Therapeutic Advances in Hematology最新文献

Aplastic anemia is a bone marrow failure disorder marked by cytopenias that impair oxygen delivery, immune defense, and hemostasis. Standard therapy traditionally combines immunosuppression with or without hematopoietic stem cell transplantation, and more recently incorporates thrombopoietin receptor agonists to stimulate residual hematopoiesis. Eltrombopag improved outcomes when added to immunosuppressive therapy, but its association with hepatotoxicity limits its suitability for patients with underlying liver disease or elevated baseline liver enzymes. Avatrombopag is a newer oral thrombopoietin receptor agonist that does not require dietary restrictions and does not undergo significant hepatic metabolism, which offers a potential therapeutic advantage in settings where liver function is compromised. This review evaluated ten clinical studies published from 2023 to October 2025 that investigated avatrombopag in acquired aplastic anemia across varied patient populations, including treatment-naive, relapsed or refractory cases, older adults, and patients with secondary aplastic anemia related to chemoradiation. Across these studies, overall response rates ranged from 55% to 85%, and complete response rates reached up to one-third of treated patients. Response onset typically occurred within 1-2 months, which aligns with clinical decision timelines for assessing therapeutic benefit. Avatrombopag supported reductions in transfusion requirements and sustained hematologic improvement in both severe and non-severe disease. Patients previously intolerant or non-responsive to eltrombopag also demonstrated clinical improvement, which suggests pharmacologic differences translate into meaningful therapeutic effects. Importantly, avatrombopag demonstrated a favorable safety profile in all reviewed settings. Reports did not identify clinically relevant hepatotoxicity, clonal evolution, or treatment-limiting adverse effects. Its tolerability in patients with liver dysfunction distinguishes it from earlier agents in this drug class. Ongoing trials will clarify optimal dosing strategies and define its future role within first-line therapy and salvage treatment pathways for aplastic anemia.

Mycosis fungoides (MF) and Sézary syndrome are primary cutaneous T-cell lymphomas with widely varying courses of disease and prognosis. Here, we report the case of a patient with MF with blood involvement who experienced many lines of skin-directed and systemic therapies throughout their disease course. The male patient presented with scaly, itchy, and painful patches on his trunk and upper extremities in 2012 and was diagnosed with MF, which progressed to erythroderma with blood involvement. Various skin-directed therapies were prescribed; however, in 2014, progression of skin lesions ensued. The patient achieved a partial response with methotrexate but discontinued after ~12 months due to elevated transaminases. Following treatment with bexarotene then gemcitabine, CHOP chemotherapy was initiated in December 2019, but, after a period of partial skin response, the patient relapsed with progression of skin lesions. Mogamulizumab was initiated in May 2020 (1 mg/kg intravenously on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of subsequent cycles) with a good initial response in skin and blood. Disease progression in the skin occurred in December 2020; mogamulizumab was continued, and the patient achieved remission with the addition of etoposide and prednisone in August 2021. Onset of progression occurred in July 2022, which did not respond to repeat combination treatment. In October 2022, the patient was diagnosed with large cell CD30⁺ transformation, and the therapeutic approach was changed to extracorporeal photopheresis, brentuximab vedotin, and topical steroids. The patient died in February 2023 due to sepsis. Our experience adds to the limited evidence that mogamulizumab may be continued in combination with etoposide following disease progression in patients with MF with blood involvement; however, more research is needed on the efficacy and safety of this approach.

Background: Ibrutinib is the only Bruton tyrosine kinase inhibitor (BTKi) with once-daily oral capsule, tablet, and oral suspension formulations approved in the United States across indications of chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, and previously treated chronic graft-versus-host disease, and for mantle cell lymphoma in Europe. Patients with difficulty swallowing capsules or tablets may require alternative formulations or administration options to optimize treatment.

Objectives: To evaluate the relative bioavailability of ibrutinib oral suspension relative to capsule or tablet formulations and to examine compatibility for optimal administration methods.

Methods: Relative bioavailability of ibrutinib oral suspension was evaluated in healthy volunteers or patients in comparison to capsule or tablet formulations. Dose recovery and delivery, presence of impurities, particle size, and hold time were evaluated after in vitro mock oral suspension administration via syringe and nasogastric and percutaneous endoscopic gastrostomy (PEG) tubes.

Results: Clinical bioavailability was comparable for ibrutinib oral suspension and capsules (420 mg/day) under the fasted state in healthy volunteers. Dose-normalized pharmacokinetic values were similar across ibrutinib formulations in patient studies. All evaluated enteral tubes achieved 90%-110% ibrutinib dose recovery regardless of tube type or syringe after 2 × 3 mL water rinses. Oral suspension preservative may be adsorbed into enteral tubes after a 60-minute hold time.

