41 reads in the past 30 days
Myeloid Neoplasms With Erythroid Predominance and Excess Blasts in Young Adults Exhibit Distinct Genetic ProfilesMay 2025
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69 Reads
Published by Wiley
Online ISSN: 1600-0609
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Print ISSN: 0902-4441
41 reads in the past 30 days
Myeloid Neoplasms With Erythroid Predominance and Excess Blasts in Young Adults Exhibit Distinct Genetic ProfilesMay 2025
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69 Reads
26 reads in the past 30 days
Characteristics and Clinical Outcomes of Multiple Myeloma in Adolescents and Young AdultsMay 2025
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26 Reads
22 reads in the past 30 days
Reviewing the impact of hydroxyurea on DNA methylation and its potential clinical implications in sickle cell diseaseJune 2024
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257 Reads
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2 Citations
20 reads in the past 30 days
Efficacy and Safety of Frontline Single‐Agent Rituximab in Extranodal Marginal Zone LymphomaSeptember 2024
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81 Reads
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1 Citation
19 reads in the past 30 days
Bone Marrow Vacuolization at the Crossroads of Specialties: Molecular Insights and Diagnostic ChallengesMay 2025
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19 Reads
The European Journal of Haematology is an international haematology journal for communication of basic and clinical research in haematology and related areas of thrombosis, haemostasis and haemophilia. We welcome manuscripts on molecular, cellular and clinical research on diseases of the blood, vascular and lymphatic tissue, and on basic molecular and cellular research related to normal development and function of the blood, vascular and lymphatic tissue. We provide a simplified submission process that works collaboratively across haematology so every submitted paper has a home.
June 2025
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4 Reads
Background Advances in fibril typing by mass spectrometry have improved the accuracy of amyloidosis diagnosis. Dual amyloidogenic proteins have been reported in deposits in sole and multiple different organs. Methods Five patients with dual amyloidoses were diagnosed between 1995 and 2022 by Congo red staining and fibril typing using the best available methods at the time of evaluation. Sequencing of TTR and GSN genes was performed. Literature search identified 46 additional cases. Results Three patients exhibited Waldenström macroglobulinemia‐associated AL (n = 3) amyloidoses in conjunction with ATTRwt or AGel amyloidosis; two patients featured AL/ATTRwt and AA/ATTRwt amyloidoses. One patient demonstrated dual amyloidoses within one anatomical site; three patients featured two amyloidosis types at different anatomical sites; and one patient had dual amyloid deposits in a single anatomical site along with different sites. The time interval between diagnoses was 0–288 months, with the heart and kidneys being the most affected organs. Conclusions Our findings underscore the complexity of clinical presentation in amyloidosis, as multiple amyloid types can co‐exist in a single individual and affect various anatomical sites. Accurate assessment of the clinical phenotype and thorough amyloid fibril typing from the target organs are essential for precise diagnosis and tailored treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT00898235
June 2025
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15 Reads
Background Liver disease is common in patients with β‐thalassemia, but data on lifetime incidence and risk factors are limited. Methods We conducted a retrospective cohort study of 557 patients with β‐thalassemia followed from diagnosis for a median of 38 years. Predictive, survival, and regression analyses were used to determine the association between liver disease and potential risk factors. Results The crude incidence of liver disease was 26.4% (fibrosis/cirrhosis 24.2%, median age 34.4 years; hepatocellular carcinoma 2.3%, median age 45.4 years, 38.5% not preceded by cirrhosis). Among evaluated risk factors, only hepatitis C virus (HCV) infection (adjusted hazard ratio [HR]: 2.195, p < 0.001) and lifetime serum ferritin level (adjusted HR per 100‐ng/mL increase: 1.030, p < 0.001) were significantly associated with liver disease, with a lifetime serum ferritin level > 1500 ng/mL being the best predictor (p = 0.001). Liver disease‐free survival was significantly shorter in patients who had both versus either or neither risk factor (p < 0.001). Mostly severe and persistent but not mild–moderate or temporary/fluctuating elevation in liver enzymes was associated with liver disease development. Conclusion Patients with β‐thalassemia have a considerably increased lifetime risk of liver disease that is primarily driven by HCV infection and/or uncontrolled iron overload, especially in the 4th–5th decades of life.
