Sickle Cell Disease (SCD) is a common autosomal recessive hemoglobinopathy caused by a point mutation in the β-globin gene, leading to aberrant production of Hemoglobin S (HbS). The pathophysiological process initiated by this mutation triggers a cascade of symptoms, including erythrocyte sickling, vasococcus occlusions, chronic hemolysis, and widespread inflammatory reactions, culminating in a multitude of clinical complications. Unfortunately, in resource-poor regions, the increasing incidence of SCD outstrips the capabilities of public healthcare systems, thereby creating a dire and urgent requirement for readily available and optimized therapies. Hydroxyurea (HU) has proven itself as a definitive treatment that promotes fetal hemoglobin production, prevents clinical complications, and thereby provides a promising, cost-effective alternative to chronic blood transfusions. Recent findings indicate that microRNAs (miRNAs) play a pivotal role in regulating hematopoiesis and globin switching, thereby making them fundamental mediators and targets of HU therapy. In this review, we explore beyond the traditional frontiers of HU therapy by critically evaluating its rationale as a two-way modifier of the miRNA-scope, which affects crosstalk within a ceRNA network, promotes upregulation of desirable miRNAs, and also triggers HU-induced adaptive miRs that can potentially destabilize therapeutic responses or even induce adverse reactions. More importantly, this review proposes a new, comprehensive conceptual framework to overcome and explore the constraints of monotherapy. In a nimble review of prior findings, we clarify and establish which specific alterations of HU-induced miRs would form a rational basis and hypotensive stimulus of mimicking therapy and thereby differentiate which specific alterations of upregulated or downregulated miRs should form a systemic basis of antagomiring therapy and thus lay out a specific and comprehensive roadmap of combinatorial medicine and therapy in managing SCD.
After allogeneic hematopoietic stem cell transplantation (allo-HSCT), the incidence of moderate-to-severe acute graft-versus-host disease (aGVHD) is approximately 13% to 47%. Currently, the standard regimen for the prevention of aGVHD is a calcineurin inhibitor (CNI) plus short-course methotrexate (MTX), with the addition of mycophenolate mofetil (MMF), anti-human thymocyte globulin (ATG), or anti-CD25 monoclonal antibody depending on the type of donor. This study aims to evaluate whether the addition of sitagliptin to standard aGVHD prophylaxis can further reduce the incidence and severity of aGVHD, while enhancing stem cell engraftment and improving the overall prognosis of patients undergoing allo-HSCT. The clinical data of 66 patients with malignant hematopoietic diseases who underwent allogeneic hematopoietic stem cell transplantation for the first time at the Department of Hematology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between 1 January 2022 and 1 January 2024 were retrospectively collected. According to the aGVHD prophylaxis regimen received, the patients were divided into the Sitagliptin group (n = 33) and the Standard group (n = 33). Statistical methods were used to compare the clinical outcomes between the two groups, including hematopoietic engraftment, acute GVHD, chronic GVHD, and overall survival (OS) after allogeneic hematopoietic stem cell transplantation. By day + 100 after transplantation, all patients in both groups had achieved engraftment. The Sitagliptin group had faster neutrophil engraftment than the Standard group (median 9 days, 95% CI 8.55–9.45 vs. median 11 days, 95% CI 10.39–11.61; p < 0.001). The cumulative incidence of grade II–IV aGVHD by day + 100 was 39.4% (95% CI 17%–35%) in the Standard group compared with 30.3% in the Sitagliptin group (p = 0.26). Corresponding values for grade III–IV aGVHD were 12.1% (95% CI 3.7%–25.8%) in the Standard group versus 9.1% (95% CI 2.3%–21.9%) in the Sitagliptin group (p = 0.70). For organ-specific aGVHD, the incidence of liver aGVHD was significantly lower in the Sitagliptin group (3.1%, 95% CI 0.2%–14%) than in the Standard group (18.2%, 95% CI 7.2%–33.1%; p = 0.044). The online version contains supplementary material available at 10.1007/s00277-026-07036-7.