Acute Lymphoblastic Leukemia Immunotherapy Treatment: Now, Next, and Beyond

Acute lymphoblastic leukemia (ALL) is a blood cancer that primarily affects children but also adults. It is due to the malignant proliferation of lymphoid precursor cells that invade the bone marrow and can spread to extramedullary sites. ALL is divided into B cell (85%) and T cell lineages (10 to 15%); rare cases are associated with the natural killer (NK) cell lineage (<1%). To date, the survival rate in children with ALL is excellent while in adults continues to be poor. Despite the therapeutic progress, there are subsets of patients that still have high relapse rates after chemotherapy or hematopoietic stem cell transplantation (HSCT) and an unsatisfactory cure rate. Hence, the identification of more effective and safer therapy choices represents a primary issue. In this review, we will discuss novel therapeutic options including bispecific antibodies, antibody–drug conjugates, chimeric antigen receptor (CAR)-based therapies, and other promising treatments for both pediatric and adult patients

Immunotherapy as a turning point in the treatment of acute myeloid leukemia

Acute myeloid leukemia (AML) is a malignant disease of hematopoietic precursors at the earliest stage of maturation, resulting in a clonalproliferation of myoblasts replacing normal hematopoiesis. AML represents one of the most common types of leukemia, mostly affecting elderly patients. To date, standard chemotherapy protocols are only effective in patients at low risk of relapse and therapy-related mortality. The average 5-year overall survival (OS) is approximately 28%. Allogeneic hematopoietic stem cell transplantation (HSCT) improves prognosis but is limited by donor availability, a relatively young age of patients, and absence of significant comorbidities. Moreover, it is associated with significant morbidity and mortality. However, increasing understanding of AML immunobiology is leading to the development of innovative therapeutic strategies. Immunotherapy is considered an attractive strategy for controlling and eliminating the disease. It can be a real breakthrough in the treatment of leukemia, especially in patients who are not eligible forintensive chemotherapy. In this review, we focused on the progress of immunotherapy in the field of AML by discussing monoclonal antibodies (mAbs), immune checkpoint inhibitors, chimeric antigen receptor T cells (CAR-T cells), and vaccine therapeutic choices

Improving accuracy of corneal power measurement with partial coherence interferometry after corneal refractive surgery using a multivariate polynomial approach

Background: To improve accuracy of IOLMaster (Carl Zeiss, Jena, Germany) in corneal power measurement after myopic excimer corneal refractive surgery (MECRS) using multivariate polynomial analysis (MPA). Methods: One eye of each of 403 patients (mean age 31.53 ± 8.47 years) was subjected to MECRS for a myopic defect, measured as spherical equivalent, ranging from - 9.50 to - 1 D (mean - 4.55 ± 2.20 D). Each patient underwent a complete eye examination and IOLMaster scan before surgery and at 1, 3 and 6 months follow up. Axial length (AL), flatter keratometry value (K1), steeper keratometry value (K2), mean keratometry value (KM) and anterior chamber depth measured from the corneal endothelium to the anterior surface of the lens (ACD) were used in a MPA to devise a method to improve accuracy of KM measurements. Results: Using AL, K1, K2 and ACD measured after surgery in polynomial degree 2 analysis, mean error of corneal power evaluation after MECRS was + 0.16 ± 0.19 D. Conclusions: MPA was found to be an effective tool in devising a method to improve precision in corneal power evaluation in eyes previously subjected to MECRS, according to our results

Il rapporto tra diritto di proprietà e ius aedifcandi nell'attuale contesto normativo

La tesi ha per oggetto l’analisi del rapporto che intercorre tra diritto di proprietà e ius aedificandi alla luce dell’attuale contesto sociale, economico e giuridico. L’analisi si propone di rielaborare la tradizionale impostazione della inerenza dello ius aedificandi al diritto di proprietà alla luce della legislazione attuale e degli strumenti di pianificazione volti, tra l’altro, alla riduzione del consumo di suolo non urbanizzato in linea con gli obiettivi dell’Unione Europea. Si è percorsa la giurisprudenza europea e nazionale in tema di diritto di proprietà, con particolare riguardo alla legislazione sulla conformazione dei suoli e pianificazione urbanistica. Inoltre, partendo dalla crisi della tecnica pianificatoria dello “zoning” si è affrontato il fenomeno dei diritti edificatori nonché la disciplina degli strumenti di pianificazione della perequazione, compensazione e premialità edilizia, di cui sono state esaminate le peculiarità e le caratteristiche essenziali. Sono state altresì evidenziate le lacune normative ed i limiti applicativi di tali istituti che hanno posto le condizioni necessarie per il nascere di una diversa e nuova concezione dell’urbanistica

CD16low/negative Tumor-Infiltrating Lymphocyte: Lymphoid or Myeloid in Origin?