Conclusion: Ibrutinib oral suspension bioavailability was comparable with ibrutinib tablet and capsule formulations. When dosed via standard enteral tube administration methods, ibrutinib oral suspension is stable and compatible with polyurethane, silicone, or polyvinyl nasogastric or PEG tubes. To ensure full dose recovery and prevent drug preservative adsorption into tubes, ibrutinib oral suspension should be administered immediately and followed by two rinses of 3 mL of water each. Ibrutinib oral suspension is a viable BTKi treatment option for patients requiring or preferring alternatives to oral capsules and tablets.

Background: Chimeric antigen receptor T-cell therapy represents a revolutionary advancement in personalized treatment for diffuse large B-cell lymphoma (DLBCL). However, data regarding the use of tisagenlecleucel (tisa-cel) outside of clinical trials remain scarce, especially in East Asia. Therefore, we conducted this study to provide insights into the logistics, efficacy, and safety profile of tisa-cel treatment in Korea.

Methods: Clinical data were collected from 46 patients with DLBCL who underwent leukapheresis for commercial tisa-cel manufacturing at Seoul National University Hospital between January 2022 and December 2023. Response evaluations were conducted at 1, 3, 6, and 12 months after tisa-cel infusion.

Results: Overall, 44 patients received tisa-cel infusion. The median time from tisa-cel order placement to product delivery and subsequent infusion was 28 days (range, 24-84) and 42 days (range, 29-118), respectively. The overall response rate was 70.5%, with a complete response rate of 47.7%. Patients who achieved an overall response at 3 months post-infusion had longer overall survival (median, not reached vs 2.6 months, p < 0.001) and progression-free survival (median, 13.0 months vs 1.4 months, p < 0.001) compared to those who did not. Additionally, an elevated baseline LDH was associated with poor survival. Cytokine release syndrome was observed in 70.5% of the patients (grade ⩾3, 4.5%), while immune effector cell-associated neurotoxicity syndrome occurred in 15.9%.

Conclusion: To the best of our knowledge, this study presents the first real-world data on tisa-cel outcomes in Korean patients with DLBCL. Commercial tisa-cel is a feasible treatment option for patients with DLBCL in real-world settings.

Several clinical trials with anti-CD20 antibodies have successfully treated Acute Lymphoblastic Leukemia. Nevertheless, systematic comparisons between different anti-CD20 antibody trials are rare, and a comprehensive evaluation of their efficacy and safety has yet to be performed. The purpose of this systematic review and meta-analysis was to assess the efficacy and safety of anti-CD20 antibodies in the treatment of acute lymphoblastic leukemia and to guide clinical decision-making regarding the use of anti-CD20 antibody therapy. According to the PRISMA guidelines, Embase, Cochrane Library, PubMed, Web of Science, and ClinicalTrials.gov were searched for clinical trials conducted up to November 1, 2024, for the evaluation of anti-CD20 antibodies (rituximab, obinutuzumab, and ofatumumab) and corresponding controls. After screening the literature and extracting data, study quality was assessed using the Cochrane ROB 2 tool (RCTs) and the Newcastle-Ottawa Scale (cohorts). Heterogeneity was assessed using the I² test. Based on the results of the heterogeneity test, meta-analysis was performed in RevMan 5.4 software with either a random-effects model or a fixed-effects model. We combined data from eight studies (n = 1330 patients, including two RCTs and six cohorts). Meta-analysis showed that anti-CD20 monoclonal antibodies significantly improved overall survival (OR = 1.89, 95% CI: 1.21-2.95, p = 0.005) and event-free survival [OR = 1.68, 95% CI: 1.32-2.14, p < 0.0001] after >1-year follow-up, and increased complete remission rates (p < 0.05). No significant differences were observed in common adverse events between groups. Subgroup analyses by study type did not alter these conclusions. Overall, anti-CD20 antibody therapy was more efficacious than the corresponding control and did not increase the incidence of grade 3-4 adverse events. Ofatumumab may be a more effective anti-CD20 antibody for the treatment of ALL.

Background: Adults with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have dismal prognoses, underscoring the need for effective salvage therapies. Inotuzumab ozogamicin (INO) and blinatumomab (BLIN) have demonstrated efficacy in achieving complete remission (CR) and measurable residual disease (MRD) response.

Objectives: We tried to evaluate the clinical outcomes and toxicities of INO in adults with R/R BCP-ALL.

Design: Prospective observational multicenter study.

