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1.
J Immunother ; 45(5): 239-242, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35404324

RESUMO

Immune check point inhibitors such as nivolumab are changing the treatment paradigm of relapsed/refractory Hodgkin lymphoma (r/rHL). Data from single arm studies have shown nivolumab to be an effective and safe therapy. Real world data from resource constrained settings are limited. Our study is a retrospective single center analysis of nivolumab in r/rHL from India. Data regarding baseline and pretreatment characteristics were collected for 20 patients treated with nivolumab from January 2016 to March 2021. Of 20, 15 patients received nivolumab in modified protocol, because of financial limitations. Postnivolumab therapy, the overall response rate was 90%, with 40% in complete remission. The median progression free survival was 13.1 month (95% confidence interval 8.33 mo, not reached) and median overall survival not reached, at a follow up of 24.3 months. No patients discontinued nivolumab because of side effects. Univariate and multivariate analysis showed no effect of dose reduction or increased duration of administration. Most common adverse effect seen was autoimmune hypothyroidism. Possible delayed immune-related side effects were seen in 3 out 5 patients in peritransplant period, in those who received nivolumab as salvage regimen before autologous stem cell transplant. In conclusion, nivolumab shows comparable efficacy and safety even with compromised dosing and schedule of administration of the drug in real world setting.

2.
Blood Cells Mol Dis ; 95: 102662, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35429905

RESUMO

Acute myeloid leukemia with normal cytogenetics (CN-AML) is the largest group of AML patients which is associated with a variegated patient outcome. Multiple molecular markers have been used to risk-stratify these patients. Estimation of expression of BAALC gene (Brain and Acute Leukemia, Cytoplasmic) mRNA level is one of the predictive markers which has been identified in multiple studies. In this study, we examined the clinical and prognostic value of BAALC gene expression in 149 adult CN-AML patients. We also utilized multi-omics databases to ascertain the association of BAALC gene expression with comprehensive molecular and clinicopathologic features in AML. BAALC overexpression was associated with CD34 positivity on leukemic blasts (p = 0.0026) and the absence of NPM1 gene mutation (p < 0.0001), presence of RUNX1 gene mutation (p < 0.001) and poor patient outcomes, particularly in NPM1-wild type/FLT3-ITD negative adult CN-AML patients. Additionally, BAALC expression was associated with the alteration of methylation of its promoter. Further, pathway analysis revealed that BAALC expression is correlated with MYC targets and Ras signalling. We conclude that high BAALC expression associates with poor patient outcome in NPM1-wild type/FLT3-ITD negative adult CN-AML patients.

3.
Am J Transl Res ; 14(2): 927-941, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35273696

RESUMO

INTRODUCTION: Prognostic scores in Ewing sarcoma including baseline clinical and laboratory characteristics are necessary for pre-treatment risk stratification. In this study, we formulated and validated a prognostic model for baseline risk categorization in Ewing sarcoma. MATERIALS AND METHODS: A retrospective single-institutional study was conducted on Ewing sarcoma patients treated uniformly between January 2003 and December 2018. Baseline clinical/pathological characteristics and survival outcomes were noted from medical records. The cohort was randomised into a derivation and validation cohort. A prognostic score was formulated by including independent prognostic factors from the derivation cohort by multivariable analysis. The prognostic model was validated in the validation cohort along with estimation of its predictive ability. RESULTS: A total of 860 patients were included with 40.3% having baseline metastases. Tumor diameter >5 cm (HR 2.04; P<0.001; score 2), baseline metastases (HR 2.33; P<0.001, score 2), and total leucocyte count >11000/mm3 (HR 1.44; P=0.015; score 1) were independent predictors of overall survival in derivation cohort and included for prognostic score calculation. Patients were categorized into low (score 0), intermediate (score 1-3) and high-risk (score 4-5) groups. Harrell's c-indexes of the model were 0.625, 0.622 and 0.624 in the derivation, validation and whole cohort respectively. The timed AUC of ROC of the prognostic score-group for 5-year survival was 0.72, 0.71 and 0.73 in the derivation, validation and whole cohort respectively. CONCLUSIONS: We have formulated and validated a prognostic score for Ewing sarcoma incorporating baseline clinical and laboratory parameters, with fair predictive ability for risk stratification and facilitating risk-adapted personalized therapy.

