Blood Research最新文献

Purpose: Central nervous system (CNS) relapse is associated with poor survival, and remains an unmet challenge in patients with diffuse large B-cell lymphoma (DLBCL). Identifying patients at high risk of CNS relapse and offering prophylactic treatment could improve patient prognosis.

Methods: Here, we studied 234 patients with DLBCL using open patient-level clinical and sequencing data to explore risk factors for CNS relapse. Patients were divided into Cohort A (CNS involvement at baseline), Cohort B (CNS recurrence), and Cohort C (patients without secondary CNS involvement and with a follow-up interval > 3 years). We investigated the risk factors for CNS relapse in Cohorts B + C.

Results: Genetic alterations with statistical significance, determined by univariate analysis, and an incidence rate ≥ 5%, together with clinical factors, correlated with CNS relapse risk in a multivariate analysis. Multivariate logistic regression analysis revealed that concomitant MYD88 L265P and CDKN2A loss (p = 0.012), TET2 mutation (p = 0.037), ARID1A mutation (p = 0.010), and INO80 (p = 0.002) were independently correlated with a high risk of CNS relapse after adjusting for the IPI risk groups, B symptom and cell of origin (COO). The classifier that integrated genomic risk factors was superior in predicting CNS relapse (area under the receiver operating characteristic curve [AUROC]: 0.91) compared with the IPI (AUROC: 0.77, p < 0.001) or IPI in combination with COO classifiers (AUROC: 0.81, p = 0.013).

Conclusion: This study identified several genomic alterations as risk factors for CNS relapse.

Older patients with classic Hodgkin lymphoma (HL) often experience poor outcomes due to age-related comorbidities and treatment-related toxicity. Comprehensive geriatric assessment and supportive care measures, including pre-phase corticosteroids, growth factor prophylaxis, and organ function monitoring, are essential for optimizing treatment tolerance in this vulnerable patient population. Recent phase III trial (S1826) demonstrated that nivolumab plus doxorubicin, vinblastine, and dacarbazine (Nivo + AVD) significantly improves progression-free survival and is better tolerated than brentuximab vedotin (BV) + AVD, particularly in patients over 60 years of age. Given its efficacy and reduced toxicity, Nivo + AVD is likely to become a key treatment option for fit older patients with HL. For frail patients, chemo-free approaches with BV and checkpoint inhibitors remain viable alternatives. Future research should refine fitness-based treatment strategies, integrate novel agents, and enhance supportive care to improve outcomes and minimize treatment-related toxicity in this population.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment option for hematologic diseases. However, limited studies have evaluated the prognosis of patients receiving single human leukocyte antigen (HLA) mismatched unrelated donor allo-HSCT (HLA 9/10 MMUD-HSCT) compared to those receiving fully matched unrelated donor allo-HSCT (10/10 MUD-HSCT). This study retrospectively analyzed 126 cases of unrelated donor allo-HSCT (URD-HSCT) at our center, in which anti-human thymocyte globulin (ATG, 7.5 mg/kg) was used as a graft-versus-host disease (GVHD) prophylaxis strategy. The MUD-HSCT group had a significantly lower incidence of grade II-IV acute GVHD (13.89% vs. 35.19% in the MMUD-HSCT group, p = 0.005). In contrast, the incidence of moderate-to-severe chronic GVHD (cGVHD) did not differ significantly between the two groups (16.67% vs. 29.63%, p = 0.083). The median follow-up time was 16.98 months (range: 7.88-38.55). There were no significant differences between the two groups in the 1-year cumulative incidence of relapse (CIR) (p = 0.707), 3-year CIR (p = 0.764), 1-year disease-free survival (DFS) (p = 0.954), 3-year DFS (p = 0.888), 1-year overall survival (OS) (p = 0.611), 3-year OS (p = 0.796), 3-year non-relapse mortality (NRM) (p = 0.711), or GVHD-free relapse-free survival (GRFS) (p = 0.546). The estimated median OS and DFS times were not reached in either group. In conclusion, under an ATG-based GVHD prophylaxis regimen, HLA 9/10 MMUD-HSCT is a viable alternative donor option, offering comparable clinical outcomes to those of fully matched unrelated donor HSCT.

Cytomegalovirus (CMV) infection remains a major complication in recipients of hematopoietic stem cell transplantation (HSCT) and contributes significantly to morbidity and mortality. Effective CMV prevention and management are essential for improving transplant outcomes. Preventive strategies include antiviral prophylaxis and preemptive treatments (PET). Letermovir, a terminase complex inhibitor, has become the standard of care for primary prophylaxis in CMV-seropositive recipients because of its efficacy and favorable safety profile. PET involves regular monitoring of CMV DNAemia via polymerase chain reaction (PCR) and initiation of antiviral therapy, most commonly ganciclovir or valganciclovir, upon detection of early viral reactivation. Refractory or resistant CMV infections present a significant therapeutic challenge and often require switching to a different antiviral class while awaiting genotypic resistance testing. Maribavir, a UL97 kinase inhibitor, has demonstrated superior efficacy and improved tolerability compared to conventional therapies in the phase 3 SOLSTICE trial, making it a promising therapy for refractory or resistant CMV. Optimal CMV management requires a risk-adapted, individualized approach that integrates prophylaxis, early detection, and timely intervention to reduce CMV-related complications.

