Impact of the Donor KIR Genotype on the Clinical Outcome of Hematopoietic Stem Cell Unrelated Transplants: A Single Center Experience

In recent years, the anti-leukemic potential of Natural Killer (NK) cells and their role in hematologic malignancies and in Hematopoietic Stem Cell Transplants (HSCT) has attracted greater interest and a recent study by Cooley S. et al. showed a better clinical outcome when patients with Acute Myeloid Leukemia received a transplant from unrelated Group B KIR haplotypes donors. As a consequence of these results, an algorithm called “KIR B-content score” was formulated. The aim of our research is a retrospective analysis of HSC unrelated transplants performed in our center to analyze the effect of the donor KIR B status on the clinical-outcome. Our results showed a better overall survival-rate in the AML recipients, HLA mismatched with the donor, when the donor KIR B content status is Best/Better (37% vs 18% at three years P=0,028). Moreover, we observed that AML recipients, whose Donors KIR B status was Best/Better, had more incidence of aGvHD grade I and II than patients whose Donors KIR B status was Neutral (70% vs 26%) and also a lower rate of relapse (36% vs 58%) and a better Disease Free Survival-rate (58% vs 38% at three years P=0,1) because of a better GvL effect

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy

Chimeric antigen receptor T (CAR-T) cells are a treatment option for patients with relapse/refractory (R/R) non-Hodgkin lymphoma (NHL), acute lymphoid leukemia and multiple myeloma. To date, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL) have been successfully treated with CAR-T cells directed against the CD19 antigen. However, when R/R disease persists after several treatment lines, patients with these diseases are often referred to transplantation centres to receive allogeneic stem cell transplantation (ALLO-SCT). ALLO-SCT and CAR-T cells share mechanism of actions, inducing immune effects of T-cells (and other cells after transplantation) against lymphoma cells, but they differ in several other characteristics. These differences justify unique positioning of each therapy within treatment algorithms. In this paper, we analyzed the results obtained after ALLO-SCT and CAR-T-cell therapy in patients with aggressive lymphomas (large B-cell lymphoma and MCL) to identify the ideal scenarios in which these 2 immunological therapies should be employed

Visual gravitational motion and the vestibular system in humans

Lacquaniti F, Bosco G, Indovina I, et al. Visual gravitational motion and the vestibular system in humans. Frontiers in Integrative Neuroscience. 2013;7: 101

Personalized Dosimetry in Targeted Radiation Therapy: A Look to Methods, Tools and Critical Aspects

Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided

Regional cerebral metabolic rate of glucose evaluation and clinical assessment in patients with idiopathic normal-pressure hydrocephalus before and after ventricular shunt placement: a prospective analysis

PURPOSE: We prospectively evaluated the regional cerebral metabolic rate of glucose (CMRglu) before and after ventricular shunt placement in idiopathic normal-pressure hydrocephalus (iNPH) patients, to investigate whether some brain regions are more involved than others; we also correlated the individual variations of CMRglu with the clinical scale score assessment after shunting. METHODS: Twenty iNPH patients (12 men; mean age 73 ± 9 years) underwent clinical scale score assessment and F-FDG PET-CT before and 1 week after shunting. RESULTS: Before shunting, CMRglu values were similar in right and left brain regions, as well as after shunting. After shunting, 17 of 20 iNPH patients were clinically improved; all scale scores decreased, and CMRglu significantly increased in all regions (P < 10). In 3 of 20 iNPH patients, the symptoms persisted, the scale scores did not change, and CMRglu increased only in 3 regions: left frontal, left putamen, and right thalamus. Before shunting, no difference in global CMRglu between clinically improved (n = 17) and not improved (n = 3) iNPH patients was found. After shunting, a significant (P = 0.01) correlation between individual variations of CMRglu and clinical assessment was found. CONCLUSIONS: These findings confirm that iNPH is a disease involving all cerebral regions almost in the same way, and shunt procedure has a similar effect on regional cerebral metabolism almost in the same way. Individual variations of CMRglu are more important than absolute values and correlate with clinical status after shunting. Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function

The quantification with FDG as seen by a physician.

Although, at the present, in the routine practice, the qualitative analysis of PET with F-18 Fluoro-deoxyglucose (FDG) remains indispensable and sufficient for clinical purposes, a quantitative approach may add a significant contribution, when rigorous and reliable. In particular, a quantitative analysis may already be clinically applied for indications as a better definition of a specificity's threshold, a more precise prognostic stratification, a correct evaluation of the tumor response and/or of the disease's evolution. The cost/effectiveness of this approach may be found in better defining diagnostic and therapeutic strategies. Conversely to be applied in the clinical practice the method has to be as easy as possible. Therefore the final goal is to apply the simplest method to allow a reliable quantitative evaluation. To arrive to this result, applicable using simplified methods hopefully including also repeated static images, it is important to validate the new procedures versus the already verified more rigorous and precise measurements. Being acceptable in the clinical practice a lower precision with respect to the one required in the research, it is mandatory to avoid problems to the patient, as those connected with an intra-arterial sampling. Similarly cannot be applied in the routine a procedure too long or requiring overmuch expertise and performing tools, therefore non diffusible for a clinical use. The goal of this review is to suggest, from the point of view of a physician, which are at the present the simplified methods that could be easily and widely applied in the clinical practice for a reliable quantification with FDG

In utero stem cells transplantation after a mild immunosuppression: evidence of paternal ABO cDNA in β β β β β-thalassaemia affected fetus

Background. In utero haematopoietic stem cell transplantation (IUHSCT) could represent an alternative option to therapeutic abortion after prenatal diagnosis of thalassaemia. However, although in immunodeficiency syndromes chimerism has been described, in thalassaemia poor clinical success has been reported. One of the reasons is probably the graft failure due to an immune response of the fetuses. Materials and methods. Therefore, we set up a clinical protocol by which two female fetuses affected by ß-thalassaemia at 20 and 21 weeks of gestation were prenatally treated with low-dose dexamethasone and then transplanted with paternal circulating haematopoietic progenitor cells. Results. Chimerism analysis performed after birth showed the presence, in both newborns, of Y cells in peripheral blood. Moreover, in one case an erythroid microchimerism was shown by the presence of paternal ABO allele A cDNA obtained from mononuclear peripheral blood cells at 2 months of age and by an unusual HbA value of 14.4%, thus indicating a slight transitory engraftment of infused paternal stem cells. However, because of both babies required transfusions before 12 months, these data confirm the difficulty for long-term successful with IUHSCT. Conclusions. To obtain safe and successful results for fetuses with β β β β β-thalassaemia will remain a challenge of the next years. Introduzione I rapidi progressi conseguiti nelle indagini genetiche e molecolari hanno consentito di individuare numerose malattie genetiche ereditarie in periodi precoci di gestazione, mediante il campionamento dei villi coriali (CVC) e l&apos;analisi del DNA. Il trapianto in utero di cellule staminali ematopoietiche (In utero Haematopoietic Stem Cell Transplantation, IUHSCT) potrebbe rappresentare una opzione alternativa all&apos;aborto terapeutico in alcune emopatie genetiche ereditarie, quali le emoglobinopatie, in quanto, potenzialmente, potrebbe consentire la nascita di un neonato sano. Tuttavia, attualmente, l&apos;attecchimento dopo IUHSCT si è ottenuto soltanto in caso di feti affetti da disordini immunologici, quali la sindrome di Bare (sindrome dei linfociti &quot;nudi&quot;) o l&apos;immunodeficienza combinata grave (Severe Combined ImmunoDeficiency, SCID

Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging

n/