Methods: A total of 100 patients (25 Ph-positive, 75 Ph-negative) received INO (0.8 mg/m² on week 1; 0.5 mg/m² on weeks 2-3) for the initial cycle, followed by 0.5 mg/m² dosing in subsequent cycles. Allogeneic hematopoietic cell transplantation (allo-HCT) was planned after remission.

Results: Among the cohort, 7 patients were primary refractory (4 post-BLIN), 36 relapsed after chemotherapy (23 post-BLIN), and 57 relapsed after allo-HCT (23 post-BLIN). Extramedullary relapse occurred in 39% of patients. After the first cycle, 60% achieved CR or CR with incomplete hematologic recovery; the overall best response rate after two cycles was 67%, with MRD negativity achieved in 63.1%. Thirty-nine patients (58.2%) underwent allo-HCT. Early mortality occurred in 12%, and hepatic veno-occlusive disease/sinusoidal obstruction syndrome was observed in 10%. With a median follow-up of 31.5 months, the 3-year overall survival was 21.3% in the entire cohort and 37.6% among transplanted patients.

Conclusion: INO represents a potent salvage option for R/R BCP-ALL. However, substantial toxicities highlight the critical need for careful patient selection and dose optimization strategies to maximize its therapeutic benefit.

Trial registration: This study was registered in Clinical Research Information Service (CRIS #KCT0010009) which is connected to WHO ICTRP (Operated by Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare, Republic of Korea).

Background: Outcomes for primary central nervous system lymphoma (PCNSL) have been improved with high-dose methotrexate (HD-MTX)/Thiotepa-based chemotherapy followed by autologous stem cell transplantation. In limited-resource settings, HD-MTX/Ifosfamide plus whole brain radiotherapy (WBRT) has become the local standard of care.

Objectives: This study investigated the real-world effectiveness, neurocognitive functions, and health-related quality of life (HRQoL) of HD-MTX/Ifosfamide in newly diagnosed PCNSL patients.

Design: A single-center retrospective and prospective study.

Methods: Newly diagnosed PCNSL patients treated with HD-MTX (±Ifosfamide) between 2011 and 2024 were analyzed for treatment effectiveness using binary logistic regression and a Cox regression model. The age range- and education-matched PCNSL and non-central nervous system (CNS) lymphoma patients in first remission were assessed using standardized cognitive tests and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/BN20 questionnaires. The categorical data and continuous data were calculated with the Chi-square test or Fisher's exact test and analysis of variance, respectively.

Results: Among 94 PCNSL patients, 56 patients received HD-MTX/Ifosfamide (median age 56 (range 16-69) years; 68% Eastern Cooperative Oncology Group (ECOG) 0-1) and 38 patients received HD-MTX monotherapy (median age 66 (range 51-82) years; 63% ECOG ⩾2). HD-MTX/Ifosfamide demonstrated a significantly longer event-free survival (39 months vs 8 months, p = 0.021) than HD-MTX monotherapy. Poor performance status (ECOG ⩾2) was associated with inferior response (54.8% vs 78.8%, p = 0.013) and overall survival (hazard ratio 2.4 (95% confidence interval 1.57-4.56), p = 0.007). Patients who received WBRT consolidation had a superior 2-year progression-free survival (74.5% vs 35.6%, p < 0.001). Comparing neurocognitive tests in 20 PCNSL and 20 non-CNS lymphoma survivors showed no difference in overall scores, but trends toward lower attention and executive function scores in the PCNSL group. Most (16/20) PCNSL survivors received WBRT. Compared to non-CNS lymphoma survivors, PCNSL survivors reported significantly lower HRQoL, particularly in physical functioning, which might be attributed to residual neurological deficits.

Conclusion: This study supports HD-MTX/Ifosfamide as an effective, well-tolerated regimen for younger, fit PCNSL patients. WBRT remains a valuable consolidation therapy to prevent recurrence without a pronounced decline in cognitive function. However, PCNSL survivors may experience subtle declines in attention, executive function, and HRQoL.

Background: FIBTEM, a rotational thromboelastometry (ROTEM) component, assesses fibrin-based clot firmness and indirectly measures fibrinogen function. It offers faster turnaround time compared to the Clauss method for fibrinogen quantification, which may support early coagulation assessment in critically ill patients with sepsis.

Objectives: Our study aims to evaluate the correlation between FIBTEM parameters and fibrinogen levels and predict the possibility of hyperfibrinogenemia using FIBTEM parameters in patients with sepsis.

Design: A retrospective secondary analysis of a prospective observational study.