June 2025
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14 Reads
Introduction Surgery is pivotal in the management of hepatoblastoma (HB) although approaches and techniques may vary. The Liver Group of the International Society of Pediatric Oncology (SIOPEL) and the International Pediatric Surgical Oncology (IPSO) group collaborated to develop an online survey to investigate specific technical aspects and challenging indications for HB surgery, with the goal of establishing shared guidelines. Methods An electronic survey with 50 items was developed to address preoperative assessment and specific surgical issues. All questions were multiple‐choice, allowing for multiple answers in complex cases. The survey was distributed via the SIOPEL and IPSO mailing lists. Results Overall, 10% of the mailing lists participated (52 respondents), including 28 transplant (LT) surgeons and 24 non‐LT surgeons from 25 countries, globally. Around 40% (20/52) work in high‐volume centers (> 10 hepatic resections/year, and > 10 liver transplants/year). For a mass at the origin of the suprahepatic veins, LT is preferred over resection (48 vs. 12), while a mass with satellite nodules favors liver resection (52 vs. 15). Non‐LT surgeons prefer LT for masses at the hilar plate, whereas LT surgeons choose resection (p < 0.05). IVC replacement is favored by transplant surgeons in case of infiltration (p = 0.043), mostly with heterologous venous grafts (p = 0.004). Discussion The heterogeneity of responses underscores the lack of a standardized approach to the various surgical scenarios encountered in the surgical management of HB. Further analysis will enhance the understanding of how different management strategies affect outcomes and promote the creation of evidence‐based guidelines for HB resection practices.
June 2025
Adult acute leukemia is a common hematopoietic malignancy. Current diagnostic methods have limitations, and there is a need for non‐invasive early diagnosis and follow‐up monitoring. This study aimed to evaluate the diagnostic and prognostic significance of peripheral blood RASSF1A, P16, and PTGER4 gene methylation in adult acute leukemia. From January 2023 to December 2024, 78 adult acute leukemia patients and 25 controls were enrolled. Peripheral blood samples were collected before chemotherapy and 30 days after initial treatment for gene methylation analysis. The results showed that the combined detection of these three genes had a diagnostic sensitivity of 82.1% and a specificity of 92.0%. Positive methylation was significantly associated with a higher proportion of bone marrow immature cells, chromosomal karyotype abnormalities, and a greater likelihood of bone marrow transplantation. After 30 days of initial treatment, peripheral blood gene methylation levels decreased significantly. In conclusion, the combined detection of peripheral blood gene methylation can identify high‐risk acute leukemia patients, serve as a prognostic marker, and be used for post‐treatment follow‐up monitoring.
June 2025
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20 Reads
The treatment of elderly, nonfit acute myeloid leukemia (AML)/MDS patients with relapsed/refractory (R/R) disease remains challenging. As histone demethylase LSD1 (KDM1A) is a rational therapeutic target in AML, we conducted a phase I trial (“rolling‐six design”) with the LSD1 inhibitor tranylcypromine (TCP, dose levels [DL] 20, 40, 60, 80 mg p.o. d1‐28) combined with fixed‐dose ATRA (45 mg/m² p.o. d10‐28) and low‐dose cytarabine (LDAC, 40 mg s.c. d1‐10). The primary endpoint was dose‐limiting toxicity (DLT) in the first 28 days of treatment. The aim was the determination of the maximum tolerated TCP dose (MTD). Twenty‐three patients with AML and 2 with MDS were accrued. TCP was administered for a median of 39.5 days (range: 11–228). No DLTs were observed at any DL; MTD could not be established. No differentiation syndrome occurred. Two patients attained a PR; SD was achieved in 10 of 22 evaluable patients. Median OS was 62 days (range: 14–325). Accompanying studies included pharmacokinetics, serial determinations of fetal hemoglobin (HbF), detection of CD38 upregulation with treatment, as well as transcriptome changes in purified blood blasts over time. In conclusion, the combination of TCP with ATRA and LDAC was well feasible, even at the highest DL. Hence, studies with more potent LSD1 inhibitors appear warranted. Trial Registration: German Clinical Trials Register (DRKS): DRKS00006055. For further Information see https://drks.de/search/en/trial/DRKS00006055
June 2025
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9 Reads
