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.
23 April 2024 in Malaysian Journal of Medical Sciences
Background: Peripherally inserted central venous catheters (PICC) are widely used in patients with haematological malignancies owing to the requirement for prolonged intravenous therapy. However, the growing use of PICCs has resulted in a multitude of complications such as infections and thrombosis, leading to prolonged hospitalisation periods and increased morbidity. This study aimed to determine the incidence of and factors associated with PICC-related complications in patients with haematological malignancies. Methods: This prospective cohort study was conducted at a single academic institution. The inclusion criteria involved all adult patients with haematological malignancies who had newly inserted PICCs. The patients were observed for a minimum duration of 60 days to evaluate the incidence of PICC-related infections and thrombosis, as well as mechanical complications. Results: A total of 119 PICCs were implanted in 85 patients. Among them, more than half of the patients were diagnosed with lymphoma (55.0%). The median dwell time was 61 days (interquartile range: 98 days). The incidence of PICC-related complications was 58.0% (6.9 per 1,000 catheter-days). Specifically, 43 PICCs (36.1%, 4.3 per 1,000 catheter-days) experienced infective complications, 25 (21.1%, 2.5 per 1,000 catheter-days) encountered mechanical complications and 1 (0.8%, 0.1 per 1,000 catheter-days) exhibited thrombotic complications. Furthermore, an underlying diagnosis of acute leukaemia was significantly associated with a higher incidence of PICC-related infections. Conclusion: Our study revealed higher incidence rates of PICC-related complications in adult patients with haematological malignancies compared to the finding of other studies. Notably, patients with underlying acute leukaemia displayed a higher incidence of PICC-related infections. These findings underscore the importance of implementing appropriate interventions and conducting thorough root cause analyses to effectively mitigate this complication and improve patient outcomes.
Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells characterized by bone marrow infiltration and excessive production of monoclonal immunoglobulins, leading to end-organ damage such as osteolytic bone lesions. Despite substantial therapeutic progress achieved with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, multiple myeloma remains incurable, and outcomes for triple-class-refractory patients remain dismal, with median survival below one year. Bispecific T cell engaging antibodies (TCEs) have recently emerged as a promising immunotherapeutic approach capable of redirecting cytotoxic T cells to eliminate malignant plasma cells. These engineered antibodies simultaneously engage CD3 on T cells and a tumor-associated antigen such as B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D), or Fc receptor homolog 5 (FcRH5), thereby forming an immune synapse that triggers T cell activation, cytokine secretion, and perforin–granzyme-mediated apoptosis of the targeted B cell. This review summarizes the molecular design, mechanism of action, and clinical development of TCEs in MM, encompassing early bi-specific T cell engagers (BiTE) constructs such as AMG 420 and next-generation IgG-like molecules including teclistamab. Pivotal clinical trials have demonstrated overall response rates between 43% and 73%, accompanied by durable remissions and manageable safety profiles. Future directions include earlier-line integration, synergistic combinations with immunomodulatory or costimulatory agents, and the development of trispecific formats to overcome antigen escape and T cell exhaustion. Collectively, TCEs represent a paradigm shift toward durable, immune-mediated disease control in multiple myeloma.
1 February 2024 in Asian Pacific Journal of Cancer Prevention
Background: Multiple myeloma is the third most common hematologic malignancy in Malaysia. The introduction of novel agents over the past decades has improved patient outcome and survival substantially. However, these agents incur significant economic burden, thus leading to limited use in less developed countries. This study aims to report on the real-world treatment pattern and outcome of newly diagnosed multiple myeloma (NDMM) patients from a resource-constraint setting. Methods: This is a retrospective study on NDMM patients diagnosed between 1 January 2008 and 31 December 2022 in a single academic center. Patients’ demographic and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS). Results: One hundred and thirty-six NDMM patients with a median age of 64.0 years (ranged from 38 to 87 years old) were included. Bortezomib-containing regimens were the most commonly used induction agent, followed by thalidomide. Almost half of the patients (47.1%) achieved very good partial response (VGPR) or complete remission (CR), while 31.6% achieved partial response (PR). Bortezomib containing regimen was associated with significantly deeper and more rapid response, (p=0.001 and p=0.017, respectively) when compared to other agents. Only 22.8% of these patients proceeded to upfront autologous haematopoietic stem cell transplantation. The median OS and PFS were 60.0 months and 25.0 months, respectively. Best initial response and upfront autologous stem cell transplantation (ASCT) were significantly associated with better PFS. Conclusion: Achieving at least a VGPR significantly associated with better outcome in NDMM patients. In a resource constrain country, we recommend incorporating bortezomib in the induction therapy followed with an upfront ASCT.
1 March 2025 in Asian Pacific Journal of Cancer Prevention
Objective: This study aims to describe the incidence and risk factors of invasive fungal infection (IFI) among patients with haematological malignancies (HM) in a tertiary hospital from Malaysia. Methods: This was a cross-sectional study in a teaching hospital involving HM patients, admitted for chemotherapy or haematopoietic stem cell transplantation (HSCT). Each admission for either chemotherapy or HSCT was considered as a separate event. Patients were followed up for development of IFI from the time of each admission to time of discharge or time of death. Outcomes of patients with IFI upon discharge were recorded. Clinical and mycological data during each admission were collected and analysed. Results: Eighty-three patients with mean age of 58.8±15.5 years were recruited. Acute myeloid leukemia (AML) was the most common diagnosis (45.8%). A total of 132 admissions were analysed from these 83 patients. Antifungal prophylaxes were prescribed in 94.7% of admissions with fluconazole being the most common agent used (88.6%). The incidence of proven and probable IFI was 7.6%. Candida tropicalis was the most common fungi isolated from these patients (22.7%), followed by Candida krusei (13.6%). The mortality rate due to IFI was 17.6%. Patients with AML and those with concomitant bacteraemia were associated with higher risk of IFI (odds ratio [OR] 3.69, 95% confidence interval [CI] 1.16–11.71, p=0.029 and OR 4.17, 95% CI 1.37–12.66, p=0.009, respectively), while the use of antifungal prophylaxis was associated with lower IFI risk (OR 0.17, 95% CI 0.03–0.83, p=0.045). After multivariate analysis, the use of antifungal prophylaxis remains significantly associated with lower risk of IFI (OR 0.54, 95% CI 0.01–0.62, p=0.019). Conclusion: IFI remains one of serious complications of HM patients undergoing chemotherapy and HSCT, most commonly due to non-albicans Candida spp. Appropriate antifungal prophylaxis is therefore crucial in the prevention of breakthrough IFI.
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.