4.
Am J Dermatopathol ; 44(5): 376-379, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234192

RESUMO

ABSTRACT: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%-42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.


Assuntos
Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutâneo Primário de Células Grandes , Transtornos Linfoproliferativos , Dermatopatias , Neoplasias Cutâneas , Idoso , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/diagnóstico , Linfoma Anaplásico Cutâneo Primário de Células Grandes/patologia , Transtornos Linfoproliferativos/patologia , Masculino , Recidiva Local de Neoplasia , Receptores Proteína Tirosina Quinases , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
5.
J Pediatr Hematol Oncol ; 44(4): 186-190, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35293880

RESUMO

The median age of presentation for Hodgkin lymphoma (HL) is lower in developing countries with a higher proportion under 5 years of age possibly attributable to the high prevalence of Epstein-Barr virus-driven disease. It is unclear whether the clinical presentation and outcomes of this cohort are different with concern regarding late effects being most pronounced in this age group. We report the outcome of children under 5 years of age enrolled in the InPOG-HL-15-01, the first multicentric collaborative study for newly diagnosed children and adolescents with HL from India. Thirty-five (9%) of the study population was younger than 5 years with a striking male preponderance of 34:1. They were less likely to have bulky disease, mediastinal or splenic involvement. The outcomes appear to be at least as favorable as in the older patient group. Efforts need to be made to evolve treatment strategies that spare this very young cohort from potential late effects.


Assuntos
Infecções por Vírus Epstein-Barr , Doença de Hodgkin , Adolescente , Criança , Pré-Escolar , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4 , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/terapia , Humanos , Masculino , Mediastino/patologia , Prevalência
6.
Trials ; 23(1): 102, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35101099

RESUMO

BACKGROUND: In the west, survival following treatment of childhood acute lymphoblastic leukaemia (ALL) approaches 90%. Outcomes in India do not exceed 70%. To address this disparity, the Indian Collaborative Childhood Leukaemia group (ICiCLe) developed in 2013 a contemporary treatment protocol for uniform risk-stratified management of first presentation ALL based on cytogenetics and minimal residual disease levels (MRD). A multicentre randomised clinical trial opened in 2016 (ICiCLe-ALL-14) and examines the benefit of randomised interventions to decrease toxicity and improve outcomes. METHODS: Patients 1-18 years with newly diagnosed ALL are categorised into four risk groups based on presentation features, tumour genetics and treatment response. Standard risk includes young (< 10 years) B cell precursor ALL (BCP-ALL) patients with low presentation leucocyte count (< 50 × 109/L) and no high-risk features. Intermediate risk includes BCP-ALL patients with no high-risk features but are older and have high presentation leucocyte counts and/or bulky disease. High risk includes BCP-ALL patients with any high-risk feature, including high-risk genetics, central nervous system leukaemia, poor prednisolone response at treatment day 8 and high MRD (≥ 0·01%) at the end of induction. Patients with T-lineage ALL constitute the fourth risk group. All patients receive four intensive treatment blocks (induction, consolidation, interim maintenance, delayed intensification) followed by 96 weeks of maintenance. Treatment intensity varies by risk group. Clinical data management is based on a web-based remote data capture system. The first randomisation examines the toxicity impact of a shorter induction schedule of prednisolone (3 vs 5 weeks) in young non-high-risk BCP-ALL. The second randomisation examines the survival benefit of substituting doxorubicin with mitoxantrone in delayed intensification for all patients. Primary outcome measures include event-free survival (overall, by risk groups), sepsis rates in induction (first randomisation) and event-free survival rates following second randomisation. DISCUSSION: ICiCLe-ALL-14 is the first multicentre randomised childhood cancer clinical trial in India. The pre-trial phase allowed standardisation of risk-stratification diagnostics and established the feasibility of collaborative practice, uniform treatment, patient enrolment and data capture. Pre-trial observations confirm the impact of risk-stratified therapy in reducing treatment-related deaths and costs. Uniform practice across centres allows patients to access care locally, potentially decreasing financial hardship and dislocation. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI) CTRI/2015/12/006434 . Registered on 11 December 2015.


