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These proceedings comprise 85 articles spanning diverse fields such as bacteriology, molecular biology, biotechnology, dermatology, infectious and parasitic diseases, epidemiology, physiotherapy, immunology, mycology, parasitology, pathology, collective health, and virology. The articles delve into a wide range of research topics, from repurposing drugs for Mycobacterium abscessus complex infections to utilising artificial intelligence for SARS-CoV-2 diagnosis. In bacteriology, investigations explore the correlation between smoking and Helicobacter pylori infection in gastric adenocarcinoma patients, as well as the resistance profiles of Staphylococcus aureus and Pseudomonas aeruginosa in tracheostomised children. Molecular biology studies focus on gene polymorphisms related to diseases like paracoccidioidomycosis. Biotechnology research emphasises bioactive molecules in species like Croton urucurana and the development of computational models for cytotoxicity prediction. Dermatology articles address stability characterisation in vegetable oil-based nanoemulsions. The section on infectious and parasitic diseases encompasses studies on COVID-19 vaccine response in pregnant women and the impact of infection prevention measures in rehabilitation hospitals. Epidemiology investigations analyse trends in premature mortality, tuberculosis in diabetic patients, and public adherence to non-pharmacological COVID-19 measures. Physiotherapy research covers topics such as telerehabilitation through a developed game and the prevalence of congenital anomalies. Immunology studies explore immune responses in HIV and Leishmaniasis, whilst mycology investigates the biotechnological potential of fungi from the cerrado biome. Parasitology research evaluates treatment efficacy against vectors parasites such as Aedes aegypti and Toxoplasma gondii. Pathology articles discuss intentional intoxication in cattle and the influence of curcumin on acute kidney injury therapy. Collective health studies focus on intervention plan development in healthcare settings and pesticide use in horticulture. Lastly, virology research investigates parvovirus occurrence in hospitalised children during the COVID-19 pandemic, hidden hepatitis B virus infection in inmates, and the prevalence of HPV and HTLV-1/2 infections in specific populations.
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Lymphocyte leukemia/lymphoma (ATLL) is a fringe T-cell harm brought about by human T-cell leukemia infection type. Lymphocyte leukemia (ATL) is an exceptionally forceful developed T-cell neoplasm related with human T-cell lymphotropic infection type 1 (HTLV-1) contamination, which influences around 10 million individuals on the planet. Of them, roughly 1-5% at last creates indicative ATL. Patient history: A 15 years male was admitted in AVBRH with complaint of fever, decrease appetite from 1 month, vomiting with blood tinged food particles and melena. Patient was diagnosed case of T-cell variant ALL. Before coming to AVBRH he was admitted to GMC Nagpur where he was diagnosed to had T-cell ALL with aberrant expression of CD10. He also had generalised lymphadenopathy and massive hepatosplenomegaly. He was advised blood transfusion but gives no H/O the same. Then he was discharged. After that patient developed malaena and blood tinged vomiting for which he came to AVBRH for further management. After his arrival, he was covid-19 positive so shifted to COVID ward. After two weeks, RTPCR status was negative then he shifted to PICU. . Clinical finding: The patient had done all necessary investigations by physician order. Medical Management: Patient was treated with IV. Fluids, platelet transfusion, chemotherapy, steroids, calcium gluconate, antibiotics, antacid, vit c and multivitamins. Nursing management: Administered fluid replacement i.e. D5, chemotherapy, platelet transfusion monitored all vital signs half hourly.
