Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis.

Background: Many of the effects of pneumoperitoneum on cardiovascular, respiratory and metabolic systems have been discussed in Literature, but very little is known about the variations of the hemocoagulative parameters in patients undergoing laparoscopic surgery. The purpose of this study is to analyze the variations of the hemocoagulative parameters in patients undergoing elective laparoscopic cholecystectomy for symptomatic gallbladder stones. An eventual statistically significant difference linked to different pressure settings of pneumoperitoneum will allow selecting a specific intrabdominal pressure for a more adequate treatment with a lower incidence of pneumoperitoneum related complications. Materials and Methods: The clinical trial was conducted on 43 patients assigned in two groups based on the intra-abdominal pressure: group A, 27 patients, 12 mmHg, and group B, 16 patients, 8 mmHg. Hemoglobin, hematocrit, platelets count, PT ratio, aPTT, Fibrinogen, D-dimer, Von Willebrand factor, Factor II, Lupus Anticoagulant, Antithrombin III, Protein C, Protein S, Anticardiolipin IgG and IgM, anti-beta 2-Glicoprotein IgG and IgM were evaluated. Results: For group A, patient’s variations were observed for D-dimer, Factor II, von Willembrand factor and protein C reactive, while for patients belonging to group B the parameters most affected were PT ratio, anti-thrombin III and protein C reactive. D-dimer values increased significantly in group A, a statistically significant decrease in anti-thrombin III levels was detected in group B, and a statistically significant difference in PT ratio in patients belonging to group B was observed. Conclusion: The statistical analysis showed no significant difference in the post-operative parameters when comparing the two groups of patients. Alterations of the coagulation parameters were present between pre- and post-operative data within the same group, namely a higher abdominal pressure is linked to a prothrombotic state. The question is worthy of further studies. Highlights:

Background/Objectives: Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) mutations carries a poor prognosis. While FLT3 inhibitors like midostaurin show benefits in combination with chemotherapy, the role of allelic ratio (AR), NPM1 mutation status, and hematopoietic stem cell transplantation (HSCT) remains uncertain. Real-world data can help refine prognostic classification and treatment strategies. Methods: We retrospectively analyzed 37 fit patients with FLT3-ITD AML treated with standard “7+3” chemotherapy, with and without midostaurin, between 2013 and 2022. Patients were stratified by FLT3-ITD AR, NPM1 status, and treatment approach. Outcomes assessed included complete remission (CR), disease-free survival (DFS), and overall survival (OS). Results: Overall, 67.6% achieved CR/CRi. Response rates did not differ significantly by AR (low vs. high: 66.7% vs. 69.2%) or midostaurin use (72.6% vs. 60%; p = 0.49). NPM1 mutations were associated with improved DFS (10.3 vs. 3 months, p = 0.036) but not OS. HSCT, performed in 54.1% of patients, mainly in first remission (CR1), significantly prolonged DFS (not reached vs. 5.3 months, p = 0.005) and remained an independent predictor in multivariate analysis (HR: 0.160, p = 0.039). OS (median 15.1 months) did not vary significantly across subgroups. Among patients achieving CR1, OS was significantly longer in those who underwent HSCT after midostaurin-based induction compared to those not transplanted (median OS not reached vs. 12.8 months; 95% CI, 6.9–18.7; p = 0.045), whereas no significant benefit was observed after standard induction. In a landmark analysis restricted to patients transplanted in CR1, those who had received midostaurin-based induction showed a trend toward improved OS compared to those treated with standard induction (median OS not reached vs. 11.5 months; 95% CI, 0.5–25.0; p = 0.086). Conclusions: This real-life study supports the importance of NPM1 mutations and HSCT in CR1, especially in the midostaurin era, for improving DFS in FLT3-ITD AML. These findings support updated guidelines for reducing the prognostic weight of AR and highlight the need for improved post-remission strategies in this setting.

Castleman disease is a rare and benign disorder, characterized by enlarged lymph nodes and angiofollicular lymphoid hyperplasia. We report a case of a 57-year-old male, who was admitted to our surgical department because of a retroperitoneal nodular mass measuring about 4 cm in maximum diameter, incidentally discovered on a radiologic exam performed for the onset of vague abdominal pain with posterior irradiation. The patient was subdue to laparoscopic removal of the mass and no intra- and post-operative complications were recorded. Histologic diagnosis of hyaline-vascular variant of the Castleman disease was confirmed. Only two cases have been found in the literature reporting the paraduodenal unicentric Castleman disease localization like our case. Although rare, the Castleman disease must be considered in the differential diagnosis among all the lymph nodes diseases, for avoiding improper therapies.

Background: Multiple myeloma (MM) is a clonal plasma cell neoplasm representing the second most common hematological malignancy. The combination of daratumumab, lenalidomide and dexamethasone (D-Rd) was first approved by the EMA (European Medicines Agency) for the treatment of relapsed/refractory multiple myeloma (RRMM) patients, and was subsequently approved for first-line therapy, based on the results of POLLUX and MAIA trials, respectively. Methods: In this survey, we retrospectively collected data from 96 consecutive transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients treated with the D-Rd combination. Results: The median age was 73 years; the median progression free survival (mPFS) and median overall survival (mOS) were not reached (NR); the overall response rate (ORR), defined as patients who obtained at least a partial response (PR), was 90%; 59% of patients achieved a very good partial response (VGPR) or better. A strong negative correlation was observed between treatment response and elevated beta-2-microglobulin levels. Conclusions: This study confirms the efficacy of the D-Rd combination as first-line therapy for TIE-NDMM patients, suggesting that achieving at least a PR—and particularly a VGPR—may represent a strong predictor of long-term remission and survival, even in the era of new combinations based on the use of quadruplets.

Background: Polycythemia vera (PV) is characterized by mutation JAK2 V617F, elevated blood counts, and risk of thrombosis. Ropeginterferon alfa-2b (ropeg) approved for PV at a low-starting dose and slow-titration schema with efficacy at 12 months with assessment visits every three months. This period might be at thrombotic risk resulting from inadequate control of hematological parameters and JAK2. The study was aimed at assessing its efficacy at less than 12 months with assessment visits every two weeks. Methods: Thirteen patients with Hydroxyurea (HU)/Intolerance (HU/I) high-risk PV and pruritus were treated with ropeg at a low-starting dose and slow-titration schema with assessment visits every two weeks. The primary endpoint was the complete hematological response (CHR) at less than 12 months. The secondary endpoints were the CHR rates, CHR dose, durable CHR, and reduction in JAK2V617F variant allele frequency (VAF). Results: The CHR of patients was 8 weeks in 30.7% (4/13), 16 weeks in 30.7% (4/13), and 24 weeks in 38.4% (5/13), respectively, with a mean time of 4.15 months. Durable CHR was at 20, 28, and 36 weeks, respectively, with a mean time of 6.55 months. JAK2 VAF continuously declined from 43.38% at baseline to 12.96% at durable CHR. Eleven patients (85%) achieved partial molecular response (PMR) and two (15.38%) complete molecular responses (CMRs) and all patients resolved the pruritus. No adverse event (AE) or thrombosis occurred. Conclusions: We report that ropeg is efficacious under the low-starting dose and slow-titration regimen in obtaining CHR and molecular response (MR) at less than 12 months.