Hematology最新文献

Objectives: This study aimed to compare clinical, and molecular features between acute myeloid leukemia (AML) patients aged <50 and ≥50 years, while also assessing their respective treatment outcomes and prognostic factors.

Methods: We conducted a retrospective analysis of clinical data from AML patients treated at our institution between October 2015 and June 2021, supplemented by data extracted from the SEER database spanning 2000 to 2019. Survival outcomes were evaluated using Kaplan-Meier methodology.

Results: In patients aged ≥50 years, we observed higher prevalence of DNMT3A, IDH2, and TP53 mutations along with -5/del (5q) karyotype abnormalities. The treatment outcomes were suboptimal, with a complete response (CR) rate of 45.9%, relapse rate of 60.8%, and two-year overall survival (OS) rate of 33.3%. VEN-treated chemotherapy-intolerant patients showed significantly improved two-year OS (36.0% vs 12.1% in non-VEN group; P = 0.006). In contrast, patients aged <50 years exhibited a distinct molecular profile characterized by a predominance of NRAS, biallelic CEBPA, WT1, and C-KIT mutations, along with a higher incidence of RUNX1-RUNX1T1 and CBFB-MYH11 fusion genes. This group demonstrated more favorable clinical outcomes, with a CR rate of 73.1%, relapse rate of 36.8%, and two-year OS rate of 68.3%.

Conclusions: This study revealed that patients aged ≥50 years displayed more complex genetic aberration profiles and experienced significantly poorer prognoses compared to their younger counterparts. These findings provided novel insights for optimizing treatment strategies for middle-aged and elderly AML patients in the Chinese population.

Objective: To identify simple clinical predictors of prognosis in multiple myeloma (MM) after chemotherapy and assess their predictive value.

Methods: We retrospectively analyzed 164 newly diagnosed MM patients treated with proteasome inhibitor- and/or immunomodulatory drug-based chemotherapy between 2018 and 2024. Baseline data included demographics, DS/ISS stage, haemoglobin (Hb), platelets, albumin, creatinine, calcium, lactate dehydrogenase (LDH), erythrocyte sedimentation rate, and serum β2-microglobulin (β2-MG). Treatment responses after four cycles (CR/VGPR vs ≤PR) and survival outcomes were recorded. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Cox models identified independent prognostic factors. Landmark 2-year ROC curves evaluated discriminative ability.

Results: After four cycles, 95/164 patients (57.9%) achieved CR/VGPR and 69 (42.1%) ≤PR. During a median follow-up of 31 months, 85 deaths and 112 progression events occurred. Multivariable analysis showed that age >60 years, Hb ≤85 g/L, β2-MG>3.5 mg/L, and ≤PR were independently associated with shorter OS, whereas Hb ≤85 g/L and ≤PR predicted shorter PFS. Two-year AUCs for mortality prediction were 0.601 for age, 0.624 for Hb, 0.647 for β2-MG, and 0.731 for response; for PFS prediction, AUCs were 0.668 for Hb and 0.749 for response, indicating fair but limited standalone discrimination.

Conclusion: Advanced age, severe anaemia, elevated β2-MG, and suboptimal early response are simple, readily available predictors of adverse survival in MM. Although their individual discriminative power is modest, these factors may inform pragmatic risk stratification, especially where cytogenetic and MRD testing are unavailable, and could be incorporated into future composite prognostic scores.

Objectives: Langerhans Cell Histiocytosis (LCH) is an inflammatory myeloid neoplasm with heterogeneous outcomes. This study aimed to identify independent risk factors influencing event-free survival (EFS) in pediatric LCH, focusing on initial white blood cell (WBC) counts and disease extent.

Methods: We retrospectively analyzed 67 pediatric LCH patients with bone involvement treated at Hebei Children's Hospital, Hebei Clinical Medicine Research Center for Children's Health and Diseases between 2013 and 2022. The primary endpoint was EFS. Cox proportional hazards regression models determined predictors of adverse outcomes.

Results: The 3-year EFS rate was 76.1% (median follow-up: 48 months). Univariate analysis linked multiple disease sites, risk-organ involvement, CNS risk site involvement, diabetes insipidus, and elevated WBC count to poor EFS. In multivariate analysis, only multiple site involvement (Hazard Ratio [HR] = 3.12, p = 0.025) and an elevated initial WBC count (>10 × 10⁹/L) (HR = 2.89, p = 0.034) remained independent predictors.

Discussion: While risk-organ involvement is a traditional stratifier, systemic inflammatory burden, reflected by leukocytosis, offers independent prognostic value. Patients with elevated WBC counts or multisite disease warrant intensive monitoring.

Conclusion: Elevated initial WBC count and multiple site involvement independently predict shorter EFS in pediatric LCH. Integrating these markers into risk stratification could optimize therapies.

Objective: To explore the application efficacy of the UK Myeloma Alliance Risk Stratification (MRP) and the Simplified Frailty Index (FI) in patients with newly diagnosed multiple myeloma (NDMM).