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BACKGROUND Patients with peripheral T-cell lymphoma (PTCL) lack good treatment options, particularly in the relapsed and refractory setting (Mak V et al. J Clin Oncol 2013). The development of the targeted therapies in PTCL has been lagging behind those developed for B cell lymphomas. Our work suggested that combinations of epigenetic therapies can be a safe and effective approach for patients with PTCL, particularly those with T-cell lymphomas with a follicular helper phenotype (Marchi E et al. Br. J Haematol 2015;O'Connor O.A. et al;Blood 2019;Falchi L et al. Blood 2020). While the reason for this is not clear, it is thought recurrent mutations in epigenetic factors, including Ten-Eleven Translocation-2 (TET2), DNA methyl transferase-3A (DNMT3A) and isocitrate dehydrogenase-2 (IDH2) may contribute for their increased vulnerability (Couronné L. et al. N Eng J Med 2012;Lemonnier F et al. Blood 2012). Despite these presumptions, a direct explanation for the sensitivity to epigenetic based treatment remains to be established. OBJECTIVES To evaluate the merits of romidepsin plus subcutaneous azacitidine in patients with PTCL when administered in a ‘real-world’ scenario. METHODS We retrospectively identified PTCL patients that were treated with azacitidine and romidepsin outside of a clinical trial based upon queries regarding off study use. The study was reviewed and approved by each Medical Center Institutional Review Board. We have identified 13 patients world-wide whose pretreatment characteristics are shown in Table 1. These patients were treated using 3 different schedules: Schedule A: azacitidine 75mg/m2 s.c. on days 1-7, romidepsin 14 mg/m2 on day 1, 8 and 15 of a 28 day cycle (total of 6 patients);Schedule B: azacitidine 75mg/m2 s.c. on days 1-5, romidepsin 14 mg/m2 on day 8, 15 and 22 of a 35 day cycle;and Schedule C (total of 2 patients): azacitidine 75mg/m2 s.c. on days 1-7, romidepsin 12-14 mg/m2 on day 8, 15 and 22 of a 28 day cycle (total of 5 patients). RESULTS We retrospectively identified 13 patients that were treated with romidepsin and azacitidine off study. Ten patients had angioimmunoblastic lymphoma (AITL), 2 had adult T-cell leukemia/lymphoma (ATLL) and 1 had PTCL-NOS. Eight of the 13 patients had next generation sequencing performed. Most common mutations found were those of TET2 (5 pts), RHOA (4pts), IDH2 (3pts) and DNMT3A (1 pt). One ATLL patient had mutations in TRAF3, FAT1 and MED12. Among these 13 patients, overall response rate (ORR) was 84% and the complete response rate (CR) was 61%. Median number of cycles was 3 (range 1-12). Treatment was well tolerated but notable adverse effects included nausea, fatigue, rash, neutropenia and thrombocytopenia. One patient experienced febrile neutropenia while another had pulmonary infiltrates (differential diagnosis included drug toxicity versus infection). Thrombocytopenia was the most common reason for dose reduction of romidepsin (to 12mg/m2) or its omission on day 8, 15 or 22. In 3 patients, azacitidine and romidepsin were used to achieve remission prior to allogeneic transplant (range of cycles 1-3), with all 3 patients were in CR at their last disease assessment. One patient died of transplant related mortality 8 months after his allogeneic stem cell transplant. There was 1 patient with AITL (treatment naïve) noted to have progression of disease at first imaging following 2 cycles of romidepsin and azacitidine. On the day of her PET/CT, she was however diagnosed with symptomatic Covid19 infection and was hospitalized. A repeat PET/CT 6 weeks later (without any additional lymphoma treatment) revealed PR. CONCLUSIONS Subcutaneous azacitidine and romidepsin administered in a ‘real-world’ situation is highly effective in patients with relapsed PTCL with tolerable toxicity, and can be used to successfully bridge patients to stem cell transplant. Notably, the efficacy was similar to the one reported on a clinical study with oral azacitidine and romidepsin. [Formula presented] Disclosures: Kalac: Astra Zeneca: Consultancy;Kyowa Kirin Consultancy;Gilead: Consultancy;Johnson and Johnson: Research Funding;Guidepoint: Consultancy;GLG: Consultancy. Tam: Beigene: Research Funding;Janssen: Research Funding;Abbvie: Research Funding;Loxo: Honoraria;Beigene: Honoraria;Janssen: Honoraria;Abbvie: Honoraria. Montanari: Seattle Genetics: Research Funding. O'Connor: Servier: Research Funding;Mundipharma: Honoraria;Myeloid Therapeutics: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees;Kymera: Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees;Astex: Research Funding;BMS: Research Funding;Merck: Research Funding;TG Therapeutics: Current Employment, Current equity holder in publicly-traded company. Marchi: BMS: Research Funding;Astex: Research Funding;Merck: Research Funding;Myeloid Therapeutics: Honoraria;Kyowa Kirin: Honoraria;Kymera Therapeutics: Other: Scientific Advisor.
