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INTRODUCTION: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). AIM: This study assessed the economic evaluation of emicizumab treatment for non-inhibitor severe haemophilia A (HA) patients in India. METHODS: A Markov model evaluated the cost-effectiveness of emicizumab prophylaxis compared to on-demand therapy (ODT), low-dose prophylaxis (LDP; 1565 IU/kg/year), intermediate-dose prophylaxis (IDP; 3915 IU/kg/year) and high-dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors. Inputs from HAVEN-1 and HAVEN-3 trials included transition probabilities of different bleeding types. Costs and benefits were discounted at a 3.5% annual rate. RESULTS: In the base-case analysis, emicizumab was cost-effective compared to HDP, with an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years (QALY) of Indian rupees (INR) 27,869. Compared to IDP, ODT and LDP, emicizumab prophylaxis could be considered a cost-effective option if the paying threshold is >1 per capita gross domestic product (GDP) with ICER/QALY values of INR 264,592, INR 255,876 and INR 305,398, respectively. One-way sensitivity analysis (OWSA) highlighted emicizumab cost as the parameter with the greatest impact on ICERs. Probabilistic sensitivity analysis (PSA) indicated that emicizumab had a 94.7% and 49.4% probability of being cost-effective at willingness-to-pay (WTP) thresholds of three and two-times per capita GDP. CONCLUSION: Emicizumab prophylaxis is cost-effective compared to HDP and provides value for money compared to ODT, IDP, and LDP for severe non-inhibitor PwHA in India. Its long-term humanistic, clinical and economic benefits outweigh alternative options, making it a valuable choice in resource-constrained settings.
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Anticuerpos Biespecíficos , Hemofilia A , Humanos , Hemofilia A/tratamiento farmacológico , Análisis de Costo-Efectividad , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Análisis Costo-Beneficio , Factor VIII/uso terapéuticoRESUMEN
BACKGROUND: India has the most significant number of children with thalassemia major worldwide, and about 10,000-15,000 children with the disease are born yearly. Scaling up e-health initiatives in rural areas using a cost-effective digital tool to provide healthcare access for all sections of people remains a challenge for government or semi-governmental institutions and agencies. METHODS: We compared the performance of a recently developed formula SCS[Formula: see text] and its web application SUSOKA with 42 discrimination formulae presently available in the literature. 6,388 samples were collected from the Postgraduate Institute of Medical Education and Research, Chandigarh, in North-Western India. Performances of the formulae were evaluated by eight different measures: sensitivity, specificity, Youden's Index, AUC-ROC, accuracy, positive predictive value, negative predictive value, and false omission rate. Three multi-criteria decision-making (MCDM) methods, TOPSIS, COPRAS, and SECA, were implemented to rank formulae by ensuring a trade-off among the eight measures. RESULTS: MCDM methods revealed that the Shine & Lal and SCS[Formula: see text] were the best-performing formulae. Further, a modification of the SCS[Formula: see text] formula was proposed, and validation was conducted with a data set containing 939 samples collected from Nil Ratan Sircar (NRS) Medical College and Hospital, Kolkata, in Eastern India. Our two-step approach emphasized the necessity of a molecular diagnosis for a lower number of the population. SCS[Formula: see text] along with the condition MCV[Formula: see text] 80 fl was recommended for a higher heterogeneous population set. It was found that SCS[Formula: see text] can classify all BTT samples with 100% sensitivity when MCV[Formula: see text] 80 fl. CONCLUSIONS: We addressed the issue of how to integrate the higher-ranked formulae in mass screening to ensure higher performance through the MCDM approach. In real-life practice, it is sufficient for a screening algorithm to flag a particular sample as requiring or not requiring further specific confirmatory testing. Implementing discriminate functions in routine screening programs allows early identification; consequently, the cost will decrease, and the turnaround time in everyday workflows will also increase. Our proposed two-step procedure expedites such a process. It is concluded that for mass screening of BTT in a heterogeneous set of data, SCS[Formula: see text] and its web application SUSOKA can provide 100% sensitivity when MCV[Formula: see text] 80 fl.
