Patient-Reported Improvements in Patients with PNH Treated with Iptacopan from Two Phase 3 Studies.

Iptacopan, a first-in-class, oral, selective complement factor B inhibitor, demonstrated efficacy and safety as monotherapy in C5 inhibitor (C5i)-experienced (APPLY-PNH [NCT04558918]) and C5i-naive (APPOINT-PNH [NCT04820530]) patients with paroxysmal nocturnal hemoglobinuria (PNH). In APPLY-PNH and APPOINT-PNH, changes in fatigue (FACIT-Fatigue) and health-related quality of life (HRQOL; EORTC QLQ-C30) from baseline to Day 168 were evaluated. The proportion of patients achieving meaningful within-patient change (MWPC) on the FACIT-Fatigue and 4 EORTC QLQ-C30 subscales (physical functioning, role functioning, fatigue, dyspnea) was evaluated using anchor-based thresholds.

Long-Term Efficacy and Safety of Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in PNH With Significant EVH.

Complement C5 inhibitor treatment with ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH) improves outcomes and survival. Some patients remain anemic due to clinically significant extravascular hemolysis (cs-EVH: hemoglobin [Hgb] ≤9.5 g/dL and absolute reticulocyte count [ARC] ≥120×109/L).

Outpatient subcutaneous alemtuzumab is feasible and safe for aplastic anemia and associated with high response rates.

Immunosuppressive therapy (IST) using horse antithymocyte globulin (h-ATG) combined with cyclosporine (CsA) and eltrombopag is the standard care for aplastic anemia (AA) in patients without a suitable matched donor. However, in many countries, h-ATG use has been discontinued, leaving rabbit ATG (r-ATG), which has a lower response rates and poorer survival, as the only alternative. In previous studies, alemtuzumab (ALZ), a humanized monoclonal antibody targeting CD52, combined with CsA resulted in an adequate ORR in AA patients.

Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients.

Limited efficacy of 3 + 7 plus gemtuzumab ozogamycin in newly diagnosed fit intermediate genetic risk acute myeloid leukemia patients.

Background: Gemtuzumab-ozogamycin (GO) is approved in combination with high-dose chemotherapy for treatment-naïve low- and intermediate-risk acute myeloid leukemia (AML).

Aims: In this retrospective real-life multicenter study, we reported efficacy and safety of GO plus high-dose chemotherapy in newly diagnosed AML patients.

Methods And Results: A total of 31 fit low- and intermediate-risk AML patients treated with GO-based regimens were retrospectively included in this real-life multicenter study, and results were compared with a control cohort treated with 3 + 7 alone.

Post-Transplant Cyclophosphamide versus Anti-Thymocyte Globulin in Patients with Hematological Malignancies Treated with Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical and Matched Unrelated Donors: A Real-Life Experience.

Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY ( = 24) or ATG ( = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared.

Towards personalized prevention of Herpes zoster infection in patients with hematologic diseases or hematopoietic stem cell transplant recipients: a position paper from an ad hoc Italian expert panel.

The identification of patients at high risk of Herpes zoster (HZ) requiring a preventive strategy with antiviral prophylaxis and anti-HZ vaccine is a clinically relevant issue in patients with immunological impairment. The absence of trials comparing vaccination to pharmacological prophylaxis or defining their sequential use makes the optimal preventive strategy uncertain. This article presents the results of group discussion among a panel of experts convened ad hoc to review the literature regarding antiviral prophylaxis and vaccine efficacy and safety in populations with malignant and non-malignant hematologic diseases, and in subjects submitted to hematopoietic stem cell transplantation.

Hemolytic paroxysmal nocturnal hemoglobinuria: 20 years of medical progress.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, thrombosis and bone marrow failure. Prior to the availability of specific therapy, PNH led to the death of around half of affected individuals, mainly through thrombotic complications, with a particular grim prognosis for patients presenting with classic PNH. The anti-C5 monoclonal antibody eculizumab has revolutionized treatment, controlling intravascular hemolysis and thrombosis occurrence, with improved long-term survival.

How we('ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future.

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by complement-mediated intravascular haemolysis, severe thrombophilia and bone marrow failure. While for patients with bone marrow failure the treatment follows that of immune-mediated aplastic anaemia, that of classic, haemolytic PNH is based on anti-complement medication. The anti-C5 monoclonal antibody eculizumab has revolutionized treatment, resulting in control of intravascular haemolysis and thromboembolic risk, with improved long-term survival.

Dyskeratosis congenita and squamous cell carcinoma of the mandibular alveolar ridge.

Dyskeratosis congenita is a rare disease caused by telomerase dysfunction classically characterised by the triad: skin pigmentation, nail dystrophy and mucosal leukoplakia. Few cases are described in literature regarding patients with head and neck squamous cell carcinoma affected by dyskeratosis congenita, and the therapeutic decisions are not yet well defined. A review of the literature of the last 20 years (2001-2021) was performed, and it was analysed the case of a 38-year-old male patient affected by dyskeratosis congenita diagnosed with a squamous cell carcinoma of the inferior alveolar ridge, treated with surgery.

Veno-occlusive Disease in HSCT Patients: Consensus-based Recommendations for Risk Assessment, Diagnosis, and Management by the GITMO Group.

Variation in clinical practice affects veno-occlusive disease management, mainly in patients who undergo allogeneic hematopoietic stem cell transplantation. Disputes about diagnostic criteria, treatment, and prophylaxis, due to the lack of high-quality data, are at the base of this variability. With the aim of limiting inconsistency in clinical care, thus improving both patient outcomes and data collection reliability, the Italian Society of Stem cell transplant (Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare) launched a collaborative effort to formulate recommendations based on integration of available evidence and expert's consensus.

Bone Marrow of Contention: A Rare Case of Recurrent Acute Hepatitis.

Hepatitis-associated aplastic anemia is a well-recognized clinical syndrome in which marrow failure follows the development of hepatitis. Although aplastic anemia is intimately related to paroxysmal nocturnal hemoglobinuria, until now, no cases of PNH-associated hepatitis have been described. We report a case of recurrent acute hepatitis preceding the clinical onset of PNH.

Oral Dysplastic Complications after HSCT: Single Case Series of Multidisciplinary Evaluation of 80 Patients.

Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem-cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft-versus-host disease (cGVHD). The aim of this study was to describe a cohort of post-HSCT patients and to evaluate the onset of oral epithelial dysplasia and/or OSCC over time.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors: A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (GITMO).

We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016).

Narrative Based Medicine as a tool for needs assessment of patients undergoing hematopoietic stem cell transplantation.

Background And Aim: In the last years we have seen an ever increasing number of patients with haematologic disorders who need hematopoietic stem cell transplantation (HSCT). The whole sector of HSCT results, infact to be in a continous scientific and technological clinical progress, offering a very advanced care. Despite this, some aspects are underconsidered, some of which could be fundamental to determine the success of the care pathway, such as the experience of the illness by the patient.

Small-molecule factor D inhibitors targeting the alternative complement pathway.

Complement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways.

Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

We analyzed the outcome of 537 adolescents (age 12-18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14).

Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival.

Easy genotyping of complement C3 'slow' and 'fast' allotypes by tetra-primer amplification refractory mutation system PCR.

Complement C3 'slow' and 'fast' allotypes are associated with immune-mediated disorders and may affect the outcome of renal transplantation. We report a tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) that provides a rapid, reproducible and cost-effective method to genotype both complement C3 'slow' and 'fast' alleles by a single tube reaction.