Publications by authors named "Jacopo Mariotti"

Background: The selection of the best donor for each specific patient is crucial for the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, there is debate on the choice of the best donor when multiple suitable donors exist.

Methods: By using own data from two transplant centers, we have developed a calculator able to provide the patients' 2-year overall survival (OS) associated with each of the potential donor options during the selection process, in order to support the transplant physician during the choice.

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Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers.

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Background Aims: Mounting evidence suggests that persistent cell expansion is the main driver for both efficacy and toxicity of chimeric antigen receptor (CAR) T-cell therapy. Hereby, we describe a case of delayed recurrent neurotoxicity associated with late CAR T-cells re-expansion.

Case Description: A 44-year-old man suffering from mantle cell lymphoma received brexu-cel.

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Article Synopsis
  • New immunotherapy treatments like bispecific T-cell engagers and checkpoint inhibitors are often used for patients with non-Hodgkin lymphoma who relapse after CAR T-cell therapy, but their long-term effects on stem cell transplants are unclear.
  • A study compared outcomes of 27 patients who received allogeneic stem cell transplants (Allo-SCT) after immunotherapy to 28 patients who underwent Allo-SCT after standard treatment, finding similar survival rates and complications between the two groups.
  • The study suggests that Allo-SCT is a safe and effective option for patients who respond to immunotherapy, potentially serving as a solid treatment strategy after CAR T-cell therapy failures.*
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Article Synopsis
  • Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a treatment for blood cancers that relies on effective immune reconstitution (IR) to prevent severe infections like Human Cytomegalovirus (HCMV).
  • The study reveals that specific types of Natural Killer (NK) cells, called KIR NK cells, significantly contribute to controlling HCMV due to their early recovery and strong antiviral properties.
  • Maintaining high levels of KIR NK cells post-transplant can serve as a predictor for HCMV infection risk and could lead to improved treatments by boosting these immune cells in donor lymphocyte infusions.
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The introduction of novel drugs ( inhibitors and/or brentuximab vedotin) into salvage regimens has improved the response rate and the outcome of patients with relapsed/refractory Hodgkin lymphoma. However, the impact of new drugs on the outcome has not been adequately investigated so far. We retrospectively analyzed 42 consecutive patients treated at our institution with high-dose chemotherapy/autologous stem cell transplantation after either one standard chemotherapy represented by BEGEV ( = 28) or >1 salvage therapy (ST) comprising novel drugs ( = 14).

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Despite the impressive results of chimeric antigen receptor (CAR) T cell treatment for lymphomas, adverse events such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections are major issues that can lead to intensive care unit (ICU) admission and death. Current guidelines recommend tocilizumab for treating patients with CRS grade (G) ≥2; however, the optimal timing of intervention has yet to be determined. Our institution adopted the preemptive use of tocilizumab in cases of persistent G1 CRS, defined as fever (≥38 °C) for >24 hours.

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Article Synopsis
  • Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment for blood cancers, but patients often face recurrent infections post-transplant.
  • A study conducted on 19 patients receiving CD45RA-depleted donor lymphocyte infusions (DLI) found that this approach enhances the immune response without increasing risks associated with naïve T-cells.
  • Results showed that specific memory T-cells, particularly those targeting cytomegalovirus (CMV), proliferated significantly and maintained their presence for at least a month post-infusion, suggesting better protection against viral infections.
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Endothelial Activation and Stress Index (EASIX) is a prognostic score reflecting endothelial damage. It can identify cohorts of patients at higher risk of non-relapse mortality (NRM) after allogeneic stem cell transplantation (SCT) from a matched-related or -unrelated donor. No data are available in the setting of haploidentical-SCT with post-transplant cyclophosphamide (PT-Cy).

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Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957).

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Even with high-dose post-transplant cyclophosphamide (PT-Cy) which was initially introduced for graft-versus-host disease (GvHD) prevention in the setting of HLA-haploidentical transplantation, both acute and chronic GvHDs remain a major clinical challenge. Despite improvements in the understanding of the pathogenesis of both acute and chronic GvHDs, reliable biomarkers that predict their onset have yet to be identified. We recently studied the potential correlation between extracellular vesicles (EVs) and the onset of acute (a)GvHD in transplant recipients from related and unrelated donors.

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Risk factors for cytomegalovirus (CMV) reactivation and the impact of CMV reactivation on patient outcomes have been extensively investigated after matched related or unrelated donor transplantation, but little is known in the setting of haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy), in which recipients are considered more severely immunocompromised. We retrospectively analyzed a cohort of 554 consecutive patients undergoing Haplo-SCT with PT-Cy at 3 different centers. Early CMV reactivation (occurring within the first 120 days post-transplantation) occurred in 242 patients, for an estimated cumulative incidence of 44%.

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Busulfan (Bu) is an alkylating agent routinely used for conditioning regimens before allogeneic stem cell transplantation (allo-SCT). Bu shows wide pharmacokinetic (PK) variability among patients. Patients can have a higher systemic exposure (expressed as area under the curve [AUC]) with an increased risk of toxicity or a lower AUC with a higher probability of graft rejection and/or disease relapse.

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Haploidentical related donor transplantation (haplo-HCT) is associated with cytokine release syndrome (CRS). We conducted a multicenter retrospective study to analyze risk factors for CRS and outcomes after haplo-HCT. We included 451 patients from four academic centers receiving both peripheral blood and bone marrow grafts.

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Article Synopsis
  • Haploidentical hematopoietic stem cell transplantation (h-HSCT) is an effective treatment for hematologic cancers, but opportunistic viral infections can negatively impact patient outcomes.
  • Recent research shows that human cytomegalovirus (HCMV) plays a role in speeding up the recovery of natural killer (NK) cells post-transplant, with specific NK cell subsets showing increased presence during HCMV infection.
  • The study highlights that these NK cells, while expanding, also exhibit signs of dysfunction due to changes in gene expression and exhaustion markers, affecting their ability to produce key immune signals like IFN-γ, largely influenced by viral interactions.
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Low-dose total body irradiation (TBI) has long been used in nonmyeloablative conditioning (NMAC) regimens before allogeneic stem cell transplantation from haploidentical donors (haplo-SCT). More recently, the use of total marrow lymphoid irradiation (TMLI) instead of TBI in conditioning is increasing. This study aimed to evaluate outcomes in a cohort of patients treated with low-dose TMLI in terms of engraftment, full donor chimerism status, graft-versus-host disease (GVHD), and extrahematologic toxicities, and to compare these outcomes with those in a cohort of patients receiving conventional TBI-containing conditioning.

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Allogeneic stem cell transplantation from haploidentical donors using unmanipulated bone marrow and posttransplantation cyclophosphamide has been largely employed to cure high-risk lymphomas. However, the increased incidence of relapse associated with the use of a nonmyeloablative conditioning regimen is still considered a concerning issue. The aim of our study was to prospectively evaluate the efficacy and feasibility of a reduced-intensity conditioning regimen, including thiotepa, cyclophosphamide, and fludarabine, in high-risk lymphoma patients.

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Allogeneic stem cell transplantation from haploidentical donor using post-transplantation cyclophosphamide has been used to cure hematological diseases. Because of slow immunological reconstitution, there is an increased incidence of viral infection. The aim of our study was to prospectively evaluate the efficacy and the feasibility of a CD45RA+ depleted donor lymphocytes infusion (DLI) in terms of reduction of viral infection early after haploidentical transplantation.

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