Introduction Bendamustine‐rituximab (BR) has demonstrated efficacy and tolerability in the treatment of various indolent B‐cell lymphomas, but there is limited data regarding its outcomes in nodular lymphocyte predominant B‐cell (Hodgkin) lymphoma (NLPBL). Methods This retrospective, population‐based study included consecutive patients ≥ 18 years old who received BR for NLPBL in Alberta, Canada. Results The study population comprised 23 patients with a median age of 39 years (range 18–74) who received BR for treatment‐naive (n = 17) or relapsed/refractory (n = 6) NLPBL. Advanced stage disease was present in 18 (78%), splenic involvement in 9 (39%), and bone marrow involvement in 8 (35%) patients. The response rate to BR was 100%, with a complete response in 78% and a partial response in 22%. After a median follow‐up of 4.3 years (range 0.8–9.0), the 4‐year progression‐free survival and overall survival rates were 83% (95% CI: 55%–94%) and 87% (95% CI: 58%–97%) for all patients and 84% (95% CI: 50%–96%) and 91% (95% CI: 51%–99%) for recipients of first‐line BR, respectively. The safety profile was in keeping with the known toxicities of BR, with the most common adverse events consisting of neutropenia, rash, and infusion reactions. Conclusion These findings suggest that BR is a promising treatment option for NLPBL, with a favorable efficacy and safety profile.
May 2025
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19 Reads
Bone marrow (BM) vacuolization is a key morphological feature observed in VEXAS (Vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic) syndrome. However, vacuolization alone is not specific to VEXAS, as it can also be seen in conditions such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), metabolic disorders, and toxic exposures. VEXAS syndrome, a postzygotic mutation‐driven autoinflammatory disease caused by somatic mutations in the UBA1 gene, leads to chronic immune activation, clonal expansion of hematopoietic cells, and systemic inflammation. UBA1 mutations result in protein misfolding, contributing to both hematologic and inflammatory abnormalities. In VEXAS syndrome, specific features of vacuolated progenitor cells suggest the diagnosis. These include a high number of vacuolated cells, increased vacuoles per cell, a predominance of vacuoles in early progenitors rather than later stages, and vacuolization in both myeloid and erythroid progenitors, with myeloid progenitors most affected. However, the absence or low frequency of vacuolated cells should not rule out the possibility of VEXAS, and UBA1 gene sequencing should still be considered, especially in patients with unexplained systemic inflammation, MDS, or associated with other hematologic disorders. These mutations may alter the BM microenvironment, promoting the survival and expansion of mutant clones, which drive disease progression. While there is no standard treatment for VEXAS, the condition provides a unique model for understanding how inflammation in the BM microenvironment contributes to clonal selection and hematologic malignancy development. Research into the genetic and molecular mechanisms behind BM vacuolization in VEXAS has improved the diagnostic approaches and enhanced our understanding of its impact on hematopoiesis. Ongoing studies into the interplay between vacuolization, clonal hematopoiesis, and immune dysregulation will be a key to developing effective therapies for this complex syndrome. We herein offer a comprehensive diagnostic approach to BM vacuolization linked to VEXAS syndrome, distinguishing it from vacuoles observed in other conditions. The analysis delves into the clinical and hematologic features, molecular pathways, and rapidly evolving diagnostic methods for VEXAS syndrome, emphasizing its impact on hematopoiesis from a hematologic perspective.
May 2025
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11 Reads
Introduction Myeloablative conditioning (MAC) for acute myeloid leukemia (AML) improves disease control by reducing relapse risk but is associated with higher non‐relapse mortality (NRM). Reduced‐intensity conditioning (RIC) aims to minimize toxicity but raises concerns about higher relapse rates. This study evaluates the impact of RIC versus MAC in AML patients under 65 years receiving GVHD prophylaxis with antithymocyte globulin, post‐transplant cyclophosphamide, and cyclosporine. Methods We retrospectively analyzed 322 AML patients undergoing allogeneic HCT with uniform GVHD prophylaxis. Propensity score matching (PSM) was applied to adjust for baseline differences. Results In the matched cohort, 2‐year overall survival (OS) did not differ significantly between RIC and MAC recipients (64.4% vs. 66.9%, p = 0.56). Relapse‐free survival (RFS) at 2 years was 65.0% for MAC and 52.7% for RIC (p = 0.20). Two‐year NRM was 19.4% for MAC and 19.1% for RIC (p = 0.84). Improved RFS was associated with non‐high‐risk DRI (HR: 0.39, p = 0.008), whereas conditioning intensity had no significant effect (HR: 0.98, p = 0.97). NRM was higher among patients with KPS < 90 (HR: 3.63, p = 0.01), with no significant impact observed from conditioning intensity (HR: 1.44, p = 0.43). Conclusion In a relatively younger cohort, conditioning intensity did not significantly impact survival, and MAC was not associated with increased NRM.
