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1.
Immunol Cell Biol ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582592

RESUMO

Recent studies have highlighted multiple immune perturbations related to SARS-CoV-2 infection-associated respiratory disease (COVID-19). Some of them were associated with immunopathogenesis of the severe COVID-19. However, the reports on immunological indicators of severe COVID-19 in the early phase of infection in patients with comorbidities like cancer are scarce. We prospectively studied ~200 immune response parameters, including a comprehensive immune-cell profile, inflammatory cytokines, and other parameters in 95 patients with COVID-19 (37 cancer patients without active disease and intensive chemo/immunotherapy, 58 patients without cancer) and 21 healthy donors. Of 95 patients, 41 had severe disease, and the remaining 54 were categorized into non-severe disease. We evaluated the association of immune response parameters with severe COVID-19. By principal component analysis, three immune signatures defining characteristic immune response in COVID-19 patients were found. Immune cell perturbations, in particular, decreased levels of circulating dendritic cells (DC) along with reduced levels of CD4 T-cell subsets such as regulatory T cells (Tregs), Th1, Th9 and relative expansion of effector NK cells were significantly associated with severe-COVID-19. Compared to patients without cancer, the levels of terminal effector-CD4 T, Tregs, Th9, effector NK cells, B cells, intermediate-type monocytes, and myeloid-DC were significantly lower in cancer patients with mild and severe COVID-19. We concluded that severely depleted circulating myeloid-DCs and helper-T-subsets in the initial phase of infection were strongly associated with the severe COVID-19 independent of age, type of comorbidity and other parameters. Thus, our study describes the early immune response associated with severe COVID-19 disease in cancer patients without intensive chemo/immunotherapy.

2.
Cancer Biomark ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34334382

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (ASCT) is the preferred treatment option for patients with several hematologic disorders and immunodeficiency syndromes. Graft versus host disease (GVHD) is an immune mediated post-transplant complication which has a major impact on long term transplant outcomes. OBJECTIVE: Current efforts are focused on identification of new markers that serve as potential predictors of GVHD and other post-transplant clinical outcomes. METHODS: This study includes donor harvests collected from twenty-three allogeneic donors during period 2008-2009 and respective transplant recipients followed for clinical outcomes till March 2019. Percent CD26+ and CD34+ cells in donor harvest were analyzed using flow cytometry. Percent expression and infused dose of CD26+ and CD34+ cells were evaluated for association with various clinical outcomes. RESULTS: Total 23 healthy donors 28 years (13 males), and transplant recipients with median age 24 years (17 males) formed the study cohort. The diagnosis included malignant (n= 13) and non-malignant (n= 10) disorders. Median CD34brCD45lo HSC expression was 057% (IQR 024-103) while median CD26 expression was 1964% (IQR 896-3356) of all nucleated cells. CD26 expression was associated with donor age (P= 0.37). CD26 percent expression correlated with WBC engraftment (P= 0.015) and with acute GVHD (P= 0.023) whereas infused CD26 cell dose correlated with WBC engraftment (P= 0.004) and risk of CMV reactivation (P= 0.020). There was no statistically significant correlation of either CD26 expression or cell dose with chronic GVHD, EFS or OS.

3.
Indian J Med Res ; 153(4): 475-483, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34380794

RESUMO

Background & objectives: B-cell chronic lymphocytic leukaemia (B-CLL) is one of the most common forms of adult leukaemia, with a highly variable clinical course. Specific chromosomal and genetic aberrations are used clinically to predict prognosis, independent from conventional clinical markers. Molecular cytogenetic methods such as fluorescence in situ hybridization (FISH) detect aberrations in up to 80 per cent B-CLL patients. This study was conducted to score the frequencies of recurrent aberrations, i.e., del(13q14), trisomy 12, del(11q22), del(17p13), del(6q21) and IgH (immunoglobulin heavy chain) translocations and to understand their role in prognostication and risk stratification. Methods: FISH studies were performed on bone marrow aspirate or peripheral blood of 280 patients using commercially available disease-specific probe set. The data were correlated with clinical and haematological parameters such as low haemoglobin, splenomegaly and lymphadenopathy. Results: Chromosomal aberrations were detected in 79 per cent of patients, with del(13q14) (57%) as the most common cytogenetic aberration, followed by trisomy 12 (27%), del(11q22) (22%), t(14q32) (19%), del(17p13) (18%) and del(6q21) (9%). Single or in coexistence with other aberration del(13q14) had a favourable outcome in comparison to del(11q22), t(14q32), del(17p13) and del(6q21) which were associated with advanced stages of the disease. Trisomy 12 had a variable clinical course. Interpretation & conclusions: FISH was found to be a sensitive and efficient technique in detecting the prevalence of recurrent cytogenetic abnormalities. Each of these aberrations is an important independent predictor of disease progression and survival which aids in designing risk-adapted treatment strategies for better disease management.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Prognóstico
4.
Indian J Med Res ; 153(5&6): 585-590, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414920

