Multiple myeloma (MM) is a plasma cell malignancy that typically follows a protracted clinical course. Extramedullary disease (EMD) represents an aggressive manifestation of MM with a relatively low incidence, traditionally involving the skin and soft tissues. While MM usually progresses indolently, fulminant disease progression characterized by extensive multivisceral and vascular infiltration is exceptionally rare and seldom documented in the medical literature. This case illustrates a 64-year-old woman who presented with left chest wall mass and pain and was diagnosed with high-risk IgG-λ-type MM (R-ISS Stage II), harboring 1q21 amplification and IGH/FGFR3 translocation. Following 12 cycles of VCD (bortezomib, cyclophosphamide, and dexamethasone) induction, she achieved partial remission and proceeded to maintenance therapy with bortezomib and ixazomib. Fifteen months post-diagnosis, the patient presented with a rapidly enlarging abdominal wall mass. 18F-FDG PET-CT revealed widespread hypermetabolic activity involving the heart, major blood vessels, liver, spleen, lungs, and multiple soft tissue sites, indicating extensive EMD. Bone marrow examination showed only 1% plasma cells, demonstrating a marked dissociation between systemic EMD and medullary involvement. Despite salvage therapy with carfilzomib, liposomal doxorubicin, and dexamethasone, the patient’s condition deteriorated rapidly. Compounded by severe hypoproteinemia, electrolyte disturbances, and respiratory infection, the disease followed a fulminant course, ultimately leading to the patient’s death. This case represents a catastrophic transition of genetically high-risk MM from initial medullary involvement to widespread multivisceral and cardiovascular infiltration upon relapse. It highlights a rare phenotype of relapsed/refractory MM where aggressive extramedullary proliferation occurs independently of bone marrow progression. Such patients face a dismal prognosis and present a formidable challenge for current salvage therapeutic strategies.
Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening hematologic disorder with high thromboembolic mortality. In the context of large patient population and limited use of complement inhibitors, the clinical characteristics and disease progression of patients in China have not been well studied. Objectives The China PNH Registry was initiated to advance understanding of the disease by collecting data and describing PNH disease burden, progression, and clinical outcomes with different medical interventions. Design This is a multi-center, prospective observational study in patients with PNH regardless of treatment for PNH. Methods This real-world study enrolled 716 PNH patients irrespective of treatment, collecting baseline demographics, clinical/laboratory data, and treatment patterns (including eculizumab dosing and safety) for descriptive analyses across PNH subtypes. Results 52.0% of the enrolled patients had classic PNH, 47.2% had bone marrow failure (BMF/PNH), and 0.8% had subclinical PNH. Classic PNH patients had a higher proportion of PNH red blood cells (RBCs) (39.0% vs. 18.0%), PNH neutrophils (86.1% vs. 52.4%), and PNH monocytes (90.2% vs. 47.7%) than BMF/PNH patients. 343/496 patients had LDH > 1.5 ULN, with a higher proportion in classic PNH than BMF/PNH (74.7% vs. 63.1%). 582 patients had at least one of the PNH-related symptoms, the most common being fatigue (63.7%), red/dark urine (46.6%). Although eculizumab has become a reimbursable complement inhibitor in China, only 28.5% of the patients received eculizumab treatment during the study period. The other main treatment methods were supportive care (46.6%), corticosteroids (28.1%), and RBC transfusion (7.5%). Conclusion Current data revealed a gap between real-world practice and guideline recommendations, indicating that standard treatment — particularly complement inhibitors — remains underutilized despite being essential for improving long-term patient outcomes. Trial registry name The China Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry. Registration number NCT06154512.
