Established disease-centered prognostic systems may be less tailored to elderly/non-transplant-eligible (NTE) patients with multiple myeloma (MM), in whom host-related factors such as age, performance status, and renal function strongly influence all-cause outcomes. We developed and evaluated the Myeloma Elderly Prognostic Score (MEPS), a pragmatic four-factor score integrating age ≥ 75 years, renal function < 40 by eGFR or available creatinine clearance (CrCl), ECOG performance status ≥ 2, and ultra-high-risk cytogenetics, using baseline registry data from 881 newly diagnosed NTE MM patients from Greece, with OS analyses performed in the 878 patients with evaluable survival follow-up, and externally evaluated it in an independent Portuguese cohort. In the Greek OS-evaluable cohort, 485 deaths were observed. Median OS by MEPS group was 96, 65, 39, and 15.3 months for scores 0, 1, 2, and ≥ 3, respectively. In a baseline score-level Cox model, each ordinal MEPS category increase was associated with inferior OS (HR 1.74, 95% CI 1.58-1.92; p < 0.001). MEPS showed higher OS discrimination than R2-ISS in the Greek cohort (C-index 0.655 vs. 0.602; bootstrap delta 0.053, 95% CI 0.021-0.085). The Portuguese validation dataset included 300 patients, of whom 290 were evaluable for the primary OS analysis, with 151 deaths. Median OS was 59.6 months (95% CI 52.4-75.7), and MEPS again showed higher discrimination than R2-ISS (C-index 0.729 vs. 0.647; bootstrap delta 0.082, 95% CI 0.041-0.127). MEPS provides a simple all-cause prognostic tool for elderly/NTE MM, complementing biologically oriented staging with routinely available host-related variables.

This report describes a paediatric case of cold urticaria (ColdU) associated with markedly elevated cold agglutinin titres following Epstein-Barr virus (EBV) infection. An 11-year-old girl developed recurrent cold-induced urticaria and anaphylaxis after a recent EBV infection. Immunohaematologic testing revealed a cold-reactive IgM autoantibody with anti-i specificity. Despite the exceptionally high peak titres (>1:262,144 at 4°C), and the unusually broad thermal amplitude extending to 30°C, no clinical or laboratory evidence of haemolysis was observed, and the direct antiglobulin test remained persistently negative. Complement components and cryoprotein assays were consistently normal. Throughout an extended 52-month longitudinal follow-up, antibody titres gradually declined in parallel with the resolution of urticarial symptoms and withdrawal of antihistamines. This case demonstrates a non-haemolytic, post-infectious immune phenotype of ColdU, in which transient, high-titre cold agglutinins coexist with cutaneous hypersensitivity without haemolytic manifestations, and highlights the importance of comprehensive immunohaematologic evaluation and long-term monitoring in ColdU cases with atypical serologic findings.

Gut microbiota plays a crucial role in regulating immune system function and shaping immunological responses to pathogens capable of causing infections. Alterations in the composition of the intestinal microbiome are associated with immune system dysfunction and increased susceptibility to infections. Patients with acute myeloid leukemia (AML) are highly susceptible to infections due to immune system deregulation caused by the disease itself, as well as chemotherapy-induced bone marrow aplasia. In these patients, gut microbiota dysbiosis and reduced microbial diversity (i.e., imbalances in the composition and function of intestinal microbes) result from multiple factors, including the underlying disease, neutropenia, dietary factors, use of antibiotics, chemotherapy regimens and prolonged hospitalization. Chemotherapy, for instance, induces damage to the intestinal mucosa and disrupts the epithelial barrier, resulting in deregulation of the intestinal microbiome. Previous studies have reported alterations in the human intestinal microbiome in patients with AML undergoing chemotherapy. Of particular interest is the capacity of some commensal bacteria to modulate the tumor microenvironment and response to chemotherapy. Moreover, increased mortality and reduced overall survival have been reported in patients who have undergone allogeneic stem cell transplantation and exhibit decreased gut microbiome diversity at the time of transplantation. These findings indicate that the composition of gut microbiota may play an important role in the prognosis of AML, especially in relation to therapeutic response. This narrative review summarizes new research into the role of the intestinal microbiome and the underlying alterations observed in patients with AML, resulting from the disease and therapeutic interventions and outlines strategies to improve its function and outcomes.