RESUMO

The ongoing SARS-CoV-2 pandemic has spread all over the world due to rapid person-to-person transmission. More information about viral load dynamics and replication is needed for clarity on duration of infectiousness of an individual, along with its implications on transmission. This is important to healthcare facilities and public health authorities in formulating guidance on the duration of isolation for patients and return to work criteria for healthcare workers. The duration of detection of viral RNA by molecular methods in the upper respiratory tract has ranged from 2 to 12 wk. Viral RNA detection by reverse transcription polymerase chain reaction (RT-PCR) does not necessarily mean that the individual is infectious to others, as the detected virus may not be replication competent. Infectious virus is generally not shed beyond 20 days of the onset of symptoms in most patients, including severely ill and immunocompromised, as indicated by failure to isolate replication-competent virus beyond this timeline in available studies. Further, detection of neutralizing antibodies in the serum, although associated with positive RT-PCR, is generally not associated with infectious virus shedding as indicated by negative viral cultures beyond this period. In this review, we analyze the current literature on the dynamics of viral load, culture, seroconversion and their implications on infectivity and the duration of isolation precautions for COVID-19 patients.

5.
Lancet Oncol ; 22(7): 970-976, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34051879

RESUMO

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.


Assuntos
COVID-19/terapia , Prestação Integrada de Cuidados de Saúde/tendências , Acesso aos Serviços de Saúde/tendências , Oncologia/tendências , Neoplasias/terapia , Assistência Ambulatorial/tendências , COVID-19/diagnóstico , Diagnóstico Tardio , Detecção Precoce de Câncer/tendências , Hospitalização/tendências , Hospitais com Alto Volume de Atendimentos/tendências , Humanos , Índia/epidemiologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Fatores de Tempo , Tempo para o Tratamento , Listas de Espera
6.
Int J Clin Pract ; 75(8): e14311, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33932309

RESUMO

It is unclear if the use of a molecular transport medium (MTM) containing guanidine isothiocyanate (GITC) would be advantageous over the CDC recommended, commonly used viral transport medium (VTM). We retested 70 SARS-CoV2 cases by RT-PCR in varying stages of follow-up using MTM and VTM in parallel and found discrepant results of RNase P, E and N genes. Majority (81%) patients tested positive with MTM as compared with VTM (27.1%). Even patients who were sampled 3 weeks after diagnosis demonstrated a significant discrepancy in the positivity rates between MTM vs VTM raising concerns about the clinical utility of VTM.


Assuntos
COVID-19 , SARS-CoV-2 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Humanos , RNA Viral
8.
JCO Glob Oncol ; 7: 361-367, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33689483

RESUMO

PURPOSE: The prognosis of relapsed and refractory multiple myeloma (RRMM) that is refractory to bortezomib and lenalidomide is very poor wherein the median survival is between 3 and 9 months. We did this retrospective analysis to study the pattern of utilization, tolerance, and outcomes with pomalidomide in these patients having RRMM. MATERIALS AND METHODS: Retrospective analysis of all the patients who were treated with generic pomalidomide at Tata Memorial Centre, Mumbai, during the period of May 2017 to March 2019 was done. Patients with secretory disease and who had completed at least one cycle of pomalidomide were analyzed for response rates, toxicity, and survival outcomes. RESULTS: A total of 81 patients received pomalidomide-based therapy during this study period, out of which 75 were included in the survival analysis. Forty-eight patients (59.3%) were refractory to both lenalidomide and bortezomib. Overall response rate was 58.7%. Five patients (6.7%) achieved complete response, very good partial response was seen in 13 patients (17.3%), and partial response was seen in 26 patients (34.7%). After a median follow-up of 11 months (range 2-27 months), median progression-free survival was 9.1 months (95% CI, 5.4 to 12.9 months). Median progression-free survival for patients who were refractory to both lenalidomide and bortezomib versus nonrefractory was 5.5 and 12.6 months, respectively, which was significant statistically (P = .04, hazard ratio, 0.35, 95% CI, 0.28 to 0.97). The median overall survival was not reached. Important toxicities included anemia (28%), neutropenia (16%), pneumonia (16%), and venous thrombosis (5%). CONCLUSION: Generic pomalidomide-based therapy is an effective option and is well tolerated in patients with RRMM. Higher response rates and longer survival seen in our study are possibly because of heterogeneity of the study population.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Atenção Terciária à Saúde , Talidomida/análogos & derivados
9.
Transpl Infect Dis ; 23(4): e13576, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33523551

RESUMO

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-ß1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.