May 2025
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6 Reads
Objectives Although gastrointestinal diffuse large B‐cell lymphoma (GI‐DLBCL) is managed variously, the optimal approach remains controversial. Methods We retrospectively analyzed 701 patients with DLBCL at our institution between March 2004 and June 2024, including 160 with GI‐DLBCL. We compared baseline characteristics and survival outcomes of GI‐DLBCL with non‐GI‐DLBCL and further analyzed gastric and intestinal DLBCL by stage. Results No significant difference in survival outcomes was observed between GI and non‐GI DLBCL groups after a median follow‐up of 5.1 years. Among patients with gastric DLBCL, advanced disease was associated with poorer overall survival (OS) (hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.18–2.58; p = 0.003) than localized disease. Similar findings were observed in intestinal DLBCL (HR: 1.60; 95% CI: 1.13–2.27; p = 0.006). Combined chemoradiation and chemotherapy yielded similar survival outcomes for localized gastric DLBCL although the former showed a higher cumulative incidence of secondary gastric cancer (p = 0.04). In localized intestinal DLBCL, multivariate analysis identified surgery followed by chemotherapy as a favorable prognostic factor for OS (HR: 0.23; 95% CI: 0.067–0.83; p = 0.024). Conclusions Gastrointestinal diffuse large B‐cell lymphoma had survival outcomes comparable to those of non‐GI‐DLBCL, suggesting site‐ and stage‐specific therapies may confer a survival benefit.
May 2025
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26 Reads
Introduction Though evidence suggests that multiple myeloma (MM) in adolescents and young adults (AYA) (< 50 years) has significant biological differences from that in older individuals (≥ 50 years), the understanding of the disease in this group is limited. We examined the outcomes in AYA hospitalizations with MM. Methods Using the National Inpatient Sample database, we examined sociodemographic, hospital‐level, and clinical characteristics between AYA and older populations with MM. Results Among 183 846 non‐elective MM hospitalizations, 13 765 (7.5%) were AYA. There was a higher proportion of males in the AYA group compared to the older group (58.6% vs. 54.8%, p < 0.001) but a lower distribution of non‐Hispanic Whites (40.6% vs. 56.7%, p < 0.001). The AYA group had lower odds of mortality (aOR: 0.59, p < 0.001) relative to the older adult group. They were more likely to receive autologous stem cell transplantation (aOR: 1.80, p < 0.001) but had similar odds of acute venous thromboembolism (aOR: 0.87; p = 0.24) and severe sepsis (aOR: 0.89; p = 0.52). Conclusion We highlight the unique characteristics and outcomes of AYA‐MM, emphasizing the need for their greater representation in clinical research. Additionally, we underscore the importance of further investigation to better understand and optimize survivorship care in AYA patients with MM.
May 2025
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9 Reads
Background Hairy Cell Leukemia (HCL) is a B‐cell lymphoproliferative disorder that predominantly affects males, yet recent evidence suggests a notable gender participation gap in HCL clinical trials. This study aims to characterize that disparity and explore potential factors contributing to the under‐enrollment of females. Methods In this descriptive, retrospective study, we searched EMBASE, PUBMED, Cochrane Central, and ClinicalTrials.gov from January 1983 to December 2023 for publications on clinical trials (CT) in HCL, descriptive statistical analysis of all the sociodemographic variables was performed. Results We analyzed 57 clinical trials totaling 4595 HCL patients, with 79.1% male and 20.9% female participants. The male‐to‐female ratio declined from 5.91 (1983–1993) to 4.19 (2014–2023). Although the gender gap narrowed over time, female participation slightly decreased to 19.2% in the most recent period (2014–2023). Conclusions Female enrollment in HCL clinical trials remains disproportionately low compared to incidence rates, underscoring the need to address underlying barriers to improve equity in clinical research and treatment outcomes. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.
