Indian Journal of Hematology and Blood Transfusion最新文献

Unlike second-generation tyrosine kinase inhibitors, effects of imatinib on the cardiovascular (CV) system are debatable. The current case–control study aimed to evaluate the CV effects of imatinib in patients with chronic myeloid leukemia (CML) using non-invasive 2D-echocardiography testing. Patients with CML ≥ 13 years attending the adult haematology clinic of a tertiary care hospital in north India were prospectively enrolled over 1.5 years. The study population (n = 110) consisted of 35 newly diagnosed patients (treatment-naïve group) and 75 patients under imatinib therapy ≥ 1 year (treated group). All the eligible patients were subjected to 2D-echocardiography to calculate pulmonary artery systolic pressure (PASP), left ventricular ejection fraction (LVEF) and deceleration time (DT). These parameters were compared between the two groups. P-value < 0.05 was considered statistically significant. The median age of study population was 40 years (range, 13–73) and M:F ratio was 1.14:1. Both the groups had similar demographics at the diagnosis including CV risk factors. The median PASP of the treated group was 2 mm Hg higher than the treatment-naïve group (25 vs 23 mm Hg, p-value = 0.919). The median LVEF of the treated group was 3.2% lower than the treatment-naïve group (58.5% vs 61.72%, p-value = 0.577). The median DT of the treated group was 7 ms shorter than treatment-naïve group (211 vs 204 ms, p-value = 0.411). Imatinib causes potential cardiac dysfunction in patients with CML. Large scale prospective follow-up trials in the same cohort of patients are needed to validate the findings of our study.

Introduction

The discard rate of blood services as a crucial quality metric for monitoring and enhancing blood safety within blood bank operations. This study investigated the prevalence and underlying causes of discarded blood and its associated components at a blood center in China.

Materials and Methods

This retrospective analysis examined data pertaining to discarded blood and its components from 2019 to 2022. Information was retrieved from the blood center's electronic blood information management system.

Results

A total of 71,346 units of whole blood and blood components (representing a discard rate of 2.34%) were discarded. The discard rates exhibited variation across different blood components: whole blood (0.15%), red blood cells (2.24%), fresh frozen plasma (4.20%), frozen plasma (5.05%), cryoprecipitate antihemophilic factor (0.91%), platelets (0.33%), and washed red blood cells (0.03%). Statistical analysis revealed a significant association (P < 0.05) between the reasons for discarding blood and the actual discard events.

Conclusion

This study presents a comparative analysis of discard rates and their corresponding justifications within a single blood center in China. The findings contribute to the advancement of quality control measures for blood and its components within blood service operations.

The optimal way of oral iron replacement for iron deficiency anaemia(IDA) is still unknown and few recent studies have reported better fractional absorption and tolerability of intermittently administered iron. This randomised, active comparator controlled, open-label trial evaluated efficacy and tolerability of 120 mg elemental iron (2 × 200 mg ferrous sulphate tablets) administered as a single dose on alternate days (alternate-day arm, ADA) vis-à-vis 60 mg elemental iron (single FeSO₄ tablet) administered daily (daily arm, DA), among women (age ≥ 18 years) having IDA, with haemoglobin (Hb) concentration between 6 and 10 g/dL and serum ferritin < 30 µg/L. Primary outcome was the Hb change on Day-28. Secondary outcomes included Hb change on Day-56, change in serum hepcidin levels from baseline to Day-14, adverse effects (AEs) and compliance to treatment. Sixty-eight participants (34 each in DA and ADA) were enrolled in the trial. Hb change at Day-28 was significantly higher in the ADA compared to DA (mean change: +2.2 ± 1.3 vs. +1.3 ± 1.1 g/dL, p = 0.003). Though Hb increment at Day-56 was also higher in ADA, it was not statistically significant. There was no significant difference in changes in serum hepcidin from baseline to Day-14 between the arms. Significantly higher proportion in the DA had AEs compared to ADA (45% vs. 9%, p < 0.005). However, treatment compliance was not significantly different between the arms. Alternate-day oral iron replacement led to significantly higher haemoglobin increment in the short run and caused significantly lesser AEs compared to daily replacement. Larger multicentric RCTs with longer duration of intervention should evaluate alternate-day replacement vis-à-vis daily therapy in future. This randomised controlled trial has been registered in Clinical Trial Registry-India (CTRI Reg. No.: CTRI/2021/12/038370, dated 2nd December 2021).