Waldenström's macroglobulinaemia (WM) is a rare B-cell lymphoproliferative disorder with multiple effective front-line treatment options. However, real-world comparative data on commonly used regimens are limited. We conducted a retrospective cohort study of 348 consecutive, newly diagnosed WM patients treated between 2002 and 2024. Patients received first-line therapy with either bortezomib-dexamethasone-rituximab (BDR, n = 35), Bruton's tyrosine kinase inhibitors (BTKis, n = 57) or dexamethasone-rituximab-cyclophosphamide (DRC, n = 256). BTKi demonstrated the highest MRR (major response rate, ≥PR) (80.7%), followed by DRC (68.4%) and BDR (40.0%) (p < 0.001). The median PFS and OS did not differ significantly among regimens. TTNT seemed to be longer in the BTKi group (log-rank p = 0.025), with a 74% reduced risk of salvage therapy compared to DRC (aHR = 0.26, p = 0.016). Cumulative WM-related mortality at 5 years was lowest in BTKi-treated patients (4.1% vs. 13.0% DRC vs. 17.1% BDR), though differences were not statistically significant. In this single-centre analysis, both BTKi and DRC led to prolonged disease control in the upfront treatment of patients with WM. Extended follow-up and prospective validation are needed to reveal potential long-term survival differences.

Identification of prognostic markers for early progressive disease (EPD) in multiple myeloma (MM) is critical for designing treatment strategies. In this retrospective study we demonstrated that R2-ISS is the only independent prognosticator for EPD. Daratumumab-based therapies and ASCT significantly reduced the probability of EPD. Background: Despite treatment improvements a considerable proportion of newly diagnosed multiple myeloma (MM) patients experience early progressive disease (EPD) defined as progression or relapse in < 18 months following initial response to first line treatment. Methods: We evaluated 1436 newly diagnosed MM patients out of whom 23.3% had EPD. Results: Patients with EPD had higher median age, beta 2-microglobulin, LDH and lower hemoglobin and eGFR, compared to others ( P < .05); EPD population presented more commonly with advanced stage (ISS3, RISS3, and R2-ISS stage III/IV). Ultra-high-risk MM (UHR-MM) i.e., detection of >= 2 high-risk molecular abnormalities was more frequent in EPD population ( P < .001). The percentage of patients treated with lenalidomide-based regimens was not significantly different. Daratumumab-based therapies (DBT) were administered less frequently in patients with EPD (2% vs. 10%; P < .001); 11% of patients with EPD versus 33% underwent ASCT ( P < .001); Complete response to induction therapy was significantly lower in EPD patients (12% vs. 27%; P < .001). Binary logistic regression analysis demonstrated that ISS, RISS, R2-ISS, UHR-MM, ASCT and DBT were significant predictors for EPD ( P < .05). In multivariate analysis R2-ISS, ASCT, and DBT were independent prognosticators for EPD ( P < .001). Median PFS and OS were 10 versus 40 months and 29 versus 76 months in patients with EPD versus others, respectively ( P < .001). Conclusion: In real-world, EPD is observed in more than one-fifth of patients, and it remains an unmet clinical need. Daratumumab-based therapies and ASCT significantly reduce the probability of EPD, while R2-ISS could serve as a useful prognostic tool for recognizing this population and guide therapeutic decisions.