Multiple myeloma (MM) remains characterized by recurrent relapse and cumulative treatment burden despite major therapeutic advances. This study compared conventional stepwise regimens with CAR-T cell therapy in terms of QoL, toxicity, cost, and ethical considerations within a model-based comparative framework. This comparative pharmacoeconomic modeling analysis was based on published clinical trial data. Kaplan-Meier survival curves were digitized to estimate mean overall survival (OS) and progression-free survival (PFS) using area-under-the-curve integration. Treatment costs were calculated based on published pricing and trial-derived treatment durations. A simple and transparent ECOG-based utility model was developed to enable clinicians, researchers, and health policy authorities to estimate quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) across regimens spanning heterogeneous treatment lines. The present analysis synthesizes outcome data from 19 pivotal trials and real-world cohorts (N = 7,793 patients). Among heavily pretreated patients, CAR-T therapy approximately doubled OS and PFS compared with other late-line regimens and yielded higher QALY estimates with lower cumulative treatment burden. Daratumumab-based combinations improved outcomes but reached very high costs (∼USD 1 million/patient), while carfilzomib-based regimens remained costly but clinically important for high-risk disease. VMP represented a practical lower-cost option for transplant-ineligible or resource-limited patients. In treatment-line–stratified analysis, later-line/RRMM regimens had higher median ICER-equivalent values than early-line/induction regimens (USD 739,050/QALY vs USD 218,687/QALY; 3.4-fold higher), whereas CAR-T regimens showed a median ICER-equivalent estimate of USD 299,723/QALY, approximately 2.5-fold lower than later-line/RRMM conventional regimens. Within this model-based comparative framework, CAR-T provided substantial survival and quality-adjusted outcome gains after three or more prior therapy lines, with promising potential for earlier use. Despite its upfront single-payment structure, CAR-T did not show a disproportionate ICER-equivalent burden compared with later-line conventional regimens. However, limited global availability raises ethical concerns regarding access, infrastructure, reimbursement, and equity. Further studies incorporating longer follow-up and patient-level QoL data are needed to refine its role in multiple myeloma care.
Background Immunoglobulins (Ig) play a crucial role in the immune system’s ability to fight infections. In incidences when their production and function is disrupted, such as in secondary immunodeficiency (SID), patients often face increased frequency and severity of infection, particularly respiratory tract infections. Ig replacement therapy administered intravenously (IVIG) or subcutaneously (SCIG) is recommended for treatment of SID, including SID caused by haematological malignancies. Subregional Ig assessment panels (SRIAPs) and prefilled syringes (PFS) for SCIG may positively impact services across the Trust and wider National Health Service (NHS) and increase patient satisfaction and treatment outcomes. Objectives Investigate the improvement in service delivery and patient satisfaction following the switch from IVIG to SCIG PFS manual push in patients with SID following an East of England Immunoglobulin Assessment Panel (EOE IAP) review. Design Following establishment of the EOE IAP, three cohorts of patients with haematological disorders and SID, currently receiving IVIG across the Mid and South Essex NHS Foundation trust, were reviewed before switching to SCIG PFS. This manuscript reports the findings from one of the three cohorts, based at Broomfield Hospital. Methods Following clinical screening, patients were reviewed by the local SRIAP to assess Ig use and suitability for transfer from IVIG to SCIG PFS. Patient outcomes and satisfaction, financial measurements, and prescribing information after transition were recorded. Results SRIAP review of Ig prescribing for ten patients resulted in six transitioning from IVIG to SCIG PFS. Patients reported improved infection rates and satisfaction with home-based SCIG PFS treatment. Service outcomes reported savings in prescribing, pharmacy, and nursing time, as well as an increase in therapy chair capacity. Conclusion SRIAP reviews and switching to SCIG PFS can improve patient satisfaction and outcomes, help clinically vulnerable patients shield via home-based treatment, improve service efficacy and lower total treatment costs, whilst promoting Ig stewardship.
Background Myelofibrosis is a debilitating neoplasm with progressive bone marrow fibrosis, splenomegaly, and leukemic transformation risk. While ruxolitinib remains the standard for intermediate/high-risk MF, new strategies, including novel JAK inhibitors and ruxolitinib-based combinations, aim to improve efficacy and safety. However, direct comparisons of these strategies in JAK inhibitor-naïve patients remain limited. Objectives To compare the efficacy and safety of ruxolitinib, novel inhibitors, and combinations in JAKi-naïve MF. Design A systematic review and network meta-analysis of RCTs. Data Sources and Methods We searched electronic databases through November 2025 for RCTs evaluating JAK inhibitors in JAKi-naïve MF. The efficacy endpoints were spleen volume reduction of ≥35% (SVR35) and total symptom score reduction of ≥50% (TSS50) at week 24. Safety outcomes included adverse events (AEs) as well as treatment discontinuation rates. Results Seven RCTs (n=2,254) were analyzed. Ruxolitinib combinations significantly improved SVR35 over ruxolitinib (OR = 3.63) but not TSS50. Momelotinib showed comparable SVR35 (OR = 0.886), while selective JAK2 inhibitors (fedratinib and pacritinib) were numerically inferior in efficacy. Regarding safety, fedratinib had the lowest risk of grade ≥3 thrombocytopenia (OR = 0.204); pacritinib, the lowest risk of all-grade thrombocytopenia (OR = 0.209); momelotinib, the lowest risk of all-grade anemia (OR = 0.226) and grade ≥3 anemia (OR=0.187). JAK2 inhibitors significantly increased diarrhea risk (OR=6.19). Notably, ruxolitinib monotherapy maintained the lowest AEs-related discontinuation rates in patients with platelets ≥ 50×10^9/L. Conclusion In first-line therapy, our findings support a stratified approach. Ruxolitinib combinations are preferred for patients where maximal splenic debulking is the primary goal. Selective JAK2 inhibitors provide a safe option for patients with profound thrombocytopenia. Momelotinib matches ruxolitinib’s efficacy via JAK1/2 inhibition while being optimal for baseline anemia via ACVR1 inhibition. Crucially, ruxolitinib remains the benchmark for symptom control and treatment retention in patients with adequate platelets. Registration CRD420261330640.
