Acute leukemias with complex karyotype show a similarly poor outcome independent of mixed, myeloid or lymphoblastic immunophenotype: A study from the Bone Marrow Pathology Group.

Mixed phenotype acute leukemia (MPAL) is a heterogenous group of acute leukemias characterized by leukemic blasts that express markers of multiple lineages. The revised 4th edition WHO classification of MPAL excludes AML with myelodysplasia related changes (AML-MRC), including those with complex karyotype (CK), from a diagnosis of MPAL. Abnormal karyotype is frequent in MPAL with the reported rate of CK in MPAL ranging from 19% to 32%. Due its rarity, the clinical and genetic features of MPAL with CK remain poorly characterized. This study aims to further characterize the genetic features of MPAL with CK in comparison to cases of AML and ALL with CK. Cases of de novo MPAL, AML, and B- and T-ALL patients with CK were collected from 8 member institutions of the Bone Marrow Pathology Group. We found no significant difference in overall survival between MPAL with CK compared to AML and ALL with CK. AML with CK was more strongly associated with TP53 mutations, however the presence of TP53 mutations conferred a worse prognosis regardless of lineage. ALL with CK seems to show increased IKZF1 mutation rates which is known to confer a worse prognosis in ALL. Additionally, MPAL with CK showed similarly poor outcomes regardless of whether a lymphoid or myeloid chemotherapy regimen is chosen. Our results suggest that acute leukemias with complex karyotype show a similarly poor outcome regardless of lineage differentiation and that mutation in TP53 confers a poor prognosis in all lineages. Our results support the exclusion of immunophenotypic MPAL with CK from MPAL and appear to confirm the approach proposed in the revised 4th edition WHO to include them as AML with myelodysplasia-related changes and similar myelodysplasia-related AML categories of newer classifications.

Spontaneous remission of acute lymphoblastic leukemia: A series of nine cases and a review of literature.

AIMS: To report a series of acute lymphoblastic leukemia (ALL) cases with spontaneous remission and provide presenting clinical and pathologic information and details of clinical course to raise awareness among oncologists and patients. METHODS: We identified and analyzed nine patients with ALL and spontaneous remission. Review of literature reveals an additional nine previously reported cases with similar clinical course. RESULTS: All of these patients, ranging in age from 2 to 12 years of age, presented with inciting signs and symptoms of viral or bacterial infection. All of the patients showed varying percentages of lymphoblasts (.2% to 90%) in diagnostic bone marrow biopsy. All B-ALL cases shared a similar blast phenotype on flow cytometry with coexpression of CD19, CD10 and TdT and variable CD20 expression. All nine patients achieved spontaneous remission of their leukemia as confirmed by flow cytometry and/or bone marrow biopsy without chemotherapeutic intervention. Time to remission from presentation ranged from 1 to 8 weeks. After remission, all patients redeveloped ALL, and time from remission to reemergence ranged from 2 to 24 weeks. CONCLUSION: Our series of cases and cases identified in literature show that ALL diagnosed with modern methods of flow cytometry and molecular analysis will recur within weeks to months from disappearance, usually with cytopenias, which provides a template for oncologic follow-up and testing in these patients.

De novo or recurrent glomerulonephritis and acute tubulointerstitial nephritis after COVID-19 vaccination: A report of six cases from a single center.

Billions of COVID-19 vaccine doses have been administered to combat the ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2. While these vaccines are considered safe, with most adverse events being mild to moderate and transient, uncommon systemic side effects of the vaccines, including de novo or re-activation of various glomerular diseases have recently been observed. We report 6 patients who developed glomerular or acute tubulointerstitial disease shortly after receiving COVID-19 vaccinations. Five of these patients received mRNA vaccines (3 Moderna, 2 Pfizer-BioNTech) and 1 received adenovirus-26 vector vaccine (Johnson and Johnson/Janssen). Four of our patients developed de novo glomerulonephritis or acute tubulointerstitial nephritis (ATIN), while the other 2 had re-activation of prior glomerulonephritis. Two patients presented with acute kidney injury (AKI) characterized by severe ATIN. While both of them also had evidence of immune complex glomerular disease, ATIN was the dominant feature on the biopsies. Two other patients presented with high-grade proteinuria and AKI. Like the aforementioned patients, these patients had evidence of immune complex glomerular disease, but acute onset nephrotic syndrome was the leading clinical feature. Another patient presented with de novo myeloperoxidase-anti-neutrophil-cytoplasmic-antibody-associated pauci-immune crescentic glomerulonephritis. Yet another patient had re-activation of immunoglobulin-A glomerulonephritis that had been quiescent for several years prior to the vaccination. It is difficult to ascertain any causal relationship between COVID-19 vaccination and onset/recurrence of kidney diseases. However, vigilance about occurrence of such complications is imperative. Importantly, all our cases responded well to the immunosuppressive treatment.

Identification of potential antiviral compounds against SARS-CoV-2 structural and non structural protein targets: A pharmacoinformatics study of the CAS COVID-19 dataset.

SARS-CoV-2 is a newly discovered virus which causes COVID-19 (coronavirus disease of 2019), initially documented as a human pathogen in 2019 in the city of Wuhan China, has now quickly spread across the globe with an urgency to develop effective treatments for the virus and emerging variants. Therefore, to identify potential therapeutics, an antiviral catalogue of compounds from the CAS registry, a division of the American Chemical Society was evaluated using a pharmacoinformatics approach. A total of 49,431 compounds were initially recovered. After a biological and chemical curation, only 23,575 remained. A machine learning approach was then used to identify potential compounds as inhibitors of SARS-CoV-2 based on a training dataset of molecular descriptors and fingerprints of known reported compounds to have favorable interactions with SARS-CoV-2. This approach identified 178 compounds, however, a molecular docking analysis revealed only 39 compounds with strong binding to active sites. Downstream molecular analysis of four of these compounds revealed various non-covalent interactions along with simultaneous modulation between ligand and protein active site pockets. The pharmacological profiles of these compounds showed potential drug-likeness properties. Our work provides a list of candidate anti-viral compounds that may be used as a guide for further investigation and therapeutic development against SARS-CoV-2.

Digital Droplet PCR for SARS-CoV-2 Resolves Borderline Cases.

OBJECTIVES: The Bio-Rad SARS-CoV-2 ddPCR Kit (Bio-Rad Laboratories) was the first droplet digital polymerase chain reaction (ddPCR) assay to receive Food and Drug Administration (FDA) Emergency Use Authorization approval, but it has not been evaluated clinically. We describe the performance of ddPCR-in particular, its ability to confirm weak-positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results. METHODS: We clinically validated the Bio-Rad Triplex Probe ddPCR Assay. The limit of detection was determined by using serial dilutions of SARS-CoV-2 RNA in an artificial viral envelope. The ddPCR assay was performed according to the manufacturer's specifications on specimens confirmed to be positive (n = 48) or negative (n = 30) by an FDA-validated reverse transcription-polymerase chain reaction assay on the m2000 RealTime system (Abbott). Ten borderline positive cases were also evaluated. RESULTS: The limit of detection was 50 copies/mL (19 of 20 positive). Forty-seven specimens spanning a range of quantification cycles (2.9-25.9 cycle numbers) were positive by this assay (47 of 48; 97.9% positive precent agreement), and 30 negative samples were confirmed as negative (30 of 30; 100% negative percent agreement). Nine of 10 borderline cases were positive when tested in triplicate. CONCLUSIONS: The ddPCR of SARS-CoV-2 is an accurate method, with superior sensitivity for viral RNA detection. It could provide definitive evaluation of borderline positive cases or suspected false-negative cases.