecular analysis may be critical to prevent relapse. Therefore, we assessed the overall agreement among chimerism (low level mixed chimerism [LL-MC] vs. complete chimerism [CC]), MFC and Wilms tumor 1 (WT1) mRNA to detect MRD and investigated the impact of MRD obtained from the three methods on patient outcome. Sixty-seven fresh bone marrow (BM) samples from 24 patients (17 acute myeloid leukemia [AML], seven acute lymphoblastic leukemia [ALL]) in complete remission (CR) after allo-SCT were investigated at different time points. A moderate agreement was found among the three techniques investigated. A higher concordance between positive results from MFC (75.0% vs. 32.7%, p = 0.010) and WT1 (58.3% vs. 29.1%, p = 0.090) was detected among LL-MC rather than CC samples. Relapse-free survival (RFS) and overall survival (OS) were found to be higher in MRD negative patients than in MRD positive patients analyzed with MFC and WT1. Our results discourage the use of low autologous signals as the only marker of MRD, and suggest the usefulness of MFC and WT1 real-time quantitative polymerase chain reaction (RQ-PCR) in stratifying patients with respect to risk of relapse.
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http://dx.doi.org/10.3109/10428194.2013.789508DOI Listing
December 2013

Regulatory T-cell number is increased in chronic lymphocytic leukemia patients and correlates with progressive disease.

Leuk Res 2011 Mar 28;35(3):363-8. Epub 2010 Sep 28.

IRCCS Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy.

Regulatory T-cells (Treg) actively maintain immunological self-tolerance and play a significant role in the progression of cancer. Treg cell numbers have been evaluated in 80 patients with previously untreated chronic lymphocytic leukemia (CLL) and in 40 normal healthy volunteers. Treg cells are higher in CLL patients than in controls and correlate with disease status (more advanced clinical stage, peripheral blood B-cell lymphocytosis, absolute CD38+ B-cell number, and more elevated LDH levels). No correlation was found with ZAP-70 expression, IgVH mutational status and cytogenetic abnormalities. This data shows that Treg cell number is abnormal in CLL patients.
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http://dx.doi.org/10.1016/j.leukres.2010.08.010DOI Listing
March 2011

Immunophenotypic profile of AC133-positive cells in bone marrow, mobilized peripheral blood and umbilical cord blood.

Leuk Lymphoma 2002 Apr;43(4):869-73

Department of Onco-Hematology, San Giovanni di Dio e Ruggi d'Aragona Hospital, Salerno, Italy.

AC133 is a molecule whose expression in the human hematopoietic system is restricted to a subset of CD34+ progenitor/stem cells with long-term repopulating ability. The antigenic features of these cells, like CD34+ cells, are described heterogeneous. The immunophenotypic profile of AC133+ cells, detected by means of dual-color flow cytometry, in bone marrow (BM), cytokine-mobilized peripheral blood (PB) and umbilical cord blood (UCB) was evaluated. The highest percentage of AC133+ cells was detected in mobilized PB despite not significantly different from that found in BM, but both are higher than that found in UCB. In addition, the highest percentage of CD34, HLA-DR and CD33 co-expressing AC133+ cells was observed in mobilized PB. Furthermore, UCB was found to be enriched in CD7+ and CD19+ cells and BM was found to be enriched in AC133+ cells co-expressing CDw90 and CD71. Our data confirm the immunophenotypic heterogeneity of cells expressing AC133 antigen, a promising new stem cell marker to be increasingly used as additional target for alternative identification and separation of early hematopoietic cells.
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http://dx.doi.org/10.1080/10428190290017015DOI Listing
April 2002