Background CEBPA double-mutation (CEBPAdm) defines a favorable-risk subgroup of acute myeloid leukemia (AML), but marked heterogeneity exists, and relapse remains common. More precise prognostic stratification is urgently needed for this population. Objectives To identify reliable prognostic factors and establish a refined risk stratification model for de novo AML with CEBPAdm. Design Single-center retrospective observational cohort study. Methods Samples were collected from AML patients at diagnosis for analysis. The proportions of different surface antigens in the bone marrow were evaluated via flow cytometry. The detection of mutations in AML patients was based on next-generation sequencing (NGS). Multiparametric flow cytometry (MFC) can detect minimal residual disease (MRD). The data were analysed via Statistical Program for Social Sciences Version 27.0 (SPSS 27.0). Results ①Univariate analysis revealed that high expression of cluster of differentiation antigen 33 (CD33)was unfavourable prognostic factor ( P =0.028). ②There was a statistically significant difference between patients with more than 2 companion gene mutations (χ 2 =9.868, P =0.002). ③Notably, patients who became MRD-negative after induction chemotherapy had more favourable outcomes (χ 2 =3.847, P =0.05). ④Overall survival (OS) was worse in the high expression of CD33 group (43.00 months vs. 39.00 months, Log Rank P =0.024). Conclusions These findings provide a more precise restratification for CEBPAdm patients on the basis of the expression of CD33.
Background:EORTC thresholds for clinical importance on the QLQ-C30 have been proposed to improve the interpretability of patient-reported outcomes (PROs), but their clinical relevance remains underexplored in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Objectives:This study aimed to evaluate the frequency of clinically important baseline PRO domains and their associations with survival and adverse events in patients with CLL/SLL. Design:This was a pooled retrospective analysis of individual patient data from three randomized clinical trials of ibrutinib-based therapy. Methods:Data were pooled from RESONATE, RESONATE-2, and HELIOS. EORTC thresholds for clinical importance were applied to baseline QLQ-C30 scores to identify clinically important PRO domains. Cox proportional hazards models were used to examine associations between the number of clinically important PRO domains and overall survival (OS), progression-free survival (PFS), and grade ≥3 adverse events. Results:Among 1,238 patients, 920 (74%) reported at least one clinically important PRO domain and 395 (32%) reported five or more. Each additional clinically important domain was independently associated with worse OS (adjusted HR [95% CI]: 1.07 [1.04-1.11]; P < 0.001), worse PFS (1.03 [1.00-1.06]; P = 0.047), and increased risk of grade ≥3 adverse events (1.03 [1.01-1.06]; P = 0.006). Compared with patients reporting no clinically important PRO domains, those with ≥5 domains had worse OS (2.04 [1.42-2.94]; P < 0.001) and higher risk of grade ≥3 adverse events (1.47 [1.17-1.85]; P < 0.001). Physical function was the strongest individual prognostic domain for OS (C-index = 0.63). Conclusion:Clinically important PRO domains were common among patients with CLL/SLL initiating ibrutinib-based therapy and were independently associated with survival and toxicity outcomes. These findings support the clinical utility of EORTC QLQ-C30 thresholds for identifying patients with higher baseline PRO burden who may benefit from enhanced risk stratification, supportive care, and individualized treatment planning.
Hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome caused by uncontrolled activation of immune cells which leads to excessive cytokine discharge and systemic inflammation, had a mortality rate of as high as 60% when left untreated or not properly managed in the past, but the HLH-94 protocol was introduced and it brought about significant improvement in patient outcomes, however, nearly 30% of patients remain unresponsive to this initial therapy, either failing to achieve remission or relapsing after an initial response. Therefore, new chemotherapy regimens, such as those incorporating doxorubicin, PEG-asparaginase, or higher-intensity etoposide dosing, and biologically targeted therapies, including monoclonal antibodies against cytokines like interleukin-6 (IL-6) or interleukin-2 (IL-2), as well as Janus kinase (JAK) inhibitors, are being explored in relapsed or refractory patients. Nevertheless, data on their application in children remain limited. Pediatric HLH presents unique challenges due to differences in disease biology, drug metabolism, and long-term toxicity concerns. This article summarizes current treatment strategies for relapsed and refractory HLH in pediatric patients, aiming to provide evidence-based guidance for clinicians managing this complex and high-risk group.
Background Optimizing chemotherapy for elderly patients with extranodal natural killer/T-cell lymphoma (ENKTL) represents a significant clinical challenge, requiring a balance between effective relative dose intensity (RDI) and treatment tolerance. The prognostic impact of RDI in this population remains unclear. Objectives To investigate the relationship between RDI and survival outcomes and to establish a clinically meaningful RDI threshold for elderly ENKTL patients. Design A retrospective observational single-center cohort study. Methods The study analyzed treatment-naïve ENKTL patients aged ≥60 years who received DDGP-like regimens or P-GEMOX regimen between May 2016 and December 2023. The optimal RDI cutoff was determined by receiver operating characteristic curve analysis. Variable selection for multivariable Cox regression was performed using least absolute shrinkage and selection operator (LASSO) regression to mitigate overfitting and adjust for potential confounders. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Results A total of 79 patients were enrolled. The median number of chemotherapy cycles was 3 (IQR: 3-5), with a median treatment interval of 26 days (IQR: 23–31). Treatment delays exceeding one week occurred in 55.7% of patients (n = 44), and only 2.5% (n = 2) received full dose intensity (RDI = 1). An average RDI ≥ 0.62 was significantly associated with prolonged PFS ( p = 0.010) and OS ( p = 0.012). Multivariable analysis confirmed higher RDI as an independent predictor of superior PFS (HR = 0.385, 95% CI: 0.186-0.801, p = 0.011) and OS (HR = 0.433, 95% CI: 0.194-0.968, p = 0.041). Furthermore, age≥70 years (vs.60-70 years; p = 0.007), diabetes (p = 0.039), and adverse events including infection (p = 0.033), rash (p = 0.043), and diarrhea (p = 0.017) were significant predictors of reduced RDI. Conclusion An ARDI ≥ 0.62 may represent a critical threshold associated with improved prognosis in elderly ENKTL. However, this observation is preliminary and warrants further validation in prospective studies.
Ewing sarcoma breakpoint region 1 ( EWSR1 ):: Fifth Ewing variant ( FEV )-positive acute leukemia is exceptionally rare, and its clinicopathological features, molecular profile, and optimal treatment remain poorly defined. Here, we report a case of acute myeloid leukemia (AML) with bone marrow hypocellularity, aberrant lymphoid antigen expression, and an EWSR1::FEV fusion. A 45-year-old man was admitted with a 1-month history of petechiae and fatigue. Complete blood count (CBC) showed pancytopenia. Bone marrow (BM) examination revealed hypocellular marrow, with blasts accounting for 62% of nucleated cells. Flow cytometry (FCM) revealed a predominantly myeloid immunophenotype accompanied by aberrant expression of lymphoid-associated antigens. Conventional karyotyping did not identify a characteristic balanced translocation. Targeted next-generation sequencing (NGS) detected concurrent PTPN11 and NRAS mutations. RNA sequencing (RNA-seq) of the bone marrow sample identified the EWSR1::FEV fusion. Based on these findings, the patient was diagnosed with de novo AML with bone marrow hypocellularity and aberrant lymphoid antigen expression. Given the hypocellular marrow, venetoclax plus azacitidine (VA) was selected as induction therapy. The patient achieved morphological complete remission after one cycle, accompanied by a marked reduction in EWSR1::FEV transcript levels, and remained in morphological remission during approximately 6 months of follow-up after subsequent homoharringtonine combined with venetoclax plus azacitidine (HVA) consolidation. Together with previously reported cases, this case further supports the notion that EWSR1::FEV -positive acute leukemia may represent a distinct molecular subset characterized by lineage ambiguity, fusion-driven biology, and potentially unique therapeutic vulnerabilities. This case also suggests potential activity of venetoclax-based therapy in EWSR1::FEV -positive leukemia and warrants further investigation in additional cases.