As induction therapy, VRd demonstrated superior efficacy in terms of response rates over VCd, but not in PFS and OS in the real-world setting. Long-term outcomes are driven by effective consolidation and use of maintenance. VCd induction remains a reasonable option for patients for which VRd may not be feasible or well-tolerated and could find a niche in novel combinations. Background: Bortezomib, dexamethasone and cyclophosphamide (VCd) remains a popular regimen, due to its activity and low toxicity, while bortezomib, lenalidomide and dexamethasone (VRd) is widely used in US and Europe; both are combined with anti-CD38 monoclonal antibodies but VCd and VRd have not been compared directly in adequately powered prospective trials. Aim: We compared the outcomes of 1216 patients treated with VCd ( N = 690) or VRd ( N = 526) in a real-world setting. Results: Patients treated with VCd had more often severe renal dysfunction, ISS3 disease, hypercalcemia, elevated LDH, anemia, thrombocytopenia, poor performance while VRd-treated were older and received less often autologous transplant but more frequently maintenance but the duration of induction was similar. VRd was associated with substantially higher overall response and CR/VGPR rates to induction( P < .001) and improved PFS and OS in univariate analysis, especially among patients with standard risk disease, without renal dysfunction and in the elderly; however, in multivariate analysis there was no significant difference in either PFS or OS. In patients strictly matched 1:1 for major prognostic variables (188 in each group, total N = 376), the super ior ity of VRd in terms of responses rates and depth of response was confirmed, but without significant PFS or OS difference. Conclusion: VRd is a more active induction regimen than VCd, although use of maintenance with lenalidomide may dilute the PFS or OS benefit. VCd induction remains an option in special circumstances. With the implementation of monoclonal antibodies, VCd backbone can be considered for patients without access to or who do not tolerate VRd.

This report describes the first successful administration of ravulizumab, a C5 complement inhibitor, in the treatment of life-threatening intravascular hemolysis (IVH) caused by delayed hemolytic transfusion reaction (DHTR) in a 22-year-old woman. The patient developed acute IVH with severe anemia and hemodynamic instability seven days after receiving a blood transfusion for posthemorrhagic anemia following a missed abortion. Laboratory investigations revealed anti-e and anti-Jka alloantibodies consistent with DHTR. Despite treatment, her hemoglobin level declined further, raising concerns for hyperhemolytic syndrome. After the administration of ravulizumab, her condition improved rapidly, and she was discharged with stable hemoglobin levels. Within three weeks there was full hematologic and biochemical recovery. This case demonstrates the therapeutic potential of ravulizumab in the management of severe complement-mediated hemolysis due to DHTR, and highlights the need for further research on complement inhibitors in similar conditions.

BACKGROUND:Waldenstrom macroglobulinemia (WM) is an indolent lymphoma with a long course; advanced age and immunosuppressive treatments may predispose for second primary malignancies (SPM). METHODS:Consecutive symptomatic, newly diagnosed patients with WM who were diagnosed, treated and followed-up until May 28, 2024 were included in this study. RESULTS:677 symptomatic patients with WM were included in the analysis; their median age was 69 years (range 24-93) and 209 were females (30.9%). Over a median follow-up of 5.32 years (range 0.01-25.61), 58 patients (8.6%) were diagnosed with a SPM. The median time from WM diagnosis to SPM diagnosis was 4.93 years (range 0.07-20.71). The incidence rate (IR) of a SPM per person-year was 0.009, translating to roughly 1 case per 100 person-years. The cumulative incidence (CI) of SPMs, accounting for death due to WM or other causes as a competing event, at 5 and 10 years was 4.0% and 7.2%. Furthermore, 23 patients (3.4%) developed transformation to high grade lymphoma. The median time from WM diagnosis to transformation was 5.36 years (range 0.01-25.6). The IR of transformation per person-year was 0.003, translating to 3 cases per 1000 person-years. The CI of transformation to high-grade lymphoma, accounting for death due to WM or other causes as a competing event, at 5 and 10 years, was 2.1% and 3.4%. CONCLUSIONS:Data from our prospectively maintained multicenter database revealed that 8.6% and 3.4% of symptomatic patients with WM developed a SPM and disease transformation, respectively, over a median follow-up of 5.3 years.