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment, which carries a high risk of complications and mortality, highlighting the necessity of discussions about life threat. This study explores the perspectives of patients, informal caregivers (ICs), and healthcare professionals (HCPs) regarding the timing, content, and challenges of these discussions. Multicenter cross-sectional survey in comprehensive care centers across Germany, involving patients with allo-HSCT, ICs, and HCPs. Questionnaires assessed perceived concerns about life threat, communication needs, and attitudes toward death. Statistical analyses included descriptive statistics, group comparisons, and multivariate logistic regressions. A total of 61 patients, 31 ICs and 125 HCPs participated in this study. Patients and ICs had a high need for discussion about life threat at diagnosis, which was corroborated by HCPs. At further time points in the transplant trajectory, there were more discrepancies between patients‘/ICs‘ and HCPs’ perceptions towards conversations about life threat. While 61.7% of patients preferred having their ICs present during discussions, ICs often felt overlooked, with only 50% finding conversations with HCPs helpful. HCPs’ avoidance of death was associated with a reduced likelihood of reporting a need for conversation in patients in the event of severe complications. These findings highlight a discrepancy between patients’ and ICs’ preferred timing for conversations about life threat and HCPs’ perceptions of when patients actually express such a need. To bridge this gap, earlier and ongoing conversations are essential. Training programs should address HCPs’ discomfort in discussing prognosis and improve interdisciplinary teamwork to standardize end-of-life communication. Trial registration number: DRKS00027290 (German Clinical Trials Register) on 10.01.2022. The online version contains supplementary material available at 10.1007/s00277-026-06981-7.
The multicenter, noninterventional, observational MMY4032 study is a large-scale, real-world study exploring daratumumab (DARA) in Chinese patients (n = 212) with multiple myeloma (MM) who have received ≤ 3 prior lines of therapy. In the first interim analysis (median follow-up, 10.5 months), DARA was often initiated in second-line therapy, often given in combination with a proteasome inhibitor and/or immunomodulatory drug, and induced high response rates (overall response rate [ORR], 71.8%) and acceptable safety. Here, we report treatment patterns, efficacy, and safety from the second interim analysis with a longer median follow-up of 16.2 months. At the time of this analysis, median duration of DARA exposure was 8.2 months. Among 189 response-evaluable patients, the ORR was 74.1% and the very good partial response or better rate was 55.6%. Minimal residual disease–negativity rate was 60.0% among tested patients. Median progression-free and overall survival were 32.8 months and not reached, respectively; 12-month rates were 77.9% and 87.8%. Response and survival rates were higher with DARA initiation in earlier lines of therapy. Median time to next treatment was not reached with most DARA-based regimens. Adverse drug reactions and serious adverse events were reported in 20.3% and 15.6% of patients, respectively. Overall, with longer follow-up of the MMY4032 study, responses deepened, and survival rates remained high with DARA-based regimens, with more favorable outcomes observed with earlier DARA initiation. No new safety concerns were observed. These real-world data continue to support early use of DARA-based regimens as a standard of care for Chinese patients with MM. The online version contains supplementary material available at 10.1007/s00277-026-06972-8.
Objective primary mediastinal B-cell lymphoma (PMBCL) is a distinct, aggressive lymphoma predominantly affecting young adults. While dose-intensive regimens are often recommended, their associated long-term toxicities and the necessity of consolidative radiotherapy remain major concerns. Given that PMBCL was explicitly excluded from the landmark POLARIX trial, we sought to evaluate the real-world efficacy and safety of first-line Pola-R-CHP in this specific population. Methods this single-center study analyzed 16 consecutive patients with newly diagnosed PMBCL treated with six cycles of Pola-R-CHP between September 2023 and June 2025. Efficacy was assessed via PET/CT (Lugano 2014 criteria) and safety via NCI-CTCAE v5.0. Results the median age was 30 years, with a female predominance (62.5%). Bulky disease was present in 62.5% of patients, and 87.5% had low-risk aaIPI scores. All patients completed six cycles of Pola-R-CHP treatment, achieving an objective response rate of 100%. The end-of-treatment complete metabolic response rate was 93.8%, with profound response deepening observed between interim and final assessments. After a median follow-up of 16.4 months, no relapses or deaths occurred, with all patients remaining in sustained remission. The most common grade 3–4 adverse event was neutropenia (43.8%). Pola-related peripheral neuropathy was predominantly low-grade (56.3% grade 1–2). Conclusion our findings provide the first preliminary clinical evidence that Pola-R-CHP is a highly effective and well-tolerated frontline strategy for PMBCL in this real-world cohort, which warrants further validation in larger, multicenter studies. The online version contains supplementary material available at 10.1007/s00277-026-07024-x.