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Talasemia beta , Niño , Humanos , Talasemia beta/diagnóstico , Tamizaje Masivo , Valor Predictivo de las Pruebas , Diagnóstico Diferencial , Toma de DecisionesRESUMEN
Beta-hemoglobinopathies exhibit a heterogeneous clinical picture with varying degrees of clinical severity. Pertaining to the limited treatment options available, where blood transfusion still remains the commonest mode of treatment, pharmacological induction of fetal hemoglobin (HbF) has been a lucrative therapeutic intervention. Till now more than 70 different HbF inducers have been identified. The practical usage of many pharmacological drugs has been limited due to safety concerns. Natural compounds, like Resveratrol, Ripamycin and Bergaptene, with limited cytotoxicity and high efficacy have started capturing the attention of researchers. In this review, we have summarized pharmacological drugs and bioactive compounds isolated from natural sources that have been shown to increase HbF significantly. It primarily discusses recently identified synthetic and natural compounds, their mechanism of action, and their suitable screening platforms, including high throughput drug screening technology and biosensors. It also delves into the topic of combinatorial therapy and drug repurposing for HbF induction. Overall, we aim to provide insights into where we stand in HbF induction strategies for treating ß-hemoglobinopathies.
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Productos Biológicos , Hemoglobinopatías , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Hemoglobina Fetal , Hemoglobinopatías/tratamiento farmacológico , HumanosRESUMEN
ß-thalassemia is a prevalent monogenic disorder characterized by reduced or absent synthesis of the ß-globin chain. Although great effort has been made to ameliorate the disease severity of ß-thalassemic patients, progress has been stymied due to limited understanding of the detailed molecular mechanism of disease pathogenesis. Recently, non-coding RNAs have been established as key players in regulating various physiological and pathological processes. Many ncRNAs are involved in hematopoiesis and erythroid development. Furthermore, various studies have also reported the complex interplay between different ncRNAs, such as miRNA, lncRNAs, etc. in regulating disease progression and pathogenesis. Both lncRNAs and miRNAs have been identified as independent regulators of globin gene expression and are intricately involved in disease pathogenesis; yet accumulating evidence suggests that the cross-talk between lncRNAs and miRNAs is intricately involved in the underlying globin gene expression, fine-tuning the effect of their independent regulation. In this review, we summarize the current progress of research on the roles of lncRNAs and miRNAs implicated in ß-thalassemia disease, including their interactions and regulatory networks. This can provide important insights into the detailed epigenetic regulation of globin gene switching and has the potential to develop novel therapeutic approaches against ß-thalassemia.
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MicroARNs , ARN Largo no Codificante , Talasemia beta , Biomarcadores , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes/genética , Globinas/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Talasemia beta/genética , Talasemia beta/terapiaRESUMEN
Hemoglobinopathies are quite common in India, and multiple awareness and screening initiatives exist for detection of thalassemia in the population. One of the most common and successfully used method for thalassemia screening is the high performance liquid chromatography (HPLC) test. However, in spite of its excellent usefulness as a screening tool, there are situations where HPLC alone may not be able to make an accurate diagnosis. Here we highlight a fairly common situation where HPLC alone failed to confirm the diagnosis. A detailed family and transfusion history along with clinical examination and investigations, such as a complete hemogram, HPLC, along with molecular studies would have aided in diagnosis. Another cause of concern raised by this case is that the most common mutation in our population, such as IVS-I-5 (G>C), HBB: c.92+5G>C, was not represented in the HPLC, and thus, was missed during the preconception screening process, leading to a chain of events.