May 2025
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4 Reads
May 2025
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69 Reads
The evolution of acute myeloid leukemia (AML) classifications has progressively shifted the diagnostic focus toward genetic criteria. Nevertheless, morphology remains a key element in clinical practice, often serving as the initial trigger for additional molecular investigations. The diagnosis of acute erythroleukemia (AEML), initially defined by the FAB group, is no longer recognized as a distinct entity in the latest WHO and ICC classifications. Some studies have indicated that AEML shares similarities with myelodysplastic neoplasms, including a high frequency of TP53 mutations and adverse karyotypes. Here, we conducted a retrospective analysis in adults with AEML defined using historical morphologic criteria (≥ 50% erythroid precursors and ≥ 20% blasts among non‐erythroid cells). In contrast to older patients, young adults (18–60 years) exhibit unique genetic profiles including a high prevalence of normal karyotypes (65%), NPM1 (35%) and UBTF (23%) mutations. AEML morphology in NPM1‐mutated cases did not impact clinical outcomes but was associated with specific molecular features, including an enrichment of WT1 and cohesin gene mutations. In this age group, our findings support that morphologically defined AEML often corresponds to AML according to current genetic criteria, consistent with recent classification systems that prioritize molecular features over morphology.
May 2025
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6 Reads
Lymphoma, a clonal malignancy from lymphocytes, includes diverse subtypes requiring distinct immunohistochemical stains for accurate diagnosis. Limited biopsy specimens often restrict the use of multiple stains, complicating diagnostic workflows. Lymphomas are typically classified into B‐cell and T‐cell types, each with specific markers. This study represents the first feasibility study in deploying deep learning models for B‐ and T‐cell lymphoma classification on histopathological images. We analyzed 1510 H&E‐stained sections (750 B‐cell, 760 T‐cell) with CNN models (Xception, NASNetL, ResNet50, EfficientNet), enhanced by Convolutional Block Attention Modules (CBAMs). All models demonstrated strong classification capabilities, with EfficientNet achieving the highest accuracy at 91.5% and the best precision at 91.9%, while Xception performed the best recall at 91.5%. Furthermore, the deep learning models significantly outperformed human pathologists in classification accuracy and inference speed, processing images in milliseconds compared to the several seconds required for manual diagnosis. These findings underscore the effectiveness of advanced CNN models in improving diagnostic precision while reducing dependency on manual staining and interpretation, and the integration of AI‐driven classification can provide valuable support for pathologists.
May 2025
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13 Reads
Hyperdiploid karyotype (HK) (49–65 chromosomes) in acute myeloid leukemia (AML) is rare. Recently, HK‐AML with only numerical changes has been reclassified into an intermediate risk group in the updated 2022 European LeukemiaNet (ELN) risk classification, which has historically been classified into an adverse risk group. However, there are limited data in the literature concerning whether these new exclusion criteria are appropriate, and the genetic landscape of HK‐AML remains unclear. We retrospectively analyzed a cohort of HK‐AML diagnosed at our institution. Among 124 cases, 72 (58.1%) had concurrent adverse risk cytogenetic abnormalities (HK‐ADV), 33 (26.6%) had other concurrent structural abnormalities (HK‐STR) and 19 (15.3%) had numerical changes alone (HK‐NUM). The most frequently gained chromosomes were chromosomes 8, 22, 21, and 19. TP53 mutation was associated with HK‐ADV, and a higher frequency of mutations in DNA methylation genes was present in HK‐NUM and HK‐STR. Patients with HK‐NUM had significantly longer overall survival (OS) and event‐free survival (EFS) compared to those with HK‐ADV. In the adjusted model accounting for confounders, the HK‐STR outcome was superior to that of HK‐ADV but was not significantly different from that of HK‐NUM. In addition, patients with a modal chromosome number of 49–53 had more favorable survival than those with ≥ 54 chromosomes. Our data support the reclassification of HK‐NUM patients in the intermediate risk group and suggest that HK‐STR might also be more appropriately classified into the intermediate risk group.
