CD19-directed chimeric antigen receptor-modified T cells (CAR T cells) achieve durable remissions in about 30-40% of relapsed/refractory large B-cell lymphomas. T cell exhaustion and/or an immunosuppressive tumor-microenvironment may contribute to CAR T-cell failure. Pembrolizumab, an anti-PD1 immune checkpoint inhibitor, may reverse T-cell exhaustion following CAR T-cell therapy. We treated 12 patients with B-cell lymphomas who were either refractory to (N=9) or relapsed after (N=3) CD19-directed CAR T cell (4-1BB-costimulated) therapy with pembrolizumab 200mg IV every 3 weeks. Median time from CAR T-cell infusion to first pembrolizumab dose was 3.3 months (range: 0.4-42.8 months). Pembrolizumab was well-tolerated and the only ≥ grade 3 adverse events related to pembrolizumab were neutropenia (N=3; 25%). Best overall response rate after pembrolizumab was 3/12 (25%) [1 complete response; 2 partial responses]. One (8%) patient had stable disease, thus, 4/12 (33%) patients had clinical benefit. After pembrolizumab, 4 patients with clinical benefit had increase in percentage of CAR T cells by mass cytometry (CyTOF); 3 of 4 of these patients also had increases in CAR19 transgene levels by qPCR. Deep immune profiling using mass cytometry revealed increased CAR T cell activation and proliferation and less T-cell exhaustion in clinical responders. Together, PD1 blockade with pembrolizumab after CD19-directed CAR T-cell therapy appears safe and may achieve clinical responses in some patients with B-cell lymphomas refractory to or relapsed after CAR T-cell therapy.
IntroductionTesticular tumors are a heterogeneous group of neoplasms exhibiting diverse histopathology and can be classified as seminomatous and non-seminomatous germ cell tumor types. Mixed germ cell tumors contain more than one germ cell component and various combinations have been reported. Here, we present a rare case of a mixed germ cell tumor composed of seminoma, choriocarcinoma and teratoma with a secondary somatic malignancy.Case presentationA 31-year-old Caucasian man presented with splenic rupture to our hospital. A right-sided testicular swelling had been present for 6 months and his alpha-fetoprotein, beta-human chorionic gonadotropin, and lactose dehydrogenase were increased. An ultrasound of his scrotum revealed an enlarged right testis with heterogeneous echogenicity. Multiple hypervascular lesions were noted in his liver and spleen. He underwent transcatheter embolization therapy of his splenic artery followed by splenectomy and right-sided orchiectomy. A computed tomography scan also showed metastasis to both lungs. During his last follow up after four cycles of cisplatin-based chemotherapy, the level of tumor markers had decreased, decreases in the size of his liver and pulmonary lesions were noted but new sclerotic lesions were evident in his thoracolumbar region raising concern for bony metastasis.ConclusionsPrognosis of testicular tumor depends mainly on the clinical stage, but emergence of a sarcomatous component presents a challenge in the treatment of germ cell tumors and the histological subtype of this component can be used as a guide to specific chemotherapy in these patients.
To our knowledge, this is the first multicenter study looking at the spectrum and incidence of BCLs in patients with T-LGL leukemia and highlights its association with large BCLs (3% of T-LGL leukemias).
Oncocytic tumors, composed of eosinophilic, mitochondria-rich cells, can occur in several locations throughout the body. These tumors can occur in the adrenal cortex and are rarely malignant. We report a case of a patient presenting with an incidental adrenal mass which was later diagnosed as a oncocytic adrenocortical neoplasm (OAN). The patient is a 53-year-old man found to have a 7.2 cm right adrenal mass, incidentally found by computed tomography (CT). After metabolic workup was negative, a right robotic adrenalectomy (RA) was performed. Pathologic analysis revealed clusters of large cells with abundant eosinophilic and granular cytoplasm, consistent with OAN. This pathology is rare, with only about 150 cases described in the literature. It occurs in females 2.5 times more frequently and more commonly on the left side. Diagnosis is usually made by imaging criteria, typically with CT or magnetic resonance imaging (MRI). Treatment is generally surgical, since OAN can be malignant in some cases. Differentiation between benign and malignant OAN is done based on the Lin-Weiss-Bisceglia criteria and can be difficult. If malignancy is diagnosed, recurrence is common and close surveillance should be performed.