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OCT Applications in Conjunctival Disease

Today the of anterior segment optical coherence tomography (ASOCT) has become an irreplaceable tool in the management of various pathologies and also in many surgical techniques. The cornea has been widely studied in many pathologies with ASOCT, but now also the conjunctival study with ASOCT allows to obtain a detailed imaging of the normal and pathological conjunctiva, so that in many conjunctival diseases the ASOCT is a useful tool to help the clinicians. In this chapter we will briefly discuss the results of the imaging of the oct appearance of the normal conjunctiva with ASOCT and its present and potential use in the conjunctival pathologies

Evaluation of Donor and Recipient Characteristics Involved in Descemet Stripping Automated Endothelial Keratoplasty Outcomes

Aims: To evaluate both donor and recipient features involved in visual acuity restoring and complication insurgence in eyes that have undergone Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: In this retrospective study, charts of 111 eyes of 96 patients (mean age 70.25 ± 8.58 years) that underwent DSAEK were evaluated. Only Fuch's Distrophy (FD) or Bullous Keratopathy (BK) due to cataract surgery eyes were included. A complete ophthalmic check with endothelial cell density (ECD) and central corneal thickness (CCT) measurement was performed before surgery and at 1, 3, 6, and 12 months follow-up. Each DSAEK was performed by the same well-trained surgeon; only pre-cut lenticules, provided by same Eye Bank, were implanted. Results: A total of 48 (43%) complications have been observed (most of them were 22 partial graft detachments and 17 IOP spikes). At the last follow-up (mean: 8.58 ± 4.09 months), a significant increase (p < 0.05) of best corrected visual acuity (BCVA) was detected. Overall mean BCVA of the eyes evaluated was 0.40 ± 0.43 LogMAR with BK eyes showing a significantly higher improvement (p < 0.05) compared to FD eyes. The only factor showing a significant correlation (p < 0.05) with visual acuity enhancement was the implant of a lenticule thinner than 100 μm. Recipient features significantly (p < 0.05) associated with complications observed after surgery were glaucoma and diabetes mellitus. Conclusion: The use of a graft thinner than 100 μm can provide better visual acuity recovery while recipients affected by glaucoma or diabetes mellitus are more prone to develop complications after surgery

Correlation between choriocapillaris density and retinal sensitivity in age-related macular degeneration

Purpose: The purpose of this study was to investigate the relationship between perfusion of the choriocapillaris (CC) and retinal sensitivity in eyes with intermediate agerelated macular degeneration (iAMD). Methods: This prospective study included patients with iAMD and healthy controls. All enrolled subjects underwent optical coherence tomography angiography (OCT-A) in order to compute the percent perfused choriocapillaris area (PPCA). In patients with iAMD, microperimetry (MP) testing was performed in order to quantify: mean retinal sensitivity (MRS), over an area of 10 degrees; mean macular sensitivity (MMS), over the macular area scanned with OCT-A; and retinal sensitivity (RS) in each macular point. Results: Eighteen eyes of 13 patients were included in the analysis. In addition, 18 eyes of 12 healthy subjects were enrolled as controls. No statistically significant difference (P value > 0.2) was observed in age between patients (73.9 ± 2.0 years) and controls (70.1 ± 2.8 years). We observed significantly lower values of PPCA between patients with iAMD and healthy controls (42.0% ± 3.8% vs. 66.4% ± 3.0%; -Β = 23.8%; P value < 0.001). Among iAMD eyes, higher values of PPCA were significantly associated with higher values of MRS (P value=0.002) and MMS (P value=0.013). Finally, higher values of RS in eachmacular point analyzedwithMPwere significantly (P value<0.001) associated with higher values of PPCA computed in circular regions of interest (ROIs) centered in each analyzed MP point with radii of 0.5 degrees and 1.0 degree. Conclusions: Using OCT-A, we demonstrated a significant association between CC impairment and macular dysfunction, quantified by MP, in iAMD eyes. Translational Relevance: OCT-A could be a useful tool for detecting CC alterations and to monitor disease progression