Methods: 205 NDMM patients diagnosed in our hospital from 1 July 2014 to 1 July 2022; frailty was assessed using MRP and Simplified FI. The Fine-Gray competing risk model compared the cumulative incidence of early grade ≥3 infections. Kaplan-Meier method and the log-rank test were applied for analyzing OS and PFS. ROC curves, AUC values, and Youden's index were used to compare the predictive values for OS, PFS, and early grade ≥3 infections. P < 0.05 indicated statistical significance.

Results: The frail groups by MRP and the Simplified FI had significantly shorter OS (36 vs. 75 months and 38 vs. 76 months) and PFS (11 vs. 21 months and 11 vs. 23 months; P < 0.001) with increased mortality risk (HR: 2.51 and 2.12). One-year mortality was significantly higher in frail patients (P < 0.005). The common frail group showed the poorest outcomes, but without significant difference from individual frailty groups (P > 0.05). Frail patients by both showed higher rates of early grade ≥3 infections, but there was no statistically significant difference (50.6% vs. 37.9% and 45.76% vs. 41.78%, P > 0.05). Regarding predictive performance, both tools effectively predicted OS and PFS (all P < 0.05). For early infections, MRP was not predictive (P = 0.237) whereas FI was (P = 0.012), though their predictive performance did not differ significantly (P > 0.05).

Conclusion: Both MRP and FI are effective frailty assessment tools in NDMM patients. They significantly correlate with OS, PFS.

Background: High Body mass index (BMI) is a well-established risk factor for various hematological malignancies. However, the relation and mechanism between high BMI and multiple myeloma remain largely unknown.

Methods: This study investigates the global disease burden of multiple myeloma (MM) associated with high BMI using data from the Global Burden of Disease (GBD) Study 2021. Bioinformatic integrative analysis was performed to uncover key therapeutic targets related to MM development.

Results: In 2021, the number of MM deaths associated with high BMI reached 9,165, marking a 203.2% increase from 1990. The age-standardized mortality rate (ASMR) and disability-adjusted life years (DALY) rate for high BMI-associated MM increased from 0.08/100,000 (95% UI: -0.03/100,000-0.21/100,000) and 1.81/100,000 (95% UI:-0.64/100,000-4.65/100,000) in 1990 to 0.11/100,000 (95% UI:-0.04/100,000-0.27/100,000) and 2.39/100,000 (95% UI: -0.97/100,000-5.94/100,000) in 2021, respectively. Notably, males and older populations exhibited higher mortality and DALY rates in 2021. Predictive modeling suggests that the mortality of high BMI-associated MM will continue to rise over the next 25 years. Solute Carrier Family 25 Member 13 (SLC25A13) and THO Complex Subunit 2 (THOC2) were identified as core target genes in high BMI-associated MM. GO analysis demonstrated that some key pathways were related to these two target genes, including immune microenvironment, cell proliferation and cell metabolism.

Conclusions: The above findings underscore the growing public health threat posed by high BMI-associated MM and highlight the need for targeted interventions. SLC25A13 and THOC2 may play an important role in high BMI-associated MM and could serve as potential treatment targets in the future.

Background: Bone disease (MBD) is common in patients with multiple myeloma (MM) and ~80% are already affected at diagnosis. MBD increases the risk of skeletal-related events (SREs) and the use of bone-targeted agents (BTAs) is recommended for their prevention and treatment.

Methods: This study retrospectively analyzed electronic health records of adults with MBD treated in real-world practice in any of eight hematology clinics in Bulgaria. The study assessed patients' demographics and clinical characteristics, BTA treatment patterns and pain management, and estimated the incidence of SREs and osteonecrosis of the jaw (ONJ).

Results: The study included 732 patients (denosumab: 177; zoledronic acid: 440; zoledronic acid and denosumab sequentially: 115). In 83%, 84%, and 84% of patients, respectively, the first recorded therapy contained a BTA either alone or in combination with an anti-myeloma therapy. The median (Q1, Q3) duration of BTA administration was longer in patients receiving both BTAs sequentially (zoledronic acid: 84 [24, 157] days; denosumab: 60 [0, 197] days). BTAs were prescribed mostly in preventive intent: only 22%, 16%, and 30%, respectively, had experienced previous SREs. While receiving BTAs, new SREs occurred in 9%, 7%, and 9%, respectively. Seven cases of ONJ were identified but only one occurred during BTA use (in the zoledronic acid cohort).

Conclusions: Patients with MM are at very high risk of SREs. When receiving BTAs with a preventive intent, only a minority (<10%) experienced an SRE. These data suggest that preventive BTA use, effectively reduces the risk of SREs in real-life clinical practice.

Objectives: To examine the nonlinear association between the red cell distribution width to platelet count ratio (RPR) and the prognosis of diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-based therapies.

Methods: Data from 170 newly diagnosed DLBCL patients on rituximab regimens were retrospectively analyzed. Clinical data and survival outcomes were collected. Patients were categorized into three RPR tertiles: Tertile 1 (<0.048), Tertile 2 (0.048-0.066), and Tertile 3 (0.066). Multivariable Cox models were used to evaluate the RPR's impact on progression-free survival (PFS) and overall survival (OS). Nonlinear RPR-PFS/OS relationships were explored using smooth curve fitting and a two-piecewise Cox model.