Assuntos
Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Estudos Multicêntricos como Assunto , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Indian J Hematol Blood Transfus ; 38(1): 1-7, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35125706

RESUMO

Faecal carriage of Carbapenem-resistant Enterobacteriaceae (CRE) is being observed as an important risk factor for bacteremia among patients with hematological malignancies. A prospective surveillance study was conducted among these patients to determine the gut colonization of CRE. Rectal/perianal swabs were collected to isolate CRE. Carbapenem resistance was detected by disk diffusion, modified-Hodge, Carba-NP test, and PCR for bla NDM-1, bla KPC, bla OXA-48, bla VIM, bla IMP genes. A total of 209 CRE isolates were identified from 151 patients. E. coli was the most common (83.2%) CRE identified, followed by Klebsiella spp. (9.6%). The majority of CRE were observed resistant to ertapenem (86%). bla NDM-1 was the most common gene (57.3%), followed by bla OXA-48 (37.8%). 26.8% isolates found to carry both bla NDM-1 and bla OXA-48 genes. CRE is increasingly observed to cause bacteremia among hematological malignancy patients due to increased colonization. Screening for gut CRE colonization is necessary to guide empirical therapy and apply infection control measures among these patients.

9.
Cancers (Basel) ; 14(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35159058

RESUMO

Selinexor, an oral selective inhibitor of nuclear export, was evaluated in the Phase 2b SADAL study in patients with diffuse large B-cell lymphoma (DLBCL) who previously received two to five prior systemic regimens. In post hoc analyses, we analyzed several categories of patient characteristics (age, renal function, DLBCL subtype, absolute lymphocyte count, transplant status, number of prior lines of therapy, refractory status, Ann Arbor disease stage, and lactate dehydrogenase) at baseline, i.e., during screening procedures, to determine their potential contributions to the efficacy (overall response rate [ORR], duration of response [DOR], overall survival [OS]) and tolerability of selinexor. Across most categories of characteristics, no significant difference was observed in ORR or DOR. OS was significantly longer for patients < 65 vs. ≥ 65 years, and for those with lymphocyte counts ≥ 1000/µL vs. < 1000/µL or lactate dehydrogenase ≤ ULN vs. > ULN. The most common adverse events (AEs) across the characteristics were thrombocytopenia and nausea, and similar rates of grade 3 AEs and serious AEs were observed. With its oral administration, novel mechanism of action, and consistency in responses in heavily pretreated patients, selinexor may help to address an important unmet clinical need in the treatment of DLBCL.

10.
Indian J Hematol Blood Transfus ; 38(1): 153-157, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35125722

RESUMO

PURPOSE: There is paucity of data regarding T-cells in paediatric AML patients. The aim of this prospective study was to evaluate trend of T-cell subset during disease course of paediatric AML patients and to see its correlation with patient characteristics and survival outcome. METHODS: T-cell subsets (CD3, CD4 and CD8) were evaluated by flow-cytometry at diagnosis, post-induction, post-treatment completion, at 3 months and 6 months post-treatment completion, and relapse in 29 pediatric AML patients. Trend of T-cells was plotted between group A (those in continuous remission) and group B (those who relapsed) patients. RESULTS: Patients with high WBC count had significantly higher number of CD3, CD4 and CD8 cell. Baseline Tcell subsets did not affect CR, EFS and OS; however, higher than median CD4 count predicted improved DFS [58% vs 25%; HR = 0.306 (0.10-0.93); P = 0.037]. On serial follow-up from post-induction till 3 months after completion of therapy, there was no difference in the absolute values of T cell subsets between group A and B patients. CONCLUSION: Our study demonstrated T cell subsets are increased in AML subjects with high WBC count. CD4 cells have a positive impact on DFS. Serial follow-up has no impact on T cell subsets. Further studies in larger patient cohorts are needed to evaluate if CD4 population may serve as an immune biomarker for AML.

