Indian Journal of Hematology and Blood Transfusion最新文献

Immunosuppressive therapy (IST) with Antithymocyte globulin (ATG) and cyclosporine is the therapy of choice in aplastic anemia (AA) patients who are more than 40 years of age and younger patients who do not have matched sibling donor for stem cell transplant (SCT). The overall response rate to IST is approximately 65%. The two preparations of ATG that are available in India are Atgam (Pfizer) and Thymogam (Bharat serum, India). Most of the published studies, from India, have used ATGAM. We present the largest study on IST (with Thymogam) from India. This is a single centre prospective study conducted in a tertiary care institute in southern India, from July 2016 to June 2022. All patients of age more than 13 years with diagnosis of aplastic anemia were included. Those with inherited bone marrow failure syndromes were excluded. Severity of AA and response rate was classified based on standard criteria. Patients were followed up till discharge and then monthly for at least 6 months. A total of 158 patients ( males-85, females- 73) received IST (Thymogam plus cyclosporine).Most of the patients had non severe AA(58%) followed by severe (28%) and very severe AA(14%). At 6 months post IST, the overall response rate (ORR) was 66% (complete response- 2% and partial response -64%) while the mortality rate was 13%.The ORR was 64% at 12 months and 61% at 24 months after IST. Age, Gender and severity at presentation did not influence response rates.

In this study, we describe and compare a simple, rapid, low cost, point-of-care diagnostic paper-based test for screening of sickle cell disease, which is based on principle of haemoglobin solubility. This observational study was carried out in 384 cases advised for screening of haemoglobin disorders by HPLC. All the cases were subjected to both HPLC and modified sickle cell paper solubility test simultaneously. The results of both the test were compared accordingly. Further to check the minimum level of HbS that can be identified by paper solubility test, a sample dilution method was used and analyzed. Out of 384 cases, 131 cases were found to have an HbS window in the HPLC report and rest 263 cases were found to have either normal or other haemoglobin variants. The paper solubility test also showed the similar results with 100% of sensitivity and specificity. Further, a > 5% of HbS can be traced and identified by paper solubility test. The paper-based haemoglobin solubility test was seen to be capable of distinguishing sickle cell patients from non sickle cell blood samples with a high degree of accuracy. It is a very rapid test that can be performed by a person with minimal training at community level (field study). The paper based Hb Solubility test is a low cost, easy, rapid, accurate, point of care and reproducible screening test for sickle cell patients.

Purpose

This study aims to investigate the increased toxicity of Cytarabine (Ara-c) by knockdown of chromosome segregation 1-like (CSE1L) in acute myeloid leukemia(AML) cells(Kasumi-1, U937, and THP-1 cells) and to explore its possible mechanisms.

Methods

Target gene silencing was achieved using the shRNA-mediated lentivirus method. Apoptosis was identified using the Annexin V PE/7-AAD double-staining assay. Cell viability was assessed with the Cell Counting Kit-8 (CCK-8) assay. Protein expression was detected by Western blotting.

Results

In vitro, knocking down CSE1L promoted caspase-3 and caspase-9 proteins expression and induced apoptosis in AML cells. Knockdown of CSE1L enhanced AML cells' sensitivity to Ara-c. knockdown of CSE1L reduced the expression levels of p-JKA2 and p-STAT3 proteins, while no significant difference was observed in the expression levels of total JAK2 and STAT3 proteins. Furthermore, JAK2 overexpression reversed the increase in Ara-c toxicity to AML cells caused by CSE1L knockdown.

Conclusion

In conclusion, our study reveals that CSE1L is a potential therapeutic target for overcoming Ara-c resistance in AML cells. Thus, we have gained new insights into the oncogenic process of CSE1L in AML cells and raised the prospect of knockdown of CSE1L in AML in combination with cytarabine-targeted therapy.