Acute myeloid leukemia (AML) is a hematologic malignancy caused by the malignant proliferation and differentiation block of immature myeloid cells (blasts) in the bone marrow. The pathogenesis, diagnostic classification, treatment, and prognosis of AML are fundamentally linked to the accumulation of genetic variants, fusion gene formation, and chromosomal karyotype abnormalities. Using mRNA sequencing (next-generation sequencing, NGS), we identified and validated two novel fusion genes, UBE2E3::PDE1A and CTC1::MEF2C, in a case of AML-M2a. This patient also harbored six single nucleotide variants (SNV) (EP300, KRAS, NRAS, RAD21, TET2, and TP53) and complex karyotype (CK). The chromosomes exhibited extreme instability and high variability, with tumor cells containing multiple clones and showing continuous karyotype evolution as the disease progressed. The patient was treated with three chemotherapy regimens (VMA, VHAA, and Decitabine-Venetoclax), but none achieved remission. We propose that the combination of these novel fusion genes, multiple SNVs, and the complex karyotype collectively contributed to the patient's multidrug resistance.
Primary immune thrombocytopenia (ITP) in pregnancy presents significant therapeutic challenges, particularly when refractory to standard treatments such as corticosteroids, intravenous immunoglobulin, and immunosuppressants. Data on thrombopoietin receptor agonists (TPO-RAs) during pregnancy remain scarce. This study reports four pregnancies in three women with refractory ITP who received Romiplostim during gestation. All cases were retrospectively analyzed, with detailed documentation of treatment courses, platelet trajectories, and maternal and neonatal outcomes. Romiplostim was introduced in the second or third trimester at doses ranging from 3.1 to 6.25 µg/kg/week, following inadequate response to conventional therapy. All patients demonstrated hematologic improvement, often within one to two weeks of initiation, enabling corticosteroid tapering and preparation for delivery. Delivery outcomes were favorable, including four term vaginal deliveries without major hemorrhagic or thromboembolic complications. Neonatal outcomes were reassuring, with all infants born healthy, exhibiting platelet counts between 73,000 and 233,000/µL and no evidence of bleeding or congenital anomalies. One patient experienced transient postpartum thrombocytosis managed with low-molecular-weight heparin prophylaxis. No maternal or neonatal adverse events were attributed to Romiplostim exposure. These findings are consistent with previous limited reports suggesting that Romiplostim may be a viable rescue therapy for severe, refractory ITP in pregnancy. The favorable hematologic responses and reassuring neonatal outcomes observed in this series highlight the potential role of Romiplostim as an alternative treatment in carefully selected cases, provided that therapy is conducted under close multidisciplinary supervision.
Background Anemia is a common hematological complication in people living with HIV (PLHIV), contributing to increased morbidity and mortality. PLHIV are vulnerable to anemia due to chronic inflammation, opportunistic infections, nutritional deficiencies, and the adverse effects of antiretroviral therapy (ART). Despite the favorable safety and efficacy profile of dolutegravir (DTG)–based regimens, emerging evidence has raised concerns about potential hematologic abnormalities, underscoring the need to investigate anemia among PLHIV on DTG-based therapy. Objective To assess the prevalence of anemia and its associated factors among PLHIV receiving DTG-based ART at Debre Markos Comprehensive Specialized Hospital (DMCSH) in Northwest Ethiopia. Design An institutional-based cross-sectional study. Methods This study was conducted among 417 participants enrolled between March 1, 2024, and June 30, 2024, at the ART clinic of DMCSH. Participants were selected using a systematic sampling technique. Socio-demographic data were collected through a structured questionnaire, anthropometric measurements were taken, and clinical data were extracted from patient medical records using a standardized checklist. Hemoglobin levels were measured using the HemoCue® Hb 301 System. The collected data were coded and entered into Epidata version 4.6, then exported to SPSS version 26 for analysis. Logistic regression was conducted to identify factors associated with anemia, with a p-value of < 0.05 considered statistically significant. Result The prevalence of anemia among PLHIV on DTG-based ART was 32.6% (95% CI: 28.1, 37.1). Among those diagnosed with anemia, 69.1% had mild anemia, 26.5% had moderate anemia, and 4.4% had severe anemia. Factors significantly associated with anemia included increasing age (AOR = 1.04; 95% CI: 1.02–1.07), female sex (AOR = 1.80; 95% CI: 1.12–2.89), duration of HIV infection ≥ 7 years (AOR = 1.88; 95% CI: 1.10–3.23), CD4 T-cell count < 500 cells/mm 3 (AOR = 1.89; 95% CI: 1.18–3.01), a family history of anemia (AOR = 3.48; 95% CI: 1.63–7.44), and a history of parasitic infection (AOR = 1.83; 95% CI: 1.03–3.27). Conclusion Anemia is a moderate public health issue among PLHIV on DTG-based ART. Factors such as female sex, increasing age, duration of HIV infection ≥ 7 years, CD4 T-cell counts < 500 cells/mm 3 , a family history of anemia, and a history of parasitic infections were identified as significant factors of anemia. Thus, routine monitoring of hemoglobin levels is essential, particularly for individuals with one or more of these risk factors, to enable timely intervention when necessary.