11.
J Surg Oncol ; 125(6): 1032-1041, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35099828

RESUMO

BACKGROUND: Conventional periacetabular pelvic resections are associated with poor functional outcomes. Resections through surgical corridors beyond the conventional margins may be helpful in retaining greater function without compromising the oncological margins. METHODS: The study included a retrospective review of 82 cases of pelvic resections for pelvic tumors. Outcomes of acetabulum preservation (Group A) were compared with complete acetabular resection (Group B). Also, we compared outcomes of Type I + half resections (Group 1) with Type I + II resections (Group 2), and Type III + half resections (Group 3) with Type II + III resections (Group 4). RESULTS: Group A (n = 44) had significantly better functional outcome than Group B (n = 38) with average MSTS93 score 22.3 versus 20.1 and average HHS 91.3 versus 82.5 (p < 0.001). Group 1 (n = 14) and Group 2 (n = 12) had similar functional outcomes (mean MSTS93 score 22.07 vs. 21.58 [p = 0.597] and mean HHS 90.37 vs. 86.51 [p = 0.205]). Group 3 (n = 11) had significantly better functional outcome than Group 4 (n = 17), with mean MSTS93 score 22.8 versus 19.7 (p < 0.001) and mean HHS 92.3 versus 80.1 (p < 0.001). Oncological outcomes were similar among the groups. CONCLUSION: Transacetabular pelvic resections provide functional benefit over conventional resections without compromising oncological margins. There is a need to revisit and revise the pelvic resection planes.


Assuntos
Neoplasias Ósseas , Neoplasias Pélvicas , Acetábulo/patologia , Acetábulo/cirurgia , Neoplasias Ósseas/patologia , Humanos , Margens de Excisão , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Pediatr Hematol Oncol ; : 1-15, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978257

RESUMO

The literature on B-non-Hodgkin lymphoma (NHL) in India is restricted to individual hospital data. The study aimed to evaluate the epidemiology and outcome of B-NHL in our country. One hundred and ninety-one patients of B-NHL from 10 centers diagnosed between 2013 and 2016 were analyzed retrospectively. B/T lymphoblastic lymphoma and patients with inadequate data were excluded. The median age was 88 months (IQR: 56, 144) with an M:F ratio of 5.6:1. Undernourishment and stunting were seen in 36.5% and 22%. Primary site was abdomen in 66.5%. Hypoalbuminemia was noted in 82/170 (48.2%). Histological subtypes: Burkitt lymphoma (BL): 69.6%, Burkitt-like: 10.4%, and diffuse large B cell lymphoma (DLBCL): 13.6%, unclassified and others (6.4%). Stage distribution: I/II, 33 (17.3%), III, 114 (59.7%), and IV, 44 (23%). One-eighty-six patients took treatment. Protocols used were LMB and BFM in 160/186 (86%). At a median follow-up of 21.34 (IQR: 4.34, 36.57) months, the disease-free-survival (DFS) was 74.4% and event-free-survival (EFS) was 60.7%. Treatment-related mortality (TRM), relapse/progression and abandonment were 14.3%, 14.5%, and 8.4%, respectively. Bone marrow positivity, stage IV disease, and lactate dehydrogenase (LDH) > 2,000 U/l predicted inferior EFS. Stage IV disease, LDH > 2,000 U/l, bone marrow positivity, tumor lysis syndrome and low albumin predicted TRM; LDH retained significance on multivariate analysis for EFS and TRM [OR: 4.54, 95% CI: 1.14-20, p 0.03; OR 20, 95%CI: 1.69-250, p 0.017]. BL was the main histological subtype. High TRM and relapse/progression are hampering survival. An LDH > 2,000 U/l was adversely prognostic. These data demonstrate a need to develop a national protocol that balances toxicity and potential for cure.