May 2025
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12 Reads
Objectives Despite frequent diagnosis of anemia of inflammation in hospitalized patients, little is known about patients' sex‐specific differences in iron deficiency (ID) and its biomarkers. We aimed to study sex‐specific differences in anemic patients with inflammation and their influence on iron biomarkers. Methods This retrospective cross‐sectional study included anemic patients with inflammation (CRP > 5 mg/L) hospitalized at a Swiss tertiary referral center (01.01.2020–31.12.2023). ID was defined as ferritin‐index (sTfR/log(ferritin)) ≥ 1.5. Patient characteristics were reported as medians for continuous variables and frequencies for categorical variables. Age, laboratory parameters, treatment, comorbidities, illness severity, and in‐hospital mortality were analyzed. Sex‐specific effects on ID biomarkers (ferritin‐index, sTfR) were assessed using linear regression models. Results Of 439 participants, 41.2% were female. 44.2% had ID (women: 49.7%, men: 40.3%, p = 0.052). Regression models showed no association between log(ferritin‐index) and sex (coefficient 0.02, 95% CI −0.13 to 0.18, p = 0.76). Ferritin levels were lower in women (221.0 vs. 373 μg/L, p = 0.014). No sex differences in in‐hospital mortality were observed (women 7.2%, men 4.3%, p = 0.21). Conclusions Despite no significant sex differences regarding ID biomarkers, treatment, illness severity, and mortality, we hypothesize that factors beyond sex, for example underlying diseases and inflammation itself, play a more prominent role in these patients' outcomes.
May 2025
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24 Reads
Objectives The objective of this systematic literature review (SLR) combined with expert clinical review was to identify and rank prognostic factors and effect measure modifiers (EMMs) systematically and comprehensively in patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) who initiate treatment after ≥ 2 prior lines of therapy (LoTs; 3L+ R/R DLBCL). Methods We performed an SLR of studies published between 2016 and 2021 and extracted study characteristics, prognostic factors, and EMMs. This was followed by clinical review and ranking of findings by subject matter experts using questionnaires, follow‐up interviews, and quantitative ranking. Results Across 46 included studies, the SLR identified 36 prognostic factors significantly associated with ≥ 1 clinical outcome. Based on subject matter expert ranking of the SLR‐derived list, the five most important prognostic variables in descending order are: early chemo‐immunotherapy failure, Eastern Cooperative Oncology Group performance status, refractory to last LoT, number of prior LoTs, and double‐ or triple‐hit lymphoma. Conclusions This SLR and expert clinical review is the first to provide a comprehensive assessment of prognostic factors for 3L+ R/R DLBCL. No statistically significant EMMs were identified. This robust multi‐method approach can assist in selecting prognostic variables for comparative analyses between real‐world studies and clinical trials.
May 2025
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11 Reads
May 2025
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35 Reads
Myelodysplastic/myeloproliferative overlap neoplasms (MDS/MPN) are rare hematological malignancies. We analyzed the outcomes of 75 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for MDS/MPN. Graft‐versus‐host disease (GvHD) prophylaxis included post‐transplantation cyclophosphamide (PTCy) in 71% of patients, with 44 (59%) receiving a combination of anti‐thymocyte globulin (ATG) and PTCy. The median follow‐up was 44.4 months. Primary graft failure occurred in three patients (4%). The incidence of grade III‐IV acute GvHD at day 100 was 13% (95% CI: 6–22). At 2 years, the incidence of moderate–severe chronic GvHD, non‐relapse mortality (NRM), relapse, GvHD‐free/relapse‐free survival (GRFS), and overall survival (OS) was 31.7% (95% CI 20.7–43.2), 37.9% (26–49), 17.4% (95% CI: 10–27), 24.8% (95% CI: 15–36), and 51.6% (95% CI: 39–63), respectively. PTCy‐based GvHD prophylaxis seemed to be associated with improved OS (HR: 0.5, 95% CI: 0.3–0.9, p = 0.03), NRM (HR: 0.4, 95% CI: 0.2–0.9, p = 0.03), and GRFS (HR: 0.5, 95% CI: 0.3–0.8, 0.009). On multivariable analysis, the use of the PTCy‐containing regimen seemed to be associated with improved NRM (HR: 0.41; 95% CI: 0.2–0.8; p = 0.03), GRFS (HR: 0.47; 95% CI: 0.3–0.8; p = 0.009), and OS (HR: 0.49; 95% CI: 0.2–0.9; p = 0.03) without an increased risk of relapse.