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The introduction of post-transplant cyclophosphamide (PTCy) has circumvented the need for T-cell depletion following haploidentical stem cell transplantation (SCT). By expanding the donor pool for patients from certain ethnic minorities, this has addressed to some degree an important health care disparity issue in SCT. However, a recent registry study showed increased incidence GvHD and inferior outcomes in patients receiving haploidentical SCT with PTCy, tacrolimus and mycophenolate mofetil for GvHD prevention as opposed to matched unrelated donor SCT with PTCy-based GvHD prevention. Seeking to improve the results of GvHD prevention in the setting of haploidentical SCT, we examined a combination of PTCy, abatacept and a short course of tacrolimus (CAST). Abatacept is a recombinant soluble fusion protein composed of the extracellular domain of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) fused to the Fc region of IgG1. Abatacept blocks CD28-CD80I86 axis and prevents T-cell co-stimulation. In early studies, abatacept has shown promising results when added to methotrexate and tacrolimus in matched and mismatched donor SCT. We initiated a phase Ib-II clinical trial for patients with hematological malignancies undergoing haploidentical SCT. Patients received G-CSF mobilized peripheral blood grafts from related haploidentical donors. GvHD prevention consisted of PTCy 50mg/kg IV on day +3 and +4 with forced hydration, abatacept 10mg/kg IV on day +5, +14 and +28 and tacrolimus. Tacrolimus was started on day +5 at 0.02mg/kg/day by continuous IV and adjusted thereafter to maintain a trough level of 5-12ng/mL. Tacrolimus taper was planned to begin on day +60 and complete by day +90 in the absence of GvHD. All patients received standard supportive care including levofloxacin until neutrophil engraftment, posaconazole until day +75, acyclovir for 1 year and, if CMV positive by serology, letermovir until day +100. Pneumocystis Jiroveci prophylaxis was started after neutrophil engraftment and continued until 6 months post-transplant. G-CSF was administered routinely until neutrophil engraftment. Since September 2020, 19 patients were enrolled. Three patients are too early in their post-transplant course and were excluded from this analysis. Patients' characteristics are summarized in the table. All but 2 patients received cryopreserved products. Median times to ANC and platelet engraftment were 18.5 days (14-30) and 28.5 (16-61). All 16 patients achieved full whole blood donor chimerism by day +30. There was no secondary graft failure. With a median follow-up was 149.5 days (41-308) with 10 patients having >120 days and 8 >180 days of follow-up, 4 patients developed skin acute GvHD (all grade I). No patient developed grade II-IV acute GvHD. Two patients developed skin chronic GvHD (limited, both moderate). Both cases were diagnosed following COVID-19 vaccination. Fifteen patients completed tacrolimus taper by day +90. Two patients received systemic steroids, one for treatment of cGvHD. The remaining patients required no further immunosuppressive therapy beyond day +90. CMV activation rate was 25%. One patient had EBV reactivation and required preemptive therapy with 2 weekly rituximab doses. There were no cases of adenovirus, HHV-6 virus or BK virus reactivation. Four patients developed renal insufficiency (3 in the setting of acute sepsis and 1 with thrombotic microangiopathy, which resolved after tapering off tacrolimus. One patient with adult T-cell leukemia/lymphoma relapsed and died. All other patients are alive and well. In summary, our preliminary results suggest that CAST with shortened course of tacrolimus is feasible and seems to offer very promising outcomes with low rates of acute GvHD. The study is accruing actively and the results of a larger cohort with longer follow-up will be