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Purpose Tyrosine kinase inhibitors (TKIs) have improved the prognosis of chronic myeloid leukaemia (CML), allowing patients with favourable disease profiles and molecular responses to attempt treatment-free remission (TFR). We aim to establish the relapse-free survival (RFS) outcomes and identify prognostic factors for successful remission maintenance among those who attempt TFR. Methods Adult CML patients who had undergone TFR from January 1, 2016, to June 30, 2024, were included. Upon TKI discontinuation, real-time quantitative polymerase chain reaction (RQ-PCR) was monitored monthly for the first 12 months, then every 3 months, with TKI reinitiated upon a transcript level above 0.1% (IS). Data analysis was performed using SPSS version 29.0 (SPSS Inc., Chicago, IL, USA). Results Fifty-seven patients (27 males and 30 females) with a median age of 46 years (range 16 – 70) were analysed. The majority had a low EUTOS long-term survival (ELTS) score (61.4%, n = 35) and received imatinib (87.7%, n = 50). The median treatment duration was 8.8 years (range 4.2 – 18.8), and the median duration for sustained deep molecular remission (DMR) was 4.6 years (range 2.1 – 11.1). RFS was 70.2% at 6 months, 62.5% at 12 months and 56.8% at 2 years after a median follow-up of 34 months (range 9 – 101). The MR5 level was identified as an independent factor associated with sustained remission. All relapsed patients achieved DMR upon treatment reinitiation. Conclusion Treatment discontinuation can be safely performed, with many achieving long-term treatment-free remission. A deeper molecular response (MR5) is associated with an improved likelihood of remission maintenance.

Background The acceptability and impact of mobile health (mHealth) applications on health outcomes in haemato-oncology remain unclear, particularly for patients undergoing long-term oral systematic anticancer therapy (SACT). Purpose This systematic review investigated the acceptability and efficacy of mHealth applications in facilitating self-management of oral SACT in patients with haematological malignancies. Methods We conducted a comprehensive search of five electronic databases, PubMed, PsycINFO, CINAHL, Cochrane Library, and Web of Science, until October 2024, and extracted data, including methodologies, application names, functionalities, and key results. This was followed by a narrative synthesis of quantitative outcomes, and a thematic analysis of qualitative data. Results Eight studies were included, comprising three qualitative studies, one randomised controlled trial, one non-randomised trial, and three mixed-method studies. mHealth applications for self-managing oral SACT exhibited acceptability, with usability and satisfaction ratings between 60% and 78%. Using the Normalisation Process Theory, four themes influencing acceptability were: (1) coherence – perceived benefits, (2) cognitive participation – barriers from technical issues, (3) collective action – burden from excessive notifications and inadequate support, and (4) reflexive monitoring – integration challenges in daily routine. Despite no major clinical or behavioural improvements, mHealth applications enhanced patient awareness of support, online health knowledge, and reduced daily life impact. Conclusion Fostering effective self-management of oral SACT in patients with haematological malignancies requires addressing issues such as application glitches, notification fatigue, and integration barriers to optimise these interventions. Future well-designed clinical trials are warranted to validate the impact of these applications on patient outcomes in cancer care.