To evaluate the efficacy and safety of the Bruton tyrosine kinase (BTK) inhibitor zanubrutinib in combination with salvage chemotherapy in patients with relapsed or refractory double-expressor diffuse large B-cell lymphoma (R/R DE-DLBCL). We performed a retrospective analysis of 35 patients with R/R DE-DLBCL treated at two hematology centers from June 2021 to June 2024. All patients received zanubrutinib combined with one of several salvage regimens, including zR-MINE, zR-DHAP, zR-GemOx, or zR2. Endpoints included objective response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). The median age was 60 years, and 91.4% of patients had the non-germinal center B-cell (non-GCB) subtype. At the end of therapy, the ORR and CRR were 45.7% (16/35) and 42.9% (15/35), respectively. After a median follow-up of 33.0 months, median PFS and OS were 8.0 and 12.0 months, respectively. Relapsed patients achieved a significantly higher CRR than refractory patients (56.5% vs. 16.7%, p = 0.034). On multivariate analysis, longer duration of response to prior therapy was an independent protective factor for OS (HR 0.88, 95% CI 0.77–0.99; p = 0.041). Grade 3–4 hematologic AEs were mainly neutropenia (42.8%) and thrombocytopenia (14.3%). Pulmonary infection was the most common non-hematologic AE (34.3%), and overall toxicity was manageable. Zanubrutinib combined with salvage chemotherapy demonstrates clinically meaningful activity with a manageable safety profile in patients with R/R DE-DLBCL and may represent a therapeutic option for this high-risk population. Sensitivity analysis confirmed the robustness of the observed survival benefit. The online version contains supplementary material available at 10.1007/s00277-026-06974-6.
For patients with transfusion-dependent β-thalassemia (TDT) and suboptimal response to iron chelator monotherapy, dual oral iron chelation (DOIC) with deferasirox (DFX) and deferiprone (DFP) represents a practical strategy to enhance iron removal. This narrative review synthesizes contemporary evidence for its use, with a focus on identifying clinical signals from real-world data and highlighting gaps requiring prospective investigation. We conducted a narrative review informed by a structured literature search of PubMed, Scopus, and regional databases (January 2016 to January 2025) for studies evaluating DOIC (DFX + DFP) in pediatric and adult TDT. Outcomes of interest included serum ferritin, MRI T2*, hepatic iron concentration, adherence, and safety. Study quality and risk of bias were assessed qualitatively using standard criteria for observational research. Evidence from clinical cohort studies and real-world audits indicates that DFX + DFP therapy produces additive or synergistic reductions in systemic iron burden, with mean serum ferritin declines of 25 to 45%. Recent real-world pediatric data (2024 to 2025) report over 80% of patients achieving ferritin below 2000 ng/mL, with high adherence rates (> 85%). MRI trends show improvement in hepatic and cardiac iron, though meaningful organ-specific changes typically require more than 24 months of therapy. The safety profile is consistent with established monotherapy profiles, primarily comprising mild gastrointestinal effects and transient transaminase elevations, with no reported agranulocytosis in reviewed cohorts. Study limitations include small samples, heterogeneous dosing protocols, and absence of randomized controlled trial data. DOIC with DFX and DFP is an effective and tolerable regimen for TDT patients with inadequate iron control on single agents. It leverages pharmacologic synergy within an all-oral, adherence-friendly regimen suitable for real-world use, including resource-limited settings. Prospective randomized trials with serial MRI endpoints are warranted to establish its superiority over optimized monotherapy for organ protection and long-term outcomes.
