Glioblastoma (GBM), a highly aggressive (WHO grade IV) primary brain tumor, is refractory to traditional treatments, such as surgery, radiation or chemotherapy. This study aims at aiding in the design of more efficacious GBM therapies. We constructed a mathematical model for glioma and the immune system interactions, that may ensue upon direct intra-tumoral administration of ex vivo activated alloreactive cytotoxic-T-lymphocytes (aCTL). Our model encompasses considerations of the interactive dynamics of aCTL, tumor cells, major histocompatibility complex (MHC) class I and MHC class II molecules, as well as cytokines, such as TGF-beta and IFN-gamma, which dampen or increase the pro-inflammatory environment, respectively. Computer simulations were used for model verification and for retrieving putative treatment scenarios. The mathematical model successfully retrieved clinical trial results of efficacious aCTL immunotherapy for recurrent anaplastic oligodendroglioma and anaplastic astrocytoma (WHO grade III). It predicted that cellular adoptive immunotherapy failed in GBM because the administered dose was 20-fold lower than required for therapeutic efficacy. Model analysis suggests that GBM may be eradicated by new dose-intensive strategies, e.g., 3 x 10(8) aCTL every 4 days for small tumor burden, or 2 x 10(9) aCTL, infused every 5 days for larger tumor burden. Further analysis pinpoints crucial bio-markers relating to tumor growth rate, tumor size, and tumor sensitivity to the immune system, whose estimation enables regimen personalization. We propose that adoptive cellular immunotherapy was prematurely abandoned. It may prove efficacious for GBM, if dose intensity is augmented, as prescribed by the mathematical model. Re-initiation of clinical trials, using calculated individualized regimens for grade III-IV malignant glioma, is suggested.

The coronavirus disease 2019 (COVID-19) pandemic has dominated nearly everyone's life since its initial outbreak in the Hubei province of China in December 2019. The disease had spread quickly throughout the world causing extensive, widespread morbidity, over two million deaths, and economical and social devastation over the entire world. Researchers and pharmaceutical companies around the globe have been racing to develop potent and safe vaccines for the disease. Pfizer-BioNTech COVID-19 vaccine followed by Moderna COVID-19 mRNA-1273 vaccine were the first to receive FDA approval. These vaccines are based on messenger RNA novel technology and considered efficient in preventing contagion ensuring safety. Known side effects for this vaccine have been reported as very similar to those known for other vaccines. Specifically, lymphadenopathy has not been considered a common manifestation of COVID-19 vaccination. Israel has been cited as leading in the introduction of these vaccines, which are available for every citizen older than 16 years. Here, we present the cases of three patients who developed lymphadenopathy after the first dose of Pfizer-BioNTech COVID-19 vaccine. Time elapsed from the injection until the appearance of the enlarged nodes, clinical symptoms, and sonographic features differed between the patients, but in all cases gradual regression was noted in the enlarged nodes until complete resolution. Accordingly, to our knowledge, this is the first report describing post-COVID-19 vaccine lymphadenopathy detailing the clinical aspects, sonographic features, and outcomes.

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Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short-lived, stressing the administration of this agent should be early in the course of the disease.

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Hematopoietic syndrome of acute radiation syndrome (HSARS) is a life‐threatening condition with no approved treatment. We compared recombinant human interleukin‐12 (rHuIL‐12; 175 ng/kg × 1) with vehicle, granulocyte‐colony‐stimulating factor (G‐CSF; 10 µg/kg/day × 18), or rHuIL‐12+G‐CSF after lethal irradiation in rhesus monkeys in a Good Laboratory Practice, randomized, blinded, placebo‐controlled study. Fluids, antibiotics, and blood products were not used. Survival at day 60 was significantly increased for rHuIL‐12 versus G‐CSF or vehicle. rHuIL‐12/G‐CSF combination provided no additional survival benefit over rHuIL‐12. Both rHuIL‐12 and rHuIL‐12+G‐CSF increased blood cell nadirs, induced earlier recovery of all hematopoietic lineages, and significantly decreased frequencies of severe cytopenias versus vehicle or G‐CSF. In bone marrow, rHuIL‐12 alone increased erythroid, myeloid, and megakaryocyte counts relative to vehicle or G‐CSF. Thus, a single injection of rHuIL‐12, without supportive medical intervention, significantly improved survival and promoted multilineage hematopoietic recovery in a nonhuman primate model of HSARS. Am. J. Hematol. 89:868–873, 2014. © 2014 Wiley Periodicals, Inc.

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Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment-related morbidity and mortality. Herein, we investigate how pre-treatment characteristics relate to early adverse outcomes in such patients. Among 205 consecutive patients, grade 4 neutropenia (i.e. absolute neutrophil count <500/µL) was associated with the development of fever (P=0.0378), documented infection (P<0.0001), bacteremia (P=0.002), delayed neutrophil count recovery (P<0.0001), and death within 35 days of chemotherapy (P=0.04) but not the requirement for intensive care unit-level care. Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic risk, and performance status, the risk of documented infection or bacteremia was 2.51 (95% confidence interval: 1.59–3.96)-fold and 1.82 (1.04–3.19)-fold higher in patients with initial grade 4 neutropenia. There was no significant relationship between adverse events and age, gender, disease type, disease risk, anthracycline type/dose, or initial peripheral blood blast count. Together, our studies identify severe baseline neutropenia as a risk factor for infection-associated adverse events and early death after induction chemotherapy and may provide the rationale for the risk-adapted testing of myeloid growth factor support in this high-risk AML/MDS patient subset.