Background Central nervous system (CNS) involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, diagnostically challenging, and historically associated with poor outcomes. Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors may improve outcomes, but evidence remains limited to case reports and small series. Objectives To summarize the clinical features, diagnostic findings, treatment patterns, efficacy, safety, and outcomes of CNS involvement by CLL/SLL treated with novel targeted therapies. Design Systematic review of published case reports, case series, and cohorts with extractable individual-level data. Methods PubMed, Scopus, and Web of Science were searched from database inception to September 15, 2025. Eligible studies reported adults with CNS involvement by CLL/SLL treated with targeted agents, including BTK inhibitors, venetoclax, duvelisib, dasatinib, or other novel therapies. Chemotherapy-only regimens and Richter transformation cases were excluded. Patient-level data were extracted, and study quality was assessed using the Murad tool. Results Twenty-six studies including 32 patients were analyzed. Median age at CNS presentation was 65.5 years, and most cases occurred at relapse. CNS disease was meningeal in 47%, parenchymal in 22%, and combined in 31%. Adverse biological features, including TP53 mutation, del(17p), and unmutated immunoglobulin heavy chain variable region (IGHV), were common. Across 34 treatment regimens, the overall response rate was 94.1%, with 55.9% complete and 38.2% partial responses. Ibrutinib was the most frequently used agent, while venetoclax and ibrutinib–venetoclax showed favorable activity. Other targeted agents showed promising responses in isolated cases. Toxicities were infrequent and consistent with known safety profiles. Conclusion BTK inhibitor- and venetoclax-based regimens show encouraging activity in CNS involvement by CLL/SLL, including in genomically adverse disease. However, the current evidence remains primarily exploratory and descriptive. Prospective multicenter studies are warranted to establish optimal treatment sequencing, combination strategies, and the role of adjunctive intrathecal therapy or radiotherapy.
Background In myeloproliferative neoplasms (MPNs), fibrosis occurs not only in the bone marrow but also in extramedullary organs such as the liver and spleen, reflected by increased tissue stiffness. Patients with MPNs frequently present with echocardiographic signs of cardiac dysfunction, which may be modifiable through targeted therapy. Objectives To evaluate changes in organ stiffness and cardiac function in patients with myelofibrosis (MF) treated with ruxolitinib at baseline, 6, and 12 months. Methods This prospective, single-center cohort study enrolled 30 MF patients diagnosed according to the current WHO criteria. At each assessment, clinical and laboratory parameters were evaluated, and abdominal ultrasound with shear wave elastography was performed to measure spleen and liver stiffness, alongside echocardiographic evaluation of cardiac function. Results The median age of patients was 50 years (range, 21–76). After 6 months of treatment, both liver size (p=0.049) and spleen size (p<0.001) significantly decreased, accompanied by reduced liver and spleen stiffness, while echocardiographic parameters remained unchanged. Significant decreases were also observed in hemoglobin (p=0.017), absolute neutrophil count (p=0.025), platelets (p=0.003), neutrophil-to-lymphocyte ratio (p=0.007), and platelet-to-lymphocyte ratio (p=0.04). Patients reported a notable reduction in symptom burden. At 12 months, organ diameters and stiffness remained stable. Echocardiography demonstrated improved systolic pulmonary artery pressure (sPAP) with a significant difference compared with baseline (p<0.001), while NT-proBNP levels decreased by 50%. Laboratory parameters were largely stable, except for a significant decrease of lactate dehydrogenase. Ruxolitinib was initiated earlier in primary MF, but no significant differences between primary and secondary MF were observed regarding organ stiffness or cardiac findings after 12 months. Conclusion Ruxolitinib demonstrated its greatest benefit at 6 months, significantly reducing organ size, stiffness, and symptom burden, followed by cardiovascular improvement and normalization of sPAP by 12 months. Further larger prospective studies with longer follow up are needed for definitive conclusion.