INTRODUCTION:Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive lymphoma with dismal outcome after disease progression. Individual risk assessment can stratify patients into different treatment strategies. METHODS:We retrospectively collected data from 326 DLBCL patients treated in a single center with RCHOP from 01/2000 to 06/2023. Immunohistochemistry by Han's algorithm was used to classify patients according to cell of origin (COO). The Kaplan-Meier estimator of survival and Cox regression analysis were used. RESULTS:Time to progression (TTP) and overall survival (OS) were not different according to COO. Univariate analysis reveals International Prognostic Index (IPI), b2-microglobulin ≥3.5 mg/L, bulky disease, and abnormal LDH, but not Han's defined COO, as the strongest predictors for progression. IPI score in multivariate analysis was the only prognostic factor for OS and together with high b2-microglobulin levels were independently prognostic factors for TTP. Accordingly, b2-microglobulin ≥3.5 mg/L was an independent prognostic factor for progression both in GC (hazard ratio [HR] 0.249 [(95% CI: 0.087-0.649), p = 0.004] and non-GC DLBCL patients (HR 0.380 [95% CI: 0.177-0.813], p = 0.011). CONCLUSION:COO according to Hans index is not a significant prognostic factor for DLBCL patients, but b2-microglobulin ≥3.5 mg/L and IPI 2-5 in both GC and non-GC patients can predict individually a higher risk for progression.

Background: New targeted therapies have revolutionized the treatment landscape in CLL. Biological features, patient characteristics and preferences and the safety profile of each treatment option should be taken into consideration for making the optimal treatment choice. This consensus practice statement on CLL treatment was developed by a group of Greek experts in CLL based on the available evidence for both first-line treatment and the relapsed/refractory setting.