Assuntos
COVID-19 , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anticorpos Monoclonais Humanizados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Transplante de Células-Tronco/efeitos adversos
10.
Blood Adv ; 5(5): 1178-1193, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33635331

RESUMO

The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.


Assuntos
Citarabina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Transplante de Células-Tronco , Adulto Jovem
11.
Leukemia ; 35(5): 1392-1404, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33558666

RESUMO

We accrued 201 patients of adult AML treated with conventional therapy, in morphological remission, and evaluated MRD using sensitive error-corrected next generation sequencing (NGS-MRD) and multiparameter flow cytometry (FCM-MRD) at the end of induction (PI) and consolidation (PC). Nearly 71% of patients were PI NGS-MRD+ and 40.9% PC NGS-MRD+ (median VAF 0.76%). NGS-MRD+ patients had a significantly higher cumulative incidence of relapse (p = 0.003), inferior overall survival (p = 0.001) and relapse free survival (p < 0.001) as compared to NGS-MRD- patients. NGS-MRD was predictive of inferior outcome in intermediate cytogenetic risk and demonstrated potential in favorable cytogenetic risk AML. PI NGS-MRD- patients had a significantly improved survival as compared to patients who became NGS-MRD- subsequently indicating that kinetics of NGS-MRD clearance was of paramount importance. NGS-MRD identified over 80% of cases identified by flow cytometry at PI time point whereas FCM identified 49.3% identified by NGS. Only a fraction of cases were NGS-MRD- but FCM-MRD+. NGS-MRD provided additional information of the risk of relapse when compared to FCM-MRD. We demonstrate a widely applicable, scalable NGS-MRD approach that is clinically informative and synergistic to FCM-MRD in AML treated with conventional therapies. Maximum clinical utility may be leveraged by combining FCM and NGS-MRD modalities.


Assuntos
Leucemia Mieloide Aguda/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Adolescente , Adulto , Progressão da Doença , Feminino , Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Neoplasia Residual/patologia , Recidiva , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-33629824

RESUMO

BACKGROUND AND AIM: Molecular mechanism of translocation and outcome in variant chronic myeloid leukaemia (vCML) has been a topic of debate. While several cytogenetic studies suggest a low response to Imatinib Mesylate, others demonstrate a similar disease course in both classical and vCML. Besides, many studies comprehensively also link tyrosine kinase domain (TKD) mutations with aggressive clinical outcome. Thus, we aim to study the molecular mechanism of translocation, identify the third partner chromosomes and comment on the disease course and clinical outcome. METHOD: We cytogenetically characterised 25 vCML cases to determine the third partner chromosome, mechanism of translocation and prognostic outcome. We also compared vCML cases with and without TKD mutation to most appropriately outline the clinical consequence and ascertain the potent cause of unresponsiveness to treatment. RESULTS: Third partner chromosome in variant translocation was defined by conventional and molecular cytogenetics. Although in our study most cases showed inadequate clinical response attributable to TKD mutation rather than variant translocation, we observed an inferior outcome in cases involving chromosome 5 as the third partner. CONCLUSION: Thus, we conclude that characterising and reporting new cases of variant translocations, involving various different chromosomes as third partner (with different breakpoints) by cytogenetics, will lead to a better understanding of the disease. To the best of our knowledge, this kind of delineate study has not been applied to precisely comment on the prospects of cytogenetically characterised vCML.