Cell-based artificial platelet production has made remarkable progress over the past three decades, driven by the need for safe and stable platelet sources in the face of donor limitations and transfusion-related risks. This review provides a chronological overview of the evolution of in vitro platelet production from various cell sources (CD34+ hematopoietic stem cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and others) and highlights key advances in the field. We outline developments from the foundational experiments of the 1990s, through the introduction of iPSCs in the mid-2000s, to the adoption of three-dimensional culture and bioreactor technologies in the late 2010s and the emergence of clinical trials in the 2020s. In addition, we discuss future perspectives, including the role of advanced gene editing and scalable biomanufacturing technologies in accelerating clinical translation. This comprehensive review underscores the promise of artificial platelet production technologies for clinical applications and discusses the remaining challenges, such as scalability, cost-effectiveness, and regulatory hurdles. The recent completion of the first human clinical trials using iPSC-derived platelets marks a significant milestone, pointing to a future in which patient-specific or human leukocyte antigen-universal platelets may be transformed into transfusion medicine and regenerative therapies.

Purpose: Neutropenia is a hematologic condition characterized by an absolute neutrophil count < 1500/μL, associated with increased infection risk. This review aimed to provide an updated overview of the classification, pathophysiology, etiology, diagnosis, and management of neutropenia in congenital and acquired forms.

Methods: We conducted a comprehensive literature review of various causes of neutropenia, including genetic syndromes, autoimmune disorders, infections, and drug-induced mechanisms. Emphasis was placed on clinical manifestations, underlying mechanisms, diagnostic algorithms, and therapeutic approaches, including recent advances in molecular diagnostics and biologic therapies.

Results: Neutropenia can result from decreased neutrophil production, immune-mediated destruction, or abnormal distribution. Congenital neutropenia is often linked to mutations in genes such as ELANE, HAX1, and SBDS. Acquired neutropenia can be caused by chemotherapy, infections, autoimmune diseases, or nutritional deficiencies. Diagnostic evaluation requires a stepwise approach incorporating clinical history, blood counts, peripheral smear, bone marrow biopsy, and molecular or serologic testing. Treatment depends on the etiology and severity and includes granulocyte colony-stimulating factor, immunosuppressants, antimicrobial prophylaxis, and hematopoietic stem cell transplantation in selected cases.

Conclusion: Neutropenia is a multifactorial disorder requiring individualized evaluation and management. Advances in genetic and immunological diagnostics combined with targeted therapies have improved risk stratification and outcomes. Early recognition and a multidisciplinary approach are essential to reduce infection-related morbidity and prevent progression to hematologic malignancies in high-risk patients.

Background: Immune thrombocytopenia (ITP) is an autoimmune condition characterized by low platelet count and increased risk of bleeding. Several pathophysiological processes contribute to the disease, including complement activation by autoantibodies bound to platelet surfaces. This study aimed to assess complement levels in ITP patients and determine their correlation with clinical presentation and disease severity.

Patients and methods: This case-control study enrolled 40 patients (both sexes, aged 18-40 years) with primary ITP and 40 healthy controls. All participants underwent a comprehensive health assessment, thorough physical examination, laboratory investigations, and abdominal ultrasound. These included a complete blood count (CBC) with blood film, renal and hepatic function tests, hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCV-Abs), human immunodeficiency virus (HIV) antibodies, hepatitis B core antibody (HBcAb), C-reactive protein (CRP), antinuclear antibody (ANA), thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), serum complement levels (C3 and C4), and Helicobacter pylori antigen in stool.

Results: Mean C3 and C4 levels were significantly lower in patients with ITP than in healthy controls. A statistical significant negative correlation was found between CRP and C4 levels in ITP patients. However, no statistically significant relationship was observed between C3 and C4 levels and platelet count in ITP patients, regardless of the presence of bleeding complications.

Conclusion: Complement levels were significantly lower in patients with ITP than in healthy controls. Complement levels were also significantly lower in treatment-naïve patients than in patients who received treatment. Therefore, complement levels could serve as a valuable laboratory test for disease activity.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS.

Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after allogeneic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases.

Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days post-INO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR. Doppler ultrasonography revealed preserved portal vein flow (range 10.2-26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56-0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression.

Conclusion: Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor. These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma. Radiation therapy (RT) has served as the primary treatment option for PMBCL; however, its role has been questioned with the advent of intensified immunochemotherapy. This study aimed to investigate the role of consolidative RT in the primary treatment of PMBCL.

Methods: This single-center retrospective study analyzed the survival outcomes of 65 patients newly diagnosed with PMBCL. The patients were divided into three treatment groups: (1) EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab), (2) R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), and (3) R-CHOP with consolidative RT.

Results: The objective response and complete remission rates were 86.2% and 63.1%, respectively, with 3-year progression-free survival (PFS) and overall survival (OS) rates of 72% and 81%, respectively. All patients in the R-CHOP + RT group achieved an objective response with better PFS) than those who did not receive consolidative RT (p = 0.028), although there was no significant difference in OS (p = 0.102). Consolidative RT benefited patients with an initially bulky disease or insufficient end-of-treatment response. The predictive value of ¹⁸F-fluorodeoxyglucose positron-emission tomography-computed tomography (PET-CT) in assessing the treatment response in PMBCL was revalidated, showing that patients who achieved negative end-of-treatment PET-CT had significantly better survival outcomes than others.

Conclusions: R-CHOP is a useful alternative regimen when intensified chemotherapy is not feasible. Consolidative RT should be considered in cases with an initially bulky disease and insufficient end-of-treatment response.