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Hemoglobinopatías , Talasemia , Humanos , Cromatografía Líquida de Alta Presión , Hemoglobinopatías/genética , Talasemia/genética , Mutación , Recuento de Células SanguíneasRESUMEN
INTRODUCTION: Hemoglobin (Hb)-F inducers are known to improve Hb level and transfusion dependence in thalassemia. This pilot study was conducted to assess the efficacy and safety of Hb-F inducer thalidomide compared to hydroxyurea (HU) in Hb E-ß thalassemia patients. METHODS: This was a prospective interventional single-centre study with 45 Hb E-beta thalassemia patients equally divided into group-I (thalidomide+folic acid), group-II (HU + folic acid) and group-III (folic acid). Response was assessed at various time intervals with 12-months follow up period. Primary end points were increment in Hb, Hb-F level and improvement in transfusion requirement; secondary end point were tolerability and safety. RESULTS: There was 100% responder (R: Hb-increment ≥1 g/dl) in group-I with 66.67% major responder (MaR: Hb-increment ≥2 g/dl), while there were 40% and 0% responder in group-II and III respectively. Hb-increment was significantly (p-value <0.0001) better in thalidomide arm compared to HU. The Hb-increment was attributable to both increase in Hb-F levels and reduction in ineffective erythropoiesis in thalidomide arm. Transfusion reduction was significantly better in group-I compared to group-II (100% vs 34%). No severe adverse effects was reported by patients of any group. CONCLUSION: Thalidomide showed a persistent significant Hb-increment and transfusion independence in Hb E-ß thalassemia patients compared to HU.
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Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Inmunosupresores/uso terapéutico , Talidomida/uso terapéutico , Talasemia beta/tratamiento farmacológico , Adolescente , Adulto , Antidrepanocíticos/efectos adversos , Niño , Femenino , Hemoglobina E/análisis , Hemoglobinas/análisis , Humanos , Hidroxiurea/efectos adversos , Inmunosupresores/efectos adversos , India/epidemiología , Masculino , Proyectos Piloto , Estudios Prospectivos , Centros de Atención Terciaria , Talidomida/efectos adversos , Adulto Joven , Talasemia beta/sangre , Talasemia beta/epidemiologíaRESUMEN
Hemoglobin E (HbE)/ß-thalassemia is a form of ß-hemoglobinopathy that is well-known for its clinical heterogeneity. Individuals suffering from this condition are often found to exhibit increased fetal hemoglobin (HbF) levels - a factor that may contribute to their reduced blood transfusion requirements. This study hypothesized that the high HbF levels in HbE/ß-thalassemia individuals may be guided by microRNAs and explored their involvement in the disease pathophysiology. The miRNA expression profile of hematopoietic progenitor cells in HbE/ß-thalassemia patients was investigated and compared with that of healthy controls. Using miRNA PCR array experiments, eight miRNAs (hsa-miR-146a-5p, hsa-miR-146b-5p, hsa-miR-148b-3p, hsa-miR-155-5p, hsa-miR-192-5p, hsa-miR-335-5p, hsa-miR-7-5p, hsa-miR-98-5p) were identified to be significantly up-regulated whereas four miRNAs (hsa-let-7a-5p, hsa-miR-320a, hsa-let-7b-5p, hsa-miR-92a-3p) were significantly down-regulated. Target analysis found them to be associated with several biological processes and molecular functions including MAPK and HIF-1 signaling pathways - the pathways known to be associated with HbF upregulation. Results of dysregulated miRNAs further indicated that miR-17/92 cluster might be of critical importance in HbF regulation. The findings of our study thus identify key miRNAs that can be extrinsically manipulated to elevate HbF levels in ß-hemoglobinopathies.
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Hemoglobina E/genética , MicroARNs/genética , Talasemia beta/genética , Células Cultivadas , Regulación hacia Abajo , Hemoglobina Fetal/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Transcriptoma , Regulación hacia ArribaRESUMEN
BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.