Isatuximab (Isa), an anti-CD38 mAb, is approved with pomalidomide and low-dose dexamethasone (Isa-Pd) for RRMM after ≥2 prior therapies. This phase 2 trial evaluates Isa-Pd in RRMM after 1 prior Len+PI-based regimen. The trial employed a response-adapted design: all patients (pts) received 6 cycles of Isa-Pd, after which responders were randomized to standard or less frequent Isa dosing, while non-responders continued on standard dosing without randomization. This exploratory analysis focuses on the continuation phase, assessing outcomes by post-Cycle 6 assignment. EAE115 (NCT05298683) is an investigator-initiated, phase 2, prospective, open-label, multicenter trial in RRMM after 1 prior Len+PI-based regimen. Key exclusions: prior anti-CD38 or pomalidomide exposure, or stem cell transplant ≤12 weeks prior. Pts initially receive six 28-day cycles of Isa 10 mg/kg IV (QW in Cycle 1, Q2W thereafter) plus Pd 4 mg/day PO (Days 1-21) and 40 mg (or 20 mg if ≥75y) PO/IV (QW) respectively. In the continuation phase (Cycle 7 onwards), pts with ≥very good partial response (VGPR) are randomized 1:1 to continue Isa Q2W or switch to Q4W plus Pd, while those with As of 15 April 2025, 56 pts were enrolled; 11 [19.6%] discontinued before Cycle 7 and 11 [19.6%] had not reached randomization yet. Thus, 34 (60.7%) entered the continuation phase: 23/34 (67.6%) non-randomized ( During the initial 6 cycles, median Isa dose intensity (DI) was 22.6 mg/kg/28-day cycle (range 1.4–40.0), corresponding to a median relative dose intensity (RDI) of 99.9% (range 5.7%–101.5%). Dose skips occurred in 22/56 (39.3%) pts. In the continuation phase, median Isa DI was 18.8 mg/kg (range 15.2–21.5) for non-randomized pts, 18.6 mg/kg (range 17.6–19.3) for Q2W-randomized, and 9.6 mg/kg (range 9.2–10.2) for Q4W-randomized, per 28-day cycle, with the corresponding median RDIs being 99.6% (range 82.0%–100.0%), 94.7% (91.7%–101.6%), and 99.9% (range 99.7%–100.0%), respectively. Dose skips occurred in 10/23 (43.5%) of non-randomized, 4/6 (66.7%) of Q2W-randomized pts; none in Q4W. At a median follow-up of 9.7 months (range 0.9–29.4), ORR was 67.9% (38/56), with ≥VGPR in 35.7% (20/56). Median time to first response was 1.0 month (range 0.9–13.8); median PFS was 15.4 months (95% confidence interval [CI]: 9.9–not reached), and median TTP was 17.5 months (95% CI: 10.8–not reached). Of the 18 patients with documented PD, 4 progressed prior to entering the continuation phase, and 14 (41.2%) during the continuation phase: 13 non-randomized and 1 Q4W-randomized. Among pts continuing to the continuation phase, ORR was 88.2% (30/34) overall and 82.6% (19/23) in the non-randomized; ≥VGPR in 50% (17/34) overall and 26.1% (6/23) of the non-randomized. At a median follow-up post-Cycle 6 of 10.0 months (range 0.2–23.3), one Q4W pt improved to CR; among non-randomized pts, 6/22 (27.3%) improved also response. TEAEs occurred in 91.1% (51/56) pts overall; Grade 3/4 in 66.1% (37/56) and Grade 5 in 8.9% (5/56). In the continuation phase, TEAEs occurred in 64.7% (22/34), with Grade ≥3 in 26.1% (6/23) of the non-randomized, 33.3% (2/6) of the Q2W-randomized and 20.0% (1/5) of the Q4W. Serious TEAEs occurred in 13.0% (3/23) of the non-randomized, 16.7% (1/6) of the Q2W-randomized, and none of the Q4W. Isa-Pd showed robust efficacy with manageable safety and rapid responses in first-relapse RRMM pts after a Len+PI-based regimen. In pts with ≥VGPR, Isa Q4W provided comparable efficacy with improved safety and compliance versus Q2W, suggesting greater convenience without compromising efficacy. Pts with

Siltuximab is the only approved treatment for idiopathic multicentric Castleman Disease but in many countries the only available treatment is rituximab based. We are performing an indirect comparison of rituximab-based regimens (RBR) and siltuximab by using single arm meta-analysis and the generalized linear mixed model methods comparing outcome in five significant clinical end-points (CR, PR, ORR, 2ysPFS and 2ysOS). Patient’s data were extracted from 14 cohort or phase I and II trials conducted with siltuximab (n = 387 pts) and six cohort studies treating iMCD patients with rituximab (n = 138 pts). Response rates and depth of response is similar between the two arms of the study but 2ys PFS is significantly better with siltuximab monotherapy. Using the generalized linear mixed model in order to provide an indirect comparison of odds to achieve the 2yPFS end-point, the reported OR is 0,358, 95