The presence of an M-band in serum and/or urine electrophoresis is a crucial diagnostic indicator for multiple myeloma and other plasma cell dyscrasias. Conventionally, on serum protein electrophoresis (SPEP), the M-band is observed as a sharp spike (M-spike), typically in the gamma region, occasionally in the beta region, and rarely in the alpha region. However, the infrequency of M-bands in the alpha region raises the possibility of overlooking them when coexisting with normal bands. This study underscores the significance of considering the potential discovery of M-bands in unusual sites, particularly in the alpha-2 region. This retrospective study spanned three years and involved conducting serum and urine protein electrophoresis followed by serum and urine immunofixation electrophoresis on a semi-automated platform (Helena Biosciences, Europe) using agarose gel and serum protein 6-band format kits. We identified five cases of multiple myeloma presenting with a monoclonal band in the alpha-2 region on SPEP and UPEP. Subsequent immunofixation electrophoresis confirmed these bands to be monoclonal bands in the lambda lane. In suspected cases of multiple myeloma, even in the absence of an M-band in the gamma region, heightened prominence in the alpha or beta region warrants further investigation through immunofixation electrophoresis (IFE).

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and the Hispanic race has the highest incidence worldwide. Disparities in survival rates exist among different regions of the world. Due to this heterogeneity and possible differences in the outcomes within Mexico, the aim of this study was to analyze the clinical outcomes of cohort of pediatric patients with ALL treated in a highly specialized medical unit located in the Bajio region of Mexico. Observational retrospective study of a cohort of pediatric patients with ALL treated in a tertiary-level hospital in the Bajio region of Mexico, between January 2016 and December 2021. A total of 146 patients were included with a median age of 7 years. The 68.5% of patients were at high risk. CNS involvement was present in 2.7%, and Philadelphia chromosome positive in 2%. Cytogenetic analysis was performed in 16.4% patients. The median follow-up of entire cohort was 32 months. The most frequently administered chemotherapy treatment was Total Therapy XV in 79.5% of patients. The complete remission rate was 89%. Refractory disease was present in 2.7%. Induction-related mortality was 8.2%. The relapse rate was present in 26%. The 3-years overall survival was 57.5%, and the 3-years event-free survival was 53.4%. A more aggressive course and worse survival occur in our cohort of pediatric patients with ALL. Strategies should be proposed inside Mexico and other low-middle income countries with the aim of improving the overall survival.

Chronic myeloid leukaemia (CML) is caused by balanced translocation t(9::22)(q34;q11) resulting in formation of pathogenic BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of CML. Ongoing treatment with TKI leads to side effects and has financial impact. Teratogenic potential of TKI and growth disturbance also represent an important challenge. Thus, TKI discontinuation in form of treatment free remission (TFR) has emerged as a new and important therapeutic goal. In this retrospective study, we reviewed CML patients who were kept on TFR. Inclusion criteria was patient age ≥ 18 years diagnosed with CML in chronic phase who met the criteria for TFR and opted for same and who were in DMR but stopped TKI for any reason. We analysed the data for baseline characteristics, molecular relapse (MR), survival without molecular relapse (SWMR), TFR duration and factors affecting MR. We included 38 patients in this analysis. Thirty five (92%) patients were treated with imatinib at diagnosis. Median duration of TKI treatment was 135 months. 37 patients (97.5%) achieved DMR on TKI and median time from TKI initiation to DMR was 96 months. Median duration of DMR prior to TKI discontinuation was 41 months. TKI was discontinued after counselling for TFR in 26 patients (68%) while it was discontinued due to intolerance in 10 patients (29%). At median molecular follow up of 25 months, nine patients (23.7%) had molecular relapse. Median SWMR was not reached and 2 year estimated SWMR was 65.2% (95%CI,47.2- 83.2). Of all relapses, 5/9 (55.5%) occurred in the first six months of TFR. On univariate analysis, duration of TKI and duration of DMR were predictive of molecular relapse. On multivariate analysis, none of these factors were found to be significant. This retrospective study suggests that for CML CP patients achieving deep molecular response, discontinuing TKI therapy in real-world settings may be feasible while potentially achieving comparable outcomes.

