Successful salvage therapy for refractory primary cutaneous gamma-delta T-cell lymphoma with a combination of brentuximab vedotin and gemcitabine.

Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very rare lymphoma with an aggressive clinical course and a dismal outcome. The prognosis is linked to a pronounced resistance to chemotherapy and radiotherapy. No standard treatment approach is defined due to the low frequency of the disease and lack of prospective studies. CD30 is expressed in almost half of the cases of PCGD-TCL, which offers a potential therapeutic option. We report the successful treatment of a 68-year-old man who suffered PCGD-TCL with a combination of Brentuximab Vedotin and Gemcitabine after the failure of two lines of previous chemotherapy. CD30 expression was only partial. The treatment was very well tolerated and allowed the patient to benefit from allogeneic hematopoietic stem cell transplantation

Anomalous Processes with General Waiting Times: Functionals and Multipoint Structure

Many transport processes in nature exhibit anomalous diffusive properties with non-trivial scaling of the mean square displacement, e.g., diffusion of cells or of biomolecules inside the cell nucleus, where typically a crossover between different scaling regimes appears over time. Here, we investigate a class of anomalous diffusion processes that is able to capture such complex dynamics by virtue of a general waiting time distribution. We obtain a complete characterization of such generalized anomalous processes, including their functionals and multi-point structure, using a representation in terms of a normal diffusive process plus a stochastic time change. In particular, we derive analytical closed form expressions for the two-point correlation functions, which can be readily compared with experimental data.Comment: Accepted in Phys. Rev. Let

Occurrence of malignant neoplasia in patients with primary hyperparathyroidism

Introduction The association between primary hyperparathyroidism (1HPT) and cancer is debated. The present study was aimed to investigate the occurrence of neoplasia in 1HPT. Patients and methods All consecutive patients (n = 1750) referred to our \u201cOsteoporosis and Metabolic Disease\u201d outpatients clinic for osteoporosis or hypercalcemia were eligible for the study. The exclusion criteria were: the finding of osteoporosis and/or altered calcium-phosphorous metabolism in the context of investigations for malignancy, the presence of diseases known to influence the cancer risk and the heavy smoking habit. Eventually, 1606 patients (1407 females, 199 males) were enrolled. In all patients calcium-phosphorous metabolism, PTH and vitamin D levels were measured and the occurrence of cancer during the 10 years prior the study inclusion was recorded. Results One-hundred-sixty-three patients had 1HPT while 1443 had not. Patients with and without 1HPT were comparable for age and gender. In 1HPT patients the occurrence of all, breast, kidney and skin cancer was significantly higher (21.5%, 12.2%, 2.5%, 1.8%, respectively) than in patients without 1HPT (12.4%, 6.9%, 0.3%, 0.3%, p < 0.05 for all comparisons). The 1HPT presence was significantly associated with the occurrence of all neoplasia and of breast, skin and kidney neoplasia (odds ratio, 95% confidence interval, p value: 1.93, 1.27\u20132.92, 0.002; 1.93, 1.11\u20133.35, 0.002; 9.18, 2.16\u201338.8, 0.003; 8.23, 1.71\u201339.5, 0.008, respectively), after adjusting for age, gender (as appropriate), smoking habit and vitamin D levels. Conclusion During the 10 years prior the diagnosis of 1HPT, the occurrence of all, breast, skin and kidney neoplasia is increased

Meningeal Relapse of Nodular Lymphocyte Predominant Hodgkin Lymphoma Transformed to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Case Report.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis

Validation of the clinical consensus recommendations on the management of fracture risk in postmenopausal women with type 2 diabetes

Background and aims: Bone fragility is recognized as a complication of type 2 diabetes (T2D). However, the fracture risk in T2D is underestimated using the classical assessment tools. An expert panel suggested the diagnostic approaches for the detection of T2D patients worthy of bone-active treatment. The aim of the study was to apply these algorithms to a cohort of T2D women to validate them in clinical practice. Methods and results: The presence of T2D-specific fracture risk factors (T2D ≥ 10 years, ≥1 T2D complications, insulin or thiazolidinedione use, poor glycaemic control) was assessed at baseline in 107 postmenopausal T2D women. In all patients at baseline and in 34 patients after a median follow-up of 60.2 months we retrospectively evaluated bone mineral density and clinical and morphometric vertebral fractures. No patient was treated with bone-active drug. Following the protocols, 34 (31.8%) and 73 (68.2%) patients would have been pharmacologically and conservatively treated, respectively. Among 49 patients without both clinical fractures and major T2D-related risk factors, who would have been, therefore, conservatively followed-up without vertebral fracture assessment, only one showed a prevalent vertebral fracture (sensitivity 90%, negative predictive value 98%). The two patients who experienced an incident fracture would have been pharmacologically treated at baseline. Conclusions: The clinical consensus recommendations showed a very good sensitivity in identifying T2D postmenopausal women at high fracture risk. Among those with treatment indication as many as 13% of patients experienced an incident fracture, and, conversely, among those without treatment indication no incident fractures were observed

Multidimensional Results and Reflections on CAR-T: The Italian Evidence

The present study aims at defining the economic and organizational impacts of the introduction of chimeric antigen receptor T-cell therapy (CAR-T) in Italy, for the management of diffuse large B-cell lymphoma (DLBCL) patients in third-line therapy, defining the overall level of sustainability for both hospitals and the National Healthcare System (NHS). The analysis focused on CAR-T and Best Salvage Care (in the following BSC), assuming the Italian hospital and NHS perspectives, over a 36-month time horizon. Process mapping and activity-based costing methodologies were applied to collect the hospital costs related to the BSC and CAR-T pathways, including adverse event management. Anonymous administrative data on services provided (diagnostic and laboratory examinations, hospitalizations, outpatient procedures, and therapies) to 47 third-line patients with lymphoma, as well as any organizational investments required, were collected, in two different Italian Hospitals. The economic results showed that the BSC clinical pathway required less resources in comparison with CAR-T (excluding the cost related to the therapy) (BSC: 29,558.41 vs. CAR-T: EUR 71,220.84, −58.5%). The budget impact analysis depicts that the introduction of CAR-T would generate an increase in costs ranging from 15% to 23%, without considering treatment costs. The assessment of the organizational impact reveals that the introduction of CAR-T therapy would require additional investments equal to a minimum of EUR 15,500 to a maximum of EUR 100,897.49, from the hospital perspective. Results show new economic evidence for healthcare decision makers, to optimize the appropriateness of resource allocation. The present analysis suggests the need to introduce a specific reimbursement tariff, both at the hospital and at NHS levels, since no consensus exists, at least in the Italian setting, concerning the proper remuneration for the hospitals who guarantee this innovative pathway, assuming high risks related to timely management of adverse events

Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996

The impact of KMT2A-AFF1 rearrangement in pediatric-like, minimal residual disease (MRD)-based clinical trials and the effect of transplant in KMT2A-AFF1 ALL are still debated