13.
Bone Marrow Transplant ; 56(7): 1558-1562, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33514924

RESUMO

Transplant associated thrombotic microangiopathy (TA-TMA) is life-threatening complication post allogeneic stem cell transplant (ASCT). Risk factors and prognosis of TA-TMA are not well defined. We retrospectively studied consecutive ASCT patients with AML, ALL, and CML from January 2008 to March 2019 to study the incidence, risk factors, and outcomes of TMA. Definitive and probable TA-TMA was defined using Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) and Cho criteria, respectively. Risk factors explored were age, gender, diagnosis, type of transplant, use of tyrosine kinase inhibitors (TKI) pre transplant, conditioning regimen, and acute GVHD. Standard statistical methods were used. Total 241 patients, 179 (74.2 %) males, median age of 29 years were studied. Diagnoses were AML in 104, ALL in 85 (Ph+ve 23) and CML 52. Total 26 (10.7%) patients (22 males) developed TA-TMA at median of day+102. On multivariate analysis, pre-HSCT TKI (OR 2.7, p = 0.028), haplo-HSCT (OR 3.16, p = 0.018) and presence of acute GVHD (OR 4.17, p = 0.003) were significant risk factors. With a median follow up of 60 months, median OS with and without TA-TMA was 18 and 97 months respectively (p = 0.021). The association of pre-HSCT with TKI with TA-TMA merits further exploration in prospective studies.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/etiologia
14.
Int J Lab Hematol ; 43(5): 990-999, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33432783

RESUMO

INTRODUCTION: Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)-based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B-cell lymphoblastic leukemia/lymphoma (B-ALL), and reports in adult B-ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin-1 in a large cohort of adult B-ALL patients and evaluated its practical utility in MFC-based MRD analysis. METHODS: CD304 was studied in blasts from adult B-ALL patients and normal precursor B cells (NPBC) from non-B-ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized-mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC-based MRD was performed at end of induction (EOI; day-35), end of consolidation (EOC; day 78-80), and subsequent follow-up (SFU) time points. RESULTS: CD304 was positive in 120/214(56.07%) and was significantly associated with BCR-ABL1 fusion (P = .001). EOI-MRD and EOC-MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD-positive B-ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI-MRD and 85.7%, 14.3%, and none of EOC-MRD samples, respectively. Low-level MRD (<0.01%) was detectable in 34 of all (EOI + EOC + SFU = 189) MRD-positive samples, and CD304 was found useful in 50% of these samples. CONCLUSION: CD304 is commonly expressed in adult B-ALL and clearly distinguish B-ALL blasts from normal precursor B cells. It is a stable MRD marker and distinctly useful in the detection of MFC-based MRD monitoring, especially in high-sensitivity MRD assay.

15.
Cancer Med ; 9(23): 8747-8753, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128509

RESUMO

BACKGROUND: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs). PATIENTS AND METHODS: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. RESULTS: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort. CONCLUSIONS: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.


Assuntos
Antivirais/uso terapêutico , COVID-19/prevenção & controle , Neoplasias/terapia , SARS-CoV-2/efeitos dos fármacos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pandemias , Estudos Prospectivos , SARS-CoV-2/fisiologia , Taxa de Sobrevida , Adulto Jovem
16.
PLoS One ; 15(10): e0240398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052962

RESUMO

Wearing face masks is highly recommended to prevent SARS-CoV-2 transmission in health care workers and for the general public. The demand for high quality face masks has seen an upsurge in the recent times, leading to exploration of alternative economic and easily available options, without compromising on the quality. Particle removal from air in terms of capture efficiency of the filter media or the face mask is a crucial parameter for testing and quality assurance. Short-term reusability of the face masks is also an important aspect as the demand for masks will potentially outstrip the supply in future. Sterilization Wraps, which are used to wrap sterile surgical instruments, have shown a promising performance in terms of removal of particles from air. In this study, we evaluate the particle filtration characteristics of face masks made of 2 different metric weights [45 and 60 gram per square metre (GSM)] respectively, using locally available Sterilization Wraps. The aerosol filtration characteristics were also studied after sterilisation by different techniques such as heat with 50% humidity (thermal treatment), ethylene oxide (ETO), steam and radiation dose of 30kGy. We found that 60 GSM face mask had particle capture efficiency of 94% for total particles greater than 0.3 microns and this capture efficiency was maintained even after sterilisation with ETO and thermal treatment. The cost of producing these masks was 30 US cents/mask at our institute. Our study suggests that sterilization wrap material made of non-woven polypropylene spunbond-meltblown-spunbond (SMS) fibres could be an appropriate readily available inexpensive material for making face masks or N95 respirators.


Assuntos
Máscaras/normas , Tamanho da Partícula , Equipamento de Proteção Individual/normas , Têxteis/normas , Aerossóis/química , Desinfecção/métodos , Desinfecção/normas , Óxido de Etileno/química , Filtração/normas , Temperatura Alta , Umidade , Polipropilenos/química
17.
Hematol Oncol ; 38(5): 808-816, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32893896

RESUMO

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1-G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45-63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91-4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26-5.76, p < 0.001).