Breast hematopoietic neoplasms (BHN) are rare and may either primarily (PBHN) or secondarily (SBHN) involve breast tissue. The widespread use of needle biopsy for diagnosis of breast lesions necessitates knowledge of their presentation, radiologic aspects, histomorphology, and outcomes for seeking appropriate hematopathology consultation. Herein, we present our clinical experience as an academic institution and referral center of BHN in the past 20 years. We identified 59 patients diagnosed at the University of Chicago Medical Center between 2002-2021. Demographic, pathologic, radiologic, therapy, relapse data, and vital status were abstracted. Data were examined using univariable statistics with event-free and overall survival (EFS, OS) as primary outcomes examined with the lymphoma subgroup using Cox PH regression adjusted for age. The cases included 27 (46%) PBHN and 32 (54%) SBHN in a cohort comprising 93% females, mostly white (56%). The mean age at diagnosis was 58.8 years. Lymphomas were the most frequent BHN (86.4% of all cases). Patients with primary breast lymphomas (PBL) were significantly older than those with secondary breast lymphomas (SBL) (61.2 vs. 49.8 yrs, p<0.02). The most frequent lymphomas were extranodal marginal zone lymphoma (MZL) (32.2%) and diffuse large B-cell lymphoma/high grade B-cell lymphoma, not otherwise specified (DLBCL/HGBCL, NOS) (33.9%). Over half of MZLs and DLBCLs were primary in the breast. Within B-cell lymphomas, 20 (37%) were high grade with inferior 10-yr overall survival (OS) (age-adjusted HR 5.47, 95% CI 1.38, 21.64) compared to low-grade without any impact on event free survival (EFS). This is one of the largest cohorts so far describing BHN. DLBCL and MZL remain the most common lymphomas involving this site. Most patients were diagnosed via core needle biopsy (CNB) and did not have a prior BHN. Radiographically, the presentation may closely mimic breast carcinoma. FDG PET is a mainstay in the diagnosis and management of BHN.
Bispecific antibodies (BiTEs) have transformed the therapeutic landscape of relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses even in heavily pretreated patients. However, their use carries substantial infectious risk due to immunosuppression, particularly hypogammaglobulinemia, induced by T-cell-redirecting therapy. To define the real-world incidence of grade 3–4 infections, we conducted a systematic review and meta-analysis of retrospective studies including RRMM patients treated with BiTEs currently approved for clinical use. Ten studies encompassing 1,373 patients were analysed using a random-effects model of pooled proportions. The overall rate of grade 3–4 infections was 0.25 (95% CI, 0.22–0.30) after a median follow-up of 8.3 months, with moderate heterogeneity (I²=52.9%). Subgroup analyses showed comparable pooled event rates for teclistamab—anti-CD3/BCMA—(0.26; 95% CI, 0.22–0.31) and talquetamab—anti-CD3/GPRC5D—(0.23; 95% CI, 0.14–0.33). Meta-regression revealed an inverse association between infection rates and mean number of prior therapy lines (p = 0.002) and prior BCMA exposure (p = 0.0019), likely because, in real world setting, clinicians select fitter, immunologically stable patients for BiTEs therapy. In summary, approximately one in four RRMM patients receiving BiTEs experiences severe infection. These findings underscore the need for proactive monitoring and standardized preventive measures, including immunoglobulin replacement, prophylaxis, vaccination, to ensure safe, effective integration of BiTEs into routine MM care. The online version contains supplementary material available at 10.1007/s00277-026-07026-9.
Bone marrow toxicity, or immune effector cell-associated hematotoxicity (ICAHT), is a notable complication of CAR T-cell therapy, characterized by persistent cytopenia’s and typically classified into three phenotypes: transient, intermittent and aplastic. This study aimed to characterize the bone marrow immune landscape associated with ICAHT phenotype( aplastic and intermittent) by analyzing patients with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene ciloleucel (axi-cel) who developed ICAHT, in comparison to healthy controls and between the two ICAHT subtypes. Bone marrow samples were profiled using mass cytometry (CyTOF) with a 41-antibody panel. Compared to healthy individuals, ICAHT patients showed increased frequencies of activated/effector T cells and reduced levels of B cells and CD34+ early hematopoietic cells. Within the ICAHT cohort, patients with the aplastic phenotype exhibited significantly higher levels of CAR T cells, activated T cells, regulatory T cells (Tregs), Th1, and Th17 cells, along with a higher proportion of CD34+ early hematopoietic cells. In contrast, the intermittent phenotype was characterized by a greater abundance of naïve T cells, Th2 cells, and myeloid lineage markers such as CD33, CD11b, and CD11c. In this small, exploratory analysis, distinct immunological patterns were observed between intermittent and aplastic ICAHT phenotypes, suggesting potentially different mechanisms of hematopoietic disruption after CAR T-cell therapy that require confirmation in larger studies. The online version contains supplementary material available at 10.1007/s00277-026-06993-3.
POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) syndrome is a rare multisystem disease, often presenting diagnostic challenges. Here, we report a case of POEMS syndrome in an elderly patient with refractory peritoneal effusion and hypoalbuminemia as the main manifestations. Physical examination revealed cutaneous hyperpigmentation of upper and lower extremities. Tests revealed elevated vascular endothelial growth factor (VEGF) and hypogonadism, while imaging showed enlargement of armpits and groin lymph nodes. Lymph node biopsy excluded tuberculosis and malignancy. Electroneuromyography (EMG) disclosed polyneuropathy of the lower extremities. Finally, he was diagnosed with POEMS syndrome via bone marrow biopsy. Notably, he presented endoscopic snakeskin-like appearance of stomach, which was consistent with previous research. POEMS syndrome, a rare cause of ascites, is frequently missed or misdiagnosed. Thus, clinicians should maintain high vigilance. In patients with unexplained refractory ascites and symptoms like neuropathy, lymph nodes enlargement, and endocrine disorders, screening for VEGF levels and M protein should be performed to facilitate early identification of POEMS syndrome. The online version contains supplementary material available at 10.1007/s00277-026-06991-5.
Decitabine, including its new oral formulation (decitabine-cedazuridine, DEC-C), is commonly used in AML and MDS, particularly in older or unfit patients. While its clinical efficacy and tolerability are well documented, evidence regarding patient-reported outcomes (PROs) and health-related quality of life (HRQoL) remains limited. We conducted a review of the available literature on PROs in patients with AML and MDS treated with decitabine, with the aim of evaluating its impact on HRQoL, symptom burden, and patient preferences. A systematic literature search of PubMed up to October 2024 identified studies evaluating HRQoL or PROs in adult AML and/or MDS patients receiving decitabine, regardless of study design. Ten studies met the inclusion critera. Decitabine-based regimens were associated with preservation of HRQoL compared with intensive chemotherapy and improvements in fatigue and physical functioning versus best supportive care. In patients with AML, baseline HRQoL scores were found to be predictive of survival outcomes. Surveys consistently indicated strong patient preference for oral DEC-C due to reduced treatment burden and greater convenience, though longitudinal data remain limited. In conclusion, currently available HRQoL evidence for decitabine provides meaningful insight to guide further research. Findings from patient surveys and the availability of decitabine in both intravenous and oral formulations emphasize new treatment aspects that can be effectively captured through PROs. Their systematic integration may help uncover critical issues such as symptom burden, adherence, and patient priorities, ultimately fostering more patient-centered care.
This study aimed to evaluate the prevalence of vitamin D deficiency and to assess the effects of vitamin D supplementation on myocardial and hepatic iron burden and organ function in children with transfusion-dependent beta-thalassemia (TDT). A cross-sectional observational study was conducted in the pediatric hematology department of our institution. Patients aged three years and older with transfusion-dependent beta-thalassemia were included. Baseline and post-treatment laboratory assessments included serum calcium, phosphate, alkaline phosphatase, parathyroid hormone (PTH), and 25-hydroxyvitamin D [25(OH)D] levels. All patients received vitamin D supplementation according to their deficiency status. Cardiac and hepatic iron deposition were evaluated using T2* magnetic resonance imaging (MRI), and left ventricular ejection fraction (LVEF) was assessed by echocardiography. A total of 88 pediatric patients were enrolled. The largest proportion of patients was aged 4–9 years (n = 53), followed by those aged 10–14 years (n = 22) and 15–19 years (n = 13). The cohort consisted of 54.5% males (n = 48) and 45.5% females (n = 40). Patients were categorized into three groups based on serum 25(OH)D levels: severe deficiency (< 10 ng/mL), mild deficiency (10–20 ng/mL), and sufficiency (≥ 20 ng/mL). Three months after vitamin D supplementation, statistically significant improvements were observed in both cardiac and hepatic MRI T2* values (p < 0.05). Vitamin D supplementation was associated with significant improvement in myocardial and hepatic iron parameters, suggesting a potential beneficial role in reducing iron-induced organ dysfunction. These findings highlight the importance of routine vitamin D monitoring and management in children with transfusion-dependent beta-thalassemia.