April 2025
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19 Reads
Objective To report data from an ITI chart review study (NCT03951103) for first‐time and rescue ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in persons with haemophilia A. Methods Retrospective and prospective real‐world data are reported from a non‐interventional, multicentre study of patients who had been or were currently being treated with rFVIIIFc ITI. ITI treatment outcome (defined by investigators) and regimens are reported. Results Forty‐one patients from 16 sites were included. First‐time ITI was used in 24 patients; 16 had an ITI outcome at study end. Thirteen patients (81.3%) had ITI success, and three had failure. Median (range) rFVIIIFc consumption was 300 (61–2800) IU/kg/week, and most (70.8%) used ≤ 300 IU/kg/week. The vast majority of patients (87.5%) received less than daily ITI. Rescue ITI was used in 17 patients; 16 had an ITI outcome at study end. Eight patients (50.0%) had ITI success/partial success, seven had failure, and one withdrew early. Median (range) rFVIIIFc consumption was 536 (98–1435) IU/kg/week; 35.3% used ≤ 300 IU/kg/week and 52.9% used > 500 IU/kg/week. Most patients (64.7%) received daily ITI. Conclusion ITI with rFVIIIFc is likely to be successful in first‐time ITI patients and is an effective option for those who have previously experienced ITI failure. Trial Registration: ClinicalTrials.gov identifier: NCT03951103
April 2025
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11 Reads
Background Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra‐rare, acquired non‐malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients. Objective This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab). Methods Respective pivotal studies provided patient‐level trial data for pegcetacoplan (16‐week PEGASUS [NCT03500549]) and published data for iptacopan (24‐week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient‐reported outcomes on the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis. Results Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change‐from‐baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level (−0.49 g/dL [−1.78, 0.80]); ARC (–34.41 × 10⁹/L [−90.02, 21.21]); LDH level (−115.16 U/L [−244.40, 14.01]); FACIT‐Fatigue score (3.57 [−5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient‐reported fatigue, providing similar point estimates and confidence intervals. Conclusion This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient‐reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease‐ and patient‐related factors. Trial Registration: ClinicalTrials.gov identifier: NCT03500549.
April 2025
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8 Reads
Autologous hematopoietic stem cell transplantation (AHSCT) is the treatment for myeloma and lymphoma. posttreatment, significant nutritional and medical issues and malnutrition assessed by Subjective Global Assessment (SGA) arise. No established effective treatment for using either parenteral (PN) or enteral routes (EN) to improve nutritional status, reduce medical complications, and be cost‐effective is available. We investigated the effectiveness of EN versus PN in terms of nutritional path of supplementation. AHSCT patients were randomized to either EN or PN and were followed at baseline, 15 and 30 days posttransplant. Age, body mass index, SGA, length of stay (LOS), medical complications, severity of complications, infections, overall survival (Day 100), albumin, random blood glucose, and C‐reactive protein were evaluated. Descriptive statistics, Spearman's, chi square, correlations, and uni‐ and multivariate by type of feed, using SPSS v 29. Thirty‐six patients with complete medical and laboratory data were followed. No significance in any of the medical or nutritional parameters between the two groups was found. No correlations between SGA at any time point and type of feeding were identified. No relationship between SGA, LOS, complications, albumin, CRP, or random blood glucose at all three time points was seen. EN is a safe, convenient, and cost‐effective option for AHSCT patients since medical and nutritional outcomes were similar between those receiving EN compared to PN.