Among inherited bleeding disorders, von Willebrand disease (VWD) is the most common disease worldwide. Type 3, the most severe form, is more prevalent in developing countries primarily due to consanguineous marriages. The enormous size of the von Willebrand factor gene, different kinds of mutations, and a partial unprocessed pseudogene make variation detection more difficult. To distinguish the VWF gene and the pseudogene sequence and prevent pseudogene amplification, it is necessary to utilize a suitable method. In this study, 42 unrelated VWD type 3 patients and 22 normal controls were included. Tetra-primer ARMS-PCR was applied for genotyping the single nucleotide variation, R1336X located on exon 28, which overlaps the pseudogene. The High percentage of heterozygotes (17% in VWD patients and 13% in controls) raised the suspicion of concomitant amplification of the VWF gene and it's pseudogene due to similarity in their primer-binding site sequence. To overcome this issue, we applied a two-step method using touch-down PCR followed by a tetra-primer ARMS-PCR. All cases with the heterozygous pattern on the first tetra-primer ARMS PCR were found to be normal homozygotes. In type 3 VWD patients genotyping is essential in decreasing the incidence of the disease, but the presence of a pseudogene with 97% homology makes it difficult. Applying appropriate methods that combine touch-down PCR and tetra-primer ARMS-PCR in terms of reliability, sensitivity, and accuracy can help to eliminate the pseudogene effect and diagnose more affected individuals.

A 15 year old boy was detected to have bilateral renomegaly when he was being evaluated for nausea. Kidney biopsy done revealed interstitial infiltration by blasts in sheets. PET scan done revelaed diffuse uptake in bilaterally enlarged kidneys. A repeat PET scan done at the end of induction therapy revealed resolution in renomegaly and SUV uptake.

Somatic mutation and fusion detection in acute myeloid leukemia to determine disease subtype and treatment regime is a common practice, but it’s not yet employed in chronic myeloid leukemia (CML). CML is still monitored by routine quantitative determination of the BCR-ABL fusion transcript and treated with tyrosine kinase inhibitors (TKIs). Despite the availability of the three generations of TKIs, resistance and progression in CML pathogenesis suggest a strong role for somatic mutations. The present study aimed to identify the role of somatic mutation profiling in CML patients in disease management. 196 CML patient samples were used in this investigation, comprising 26 CML-BP, 8 CML-AP, and 162 CML-CP samples. Following cytogenetic analysis for confirmation, each sample was sequenced utilizing the Ion Torrent platform by a targeted panel. Of the 196 CML samples, 81 (41.33%) had 125 variations affecting 27 genes, while 115 (58.67%) harboured no mutations. The study revealed that ASXL1 (31.2%), ABL1 (14.4%), and TET2 (8.8%) were the most frequently altered genes. These genes are recognized indicators of CML disease. Few samples found with mutated GATA2, IDH1, NRAS, SETBP1, WT1, PHF6, KIT, etc. and fusions like RUNX1(5)-MECOM (2) and CBFB- MYH11 are indicative of disease progression. The outcome of this study suggests that mutational profiling of CML patients can help in the prognostication of disease. Based on the results of the study, the authors have also provided possible future risk stratification and diagnosis workflow for CML disease.

Combination chelation with deferiprone (DFP) and deferasirox (DFX) is one of the treatment modalities for iron overload in children with Transfusion-dependent Thalassemia (TDT). We report our experience with dual oral iron chelation. Retrospective chart review was conducted on all children started on Dual Oral Iron Chelation (DOIC) from 2015 to 2022. Children with TDT requiring DOIC were included in the study. Forty-five children required DOIC. The mean SF before DOIC initiation was 2929 ng/dl (SD 1465.07). The mean ferritin following DOIC was 1962.10 ng/dl (SD 1165.83) at 30 months. Mean duration on DOIC was 44.6 months (IQR 60–30). With DOIC, 82.22% children had a fall in ferritin to < 2000 ng/dl and in 60% of them had fall to < 1000 ng/dL. Dual Oral Iron Chelation (DOIC) is efficacious in reducing ferritin in iron-overloaded patients. Higher ferritin values (> 2500 ng/dL) drop rapidly in the first 12–24 months. DOIC was well-tolerated with no severe adverse effects.

Clinical translation of autophagy modulators is tied to thoroughly acquainted with the precise state of this process and its regulators in a particular cancer. LC3Av1 is a marker of autophagosome membrane that has been contributed with pathobiology of myriad of human cancers. In the present study, we examined the effect of promoter methylation and miR-155 and LncRNA-GAS5 (GAS5) expression levels on transcription of LC3Av1 in AML patients. The study included 60 patients with de novo AML and 20 subjects with normal bone marrow cellular composition. Methylation-Sensitive high resolution melting (MS-HRM) was performed for analysis of LC3Av1 CpG island methylation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for assessing LC3Av1, GAS5 and miR-155 expression levels. There was a significant elevation in the expression level of miR-155 and repression of LC3Av1 in AML samples. We found that LC3Av1 downregulation was negatively associated with its CpG island hypermethylation and miR-155 expression. Aging leads to overexpression of LC3Av1. GAS5 neither was differently expressed in AML patients compared to control samples nor has been related to LC3Av1 expression. The present study revealed that epigenetic changes like DNA methylation and alteration of miR-155 have a pivotal role in repression of autophagy marker LC3Av1, which potentially could provide the important clues of prognostic and therapeutic targets. The optimal strategies for clinical implementation of autophagy in AML is yet to be fully achieved and deserve further studies.