The text reports the clinical case of a 61-year-old woman with a long history of generalized pruritus who was eventually diagnosed with T-cell prolymphocytic leukemia (T-PLL), a rare and aggressive T-cell lymphoproliferative disorder. At presentation, the patient had fever, skin lesions, lymphocytosis, thrombocytopenia, coagulation abnormalities, and marked splenomegaly without lymphadenopathy. Morphological, immunophenotypic, and histological analyses of peripheral blood and bone marrow revealed diffuse infiltration by mature T lymphocytes with strong TCL1 expression, and T-cell receptor gene rearrangement confirmed clonality, supporting the diagnosis of T-PLL. The patient initially received bendamustine chemotherapy, which failed to induce a response. Second-line treatment with the anti-CD52 monoclonal antibody alemtuzumab was subsequently initiated, but the disease proved refractory, with persistent bone marrow involvement, worsening cytopenias, disease progression, and clinical deterioration. As a result, alemtuzumab was discontinued and the patient was transitioned to palliative care. A particularly notable finding was the detection, by next-generation sequencing, of a pathogenic KRAS G12A mutation, which has not previously been reported in T-PLL. This mutation was identified incidentally using a myeloid-targeted NGS panel. The finding broadens the known mutational spectrum of T-PLL and suggests that activation of the RAS signaling pathway may represent an alternative oncogenic mechanism beyond the canonical TCL1 and JAK–STAT pathways. We suggest that investigating for KRAS mutations in additional T-PLL cases may be beneficial to explore this pathogenetic pathway and could open new avenues for future targeted therapeutic strategies. The online version contains supplementary material available at 10.1007/s00277-026-06986-2.
Congenital sideroblastic anemia (CSA) and thalassemia are both hereditary disorders of erythropoiesis, primarily affecting erythroid cells. Their typical manifestations include anemia and iron overload. In this study, we conducted clinical and molecular analyses on a male patient who was concurrently diagnosed with thalassemia and CSA. The patient underwent a series of tests including complete blood count, bone marrow smear, and serum ferritin levels. Whole exome sequencing technology was employed for genetic mutation analysis, and bioinformatics methods were utilized to assess the functional impact of the predicted variants. The patient was previously diagnosed with alpha thalassemia (with genotype of --SEA/-α4.2), and has been receiving frequent blood transfusions over the past two years, presenting with severe anemia (Hb level of 44 g/L), iron overload, and 52% ring sideroblasts in the bone marrow. Whole exome sequencing revealed a hemizygous nonsense mutation (c.224 C > A) in the 5-aminolevulinate synthase (ALAS2) gene, which introduces a premature stop codon at the 75th amino acid position in the N-terminal region (P.S75X). Family analysis showed that the patient, her mother, and her sister all carry this variant, suggesting it is a de novo mutation. Computational analysis using various online software tools predicted the variant to be deleterious. The patient was treated with a combination of vitamin B₆, folic acid, and deferasirox. After six months, the Hb level increased to 104 g/L, while the serum ferritin level initially rose and subsequently decreased. This study identified and reported a novel variant, ALAS2 c.224 C > A (P.S75X), which led to the co-occurrence of sideroblastic anemia in a male patient with thalassemia. The anemia symptoms induced by this variant were responsive to pyridoxine (vitamin B₆) supplementation therapy. The online version contains supplementary material available at 10.1007/s00277-026-06984-4.
