Wasithep Limvorapitak

Aims: Measurable residual disease (MRD) is a key prognostic marker for patient survival. This study evaluated concordance between 10‐color flow cytometry and next‐generation sequencing (NGS)–based immunoglobulin heavy chain (IGH) gene assays for MRD detection and to assess prognostic significance in adult B‐cell acute lymphoblastic leukemia (B‐ALL). Methods: This multicenter prospective study enrolled 51 patients with newly diagnosed B‐ALL. Bone marrow samples were obtained at diagnosis, post‐induction (1 month), and post–early consolidation (3 months). Flow cytometry and NGS‐IGH were performed at three timepoints to assess MRD B‐ALL. Results: Patients were classified as high risk according to white blood cell count and cytogenetic features in 37.3% and 64.7% of patients, respectively. Treatment protocols included pediatric‐inspired regimens (41.2%), adult‐ALL protocols (52.9%), and low‐intensity chemotherapy. All 16 Philadelphia chromosome–positive patients received tyrosine kinase inhibitors. Twenty patients underwent allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR). Median relapse‐free survival (RFS) and overall survival were 19 and 39 months, respectively. MRD negativity at 3 months by either method correlated with significantly superior RFS. Allogeneic HCT also conferred RFS benefit. MRD positive patients without HCT had the worst RFS. Flow cytometry MRD positivity at 3 months independently predicted inferior RFS (HR 3.81; 95% CI 1.01–14.43). The overall concordance between flow cytometry and NGS was 80.7%. Conclusion: MRD positivity at 3 months post‐treatment strongly predicted relapse, supporting its use to guide therapeutic modifications of B‐ALL. Apart from NGS‐based IGH clonality assays, 10‐color flow cytometry offers an alternative in resource‐limited settings.

Hypomethylating agents (HMAs) are the standard of care for higher‐risk myelodysplastic syndromes (MDSs); however, their accessibility remains limited. This retrospective multicenter cohort study aimed to evaluate the real‐world overall survival (OS) of HMAs compared to best‐available treatments (BATs) in newly diagnosed higher‐risk MDS in Thailand. Higher‐risk MDS was defined by a Revised International Prognostic Scoring System (IPSS‐R) score > 3.5. Data were extracted from the MDS registry of multicenter hospitals in Thailand from 2013 to 2023. Patients who underwent hematopoietic stem cell transplantation were excluded. A total of 155 patients were included, with a median age of 70 years and a male predominance. The median follow‐up time was 36 months. Of these, 86 patients (55.5%) received BATs, while 69 patients (44.5%) were treated with HMAs. HMAs were found to significantly improve OS compared to BATs (log‐rank test: p = 0.03), with a median OS of 15 months versus 6 months, respectively. Multivariable Cox regression analysis revealed that HMAs were associated with a decreased risk of death (hazard ratio: 0.58, 95% CI, 0.38–0.89, p = 0.01), while age and high‐ and very high‐risk IPSS‐R were identified as poor prognostic factors. This study underscores the real‐world effectiveness of HMAs for higher‐risk MDS in Thailand.

This study demonstrated the incidences of hospital-acquired colonization by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and vancomycin-resistant enterococci (VRE) of 22%, 8%, and 8% among hematologic malignancy patients. Difference in time to colonization detection between VRE (14 d) and ESBL-E and CRE (7 d) may inform appropriate surveillance measures.

Invasive aspergillosis (IA) is a common opportunistic infection in patients with acute myeloid leukemia (AML) and allogeneic stem cell transplant (SCT) recipients. Identifying at–risk patients may improve clinical outcomes when universal prophylactic therapy is not possible in a resource-limited setting. Aspergillus spp. colonization has been listed as a potential risk for infection development among patients with hematologic diseases, but this has not been explored in real-life clinical practice. To evaluate the correlation of Aspergillus spp. colonization and invasive aspergillosis development and to assess nasal wash galactomannan as a potential predictor for IA among AML patients and allogeneic SCT recipients. A prospective pilot study at four tertiary care hospitals in Thailand was conducted from April 2021 to January 2023. All AML individuals requiring induction chemotherapy and patients admitted for a conditioning regimen for allogeneic SCT were enrolled. Nasal wash fluid was obtained for galactomannan and fungal culture to assess Aspergillus spp. colonization before chemotherapy. The patient’s demographic and relevant data were retrieved. All patients were monitored for IA development and the need for antifungal use for IA treatment. 25 AML patients and nine allogeneic SCT recipients were included. A nasal wash fungal culture positive for Aspergillus spp. was identified in 3/34 patients. Eighteen (52.9%) patients were diagnosed with invasive aspergillosis after a six-month follow-up, 15/25 among AML patients, and 3/9 among allogeneic SCT. 8 patients (23.5%) had nasal wash galactomannan >0.46, and 5/8 patients had IA. The cut-off value of nasal wash fluid galactomannan of 0.46 provided a sensitivity of 55.56% and specificity of 78.57% in diagnosing IA in AML patients. The incidence of Aspergillus spp. colonization by the traditional culture-based method was low at treatment initiation and did not suggest future IA development in this study. However, nasal wash galactomannan may help predict future IA development in AML patients, but due to low sensitivity may limit its role in actual clinical practice at a larger scale. Further studies are needed to verify the best strategy to predict the risk of IA in this population. All Authors: No reported disclosures