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COVID-19/epidemiología , Neoplasias Hematológicas/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , COVID-19/terapia , Niño , Preescolar , Comorbilidad , Femenino , Neoplasias Hematológicas/terapia , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
In the phase 3 BOSTON study, patients with multiple myeloma (MM) after 1-3 prior regimens were randomized to once-weekly selinexor (an oral inhibitor of exportin 1 [XPO1]) plus bortezomib-dexamethasone (XVd) or twice-weekly bortezomib-dexamethasone (Vd). Compared with Vd, XVd was associated with significant improvements in median progression-free survival (PFS), overall response rate (ORR), and lower rates of peripheral neuropathy, with trends in overall survival (OS) favoring XVd. In BOSTON, 141 (35.1%) patients had MM with high-risk (presence of del[17p], t[4;14], t[14;16], or ≥4 copies of amp1q21) cytogenetics (XVd, n = 70; Vd, n = 71), and 261 (64.9%) exhibited standard-risk cytogenetics (XVd, n = 125; Vd, n = 136). Among patients with high-risk MM, median PFS was 12.91 months for XVd and 8.61 months for Vd (HR, 0.73 [95% CI, (0.4673, 1.1406)], p = 0.082), and ORRs were 78.6% and 57.7%, respectively (OR 2.68; p = 0.004). In the standard-risk subgroup, median PFS was 16.62 months for XVd and 9.46 months for Vd (HR 0.61; p = 0.004), and ORRs were 75.2% and 64.7%, respectively (OR 1.65; p = 0.033). The safety profiles of XVd and Vd in both subgroups were consistent with the overall population. These data suggest that selinexor can confer benefits to patients with MM regardless of cytogenetic risk. ClinicalTrials.gov identifier: NCT03110562.
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Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Hidrazinas/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Triazoles/uso terapéutico , Adulto , Anciano , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/efectos adversos , Análisis Citogenético , Dexametasona/efectos adversos , Femenino , Humanos , Hidrazinas/efectos adversos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Supervivencia sin Progresión , Resultado del Tratamiento , Triazoles/efectos adversos , Adulto JovenRESUMEN
Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p = .024), ≥VGPR (OR, 1.68, p = .027), PFS (HR 0.55, p = .002), and improved OS (HR 0.63, p = .030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p = .08) and OS (HR 0.62, p = .062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p = .0060) and frail patients (15% vs. 44%; p = .0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/efectos adversos , Dexametasona/efectos adversos , Fragilidad/complicaciones , Hidrazinas/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Triazoles/efectos adversos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Dexametasona/administración & dosificación , Esquema de Medicación , Femenino , Fragilidad/diagnóstico , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Hematológicas/inducido químicamente , Humanos , Hidrazinas/administración & dosificación , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Mieloma Múltiple/complicaciones , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Triazoles/administración & dosificaciónRESUMEN
Background & objectives: Evaluation of bone marrow infiltration in lymphoma is usually done by bone marrow biopsy (BMB). This study analyzed the utility of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) to detect bone marrow involvement (BMI) compared to BMB. Methods: Treatment-naïve lymphoma patients underwent both 18F-FDG PET/CT scan and BMB before treatment initiation. BMI detected on PET/CT was compared with BMB. Results: The study population consisted of 80 patients and comprised 37 Hodgkin's lymphoma (HL) patients, 30 aggressive non-HL (NHL) and 13 indolent NHL patients. The majority of the aggressive NHLs were diffuse large B-cell lymphoma (20/30) and major indolent lymphoma was follicular lymphoma (5/13). When compared to BMB, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of focal (±diffuse) marrow FDG uptake on 18F-FDG PET/CT were 100, 61.3, 33.3 and 100 per cent, respectively, for HL; 100, 65.4, 30.8 and 100 per cent, respectively, for aggressive NHL and 75, 80, 85.7 and 66.7 per cent, respectively, for indolent NHL. When comparing marrow involvement on 18F-FDG PET/CT to baseline BMB and/or resolution of bone marrow FDG uptake at interim/end-of-treatment 18F-FDG PET/CT, the sensitivity, specificity, PPV and NPV were 100 per cent each for HL and aggressive NHL and 77.3, 100, 100 and 66.7 per cent, respectively, for indolent NHL. Interpretation & conclusions: 18F-FDG PET/CT has a good sensitivity and NPV for detecting BMI in HL and aggressive lymphoma. The low specificity and PPV improved if marrow uptake pattern on interim or end-of-treatment 18F-FDG PET/CT scan was analyzed. In patients with HL who are staged with18F-FDG PET/CT at baseline and followed up with an interim/end-of-treatment PET/CT, baseline BMB may be avoided. For all other lymphoma subtypes, BMB may be essential if there is no marrow FDG uptake on PET/CT scan performed at baseline.