Background: Immune thrombocytopenia (ITP) is well characterized in Western, European and other Asia-Pacific countries. Nevertheless, the clinical epidemiology, treatment pattern and disease outcome ofITP in Malaysia are still limited and not well known. Objective: This study aimed to describe the clinical epidemiology, treatment outcome and mortality of ITP patients in haematology tertiary multicentre in Malaysia. Methods: Clinical and laboratory data of newly diagnosed adults with ITP by a platelet count <100 * [10.sup.9]/L from January 2010 to December 2020 were identified and analyzed. Results: Out of 500 incident ITP, 71.8% were females with a striking age preponderance of both genders among those aged 18-29 years. The median age was 36 years. The median platelet count was 17.5 * [10.sup.9]/L, 23.0% had a secondary ITP, 34.6% had a Charlson's score [greater than or equal to] 1, 53.0% had bleeding symptoms including 2.2% intracranial bleedings (ICB). Helicobacter pylori screening was performed in <5% of cases. Persistency and chronicity rates were 13.6% and 41.8%, respectively. Most (80.6%) were treated at diagnosis onset and 31.2% needed second-line treatment. Throughout the course ofITP, 11.0% of patients died; 3.0% and 8.0% with bleeding and nonbleeding related ITP. Conclusion: This study confirms the epidemiology ofITP is comparable with worldwide studies. Our incidence is high in the female, Malay ethnicity, primary ITP and events of cutaneous bleeding at ITP onset with 18-29 years predominance age group for both genders. The frequency of persistent and chronic ITP is inconsistent with published literature. Corticosteroids and immunotherapies are the most prescribed first-line and second-line pharmacological treatments. Thrombopoietin receptor agonist medications (TPO-RAs) usage is restricted and splenectomy is uncommon. Our mortality rate is similar but ITP related bleeding death is fourth-fold lower than previous studies. Mortality risks of our ITP patients include age >60 years, male, severe bleeding at presentation, CCI>1 and secondary ITP. Keywords: epidemiology, immune thrombocytopenia, mortality, treatment outcome

Abstract The incidence of invasive fungal infection (IFI) is increasing, especially among patients diagnosed with hematological malignancies due to their immunocompromised nature. Other risk factors include advanced age, exposure to immunosuppressants, neutropenia, and catheter use. Some of the most common IFI organisms reported are Candida and Aspergillus species, and other fungal species, including Scedosporium, Trichosporon, Cryptococcus, and Fusarium have also increasingly been reported in the past years. However, the epidemiologic data on IFI among patients with hematological malignancies in Asian countries are lacking. Therefore, we investigated published epidemiologic data on such cases from the past 10 years (2011–2021) and discuss the challenges faced in the diagnosis and management of IFIs in Asia.

Multiple myeloma (MM) is characterized by the malignant proliferation of plasma cells within the bone marrow. The transcriptional mechanisms governing plasma cell differentiation and MM pathogenesis are regulated by an intricate network of transcription factors, the role of RUNX1 in this process remains poorly defined. This study aimed to characterize plasma cell subsets in MM and evaluate the expression and functional role of RUNX1 during B cell differentiation. Bone marrow and peripheral blood samples were collected from 61 MM patients and 18 healthy donors. Flow cytometry was used to identify B cell and plasma cell subsets and measure RUNX1 expression across B cell maturation stages. Functional validation was conducted via siRNA-mediated RUNX1 knockdown in CD19 + B cells followed by in vitro plasma cell differentiation assays. Our data showed that MM patients exhibited significantly increased proportions of plasma cells in bone marrow compared to healthy controls. Intriguingly, RUNX1 expression was low in naive B cell subsets but increased progressively through plasmablast, pre-plasma, and plasma stages. Although RUNX1 expression did not significantly differ across MM stages or between newly diagnosed and relapsed/refractory cases, plasmablasts from MM patients showed higher RUNX1 levels than those from controls. Knockdown of RUNX1 in vitro using siRNA delayed B cell differentiation transiently. In summary, RUNX1 expression is dynamically upregulated during terminal B cell differentiation and is elevated in MM-derived plasmablasts. These findings provide new insights into a potential role for RUNX1 in the B cell differentiation axis and MM disease progression.