Allogeneic hematopoietic stem cell transplant (aHSCT) patients are well known to be at high risk of vitamin D (vit D) deficiency. This study assessed whether a loading dose (100,000 IU) of vitamin D₃ pre-aHSCT could effectively achieve and maintain sufficient post-transplant vit D levels (serum total 25 hydroxy vitamin D (25(OH)D) ≥ 75nmol/L). Dual-energy X-ray absorptiometry (DXA) was also conducted for bone health evaluation. 74 patients were enrolled and randomly assigned, in a 1:1 ratio, either to the high vit D group (single loading dose (100,000 IU) plus 2,000 IU vit D₃ daily) or the control group (2,000 IU vit D₃ daily). Vit D levels were measured at three time points (baseline, day 30 and day 100 post-aHSCT). At baseline, fewer than 50% patients had a sufficient 25(OH)D (control: 42.9%; high vit D: 43.6%). The proportion of patients with sufficient 25(OH)D (nmol/L) was increased at day 30 and day 100, with a trend of higher proportion in the high vit D group at day 30 (high vit D vs. control: 89.7% vs. 74.3%, p = 0.08). The increased 25(OH)D was significantly higher in the high vit D group at day 30 (high vit D vs. control: 29±25.2 vs. 14 ±21.9, p = 0.01). Insufficient vit D level before transplant (baseline) was an independent risk factor for vit D insufficiency (serum 25(OH)D < 75nmol/L) post-aHSCT (OR = 4.16, p = 0.03). DXA suggested significant bone loss for total hip in both groups, and in the femoral neck for the control group only. In conclusion, single loading dose vitamin D₃ significantly increased total 25(OH)D levels at day 30 post-transplant, and the intervention was especially beneficial for patients with baseline vit D insufficiency. We acknowledge that the primary outcome at day 100 post-aHSCT indicating superiority of loading dose versus daily dose supplementation was not met.

Early detection of dengue virus infection will lead to proper management and reduction in morbidity/mortality. Monocyte distribution width (MDW) was recently approved for use in the early detection of sepsis. Because monocytes are involved in the innate immune system against viral infection, we sought to determine changes in MDW to develop and validate a new predictive score for dengue viral infection. This study included patients who presented with symptoms or signs related to dengue infection and who had a complete blood count and dengue investigation performed during September 2019 to May 2020. The proportion of dengue infection was 29.5% in the current study. The MDW was significantly higher in dengue infection (median, 29.7 versus 24.2; P < 0.001). We then randomly separated patients into training and validation cohorts. Independent predictive factors of dengue infection were white blood cells < 4 × 10⁹/L (score 1), platelets < 100 × 10⁹/L (score 1), and MDW > 24 (score 1). Clinical features were not significantly predictive of dengue infection. The areas under the receiver operating characteristic curve (95% CI) of the prognostic score were 0.839 (0.779–0.899) in the training cohort and 0.742 (0.674–0.811) in the validation cohort. With a cutoff score ≥ 1, the sensitivity and specificity of the scores were 92.2% and 40.8% in the training cohort and 88.9% and 44.1% in the validation cohort, respectively. We concluded that MDW increases with dengue infection and MDW could easily be incorporated in the predictive scores for dengue infection.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma. The standard first-line therapy for DLBCL consists of rituximab cyclophosphamide doxorubicin vincristine and prednisone (R-CHOP). About 50–70% of patients may be cured by R-CHOP. There was no data on external validation and comparison of the international prognostic index, revised-IPI (R-IPI), and enhanced-IPI (NCCN-IPI) to predict treatment outcomes in the middle-income country with a resourced-limited setting. We aimed to externally validate and compare IPI, R-IPI, and NCCN-IPI in predicting 2-year progression-free survival (2-y PFS) of newly diagnosed DLBCL patients treated with R-CHOP. This ambispective observational study recruited consecutive patients diagnosed between 1 January 2014 and 30 June 2020, with the last follow-up on 1 July 2022 from Thammasat University Hospital and Ramathibodi Hospital. We assessed discrimination by Harrell‘s concordance index (c-index), calibration by calibration plot, and absolute difference in survival (ADS) between the lowest-and the highest-risk groups. The cohort of 292 patients (median age 63 years and median follow-up 3.6 years) had 131 progressions and 96 deaths. The 2-y PFS was 63%. The c-indices were NCCN-IPI 0.6216, R-IPI 0.6004 (P = 0.215), and IPI 0.6104 (P = 0.463). The calibration plots of NCCN-IPI and R-IPI showed nearly perfect agreement (moderate strength), while IPI had miscalibrations. The ADSs were NCCN-IPI 52%, R-IPI 42%, and IPI 25%. NCCN-IPI is the best prognostic index compared to IPI and R-IPI in prior studies. However, the prognostic model for DLBCL patients treated with R-CHOP requires updating or integrating biomarkers to improve discrimination to the acceptable level (c-index 0.7).

The antibiotic stewardship program (ASP) is a necessary part of febrile neutropenia (FN) treatment. Pharmacist-driven ASP is one of the meaningful approaches to improve the appropriateness of antibiotic usage. Our study aimed to determine role of the pharmacist in ASPs for FN patients. We prospectively studied at Thammasat University Hospital between August 2019 and April 2020. Our primary outcome was to compare the appropriate use of target antibiotics between the pharmacist-driven ASP group and the control group. The results showed 90 FN events in 66 patients. The choice of an appropriate antibiotic was significantly higher in the pharmacist-driven ASP group than the control group (88.9% vs. 51.1%, p < 0.001). Furthermore, there was greater appropriateness of the dosage regimen chosen as empirical therapy in the pharmacist-driven ASP group than in the control group (97.8% vs. 88.7%, p = 0.049) and proper duration of target antibiotics in documentation therapy (91.1% vs. 75.6%, p = 0.039). The multivariate analysis showed a pharmacist-driven ASP and infectious diseases consultation had a favorable impact on 30-day infectious diseases-related mortality in chemotherapy-induced FN patients (OR 0.058, 95%CI:0.005–0.655, p = 0.021). Our study demonstrated that pharmacist-driven ASPs could be a great opportunity to improve antibiotic appropriateness in FN patients.