Background Advanced-phase chronic myeloid leukemia (CML) remains associated with poor outcomes despite advances in tyrosine kinase inhibitor (TKI) therapy, underscoring the need for more effective treatment approaches. Objectives This multicenter study evaluated the efficacy and safety of tyrosine kinase inhibitor (TKI) plus azacitidine (with optional low-dose chemotherapy) in advanced-phase CML. Design Prospective multicenter single-arm study. Methods 41 patients with accelerated- (AP) or blast-phase (BP) CML received azacitidine 75 mg/m 2 /day for 7 days per 28-day cycle (6 cycles) plus TKIs selected by ABL1 mutation status; chemotherapy was added based on early response. Major hematologic response (MaHR) was the primary endpoint. The secondary endpoints included cytogenetic/molecular responses—major cytogenetic response (MCyR), major molecular response (MMR), and undetectable minimal disease (UMD) — along with progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were documented. Results Among 36 evaluable patients (median age 51 years; range: 24-77; AP: 13, BP: 23) after excluding 5 noncompliant patients, 63.9% achieved MaHR, with a median response time of 1.33 months. The cumulative 3-year response rates were as follows: MCyR, 48.5%; MR2.0 (BCR::ABL1 IS ≤1%), 16.3%; MMR, 21.8%; and UMD, 14.2%. Patients maintained sustainable responses during follow-up. Four hematopoietic stem cell transplantation (HSCT) recipients maintained durable remission with TKI consolidation. At 28.1-month median follow-up, median OS was not reached and median PFS was 8.17 months; estimated 3-year OS and PFS rates were 50.3% and 41.1%, respectively. Elevated baseline WBC count and BCR::ABL1 transcript levels predicted poor survival. Hematologic toxicities of grade 3 or higher occurred in 55.6% of patients, including neutropenia (36.1%), thrombocytopenia (33.3%). Conclusion TKI–azacitidine therapy demonstrated promising efficacy and acceptable tolerability in patients with advanced-phase CML and may represent a feasible treatment option for this high-risk population.
Background Sickle cell hepatopathy (SCH) is a general term used to describe the acute and chronic manifestations of liver damage in sickle cell disease (SCD). One of the most effective methods used to examine the liver is transient elastography (Fibro Scan), a noninvasive, rapid, and reproducible method that can assess liver fibrosis by measuring liver stiffness. Objectives: This single-center study aims to investigate the role of transient elastography (Fibro Scan) in the detection of liver disease among patients with SCD in the Eastern Province of Saudi Arabia, where the rates of SCD are found to be among the highest. Design: This is a prospective, observational study. Methods The study was conducted among n=101 SCD patients of any phenotype between January and December 2024. Data on demographics, hospitalization rates, hydroxyurea use, transfusion, and complications were obtained from the health informatics system. All included patients were examined using non-invasive transient elastography (Fibro Scan) for the presence of fibrotic changes. Results Among n = 101 SCD patients, 13.9% had G6PD deficiency, 40.6% required one hospitalization per year, and 65.3% required blood transfusion. The transient elastography through Fibro Scan assessments revealed that 94.1% of patients had normal liver tissue (fibrosis score 2–7 kPa), 4.0% showed moderate scarring (7–11 kPa), and 2.0% had moderate to severe scarring (11–15 kPa). Radiographic evidence of fatty liver was present in 24.8% of cases, with a significant association with moderate or severe fibrosis (p = 0.049). Conclusions Patients with SCD without iron overload had a low prevalence of liver fibrosis. However, fatty liver in SCD likely leads to a risk of fibrosis progression, which is an area for further study.
Background Delayed platelet engraftment is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives This retrospective study evaluates the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, in promoting platelet engraftment post-allo-HSCT. Design Retrospective observational cohort study. Methods A cohort of 133 patients was analyzed, including 68 treated with hetrombopag post-transplant and 65 controls. Cumulative incidence function evaluated platelet engraftment, with propensity score matching and competing risk analysis to strengthen robustness. Factors associated with platelet engraftment were examined using multivariate Cox models with time-dependent coding of hetrombopag exposure. Results Hetrombopag significantly reduced the time to overall response (OR: 15.0 days vs. 20.0 days; p = 0.009) and complete response (CR: 17.5 days vs. 34.0 days; p < 0.001). The cumulative incidence of CR was higher in the hetrombopag group (92.78% vs. 86.58%; p = 0.001), with a significantly shorter median time to CR (19 days vs. 38 days) defined by the cumulative incidence function. Multivariate Cox regression identified hetrombopag as a protective factor for platelet recovery (HR: 2.04; p = 0.004). Competing risk and PSM analyses confirmed hetrombopag’s role in faster platelet engraftment. The treatment was well-tolerated, with manageable mild liver enzyme elevations and hypomagnesemia but no grade 3/4 adverse events. Conclusion Hetrombopag significantly accelerates platelet engraftment and has a favorable safety profile, suggesting its potential as a therapeutic adjunct in managing thrombocytopenia post-allo-HSCT. This study complements and validates findings from prior prospective studies, providing external confirmation in a real-world cohort.
