Case report: Ensitrelvir for treatment of persistent COVID-19 in lymphoma patients: a report of two cases

Persistent COVID-19 is a well recognized issue of concern in patients with hematological malignancies. Such patients are not only at risk of mortality due to the infection itself, but are also at risk of suboptimal malignancy-related outcomes because of delays and terminations of chemotherapy. We report two lymphoma patients with heavily pretreated persistent COVID-19 in which ensitrelvir brought about radical changes in the clinical course leading to rapid remissions. Patient 1 was on ibrutinib treatment for mantle cell lymphoma when he developed COVID-19 pneumonia which was severe and ongoing for 2 months despite therapy with molnupiravir, multiple courses of remdesivir, one course of sotrovimab, tocilizumab, and steroids. Patient 2 was administered R-CHOP therapy for diffuse large B-cell lymphoma when he developed COVID-19 which was ongoing for a month despite treatment with multiple courses of remdesivir and one course of sotrovimab. A 5-day administration of ensitrelvir promptly resolved the persistent COVID-19 accommodated by negative conversions of RT-qPCR tests in both patients within days. Ensitrelvir is a novel COVID-19 therapeutic that accelerates viral clearance through inhibition of the main protease of SARS-CoV-2, 3-chymotrypsin-like protease, which is vital for viral replication. Ensitrelvir is a promising treatment approach for immunocompromised lymphoma patients suffering from persisting and severe COVID-19

Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Blast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML

Subcutaneous panniculitis‐like T‐cell lymphoma post‐mRNA‐1273 COVID‐19 vaccination

Abstract This is a case of subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) was diagnosed by skin biopsy in a patient who presented with fever and erythema nodosum in the umbilicum following mRNA‐1273 COVID‐19 vaccination. COVID‐19 vaccines may cause SPTCL and skin biopsy may help in the diagnosis of erythema nodosum

Lack of Phenotypical and Morphological Evidences of Endothelial to Hematopoietic Transition in the Murine Embryonic Head during Hematopoietic Stem Cell Emergence

<div><p>During mouse ontogeny, hematopoietic cells arise from specialized endothelial cells, i.e., the hemogenic endothelium, and form clusters in the lumen of arterial vessels. Hemogenic endothelial cells have been observed in several embryonic tissues, such as the dorsal aorta, the placenta and the yolk sac. Recent work suggests that the mouse embryonic head also produces hematopoietic stem cells (HSCs)/progenitors. However, a histological basis for HSC generation in the head has not yet been determined because the hematopoietic clusters and hemogenic endothelium in the head region have not been well characterized. In this study, we used whole-mount immunostaining and 3D confocal reconstruction techniques to analyze both c-Kit⁺ hematopoietic clusters and Runx1⁺ hemogenic endothelium in the whole-head vasculature. The number of c-Kit⁺ hematopoietic cells was 20-fold less in the head arteries than in the dorsal aorta. In addition, apparent nascent hematopoietic cells, which are characterized by a “budding” structure and a Runx1⁺ hemogenic endothelium, were not observed in the head. These results suggest that head HSCs may not be or are rarely generated from the endothelium in the same manner as aortic HSCs.</p></div

Three-dimensional analysis of c-Kit⁺ cells in the embryonic head.

<p>(A) 3D confocal image of c-Kit (green) and CD31 (magenta) expression in the mouse head region at E10.5 (35 sp). The whole-head image was acquired using tile scanning (20 tiles). (B) Cartographic distribution of c-Kit⁺ cells in the head. The c-Kit⁺ cells observed in the left half of the head are plotted. The head region for counting c-Kit⁺ cells is indicated by the broken line (above the first pharyngeal arch). PA1: first pharyngeal arch. (C) The number of c-Kit⁺ cells in the head vasculature at different times of development. E9.5 (n = 2, 25 and 26 sp), E10.5 (n = 4, 35 and 36 sp) and E11.5 (n = 4, 45–47 sp) were analyzed.</p

Intravascular large B-cell lymphoma as a recurrence of primary central nervous system lymphoma after chemotherapy: A case report

We report about a 48-year-old woman diagnosed with primary central nervous system lymphoma (PCNSL). After chemotherapy and autologous stem cell transplantation, she presented with a continuous high-grade fever. Positron emission tomography-computed tomography revealed prominent hepatosplenomegaly and high diffuse uptake of 18F-fluorodeoxyglucose in the liver, spleen, and lungs. Intravascular large B-cell lymphoma (IVLBCL) was diagnosed using random skin biopsy. There were no symptoms of IVLBCL at the time of diagnosis of PCNSL. The histopathological features of PCNSL and IVLBCL were nearly similar. These findings suggest that IVLBCL was the recurrence of PCNSL rather than a separate entity

Runx1-GFP and CD45 expression in head c-Kit⁺ cells.

<p>(A-C) Whole-mount immunostaining of E10.5 <i>Runx1-GFP</i> transgenic mice for GFP (green), c-Kit (red) and CD31 (blue) expression. (A) Sagittal image of the dorsal aorta (35 sp). The c-Kit⁺ circulating cells (arrowheads) were negative for Runx1-GFP. (B and C) Runx1-GFP expression in c-Kit⁺ cells. (C) Quantitation of GFP⁺ cells from two embryos (35 sp). The frequency of Runx1-GFP⁺ cells in the head artery c-Kit⁺ cells is similar to that of circulating blood c-Kit⁺ cells. (D and E) Whole-mount immunostaining of E10.5 mouse embryos for c-Kit (green), CD31 (blue) and CD45 (magenta) expression. (D) Representative confocal images of the dorsal aorta and head region (36 sp). The arrowheads indicate c-Kit⁺CD45⁺ cells. (E) Quantitation of CD45⁺ cells from three embryos (36 and 37 sp). The frequency of CD45⁺ cells in the head artery c-Kit⁺ cells is similar to that of circulating blood c-Kit⁺ cells. Scale bars: 50 μm.</p

Majority of head artery c-Kit⁺ cells originate from other organs.

<p>(A) Experimental design for tracing the progenies of yolk sac hemogenic endothelium. <i>Runx1</i>^{<i>SACre/+</i>}:: <i>ROSA26</i>^<i>YFP/+</i> embryos were labeled at E7.5 and analyzed at E10.5. Note that many YFP⁺ endothelial cells (arrowheads) were observed in the yolk sac but not in the head. Scale bar: 50 μm. (B) Representative confocal image of an YFP⁺ c-Kit⁺ cell (arrowhead) in the head. Scale bar: 20 μm. (C) Quantitation of YFP⁺ c-Kit⁺ cells from three embryos (36–38 sp).</p

Absence of Runx1-GFP⁺ endothelial cells in the head vasculature.

<p>Whole-mount immunostaining of the E10.5 (35 sp) <i>Runx1-GFP</i> transgenic mice for GFP (green) and CD31 (magenta) expression. (A) Dorsal aorta. Note that Runx1-GFP is expressed in the flat endothelial cells (arrow) and the hemispherical cells (arrowhead). VA: vitelline artery. Scale bars: 100 μm in the left panel; 50 μm in the right panel. (B) Head. Runx1-GFP was detected in the round cells (blue arrows), but not in the endothelial cells. Scale bars: 300 μm in the left panel; 100 μm in the right panel.</p