Assuntos
Biomarcadores Tumorais , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Proteínas de Neoplasias/genética , Adolescente , Adulto , Aberrações Cromossômicas , Análise Mutacional de DNA , Feminino , Regulação da Expressão Gênica , Humanos , Cariotipagem , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Medição de Risco , Análise de Sobrevida , Regulador Transcricional ERG/genética , Adulto Jovem
18.
Int J Hematol ; 112(6): 835-840, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32876851

RESUMO

Hematopoietic stem and progenitor cell (HSPC) mobilization regimens in multiple myeloma typically use filgrastim (GCSF) alone or combination of GCSF with plerixafor or high-dose cyclophosphamide. Murine model and human studies have shown HSPC mobilization potential of bortezomib. A total of 37 patients underwent mobilization using bortezomib 1.3 mg/m2 on day 1, 4, 8 and 11, cyclophosphamide 1 g/m2 on day 8 and 9, and GCSF 10 µg/kg from day 10 (B-Cy-GCSF). This regimen was compared with our earlier cohort of patients where cyclophosphamide was given at dose of 1 g/m2 on day 1 and day 2 followed by GCSF 10 µg/kg from day 4 (Cy-GCSF). In B-Cy-GCSF group, median CD34 cells collected were 9.21 × 106/kg (range 4.95-17.1) while in the Cy-GCSF cohort, the median CD34 cell yield was 8.2 × 106/kg (0.4-24.2). Target CD34 cells yield of 5 × 106/kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-GCSF group (p = 0.07). Three patients failed mobilization after Cy-GCSF, while no patients failed mobilization in bortezomib group. Addition of bortezomib to Cy-GCSF mobilization showed a trend towards increased CD34 collection and reduced need for apheresis sessions.


Assuntos
Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Adulto , Idoso , Antígenos CD34/metabolismo , Remoção de Componentes Sanguíneos , Feminino , Filgrastim/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade
19.
Leuk Lymphoma ; 61(13): 3154-3160, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32757686

RESUMO

Panel based next generation sequencing was performed on a discovery cohort of AML with RUNX1-RUNX1T1. Supervised machine learning identified NRAS mutation and absence of mutations in ASXL2, RAD21, KIT and FLT3 genes as well as a low mutation to be associated with favorable outcome. Based on this data patients were classified into favorable and poor genetic risk classes. Patients classified as poor genetic risk had a significantly lower overall survival (OS) and relapse free survival (RFS). We could validate these findings independently on a validation cohort (n = 61). Patients in the poor genetic risk group were more likely to harbor measurable residual disease. Poor genetic risk emerged as an independent risk factor predictive of inferior outcome. Using an unbiased computational approach based we provide evidence for gene panel-based testing in AML with RUNX1-RUNX1T1 and a framework for integration of genomic markers toward clinical decision making in this heterogeneous disease entity.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Genômica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Aprendizado de Máquina , Mutação , Proteína 1 Parceira de Translocação de RUNX1/genética
20.
J Surg Oncol ; 122(7): 1288-1292, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32841386

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 has caused substantial disruptions in routine clinical care. Emerging data show that surgery in coronavirus disease (COVID)-positive cases can be associated with worsening of clinical outcomes and increased postoperative mortality. Hence, preoperative COVID-19 testing for all patients before elective surgery was implemented in our institution. MATERIALS AND METHODS: Two hundred and sixty-two asymptomatic cancer patients were preoperatively tested for COVID-19 using reverse-transcription polymerase chain reaction technique with nasopharyngeal and oropharyngeal swabbing. All negative patients were operated within 72 hours, and positive patients were quarantined for a minimum 14 days before re-swabbing. RESULTS: In our cohort, 21 of 262 (8.0%) asymptomatic preoperative patients, who were otherwise fit for surgery, tested positive. After adequate quarantine and a negative follow-up test report, 12 of 21 (57%) had an operation. No major postoperative morbidity due to COVID-19 was noted during the immediate postoperative period before discharge from the hospital. CONCLUSION: Routine preoperative COVID-19 testing was successful in identifying asymptomatic viral carriers. There was no incidence of symptomatic COVID-19 disease in the postoperative period, and there was no incidence of morbidity attributable to COVID-19. These data suggested a beneficial role for mandatory preoperative COVID-19 testing.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Testes Obrigatórios/métodos , Neoplasias/cirurgia , Neoplasias/virologia , COVID-19/epidemiologia , COVID-19/virologia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Pandemias , Cuidados Pré-Operatórios/métodos , Saúde Pública
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