Methods: Patients diagnosed with sepsis were recruited and admitted to the University Medical Center Ho Chi Minh City intensive care unit from June 2020 to December 2021. The international normalized ratio, activated partial thromboplastin time, platelet counts, fibrinogen levels, and FIBTEM parameters (A5, A10, A20, and maximum clot firmness (MCF)) were assessed for each patient. The correlations among laboratory parameters were assessed using the Pearson's correlation coefficient. Predicted values of fibrinogen and FIBTEM were analyzed using simple linear regression, Bland-Altman plots, and Lin's concordance correlation coefficient (CCC). The area under the receiver operating characteristic curve (AUC) and Kappa coefficients were calculated.

Results: The median age of 159 patients with sepsis was 69. Males represented 51.6% of the participants. The percentage of patients with comorbidities was 88.1%. The mean plasma fibrinogen level was 5.4 ± 1.8 g/L. Fibrinogen levels were strongly correlated with FIBTEM parameters (p < 0.01 for all values), including A5 (r = 0.701), A10 (r = 0.717), A20 (r = 0.723), and MCF (r = 0.735). MCF could not predict exact fibrinogen levels (CCC = 0.703). The AUC of the MCF to predict hyperfibrinogenemia was 0.905 (95% CI: 0.866-0.945), with a sensitivity of 85.5%, a specificity of 83.1%, and a Kappa coefficient of 0.69 at the optimal cut-off value of 22.5 mm.

Conclusion: FIBTEM MCF could be a practical, rapid, surrogate tool for detecting hyperfibrinogenemia in sepsis and may help guide early clinical decisions before fibrinogen test results are available, although further validation in larger studies is required.

Background: Acquired aplastic anemia (AA) is rare bone marrow failure syndrome characterized by pancytopenia due to immune-mediated destruction of hematopoietic stem and progenitor cells, and leads to an increased risk of bleeding and infectious complications. The first-line treatment option for individuals with severe AA who are ineligible for allogeneic hematopoietic stem cell transplantation is triple therapy, comprised equine anti-thymocyte globulin, calcineurin inhibitor (CNI), and eltrombopag (EPAG). However, this approach is associated with considerable treatment-related complications, requires close inpatient monitoring as well as specialized care and expertise, limiting its feasibility in less-experienced centers. Emerging evidence suggests that double therapy with CNI and EPAG combination reduces the transfusion burden in severe AA.

Objective: Evaluate the real-world effectiveness of CNI and EPAG combination therapy in reducing transfusion burden among adults with AA.

Methods: We conducted a retrospective cohort study using Blue Cross Blue Shield Axis Database to examine the change in transfusion requirements in adult patients with newly diagnosed AA who have received combination therapy with CNI and EPAG. Individuals were stratified into baseline transfusion-independent, low, and high transfusion subgroups. Transfusion requirements were reassessed after 6 months from initiation of double therapy.

Results: The majority of the 153 identified patients with AA started therapy shortly after diagnosis and were adherent to treatment and monitoring during the initial 6 months. Among patients with baseline transfusion requirements (97; 63.4%), 66% achieved TI status. Additionally, 75.5% of patients with a high baseline transfusion burden demonstrated a ⩾50% reduction in transfusion requirements.

Conclusion: These findings underscore the efficacy and feasibility of double therapy with CNI and EPAG for adults with AA in the real-world setting, offering an alternative for patients when triple therapy is not possible.

Background: Patients with transfusion-dependent thalassemia frequently experience significant psychological distress, with high rates of anxiety and depression reported. Despite this, the psychological status of thalassemia patients after hematopoietic stem cell transplantation (HSCT) remains less explored. Gaining insights into the symptoms of depression and anxiety in this population is crucial, as it can inform tailored support and improve quality of life.

Objectives: This study aimed to assess the prevalence of anxiety and depression in post-HSCT thalassemia patients and to identify potential risk factors.

Design: This was a cross-sectional study.

Methods: A cross-sectional study involved 170 transfusion-dependent thalassemia patients who underwent HSCT from January 2017 to November 2022. The Hospital Anxiety and Depression Scale (HADS), a self-report questionnaire, was used to evaluate the levels of anxiety and depression.

Results: The prevalence of anxiety and depression was 11.2% and 8.8%, respectively. Patients with a history of splenectomy and those with chronic graft-versus-host disease (cGVHD) exhibited significantly higher HADS scores (p < 0.01). Correlation analysis revealed positive associations between these variables and HADS scores, with correlation coefficients of 0.256 for splenectomy with HADS-Anxiety (HADS-A) and 0.227 with HADS-Depression (HADS-D) scores. For cGVHD, the correlation coefficients were 0.290 with HADS-A and 0.388 with HADS-D scores.

Conclusion: The study revealed the psychological burden faced by post-transplant thalassemia patients, particularly those with a history of splenectomy and cGVHD. These findings underscore the need for targeted psychological support and interventions for this vulnerable patient group.