With the widespread application of third-generation sequencing (TGS) technology, an increasing number of rare or previously unreported β-globin gene variants have been discovered. This study aims to characterize two rare complex β-globin gene variants identified in the Chinese population using TGS, aiming to enrich the spectrum of globin gene variations in this ethnic group. Two unrelated Chinese families residing in Fujian Province were recruited for this study. Hematological screening was conducted via routine blood tests and capillary hemoglobin (Hb) electrophoresis. To detect both common and rare globin gene variants, a combination of conventional thalassemia gene detection, TGS, gap-PCR, and Sanger sequencing was employed. Hematological screening of the proband from Family 1 revealed a decreased Hb level (102 g/L), elevated Hb A2 (9.3%), and an abnormal Hb band in zone 10. TGS identified a rare αααanti4.2 variant co-existing with Hb Stockholm [β7(A4)Glu > Asp; HBB:c.24G > T] in this proband. Pedigree analysis showed that the proband’s 6-month-old daughter inherited the αααanti4.2 variant (presenting with reduced MCV and MCH) but without Hb variant. The 29-year-old female proband from Family 2 exhibited remarkably reductions in MCV, MCH, and Hb A2, along with an abnormal Hb band in zone 12. Conventional testing detected the common –SEA deletion, while TGS further identified an additional rare Hb Pyrgos [β83(EF7)Gly > Asp; HBB:c.251G > A] variant combined with a rare IVS-II-180(T > C) (HBB:c.315 + 180 T > C) variant in the proband. This study is the first to describe these two rare complex Hb variants in the Chinese population. Our findings expand the knowledge of rare Hb variants and further strengthen the clinical utility of TGS in thalassemia gene testing. The online version contains supplementary material available at 10.1007/s00277-026-06997-z.
High-frequency plateletpheresis is crucial for meeting transfusion demands but poses a significant risk of cumulative iron depletion in donors. Current screening protocols relying solely on hemoglobin (Hb) fail to detect latent iron deficiency (LID), a condition where depleted iron stores coexist with normal Hb levels. This study investigated the longitudinal trajectory of iron parameters in high-frequency plateletpheresis donors and quantified the impact of LID on donor deferral and attrition. A retrospective longitudinal cohort study was conducted on 538 eligible plateletpheresis donors at a regional blood center in China from January 2021 to December 2024. Donors were stratified into high-frequency (≥ 10 donations/year) and low-frequency (< 10 donations/year) groups. Longitudinal changes in serum ferritin and Hb were modeled using Generalized Estimating Equations (GEE), adjusting for time-varying inflammation (WBC) and demographics. The association between baseline LID (ferritin < 30 ng/mL) and temporary Hb deferral was assessed using a multivariable modified Poisson regression. Predictors of donor attrition (lapse > 12 months) were identified using a time-dependent Cox proportional hazards model. High-frequency donors exhibited a precipitous decline in serum ferritin over four years (β = -0.42, p < 0.001), with a significant time-by-frequency interaction (β = -0.15, p < 0.001), while Hb levels remained stable. Baseline LID was a potent predictor of future temporary deferral (Adjusted Relative Risk = 3.8, 95% CI: 2.6–5.5). Survival analysis revealed that both the experience of a deferral event (Hazard Ratio [HR] = 2.42, 95% CI: 1.85–3.16) and baseline LID (HR = 1.58, 95% CI: 1.21–2.06) were independent predictors of donor attrition. Subgroup analyses confirmed these risks were consistent across sex, age, and residence status. High-frequency plateletpheresis induces progressive LID that is masked by stable Hb levels. LID serves as a silent precursor to both operational deferral and long-term donor attrition through physiological and psychological pathways. Integrating routine ferritin monitoring and personalized donation intervals into donor management strategies is essential to safeguard donor health and ensure a sustainable platelet supply. The online version contains supplementary material available at 10.1007/s00277-026-06992-4.