This review summarizes the research progress on high-altitude polycythemia (HAPC). At the fundamental theoretical level, it provides an in-depth analysis of the epidemiological characteristics influenced by factors such as altitude, genetics, and gender, as well as the pathological mechanisms triggered by chronic hypoxia, including alterations in gene expression, immune imbalance, and disorders of iron metabolism. In the section on clinical manifestations and diagnosis, the multisystem symptoms are elaborated in detail, diagnostic criteria based on hematological indicators combined with high-altitude residence history are clarified, and the key points for differentiating HAPC from primary and other secondary polycythemia are summarized. Regarding treatment strategies, the current application and efficacy of pharmaceutical interventions, non-pharmaceutical methods such as therapeutic erythrocytapheresis (TE), and comprehensive treatment regimens are outlined. Technological advancements focus on genetic research, biomarker development, and imaging technology innovation, providing support for precise diagnosis and treatment. A review of historical development and current status reveals the evolution of research, clarifies present trends in disease prevalence, and identifies challenges in diagnosis and treatment. In the outlook for the future, innovative preventive strategies are proposed, including health education, genetic screening, and the development of novel drug formulations. The research direction of multidisciplinary integration is emphasized, such as elucidating the gene-environment interaction mechanism and developing targeted drugs. Meanwhile, controversial issues including understanding of etiology, evaluation of treatment efficacy, and ethical and social implications, aiming to provide a systematic reference for HAPC research and clinical practice.
Background Blinatumomab has gained attention for its effectiveness in improving overall survival in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and eradicating minimal residual disease (MRD). Objectives We conducted a retrospective study to assess whether combining reduced-dose blinatumomab with chemotherapy for consolidation could improve outcomes in newly diagnosed B-ALL. Design Patients with Philadelphia chromosome (Ph)-positive or Ph-negative B-ALL who achieved complete remission (CR) after induction received consolidation therapy consisting of blinatumomab (cycle 1, 3, 5, and 7) and hyper-CVAD (course B for cycles 2 and 6; course A for cycle 4 and 8). After completion of the cycle 2, the decisions to continue treatment or receive hematopoietic stem-cell transplantation were made based on multiple factors. Methods The final endpoint was molecular remission, overall survival (OS), relapse-free survival (RFS). Molecular remission referred to MRD-related methods, including MFC (multiparameter flow cytometry)-based MRD, next generation sequencing (NGS)-based MRD, and complete molecular remission (CMR). Meanwhile, we assessed the safety profile of this combination regimen, including adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Results 32 newly diagnosed B-ALL patients (14 Ph+ B-ALL and 18 Ph- B-ALL) achieving CR were analyzed. At the time of study inclusion, 12 Ph+ B-ALL and 12 Ph- B-ALL patients were MFC-MRD negative, and 5 Ph+ B-ALL patients achieved CMR. After the first blinatumomab consolidation and hyper-CVAD B cycle, seven additional patients (one Ph+ B-ALL and six Ph- B-ALL) achieved MFC-MRD negativity, and six additional Ph+ B-ALL patients achieved CMR. With a median follow-up of 16.5 months, the overall rate of MFC-MRD was 96.88% (Ph+ B-ALL 92.86% and Ph- B-ALL 100%), and CMR was 78.57%. The estimated RFS and OS rates at 30 months for whole patients were 83.5% (95% CI, 79.1%–100%) and 96.8% (95% CI, 90.8%–100%), respectively. The most common adverse events were observed during chemotherapy cycles due to myelosuppression. Eight patients developed a grade 1-2 blinatumomab-related CRS with a prevalence of 17.78%, which was completely reversible. Conclusion Reduced-dose blinatumomab combined with hyper-CVAD chemotherapy as consolidation therapy seems to be feasible for adult B-ALL with acceptable side effects.