Background Prognostication of myeloproliferative neoplasm (MPN) has always been challenging, even with the advent of Janus kinase 2 (JAK2 V617F) molecular studies. The survival pattern of patients diagnosed with MPN in developing countries is still undetermined. Materials and methods The national MPN registry conducted from 2009 to 2015 in Malaysia provided a comprehensive insight into the demographics, clinical characteristics and laboratory parameters of patients diagnosed with MPN nationwide. The study analysed the survival patterns and mortality outcomes and risk among 671 patients diagnosed with essential thrombocythaemia (ET), polycythaemia vera (PV), primary myelofibrosis (PMF) and unclassified MPN (MPN-U). Mortality status was traced and confirmed until the end of December 2018, with right censoring applied to patients alive beyond that. Results The analysed cohort consisted of 283 (42.2%) ET, 269 (40.1%) PV, 62 (9.2%) PMF and 57 (8.5%) MPN-U incident cases with diagnosis made between 2007 and 2015. The majority of patients were male (52.3%) and Malay (48.9%), except for ET, in which the majority of patients were female (60.1%) and of Chinese origin (47.0%). Female patients were found to have significantly better overall survival (OS) rates in ET ( p  = 0.0285) and MPN-U ( p  = 0.0070). Patients with JAK2 V617F mutation were found to have marginally inferior OS over time. Multivariable Cox regression identified patients with increased age [hazard ratio (HR) 1.055, 95% CI 1.031; 1.064], reduced haemoglobin (HB) level (HR 0.886, 95% CI 0.831; 0.945, p  = 0.0002), being male (HR 1.545, 95% CI 1.077; 2.217, p  = 0.0182), and having MPN-U (HR 2.383, 95% CI 1.261; 4.503, p  = 0.0075) and PMF (HR 1.975, 95% CI 1.054; 3.701, p  = 0.0335) at increased risk for worse mortality outcomes. Conclusion Myeloproliferative neoplasm reduces patient survival. The degree of impact on survival varies according to sub-type, sex, bone marrow fibrosis and HB levels. The JAK2 V617F mutation was not found to affect the survival pattern or mortality outcome significantly.

The CD34+ hematopoietic cell count was used to define cell harvest goals. Successful peripheral blood stem cell transplantation depends on infusion of an appropriate number of HPCs to achieve rapid and durable hematologic recovery. In this study, we evaluated the use of the Hematopoietic Progenitor Cell count program on the Sysmex XN-3000 hematology analyzer as an effective parameter for enumerating CD34+ cells. Whole blood samples from 144 subjects who are either healthy donors or patients scheduled to undergo peripheral blood stem cell collection were collected and hemopoietic stem cells were quantified using CD34 cell enumeration by flow cytometry and XN-HPC by hematology analyzer. The correlation between the two methods was high (r = 0.766; 95% CI: 0.702-0.818). Passing-Bablok showed an intercept at 3.45 (2.54 to 4.74) with a slope of 0.78 (95% CI 0.69 to 0.89). Residual analysis of this model indicated no significant deviation from linearity (p = 0.360). The receiver operating characteristic curve demonstrated an area under curve to be 0.88 (0.82 to 0.92), with a positive predictive value of 80.3%. The correlation between CD34+ and XN-HPC showed a strong relationship and good agreement with minimal bias. The XN-HPC showed good analytical performance. With the increasing requirements for stem cell transplantation, a technically simple and rapid alternative for stem cell enumeration that is sustainable is highly useful.

Abstract Hepatosplenic T-cell lymphoma is a rare form of T-cell lymphoma that predominantly emerges from neoplastic proliferation of cytotoxic T cells of γ/δ T-cell receptor-expressing lymphocytes. Isochromosome 7q and trisomy 8 are the most prevalent chromosomal abnormalities associated with hepatosplenic T-cell lymphoma, and most patients have mutations in genes related to chromatin remodeling or the JAK/STAT system. Hepatosplenic T-cell lymphoma can mimic various infectious diseases, immunological conditions, and other malignancies. Patients usually present with nonspecific constitutional symptoms and spleen and liver enlargement, with variable degrees of cytopenia. The rarity of this disease, coupled with the lack of lymph node involvement that is usually seen in lymphomas, causes significant difficulty in diagnosis, which inevitably delays the initiation of treatment. Managing this lymphoma is arduous because of its late presentation and aggressive nature, frequently resulting in rapid progression in its clinical course and refractoriness to conventional chemotherapy. There is a lack of international guidelines for its treatment, and in most cases, treatment is guided by case series. Here, we highlight the clinicopathological features and management of hepatosplenic T-cell lymphoma over a 10-year span in a single hematology referral center and review the literature.