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Enfermedad de Hodgkin , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Biopsia , Médula Ósea/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Enfermedad de Hodgkin/patología , Humanos , Linfoma de Células B Grandes Difuso/patología , Linfoma no Hodgkin/diagnóstico por imagen , Linfoma no Hodgkin/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones , Radiofármacos , Estudios RetrospectivosRESUMEN
The 3'-untranslated region (3'-UTR) is well known to be associated with the post-transcriptional regulation, because of the presence of important sequences that influence the fate of mRNA, and thus, in protein synthesis. The present study describes a point mutation on the ß-globin 3'-UTR, +1506 (A>C) (HBB: c.*32A>C) in an Indian family during prenatal diagnosis (PND) screening of an at-risk couple. The members of the family heterozygous for this mutation presented with a typical ß-thalassemia (ß-thal) phenotype. The haplotype analysis of the ß-globin gene cluster was determined for this mutation and observed to be linked with haplotype [- + - + + + +]. Common α-globin gene deletions, triplication, and the Xmnl polymorphism, were also looked for and found to be absent in the family. The identified HBB: c.*32A>C mutation is located in the first adenylate uridylate (AU) motif of the four AU motifs situated in the 3'-UTR region of the ß-globin gene. Bioinformatics analysis revealed binding of two miRNAs, hsa-miR-451a and hsa-miR-3914, at the mutation position, possibly influencing the mRNA stability by recruiting RNA binding proteins. This is the third publication reporting the 3'-UTR +1506 (A>C) mutation worldwide and the first report of the existence of this mutation in the Indian population, emphasizing the high heterogeneity of this population.
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MicroARNs , Globinas beta , Talasemia beta , Regiones no Traducidas 3' , Femenino , Humanos , Mutación , Fenotipo , Embarazo , Globinas beta/genética , Talasemia beta/diagnóstico , Talasemia beta/genéticaRESUMEN
Deferiprone (DFP) and deferasirox (DFX) are the most well-known, efficacious and safe chelators to reduce the serum ferritin (SF) level in multi transfused thalassemic children, although there are few reports available for assessing the efficacy between DFP and DFX. We compared the efficacy of DFP vs. DFX as iron chelating drugs in ß-thalassemia major (ß-TM) patients. Pediatric patients diagnosed to carry ß-TM, aged between 2 and 10 years, were recruited. A suitable data collection form and questionnaire were used. Paired and unpaired t-tests were used to compare the safety and efficacy of the chelating drugs DFP and DFX. The mean SF level at the 12th month was found to be 3016.73 ± 670.04 ng/mL (p = 0.002) in the DFX-treated group, which was quite significant in contrast to DFP response, where the value was 3204.06 ± 690.15 ng/mL (p = 0.14). There is no statistically significant (p = 0.15) difference on relative changes of the left ventricular ejection fraction (LVEF), between these two groups. The adverse effects were transient and none of them required stoppage of therapy. Deferasirox is more effective when compared to DFP in reducing chelating drug-related complications and iron overload specially in multiple transfusion dependent ß-TM patients.