Background. We report here a trial in progress for the evaluation of a novel system aimed to provide an all-digital standardized bone marrow aspirate (BMA) analysis, Scopio Labs X100, empowered by artificial intelligence (AI) based cell pre-classification. Current methods for the analysis and reporting of BMA specimens are based on analog microscopy, as whole slide imaging at x100 magnification is not practically available. The lack of uniformity between experts in the field, originating from a subjective manual review, can lead to inconsistencies in disease diagnosis and classification, and thereby affect treatment and clinical outcomes. For example, ICSH and WHO guidelines require that at least 500 cells should be counted in at least two smears when a precise percentage of an abnormal cell type is required for diagnosis and classification. It is also recommended that in order reduce imprecision from sampling error, the total number of cells counted in the differential should be increased, specifically if the abnormal cell count is very close to a critical threshold for disease stratification or response assessment. For the general evaluation of hematopoiesis, Myeloid to Erythroid (M:E) ratio is reported. Considering the complexity of the manual BMA analysis, even more so in routine laboratory settings with competitive turnaround times, a digital transformation can sustain the desired standardization, and increase sensitivity and efficiency in routine workflow. Study Design and Methods. This multisite study is taking place at: Hospital of the University of Pennsylvania (HUP), Oregon Health and Science University (OHSU), and Tel Aviv Sourasky Medical Center (TASMC). BMA analysis is performed with a manual microscope as the reference arm and in Scopio Labs X100 Full Field BMA application as the test arm (Figure 1A). Two hematopathologists at each site independently review 265 BMA specimens, including 205 with a Romanowsky stain and 60 with a Prussian Blue stain, in both the test and the reference arms. There is a 3 week washout period between arms (Figure 1B, right). ICSH guidelines were rigorously translated into a comprehensive report format used in both study arms. The report presents 27 primary and 13 secondary characteristics for the morphological assessment of BMA (Figure 1C). These include evaluation of specimen quality, evaluation of count, maturation and morphology of trilineage hematopoietic elements (myeloid, erythroid and megakaryocytic), as well as lymphocytes and plasma cells. For a repeatability study, 8 representative samples are analyzed through 20 days, 2 daily runs and 2 replicas in one site. For reproducibility study, 8 representative samples are analyzed in all sites for 5 days with 5 replicas (Figure 1B, left). The collected BMA samples hold a distribution of 55.61% males, with 2.02%, 9.46%, 16.39%, 54.73% and 17.40% of ages 13-21, 22-39, 40-55, 56-75 and >75 respectively. All samples were diagnosed by WHO criteria. Diagnoses include AML, ALL, MPN, MDS, PCN, lymphoid neoplasms, aplastic anemia, ITP and normal morphology marrow and hemodiluted samples. All samples were retrieved from the sites' bone marrow sample storage. For the method comparison study, the primary and secondary characteristics are aggregated into three primary and secondary evaluation categories of specimen quality, count, and morphology and maturation assessments (Figure 1B, left, 1C). For the primary groups, confusion matrix will be produced. For the secondary groups, contingency tables will be generated (Figure 1B, left). For the repeatability and reproducibility (R&R) studies, two-way nested ANOVA tables will be created (Figure 1, right). Primary groups will be measured for accuracy in the form of efficiency, sensitivity and specificity. Secondary groups will be measured for overall agreement. R&R will be measured for SD and CV. The introduction of Scopio's full field morphological evaluation of BMA smears, promotes an accurate diagnosis of hematological disorders including hematological malignancies, and enables a remote evaluation of BMA smears. By reviewing the entire BMA smear, and by counting a very large number of cells, this novel approach provides a new and highly accurate tool for early detection of pathological conditions, including residual disease following therapy. Figure 1 Figure 1. Disclosures Bagg: Scopio Labs: Research Funding. Raess: Scopio Labs: Research Funding. Jengehino: Scorpio Labs: Other: Partial Salary Support. Wiszniewska: Scopio Labs: Research Funding. Huynh: Scorpio Labs: Other: Salary Support. Fan: Scopio Labs: Research Funding. Bhattacharyya: Scorpio Labs: Other: Partial Salary Support. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. Katz: Scopio Labs: Consultancy.
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