Results: Over a median follow-up of 30.5 (range: 3-92) months, there were 42 deaths and 67 events (death or progression). Patients in the first and third RPR tertiles had a higher risk of poorer PFS compared to the second RPR tertile. A U-shaped relationship was found between RPR and PFS, with an inflection point at an RPR level of 0.051. For PFS, the HR per 0.01 increment was 0.58 (0.39, 0.87) on the left and 1.10 (1.01, 1.19) on the right of this point (p < 0.05).

Conclusion: Both low and high RPR levels are linked to reduced PFS, confirming a U-shaped association.

Background: Platelet concentrates play an important role in clinical treatment such as platelet function disorders and thrombocytopenia. In the process of preparation and storage of platelets, centrifugation, leukofiltration, and agitation will cause morphological changes and impaired function of platelets, which is associated with the increase of platelet transfusion refractoriness, and named as platelet storage lesion (PSL).

Method: This paper proposes three major operations (centrifugation, agitation, and leukofiltration) that platelets experience during the preparation and storage process, to explore the effect of physical cues on PSL. The analysis of morphology, metabolism index, and levels of activation markers are used to monitor the quality of stored platelets and definite the role of physical cues in PSL.

Result: In this study, centrifugation, leukofiltration and agitation lead to different degrees of platelet activation, with the extension of storage time. At one hour after separation, PSL can be found through structural change, metabolic parameters, and activation markers of platelets. Agitation maintains more cell numbers, better cell morphology, and lower metabolism rate in platelets, and keeps the low activation state of platelets throughout the storage period. The hard centrifugation group showed the highest level of CD62P expression throughout the storage.

Conclusion: our results indicate that agitation can mitigate PSL by supplying sufficient O₂ during preservation, shear stress may cause PSL immediately after the physical cues were applied; however, hydrostatic pressure induced by filtration is negligible for its effects on PSL. Meanwhile, when the physical cues are big enough, the activation of platelets is irreversible, such as spin at 2000 g. The granule secretion of platelets is a kind of irreversible activation; however, the membrane reorganization of platelets is a kind of reversible activation.

Background: Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. Patients with IDA often present thrombocytosis, but little is known about its degree and prevalence, and its response to iron replacement.

Methods: We conducted a retrospective review of 76 consecutive patients with anemia secondary only to iron deficiency. Laboratory data were collected both at baseline and at 3 months after either oral or intravenous iron replacement therapy. We defined thrombocytosis as a platelet count >400 × 10⁹/L.

Results: The median age of the patients was 54 years (range, 22-90 years), and 59 of 76 (78%) patients were females. The replacement therapy consisted of oral iron (n = 13), intravenous iron (n = 33), or both (n = 30). The median Hb and ferritin levels at baseline and at 3 months after the iron replacement were 9.9 g/dL and 18 mg/dL, and 12.4 g/dL (p < 0.0001) and 113 mg/dL (p < 0.0001), respectively. Thrombocytosis before and after the iron administration was present in 17 (22%) and 4 (5%) patients, respectively. Regardless of thrombocytosis, the platelet count decreased in 55 (72%) patients. The median platelet level at baseline and at 3 months after the iron replacement was 299 (95% CI, 276-330) and 265 (95% CI, 245-295) × 10⁹/L (p < 0.0001), respectively.

Conclusion: Thrombocytosis is found in about one fifth of patients with IDA at baseline, and it is expected to resolve within 3 months of iron replacement therapy in most of them. Iron administration is associated with a decrease of the platelet counts, even in the absence of preexisting thrombocytosis.

Background: While there has been no direct head-to-head comparison, it is assumed that second-line treatment with dasatinib and nilotinib has comparable efficacy but distinct safety profiles in the treatment of patients with chronic phase chronic myeloid leukemia (CML-CP). Our aim was to conduct a real-world analysis to compare the efficacy and safety profiles of these two agents.

Methods: Data from 73 CML-CP patients, who received either dasatinib or nilotinib in second-line treatment, were analyzed. The primary interest of the efficacy assessment was a major molecular response (MMR) at the 12-month, 5-year cumulative incidence of treatment failure, and overall survival.

Results: A total of 73.5% of 34 patients in the dasatinib and 76.9% of 39 patients in the nilotinib group achieved MMR at 12 months. Five-year cumulative probability of treatment failure in patients, who previously achieved MMR was 0 and 7.6% for patients receiving dasatinib and nilotinib, respectively (p = 0.25). Eight-year OS was 82.7 and 86.3% for dasatinib and nilotinib groups, respectively (p = 0.90). Pleural effusions were more common in the dasatinib group, leading to treatment discontinuation, while cardiovascular events and thrombotic incidents were more prevalent in the nilotinib group.

Conclusion: Dasatinib and nilotinib exhibit similar efficacy in the CML-CP treatment. Individualized patient management should consider patient comorbidities and safety profiles.