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Deferasirox , Deferiprona , Quelantes del Hierro , Sobrecarga de Hierro , Talasemia beta , Niño , Preescolar , Deferasirox/efectos adversos , Deferasirox/uso terapéutico , Deferiprona/efectos adversos , Deferiprona/uso terapéutico , Ferritinas , Humanos , Quelantes del Hierro/efectos adversos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/etiología , Volumen Sistólico , Función Ventricular Izquierda , Talasemia beta/tratamiento farmacológicoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedades Renales , Mieloma Múltiple , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Hidrazinas/administración & dosificación , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/mortalidad , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Tasa de Supervivencia , Triazoles/administración & dosificaciónRESUMEN
Aplastic anemia (AA) is a rare immunologically mediated bone marrow failure syndrome, characterized by progressive loss of hematopoietic stem cells resulting in peripheral pancytopenia. Elaborative investigation including molecular tests is required to exclude inherited bone marrow failure syndrome (IMBFS) as the treatment and prognosis vary dramatically between them. Haematopoietic stem cell transplant with a fully matched sibling donor (MSD-HSCT) is still the only curative treatment. Management of AA is a real-time challenge in India, because of the delay in the diagnosis, lack of proper supportive care, limited availability of the expertise centre, and the patient's affordability. Recently, results with intensified immunosuppressive therapy that includes anti-thymocyte globulin with cyclosporine-A (CsA) and eltrombopag, are enough encouraging to consider it as treatment of choice in patients lacking MSD or who are not fit for HSCT. However, limitations in resource constraints settings including the cost of therapy limit its full utilization. Relapse of the disease or evolution to myelodysplasia or paroxysmal nocturnal haemoglobinuria (PNH) in a proportion of patients is another challenge with immunosuppressants. The majority of the AA patients still receive CsA with or without androgens in India, mostly because of increased cost and limited availability of HSCT and ATG. The use of the unrelated or alternative donor is still upcoming in India, with unavailable data in terms of response and survival. Therefore, there is an utmost need for novel agents for the better management of AA having a balanced efficacy and toxicity profile to improve the survival and quality of life.
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Introduction: Currently, there are no guidelines for the management of B-cell lineage acute lymphoblastic leukemia (B-ALL) from an Indian perspective. The diagnostic workup, monitoring, and treatment of B-ALL vary among different physicians and institutes. Objective: To develop evidence-based practical consensus recommendations for the management of B-ALL in Indian settings. Methods: Modified Delphi consensus methodology was considered to arrive at a consensus. An expert scientific committee of 15 experts from India constituted the panel. Clinically relevant questions belonging to three major domains were drafted for presentation and discussion: (i) diagnosis and risk assignment; (ii) frontline treatment; and (iii) choice of therapy (optimal vs. real-world practice) in relapsed/refractory (R/R) settings. The questionnaire was shared with the panel members through an online survey platform. The level of consensus was categorized into high (≥ 80%), moderate (60%-79%), and no consensus (< 60%). The process involved 2 rounds of discussion and 3 rounds of Delphi survey. The questions that received near or no consensus were discussed during virtual meetings (Delphi rounds 1 and 2). The final draft of the consensus was emailed to the panel for final review. Results: Experts recommended morphologic assessment of peripheral blood or bone marrow, flow cytometric immunophenotyping, and conventional cytogenetic analysis in the initial diagnostic workup. Berlin-Frankfurt-Münster (BFM)-based protocol is the preferred frontline therapy in pediatric and adolescent and young adult patients with B-ALL. BFM/German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia-based regimen is suggested in adult patients with B-ALL. Immunotherapy (blinatumomab or inotuzumab ozogamicin) followed by allogeneic hematopoietic cell transplantation (allo-HCT) is the optimal choice of therapy that would yield the best outcomes if offered in the first salvage in patients with R/R B-ALL. In patients with financial constraints or prior allo-HCT (real-world practice) at first relapse, standard-intensive chemotherapy followed by allo-HCT may be considered. For subsequent relapses, chimeric antigen receptor T-cell therapy or palliative care was suggested as the optimal choice of therapy. Conclusion: This expert consensus will offer guidance to oncologists/clinicians on the management of B-ALL in Indian settings.