April 2025
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53 Reads
Advancements in the understanding of ITP pathogenesis have led to significant improvements in disease management through the use of both traditional immunosuppressive strategies and novel targeted therapies. However, a subset of patients remains refractory to treatment or achieves only transient benefits, underscoring the need for alternative therapeutic approaches. Bruton's tyrosine kinase (BTK) inhibitors have emerged as a promising strategy for autoimmune cytopenias, including ITP, due to their ability to modulate key immune pathways. Rilzabrutinib, an oral, reversible BTK inhibitor, represents a novel therapeutic approach for ITP. Rilzabrutinib, an oral, reversible BTK inhibitor, offers a novel mechanism of action by preserving platelet aggregation while reducing macrophage‐mediated platelet clearance, distinguishing it from irreversible BTK inhibitors. This review provides an updated and comprehensive analysis of the Phase 1/2 LUNA 2 trial and its long‐term extension, contextualizing rilzabrutinib within the broader treatment landscape. We also offer a comparative assessment of other BTK inhibitors investigated for ITP and discuss rilzabrutinib's potential positioning relative to existing therapies, including thrombopoietin receptor agonists (TPO‐RAs), rituximab, fostamatinib, and immunosuppressants. Results from the phase 1/2 LUNA 2 trial and its long‐term extension demonstrated that Rilzabrutinib induced a durable platelet response in 40% of patients, with a median time to response of 11.5 days. The treatment exhibited a favorable safety profile, with predominantly grade 1 or 2 adverse events and no significant safety concerns commonly associated with BTK inhibitors, such as increased bleeding risk, hepatic toxicity, or cardiac arrhythmias. Preliminary data presented at ASH 2024 from the ongoing Phase 3 LUNA 3 trial, a randomized, double‐blind study, further support rilzabrutinib's efficacy and long‐term safety. If confirmed, these findings suggest that rilzabrutinib could represent a valuable therapeutic option for patients with refractory ITP, addressing a critical unmet need and potentially redefining treatment paradigms.
March 2025
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14 Reads
Objective Multiple myeloma is an incurable cancer with lifelong treatment needs. This, together with a global nursing shortage, calls for new approaches for future treatment. In this study, we therefore investigated the feasibility of home‐based subcutaneous daratumumab administered by primary care nurses outside the hospital. Methods Applying a mixed‐methods prospective design, we included 30 patients; 18 had completed ≥ 6 cycles of daratumumab treatment, and 12 were newly started. New patients were followed for six 28‐day cycles, with every second treatment administered outside the hospital. Patients already on treatment were followed for seven cycles with 2/3 treatments administered outside the hospital. Results Of 123 administrations planned at the hospital, 122 (97.6%) were administered and three were cancelled. Of 144 administrations planned outside the hospital, 133 (92.4%) were administered, six were redirected to the hospital, and five were cancelled. No significant difference between numbers of cancellations/redirections was observed. Patients spent significantly longer time on treatment at the hospital, even when deducting travel time. Reducing patients' visits to the hospital did not cause additional unplanned contacts with the healthcare system. Conclusion This study thus concludes that administration of daratumumab outside the hospital is safe, feasible, and time saving. Trial Registration: ClinicalTrials.gov ID: NCT05306587
March 2025
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Provirus Integration site for Moloney leukemia virus (Pim) family members are well‐known oncogenes, with an expression that is restricted to few cell types including hematopoietic cells in adult organisms, making it a promising target for lymphoma treatment. Indeed, previous studies in mature T‐cell lymphoma (mTCL) cells revealed frequent upregulation of Pim expression. Nevertheless, inhibition of Pim kinases showed only minor effects on the viability of mTCL cells so far. Thus, we here addressed cellular responses to therapeutic inhibition of Pim kinases and identified a PI3K/Akt‐driven activation of mTOR as a significant escape mechanism mitigating the anti‐lymphoma effects of Pim inhibition. Indeed, dual inhibition of Pim and PI3 kinases showed synergistic anti‐lymphoma effects in vitro through downregulation of mTOR‐induced protein translation and mitigation of BCL‐xL‐mediated anti‐apoptotic mechanisms. Based on this finding, we next explored the therapeutic potential of the dual Pim/PI3K inhibitor IBL‐202 in mTCL cell lines. Strikingly, IBL‐202 strongly induced cell‐cycle‐dependent cell death in cell lines of different mTCL subtypes. Together, our study provides mechanistic evidence supporting a therapeutic strategy of dual Pim‐ and PI3‐kinase inhibition in mature T‐cell lymphoma.
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University of Cologne, Germany