presented at the meeting. If confirmed, by improving the outcomes of haploidentical SCT, this regimen may further address a health care disparity issue, offering almost every patient in need of allogeneic SCT an alternative donor op ion with equal outcomes. [Formula presented] Disclosures: Al-Homsi: Daichii Sanyko: Consultancy;Celyad: Other: Advisory Board. Abdul-Hay: Abbvie: Consultancy;Servier: Other: Advisory Board, Speakers Bureau;Jazz: Other: Advisory Board, Speakers Bureau;Takeda: Speakers Bureau;Amgen: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Abatacept - off label use as GvHD prevention Cyclophosphamide - off label use as GvHD prevention
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Circulating full-length osteopontin (FL-OPN) is elevated in plasma from patients with various infectious diseases, such as adult T-cell leukemia, Mycobacterium tuberculosis (TB), hepatitis virus infection, leptospirosis, acquired immune deficiency syndrome (AIDS), AIDS/TB, and coronavirus disease 2019 (COVID-19). Proteolysis of OPN by thrombin, matrix metalloproteases, caspase 8/3, cathepsin D, plasmin, and enterokinase generates various cleaved OPNs with a variety of bioactivities by binding to different target cells. Moreover, OPN is susceptible to gradual proteolysis. During inflammation, one of the cleaved fragments, N-terminal thrombin-cleaved OPN (trOPN or OPN-Arg168 [OPN-R]), induces dendritic cell (DC) adhesion. Further cleavage by carboxypeptidase B2 or carboxypeptidase N removes Arg168 from OPN-R to OPN-Leu167 (OPN-L). Consequently, OPN-L decreases DC adhesion. In particular, the differences in plasma level over time are observed between FL-OPN and its cleaved OPNs during inflammation. We found that the undefined OPN levels (mixture of FL-OPN and cleaved OPN) were elevated in plasma and reflected the pathology of TB and COVID-19 rather than FL-OPN. These infections are associated with elevated levels of various proteases. Inhibition of the cleavage or the activities of cleaved products may improve the outcome of the therapy. Research on the metabolism of OPN is expected to create new therapies against infectious diseases.
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Although some patients with COVID-19 develop only mild symptoms, fatal complications have been observed among those with comorbidities. As patients with cancer are immunocompromised, they are thought to have a high risk of severe illness associated with COVID-19. We report a COVID-19 patient with adult T-cell leukemia-lymphoma (ATL) who was treated using favipiravir. A 69-year-old woman with lymphoma-type ATL was treated using cyclophosphamide, doxorubicin, vincristine, prednisolone and mogamulizumab (M-CHOP) with substantial efficacy. However, in cycle 4 of M-CHOP therapy, she developed fever with mild cough. The patient was admitted to the hospital and CT revealed bilateral ground-glass opacities. SARS-CoV-2 was detected by RT-PCR and the patient was diagnosed with COVID-19. Considering severe immunosuppression caused by ATL, we initiated favipiravir therapy. Subsequently, the fever improved without antipyretics and her C-reactive protein level decreased rapidly. SARS-CoV-2 PCR tests were negative on days 17 and 18 of favipiravir therapy, and the patient was discharged without residual disease on the final CT. This is the first documented case of COVID-19 in a patient with ATL. Although severe immunosuppression caused by ATL was present, severe COVID-19 pneumonia did not develop. The immunosuppressed condition caused by hematological malignancy may not always be a risk factor for severe illness associated with COVID-19. Further accumulation of data regarding COVID-19 in patients with hematological malignancies is warranted to clarify the risk factors for severe illness, the best-in-class antiviral agent, and the optimal treatment strategy in this population.