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Malaria prevalence has become medically important and a socioeconomic impediment for the endemic regions, including Purulia, West Bengal. Geo-environmental variables, humidity, altitude, and land use patterns are responsible for malaria. For surveillance of the endemic nature of Purulia's blocks, statistical and spatiotemporal factors analysis have been done here. Also, a novel approach for the Pf malaria treatment using methanolic leaf extract of Morus alba S1 has significantly reduced the parasite load. The EC50 value (1.852) of the methanolic extract of M. alba S1 with P. falciparum 3D7 strain is close to the EC50 value (0.998) of the standard drug chloroquine with the same chloroquine-sensitive strain. Further studies with an in-silico model have shown successful interaction between DHFR and the phytochemicals. Both 1-octadecyne and oxirane interacted favourably, which was depicted through GC-MS analysis. The predicted binary logistic regression model will help the policy makers for epidemiological surveillance in malaria-prone areas worldwide when substantial climate variables create a circumstance favourable for malaria. From the in vitro and in silico studies, it can be concluded that the methanolic extract of M. alba S1 leaves were proven to have promising antiplasmodial activity. Thus, there is a scope for policy-driven approach for discovering and developing these lead compounds and undermining the rising resistance to the frontline anti-malarial drugs in the world.
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Malaria Falciparum , Malaria , Morus , Malaria/tratamiento farmacológico , Cloroquina , Metanol , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
PURPOSE: Very few studies have demonstrated the rituximab biosimilarity in terms of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity in patients with diffuse large B-cell lymphoma (DLBCL) in India. Therefore, we compared the efficacy, safety, pharmacokinetic, pharmacodynamic, and immunogenicity of our biosimilar rituximab with the reference rituximab (Ristova, Roche products [India] Pvt. Ltd) in patients with DLBCL in India. METHODS: A phase 3, randomized, assessor-blind, parallel-group, two-arm study was conducted across 28 sites in India. A total of 153 newly diagnosed DLBCL patients were randomized to receive either biosimilar rituximab or reference rituximab. The study drugs were administered at a dose of 375 mg/m2 by intravenous infusion every 3 weeks for six cycles. The primary end point was objective response rate (ORR) at the end of Cycle 6. Secondary end points included: pharmacokinetic, pharmacodynamics, immunogenicity, and safety assessment. RESULTS: The ORR at the end of Cycle 6 was 82.14% in the biosimilar rituximab and 85.71% in the reference rituximab group. The risk difference (90% CIs) was - 3.57 (- 14.80, 7.66). It met the non-inferiority margin of - 20%. The pharmacokinetic and pharmacodynamic parameters were comparable between the two treatment groups. The incidence rate of immunogenicity was very low and similar in both the treatment groups. The safety profile of both the treatments was comparable with no major difference in terms of nature, frequency and severity of TEAEs. CONCLUSION: The study demonstrated the biosimilarity between the biosimilar rituximab and the reference rituximab. Our biosimilar rituximab could add to the cost-effective treatment alternatives for patients with DLBCL in India.
