Incidence, characteristics and outcome of therapy-related myeloid neoplasms in women with epithelial ovarian cancer after exposure to poly-ADPribose polymerase inhibitors: A cancer center experience.

Poly(ADP-ribose) polymerase inhibitors (PARPi) target the DNA repair pathways and have been established in epithelial ovarian cancer (EOC) as maintenance therapy inducing prolonged survival. However, recently published data showed that PARPi may increase the risk of therapy-related myeloid neoplasms (t-MN) including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Herein, we investigated the incidence, characteristics, and management of t-MN among EOC patients after exposure to PARPi in a Greek Cancer Center.

Safety and Efficacy of Extracorporeal Photopheresis for Acute and Chronic Graft-versus-Host Disease.

Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients with steroid-dependent or refractory grade II-IV aGvHD post-alloHSCT.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR), Growth Differentiation Factor-15 (GDF-15), and Soluble C5b-9 (sC5b-9) Levels Are Significantly Associated with Endothelial Injury Indices in CAR-T Cell Recipients.

Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients.

The seasonal distribution of immune thrombotic thrombocytopenic purpura is influenced by geography: Epidemiologic findings from a multi-center analysis of 719 disease episodes.

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included.

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study.

Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome.

Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) and Growth Differentiation Factor-15 (GDF-15) Levels Are Significantly Associated with Endothelial Injury Indices in Adult Allogeneic Hematopoietic Cell Transplantation Recipients.

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) and graft-versus-host disease (GvHD) represent life-threatening syndromes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both conditions, endothelial dysfunction is a common denominator, and development of relevant biomarkers is of high importance for both diagnosis and prognosis. Despite the fact that soluble urokinase plasminogen activator receptor (suPAR) and growth differentiation factor-15 (GDF-15) have been determined as endothelial injury indices in various clinical settings, their role in HSCT-related complications remains unexplored.

Pre-Emptive Use of Rituximab in Epstein-Barr Virus Reactivation: Incidence, Predictive Factors, Monitoring, and Outcomes.

Post-transplant lymphoproliferative disease (PTLD) is a fatal complication of hematopoietic cell transplantation (HCT) associated with the Epstein-Barr virus (EBV). Multiple factors such as transplant type, graft-versus-host disease (GVHD), human leukocyte antigens (HLA) mismatch, patient age, and T-lymphocyte-depleting treatments increase the risk of PTLD. EBV reactivation in hematopoietic cell transplant recipients is monitored through periodic quantitative polymerase chain reaction (Q-PCR) tests.

Context-dependent T-cell Receptor Gene Repertoire Profiles in Proliferations of T Large Granular Lymphocytes.

T cell large granular lymphocyte (T-LGL) lymphoproliferations constitute a disease spectrum ranging from poly/oligo to monoclonal. Boundaries within this spectrum of proliferations are not well established. T-LGL lymphoproliferations co-occur with a wide variety of other diseases ranging from autoimmune disorders, solid tumors, hematological malignancies, post solid organ, and hematopoietic stem cell transplantation, and can therefore arise as a consequence of a wide variety of antigenic triggers.

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance.

Targeted genotyping of COVID-19 patients reveals a signature of complement C3 and factor B coding SNPs associated with severe infection.

We have attempted to explore further the involvement of complement components in the host COVID-19 (Coronavirus disease-19) immune responses by targeted genotyping of COVID-19 adult patients and analysis for missense coding Single Nucleotide Polymorphisms (coding SNPs) of genes encoding Alternative pathway (AP) components. We have identified a small group of common coding SNPs in Survivors and Deceased individuals, present in either relatively similar frequencies (CFH and CFI SNPs) or with stark differences in their relative abundance (C3 and CFB SNPs). In addition, we have identified several sporadic, potentially protective, coding SNPs of C3, CFB, CFD, CFH, CFHR1 and CFI in Survivors.

Adolescents and young adults (AYA) with acute myeloid leukemia (AML): real-world long-term results and age-specific outcomes.

Opposing acute lymphoblastic leukemia, sparse data about AYAs with acute myeloid leukemia (AML) is available. Overall, 125 AYAs (age 10-35 years) treated during the last two decades were evaluated and compared to 385 older patients. CBF leukemia was more frequent in AYAs (21.

Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection.

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020-March 2021) in three major groups.

Patient risk stratification and tailored clinical management of post-transplant CMV-, EBV-, and BKV-infections by monitoring virus-specific T-cell immunity.

Background: Despite routine post-transplant viral monitoring and pre-emptive therapy, viral infections remain a major cause of allogeneic hematopoietic cell transplantation-related morbidity and mortality.

Objective: We here aimed to prospectively assess the kinetics and the magnitude of cytomegalovirus-(CMV), Epstein Barr virus-(EBV), and BK virus-(BKV)-specific T cell responses post-transplant and evaluate their role in guiding therapeutic decisions by patient risk-stratification.

Study Design: The tri-virus-specific immune recovery was assessed by Elispot, in 50 consecutively transplanted patients, on days +20, +30, +60, +100, +150, +200 post-transplant and in case of reactivation, weekly for 1 month.

Genetic and Functional Evidence of Complement Dysregulation in Multiple Myeloma Patients with Carfilzomib-Induced Thrombotic Microangiopathy Compared to Controls.

Background: Carfilzomib, an irreversible proteasome inhibitor approved for the treatment of relapsed/refractory Multiple Myeloma (MM) has been associated with Thrombotic Microangiopathy (TMA). Several pathogenetic mechanisms of carfilzomib-induced TMA have been proposed; however, recently, there has been a shift of focus on the potential contribution of complement dysregulation. Our aim was to explore whether patients with carfilzomib-induced TMA harbor germline variants of complement-related genes, which have been characterized as risk factors for TMA.

Immune Response of Adult Sickle Cell Disease Patients after COVID-19 Vaccination: The Experience of a Greek Center.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential weapons to control the spread of the coronavirus disease-19 (COVID-19) pandemic and protect immunocompromised patients. With a greater susceptibility to infection, sickle cell disease (SCD) patients are considered as "high risk" patients during the current COVID-19 pandemic. In our study, we try to determine the immune response of adult SCD patients monitored at our center after the first and second dose of the qualified mRNA vaccines available and correlate them to several disease-specific markers, as well as complement activation.

Secondary Acute Myeloid Leukemia (sAML): Similarly Dismal Outcomes of AML After an Antecedent Hematologic Disorder and Therapy Related AML.

Therapy related acute myeloid leukemia (tAML) and secondary AML after an antecedent hematologic disorder (sAML-AHD) are often addressed together, blurring any clinical and prognostic differences. Among 516 AML patients, we compared characteristics and outcomes of 149 patients with "sAML" (sAML-AHD: 104, tAML: 45), uniformly and intensively treated during the last 2 decades at 1 center. Clinical outcomes of the whole "sAML" cohort were significantly inferior compared to de novo AML and in both intermediate and poor cytogenetic risk groups.

Predictors of Transplant-Associated Thrombotic Microangiopathy in Patients With Overlap or Chronic Graft-vs-Host-Disease.

Background: Recent data suggest that novel biologic agents are associated with increased risk of thrombotic microangiopathy (TMA). Ruxolitinib, an approved treatment for graft-vs-host-disease (GVHD), has been associated with thrombocytopenia of unclear etiology.

Methods: We investigated factors and outcomes associated with transplant-associated thrombotic microangiopathy (TA-TMA) in patients with GVHD.

Survival Advantage of Treosulfan Plus Fludarabine Before Allogeneic Hematopoietic Cell Transplantation for Older or Comorbid Patients With Myeloid Malignancies.

We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150 mg/m, Treosulfan 42 g/m, FluTreo) compared to a reduced-intensity regimen. We aimed to determine long-term safety and efficacy of FluTreo. We prospectively studied consecutive patients who received FluTreo in our center (2014-2019) on the basis of age (≥50 years), hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2, or both.

Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pretransplant genetic susceptibility is evident in adult TA-TMA and further investigated the association of TMA-associated variants with clinical outcomes. We studied 40 patients with TA-TMA, donors of 18 patients and 40 control non-TMA HCT recipients, without significant differences in transplant characteristics.