In this multi-institutional retrospective study, we analyzed the characteristics and outcomes of 118 patients with solitary bone plasmacytoma (SBP) and 57 with extramedullary plasmacytoma (SEP) diagnosed over 30 years. We also evaluated the impact of systemic therapy (ST), which is not routinely recommended, compared to standard radiation therapy (RT). The median age was 62 years (range: 17-85). Treatment included RT (n = 94), RT with ST (n = 47), ST alone (n = 22), and surgical excision alone (n = 12). Overall and complete response (CR) rates were 93% and 53%, respectively; 70 patients relapsed, 56 progressing to multiple myeloma (MM). The median follow-up was 10 years (95% CI: 7.1-13). Median estimated overall survival (OS) was 18.5 years with a 5- and 10-year OS rate of 85% and 70%, respectively, similar across groups (p > 0.05). Median progression-free survival (PFS) was 75 months (95% CI: 53-97), with a 5- and 10-year PFS rates of 57% and 44%. The 5- and 10-year MM-free survival (MMFS) was 66% and 53%, respectively. We identified age ≤ 60 years, achieving CR, and an abnormal serum FLC ratio at diagnosis as the strongest prognosticators for OS (HR: 0.25), PFS (HR: 0.54), and MMFS (HR: 5 + 0.4), respectively (p < 0.05); ST alone or combined with RT did not significantly improve survival outcomes or MMFS (p > 0.05). In conclusion, ST increased toxicity without offering outcome benefits, reaffirming RT as the cornerstone of SP management. Despite therapeutic advancements in MM, the persistent challenge of progression to MM underscores the importance of identifying high-risk SP patients, enabling early intervention with more aggressive treatments.

Younger multiple myeloma (MM) patients, representing 10% of cases, show distinct clinical features, including lower anemia and renal impairment rates but higher lytic bone disease and adverse cytogenetics. Retrospective analysis reveals better complete response and survival outcomes, with median OS exceeding 15 years. Key prognostic factors include anemia and high-risk cytogenetics, while autologous stem cell transplantation significantly improves outcomes, highlighting the importance of tailored, intensive treatment strategies. Background: Multiple myeloma (MM) is predominantly a disease of the elderly, but approximately 10% of patients are younger than 50 years at diagnosis. Methods: This study aimed to investigate the clinical characteristics, treatment outcomes, and prognostic factors in younger MM patients using retrospective data from the Balkan Myeloma Study Group registry. Results: A total of 350 patients under 50 years old were included, comprising 10.4% of the overall cohort. The study found that younger patients had lower rates of renal impairment and anemia but a higher incidence of lytic bone disease and adverse cytogenetics. Treatment regimens, including proteasome inhibitors and immunomodulatory agents, were comparable between younger and older patients, but younger patients had significantly better complete response rates and overall survival (OS). The 5- and 10-year OS rates were 76% and 64%, respectively, with a projected median OS exceeding 15 years. Factors such as anemia, hypercalcemia, and high-risk cytogenetics were associated with worse survival outcomes. Autologous stem cell transplantation (ASCT) emerged as a key contributor

Introduction: Recommendations about proper anticoagulation in obese patients, body mass index (BMI) > 30 kg/m2, are not yet clearly defined. Obese patients were included in randomized controlled trials comparing new anticoagulants (NOACs) with warfarin in patients with atrial fibrillation or thromboembolism. Methods: We performed a medline search entering proper criteria and finally 6 post-hoc analysis of RCTs, reporting outcome according to BMI, were included in this meta-analysis. Two major outcomes were considered end points in our meta-analysis; thrombosis, including ischemic cerebral events (transient or not) and venous thrombosis (DVD) /pulmonary embolism (PE) and bleeding, including major bleeding and clinically relevant non-major bleeding. Results: In the NOACs treated group, thrombosis occurred less frequently in obese vs non-obese patients; RR and 95 % CI 0,75 (0,58-0,97), p = 0,03, while low heterogeneity was observed (I-2= 40 %). In the warfarin treated subgroup there was statistically significant difference with less thrombotic events occurring in the obese vs non-obese patients; RR and (95 % CI) 0,80 (0,66-0,98), p = 0,03, and heterogeneity was low (I-2 = 24 %). This protective effect called the obesity paradox is limited to obese patients anticoagulated for non-valvular atrial fibrillation (NVAF); RR (95 % CI) was 0,70 (0,58-0,85) p = 0,03 and I-2 = 24 %. Bleeding events were similar under both NOACs and warfarin in obese vs non-obese analysis. Conclusions: Obese patients anticoagulated for NVAF with either standard dose of xabans or INR guided warfarin are more efficiently protected against thrombosis compared to non-obese patients.