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Biosimilares Farmacéuticos , Linfoma de Células B Grandes Difuso , Humanos , Rituximab/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Infusiones Intravenosas , India , Resultado del TratamientoRESUMEN
India is in the thalassemia belt of the world. Both α- and ß-thalassemia (α- and ß-thal) are found in West Bengal, a state in the eastern part of India. There was no systematic large published study to investigate the prevalence rates of different hemoglobinopathies in West Bengal. This study was conducted in school and college students, newly married couples and pregnant women after proper counseling in the rural areas of five districts of West Bengal state in eastern India. Thalassemia testing was done using high performance liquid chromatography (HPLC). A total of 35,413 individuals were screened for hemoglobinopathies. ß-Thalassemia trait was found in 10.38%, Hb E [ß26(B8)GluâLys] trait in 4.30%, sickle cell trait in 1.12%, borderline Hb A(2) value 0.73%, low Hb A(2) 0.68% and Hb D trait 0.37%. This is the first study that addresses the prevalence of different hemoglobinopathies in rural areas of West Bengal. The prevalence of ß-thal trait is higher in West Bengal than other parts of India. This data is likely to be helpful in planning screening programs in rural areas of West Bengal, India.
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Pruebas Genéticas/métodos , Hemoglobinopatías/epidemiología , Hemoglobinopatías/genética , Salud Rural/estadística & datos numéricos , Adolescente , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Hemoglobina A2/genética , Hemoglobina E/genética , Hemoglobina Falciforme/genética , Hemoglobinas Anormales/genética , Humanos , India/epidemiología , Masculino , Embarazo , Complicaciones Hematológicas del Embarazo/epidemiología , Complicaciones Hematológicas del Embarazo/genética , Prevalencia , Adulto Joven , Talasemia beta/epidemiología , Talasemia beta/genéticaRESUMEN
Purpose: Autologous stem cell transplantation (ASCT) is an established therapy for many hematological diseases. This study assessed the pattern of ASCTs at a tertiary care center and associated factors, including pre-harvest CD34+ stem cell levels, leading to improved engraftment outcomes. Methodology: A retrospective study was conducted in India, between February 2009-August 2020. Patients who underwent ASCT for different hematological malignancies (n=65) were included, and the patients' age, sex, type and stage of disease, pre- and post-harvest CD34+ counts, and time to attain platelet/neutrophil engraftment or febrile neutropenia were analyzed. The post-harvest CD34+ dose was calculated. Pre-conditioning was performed using Granulocyte Colony Stimulating Factor (GCSF)±Plerixafor. Progression-free survival (PFS) was calculated using relapse/death as the endpoint. Results: The median age of the cohort (n=65) was 49 years, with a male preponderance. Multiple myeloma was the most common malignancy (70.8% [46/65]), requiring ASCT. The median time to ASCT was 13 months. All patients had received GCSF, while Plerixafor was used in 17 patients with a pre-harvest CD34+ count of <10 cells/µL. The median pre-harvest CD34+ concentration and post-harvest CD34+ cell dose was 27.54 cells/µL (n=26) and 5.23×106 cells/kg body weight (n=65), respectively. The median time to engraftment was 11 and 12 days, for neutrophils and platelets, respectively. One patient did not engraft and was excluded from the analysis. The time required to attain neutrophil engraftment was significantly lower (p=0.02) among freshly harvested stem cells (n=48) than that of cryopreserved products (n=17). Platelet engraftment associated with CD34+ pre- and post-harvest levels was not significant (p=0.06). The time to attain neutropenia and subsequent febrile neutropenia was significantly lower with an adequate post-harvest CD34+ dose (p=0.009). Febrile neutropenia was seen in 83.1% (54/65) patients. The median time for febrile neutropenia was 4 days post-ASCT. Pre- and post-harvest CD34+ concentrations were directly proportional to each other (p<0.001). The median PFS was 112 months (n=65). Survival was better in males (median PFS: 112 months) vs. females (median PFS: 59 months) (p=0.27). Eight patients relapsed, and eight patients had died. Conclusion: Although unrelated to age or sex, the post-harvest CD34+ dose was inversely related to febrile neutropenia. As pre- and post-harvest CD34+ levels were directly proportional, pre-harvest CD34+ concentrations may be reliably used to assess engraftment outcomes. Rapid neutrophil engraftment was noted in fresh stem cells with PFS of 112 months, and was better among males, the exact reason being unknown. Thus, a larger number of patients should be followed up to obtain an accurate picture.