14.
Eur J Radiol ; 148: 110170, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35086004

RESUMO

OBJECTIVES: To characterize baseline T1 values of tumors, measure changes after the course of chemotherapy, and evaluate its potential as a marker of response assessment in patients with osteosarcoma. MATERIALS AND METHODS: A total of 35 patients (male:female = 27:8; age = 17.9 ± 6 years; metastatic:localized = 11:24) with biopsy-proven osteosarcoma were analyzed prospectively. All patients underwent magnetic resonance imaging before neoadjuvant chemotherapy (NACT) (baseline) and after NACT completion (follow-up), followed by surgery and histopathological evaluation. Histopathological necrosis served as the gold standard for assessing chemotherapy response (responder: ≥50% necrosis and non-responder: <50% necrosis). Three-dimensional spoiled gradient recalled echo images were acquired with varying flip angles (50, 100, 200, and 300) using a 1.5 Tesla scanner. T1 values were estimated in healthy muscle tissue and tumors at baseline and follow-up, and the relative percentage changes after NACT (ΔT1) were evaluated, and histogram analysis was performed to characterize the T1 value of the tumor and predict the NACT response using the Pearson correlation coefficient (r) and receiver operating characteristic curve analysis. RESULTS: At baseline, a significantly higher T1-mean (830.96 ± 193.88 msec versus 683.29 ± 210.00 msec; p = 0.003) and lower T1-skewness (0.86 ± 1.66 versus 1.60 ± 1.55; p = 0.02) were observed in osteosarcoma than healthy tissue. Responder:non-responder ratio was 13:22. At baseline, a significantly higher T1-mean (936.14 ± 193.17 msec versus 768.82 ± 169.25 msec; p = 0.018) and lower T1-skewness (-0.17 ± 0.85 versus 1.47 ± 1.73; p = 0.003) were observed among responders, than non-responders. After NACT, ΔT1 in tumor was significantly higher among responders than non-responders (-27.22 ± 12.17% versus -15.70 ± 18.99%; p = 0.034). ΔT1-mean and ΔT1-skewness after NACT were moderately correlated (r =  - 0.4, p = 0.030; r = 0.4, p = 0.011) with histopathological necrosis. For predicting NACT response, T1-mean and T1-skewness jointly produced an area under the curve (AUC) = 0.80 at baseline, and ΔT1-mean and ΔT1-skewness jointly produced AUC = 0.76 after NACT. CONCLUSION: The mean and skewness of T1 values in osteosarcoma are potential non-invasive imaging markers for chemotherapy response assessment.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Adolescente , Adulto , Área Sob a Curva , Biomarcadores , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Criança , Feminino , Humanos , Masculino , Terapia Neoadjuvante , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Adulto Jovem
15.
JAMA Netw Open ; 5(1): e2142210, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34994793

RESUMO

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.


Assuntos
COVID-19/epidemiologia , Pessoal de Saúde , Reinfecção , SARS-CoV-2 , Adulto , COVID-19/etiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Imunogenicidade da Vacina , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Centros de Atenção Terciária , Vacinas de Produtos Inativados/administração & dosagem , Vírion/imunologia , Adulto Jovem
16.
Pediatr Surg Int ; 38(2): 257-267, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34674019

RESUMO

INTRODUCTION: Wilms tumor is the most common renal malignancy in children and difficult to differentiate from other paediatric abdominal tumors radiologically, necessitating an invasive procedure for diagnosis. Previous studies have shown the potential role of miRNA as biomarkers for diagnosis, histological subtyping and prognosis. In this study, we are exploring the role of miRNA in the histological subtyping of Wilms tumor in the Indian population. MATERIALS AND METHODS: A total of 15 cases of Wilms tumor were evaluated for global miRNA expression analysis by microarray. Total RNA was extracted from fresh frozen tumor and miRNA expression analysis was performed using Agilent platform. Unsupervised clustering was done to analyse the data. RESULTS: Using unpaired student T test, top 10 significantly differentially expressed miRNA were selected which could differentiate among different histological subtypes by unsupervised hierarchical clustering and principal component analysis. The presence of necrosis, heterologous differentiation led to change in miRNA expression profile and led to a distinct cluster formation. CONCLUSIONS: A panel of 5 miRNAs (miR1, 133b, 299-3p, 499a-5p, 491-3p) could differentiate among different histological subtypes of Wilms tumor, thus avoiding an invasive procedure in children, however, further confirmation using real time PCR analysis will be needed.


Assuntos
Neoplasias Renais , MicroRNAs , Tumor de Wilms , Biomarcadores Tumorais/genética , Criança , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , MicroRNAs/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Tumor de Wilms/genética
17.
Cancer ; 128(3): 579-586, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34618361