Prevention of birth of thalassemia major children by identification of risk couples and prenatal diagnosis has been recommended as a realistic and cost effective method for control of thalassemia. We present our experience of antenatal thalassemia screening and prenatal diagnosis (PND) in a tertiary care teaching hospital. All antenatal women presenting to the antenatal clinic over 6 years were counseled for beta thalassemia screening. If the lady was detected heterozygous for thalassemia/hemoglobinopathy, partner screening was advised. If the husband was also detected to be heterozygous, the risk couple was offered prenatal diagnosis by chorionic villus tissue DNA analysis. A total of 5392 antenatal women were counseled for beta thalassemia screening, with compliance in 4376 (81.1%) cases. Beta Thalassemia heterozygosity was detected in 147(3.4%) cases, borderline HbA2 in 75(1.7%) and other hemoglobin variants in 91(2.1%). Partner screening was advised in 313 (7.1%) affected antenatal women, with non-compliance in 33.8% cases. Of 27 risk couples identified, prenatal diagnosis was done in 19 couples, detecting 3 affected fetuses. In 8 couples, PND could not be done because of late gestation, financial constraints, lost follow up, failed CVS tissue aspiration and miscarriage prior to CVS tissue biopsy. Late presentation to the antenatal clinic, non-compliance to screening advice and financial constraints could be the factors impeding the thalassemia control program. This emphasizes on the need for community level awareness and inclusion of Thalassemia screening and prenatal diagnosis in the healthcare system.

To study the prevalence of pulmonary arterial hypertension (PAH) in individuals with sickle cell disease (SCD) and its relationship with serological markers. Data of ninety-two SCD patients who visited the Department of Clinical Haematology between 2020 and 2021 was retrieved through the hospital record system. These patients underwent laboratory testing, including a clinical evaluation was done at baseline. They underwent Doppler echocardiography to determine the maximum tricuspid regurgitation jet velocity. Among 92 patients, 43 were men and 49 were female, with the mean age being 29.9 ± 8.8 years. Using Doppler echocardiography, their pulmonary artery systolic pressure was determined. Pulmonary arterial hypertension was found in 29 out of 92 patients (31.5%). The prevalence of PAH was 20.9% in males and 40.8% in women. A significant association was shown with females (p = 0.041.) There was a positive correlation with hemolytic markers, including reticulocyte count (r = 0.212, p < 0.05), lactate dehydrogenase (r = 0.322, p < 0.01 with tricuspid regurgitation velocity (TRvmax) (r = 0.322, p < 0.01) along with NT-ProBNP (r = 0.310, p < 0.01). The maximal tricuspid regurgitation velocity and haemoglobin concentration had a negative correlation. (r = -0.340, p < 0.01). In resource-limited settings, NT Pro BNP and transthoracic echocardiography can be used as screening tools for pulmonary hypertension in SCD.

The incidence of deep vein thrombosis (DVT) is increasing with aging, which needs a screening and monitoring biomarker. This study focused on the significance of aging- and angiogenesis-related lncRNA RAMP2-AS1 (RAMP2-AS1) aiming to identify a promising biomarker for the incidence of DVT. Serum samples were collected from 63 healthy individuals and 98 patients with DVT. The serum RAMP2-AS1 level was analyzed by PCR and its significance in DVT detection and development prediction was evaluated by ROC and multivariate Cox regression analysis. The regulatory effect of RAMP2-AS1 on endothelial progenitor cells (EPCs) was evaluated by CCK8 and transwell assays. RAMP2-AS1 was significantly downregulated in patients with DVT, which could discriminate patients with DVT from healthy individuals with relatively high sensitivity and specificity. The downregulation of RAMP2-AS1 could predict poor outcomes and was associated with activities of daily living (ADL), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and monocyte to high-density lipoprotein cholesterol ratio (MHR) of patients with DVT. RAMP2-AS1 was identified as an independent prognostic factor of DVT by Cox regression analysis. In EPCs, overexpressing RAMP2-AS1 significantly suppressed cell proliferation, migration, and invasion. Downregulated serum RAMP2-AS1 could predict the incidence and progression of DVT. RAMP2-AS1 inhibited EPCs growth and motility, which provides a target for thrombolytic therapy. RAMP2-AS1 level could be included in the risk assessment model of DVT.