Hodgkin Lymphoma (HL) is a heterogeneous malignant disorder in the human body's lymphatic system with distinct clinical and molecular features. The objective of this research was to assess the hematological and molecular status of HL patients in Palestine and explore potential prognostic indicators and potential targets requiring further evaluation. Certain hematological factors, i.e., anemia, increased levels of lactate dehydrogenase, and inflammatory markers, are included in the International Prognostic Score (IPS) for HL. This study highlights the clinical value of accessible hematological biomarkers in resource-limited healthcare settings. A retrospective cohort study was conducted on 557 HL lymph node biopsies (2017-2023) from Palestinian Health Information Center (PHIC) database and hospital medical records. Hematological parameters (hemoglobin, MCV) and biochemical markers (ESR, LDH) were analyzed. Claudin-6 (CLDN6) mRNA expression was quantified in lymph node tissues from HL patients (n = 25) and healthy donors (n = 25) via qRT-PCR, while protein levels were assessed by Western blot. Serum GATA-4 concentrations were measured by ELISA. Nodular Sclerosis was the most common form, which predominantly occurred in young patients with a relatively equal sex distribution. The highest frequency was found in Hebron. Hemoglobin levels differed between subtypes, with the lymphocyte-depleted subtype showing the lowest mean hemoglobin values; the Lymphocyte-Depleted (LD) subtype exhibited the lowest hemoglobin and MCV (74.77 fL), indicating microcytic anemia. ESR was elevated across subtypes, with the highest levels observed in the NOS (63.5 mm/h), reflecting aggressive disease. Male mortality was highest in Mixed Cellularity (87.5%) and NS (75%), while LD and Lymphocyte-Predominant subtypes showed no male deaths. Molecularly, CLDN6 mRNA and GATA-4 levels were significantly elevated in HL tissues (P < 0.001), though Claudin-6 protein expression remained unchanged, suggesting post-transcriptional regulation. This study represents the first combined hematological and molecular characterization of Hodgkin lymphoma in Palestine and provides preliminary evidence for CLDN6-GATA4 regulatory involvement in HL pathogenesis. The hematological changes in Palestinian HL patients are unique. The roles of CLDN6 and GATA-4 as potential markers remain preliminary and require further validation in the context of Hodgkin lymphoma.
The optimal role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma (MM) remains uncertain particularly in the context of modern induction regimens and emerging immune-based therapies. We compared long-term outcomes of allo-SCT versus autologous SCT (ASCT) in a large single-center cohort. In this retrospective study, conducted at a single center, 1,342 MM patients underwent transplantation between 1992 and 2022 (1,226 ASCT; 116 allo-SCT), with inherent differences in age and transplant eligibility between groups. Median follow-up was 101 months. Outcomes included overall survival (OS), progression-free survival (PFS), relapse incidence, and non-relapse mortality (NRM). Ten-year OS was comparable between ASCT and allo-SCT groups (59.2% vs. 64.0%; p = 0.38). However, allo-SCT conferred superior PFS (50.6% vs. 26.0%; p = 0.002), driven by a markedly lower relapse incidence (32.5% vs. 68.7%; p < 0.001). This benefit was offset by higher NRM with allo-SCT (23.4% vs. 12.9%; p < 0.001). Baseline laboratory markers, including elevated LDH and hypoalbuminemia, were associated with relapse and non-relapse mortality, respectively. Allo-SCT offers durable disease control but is limited by treatment-related toxicity. ASCT remains the standard of care, while allo-SCT should be reserved for selected high-risk patients.
This study aimed to develop an effective model for predicting Hodgkin lymphoma (HL) prognosis as to assist clinicians in making optimal clinical decisions. This study screened HL patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. Feature selection was performed using the Boruta algorithm. Four ML models were built based on the feature selection algorithm. The area under the curve (AUC), decision curve analysis, and Brier score were employed to evaluate the reliability of the four ML models. The feature importance was ranked through the Shapley Additive Explanation (SHAP). Based on the results of the SHAP plot, Kaplan-Meier analysis was used to compare the survival probabilities among different groups. Among the 11,259 enrolled HL patients, 8,928 were alive and 2,331 had died. Primary site, year of diagnosis, B symptoms, surgery, marital status, Ann Arbor stage, radiation, SEER stage, chemotherapy, delay (diagnosis to treatment), age were associated with HL overall survival (OS). Of four ML models, the eXtreme Gradient Boosting (XGBoost) model exhibited superior predictive performance. For predicting 1-year OS, the net benefit of XGBoost, Cox proportional hazards (Coxph), and Random Survival Forest (RSF) models was significantly higher than that of the Light Gradient Boosting Machine (LightGBM) model, the treat-all model, and the treat-none model. Age, Ann Arbor stage, B symptoms, marital status, and radiation were the top five indicators in the feature importance ranking for HL OS. The XGBoost had excellent predictive performance in the prognostic model, which further helps clinicians to select appropriate treatment options. Not applicable.