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led the Indian government to announce a nationwide lockdown on March 23, 2020. This study aimed to explore the impact of the pandemic on the accessibility of care for children with cancer and to view strategies adopted by hospitals for service delivery. METHODS: Weekly average of childhood cancer (≤18 years) patient registrations during pre-lockdown period (January 1 to March 23, 2020) were compared with post-lockdown period (March 24 to May 31, 2020). The effect on the scheduled treatment was investigated for post-lockdown period. A survey of health care providers was conducted to determine centers' adopted strategies. RESULTS: In 30 participating centers, 1146 patients with childhood cancer (797 pre-lockdown period and 349 post-lockdown period) were registered. The weekly average registration was 67.3 and 35.5 patients during pre-lockdown and post-lockdown respectively (decline of 47.9%). Although most centers experienced this decline, there were 4 that saw an increase in patient registrations. The distribution of patients registered post-lockdown was found significantly different by age (lesser older age, P = .010) and distance (lesser travel distance, P = .001). 36.1% of patients, who were scheduled for any of the treatment modalities (chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation) during the post-lockdown period, experienced delays. Centers adopted several strategies including modifications to treatment protocols, increased use of growth factors, and increased support from social organizations. CONCLUSIONS: This multicenter study from India suggests that the COVID-19 pandemic and the lockdown impacted 2 out of 3 children with cancer. The effect of this on survival is yet to be established.


Assuntos
COVID-19 , Neoplasias , Idoso , Controle de Doenças Transmissíveis , Acesso aos Serviços de Saúde , Humanos , Índia/epidemiologia , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , SARS-CoV-2
18.
Ann Diagn Pathol ; 56: 151846, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34749048

RESUMO

PURPOSE: VEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. METHODS: VEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. RESULTS: Immunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872-150.495; P = 0.012) was the most significant poor prognostic factor. CONCLUSIONS: This study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Neoplasias Oculares/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Doenças do Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/mortalidade , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/mortalidade , Feminino , Seguimentos , Humanos , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
19.
J Pediatr Hematol Oncol ; 44(2): e460-e462, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34054049

RESUMO

Though allogeneic hematopoietic stem cell transplant (HSCT) is standard for relapsed pediatric acute myeloid leukemia, often it may not be accessible due to donor unavailability and resource limitations. We retrospectively analyzed outcomes of 26 children (mean age: 10.9±4.5 y) who underwent autologous HSCT in complete remission 2. Three-year event-free survival and overall survival were 50.1±10.7% and 63.3±9%, respectively; with 1 treatment-related death and 46% relapse rate. Notwithstanding the retrospective study design and somewhat favorable patient characteristics, the outcomes are comparable with those of other series and our own allogeneic HSCT data. Autologous HSCT is a potential alternative to allogeneic HSCT, especially in countries with poorly maintained donor registries.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Criança , Humanos , Leucemia Mieloide Aguda/terapia , Recidiva , Estudos Retrospectivos , Irmãos
20.
Indian J Pediatr ; 89(4): 327-332, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34106443

RESUMO

OBJECTIVES: To evaluate the presence of developmental dental anomalies, like microdontia, hypodontia, abnormally shaped teeth (AST), and developmental defects of enamel (DDE) in childhood cancer survivors and compare it with the healthy controls. METHODS: This cross-sectional analytical study was conducted in 2 groups: childhood cancer survivors (CCS) group including children (> 12 y, m/f) who had undergone anticancer therapy (ACT) before 8 y of age and healthy control group (> 12 y, m/f) without any systemic disease. Pearson chi-square test was used to analyze the difference between the CCS group and the control group for microdontia, hypodontia, AST, DDE and for intragroup analysis in CCS group. Odds ratio was also calculated. RESULTS: A total of 120 and 121 children were included in CCS and control group, respectively. The prevalence of microdontia, hypodontia, abnormally shaped teeth, and DDE was 17.5% (21), 5% (6), 8.33% (10), and 37.5% (45), respectively in CCS group. It was 8.2% (10), 2.5% (3), 1.65% (2), and 22.3% (27), respectively in the control group. A statistically significant difference was seen in microdontia (p = 0.032), abnormally shaped teeth (p = 0.017) and DDE (p = 0.01). Higher prevalence was seen when ACT began at an early age. CONCLUSION: An association between developmental dental anomalies and anticancer therapy (ACT) exists with significantly higher difference in microdontia, abnormally shaped teeth and DDE among survivors of childhood cancer as compared to healthy population. These known adverse effects of ACT on developing teeth should be considered during treatment planning of the children having cancers.


Assuntos
Sobreviventes de Câncer , Neoplasias , Anormalidades Dentárias , Criança , Estudos Transversais , Dentição , Humanos , Neoplasias/tratamento farmacológico , Prevalência , Anormalidades Dentárias/epidemiologia
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