A major challenge after allogeneic haematopoietic stem cell transplantation for haematologic malignancies is the management of acute graft-versus-host disease (aGVHD), which remains associated with poor prognosis despite therapeutic advancements. We conducted a randomized, double-blinded, placebo-controlled Phase I/II clinical trial to assess the safety and efficacy of umbilical cord-derived mesenchymal stem cells (Cyto-MSC) as an upfront treatment in patients with grade II-IV aGVHD.BackgroundA major challenge after allogeneic haematopoietic stem cell transplantation for haematologic malignancies is the management of acute graft-versus-host disease (aGVHD), which remains associated with poor prognosis despite therapeutic advancements. We conducted a randomized, double-blinded, placebo-controlled Phase I/II clinical trial to assess the safety and efficacy of umbilical cord-derived mesenchymal stem cells (Cyto-MSC) as an upfront treatment in patients with grade II-IV aGVHD.In this multicentre trial, 22 grade II-IV aGVHD patients were randomized to receive up to three infusions of Cyto-MSC (n = 14) or placebo (n = 8), alongside standard corticosteroid therapy. The primary endpoints were overall response (OR) at Day 28 and overall survival (OS) at 12 months. The secondary endpoints included correlation between responses at Day 28 with 12-month OS and exploratory analyses of immune cell subsets.MethodsIn this multicentre trial, 22 grade II-IV aGVHD patients were randomized to receive up to three infusions of Cyto-MSC (n = 14) or placebo (n = 8), alongside standard corticosteroid therapy. The primary endpoints were overall response (OR) at Day 28 and overall survival (OS) at 12 months. The secondary endpoints included correlation between responses at Day 28 with 12-month OS and exploratory analyses of immune cell subsets.No treatment-related adverse events were observed. There were no significant differences between Cyto-MSC and placebo in the OR at Day 28 and 12-month OS. Among patients with severe grade III-IV aGVHD who achieved OR by Day 28, those treated with Cyto-MSC had significantly improved 12-month OS compared to placebo (100% vs 50%, p=0.039). Furthermore, in patients with severe aGVHD and baseline CD4+ TEMRA >35% or CD8+ TEMRA >70%, the survival benefit was pronounced in the Cyto-MSC group (83.3% and 100%, respectively). In contrast, none of the placebo-treated patients with baseline CD4+ TEMRA <35% (p=0.007) or CD8+ TEMRA <70% (p=0.005) survived at 12 months. OS was significantly associated with OR at Day 28 (p<0.001), baseline CD4⁺ TEMRA (p=0.004), and baseline CD8⁺ TEMRA (p=0.004).ResultsNo treatment-related adverse events were observed. There were no significant differences between Cyto-MSC and placebo in the OR at Day 28 and 12-month OS. Among patients with severe grade III-IV aGVHD who achieved OR by Day 28, those treated with Cyto-MSC had significantly improved 12-month OS compared to placebo (100% vs 50%, p=0.039). Furthermore, in patients with severe aGVHD and baseline CD4+ TEMRA >35% or CD8+ TEMRA >70%, the survival benefit was pronounced in the Cyto-MSC group (83.3% and 100%, respectively). In contrast, none of the placebo-treated patients with baseline CD4+ TEMRA <35% (p=0.007) or CD8+ TEMRA <70% (p=0.005) survived at 12 months. OS was significantly associated with OR at Day 28 (p<0.001), baseline CD4⁺ TEMRA (p=0.004), and baseline CD8⁺ TEMRA (p=0.004).Patients with severe grade III-IV aGVHD, particularly those who respond early or have elevated baseline CD4+ TEMRA (>35%) or CD8+ TEMRA (>70%) levels, may have an overall survival advantage when treated with Cyto-MSC as an upfront therapy in combination with standard corticosteroids.ConclusionPatients with severe grade III-IV aGVHD, particularly those who respond early or have elevated baseline CD4+ TEMRA (>35%) or CD8+ TEMRA (>70%) levels, may have an overall survival advantage when treated with Cyto-MSC as an upfront therapy in combination with standard corticosteroids.