Coronavirus-2019 (COVID-19) mortality is higher in patients with cancer than in the general population, yet the cancer-associated risk factors for COVID-19 adverse outcomes are not fully ...characterized.
We reviewed clinical characteristics and outcomes from patients with cancer and concurrent COVID-19 at Memorial Sloan Kettering Cancer Center until March 31, 2020 (n = 309), and observed clinical end points until April 13, 2020. We hypothesized that cytotoxic chemotherapy administered within 35 days of a COVID-19 diagnosis is associated with an increased hazard ratio (HR) of severe or critical COVID-19. In secondary analyses, we estimated associations between specific clinical and laboratory variables and the incidence of a severe or critical COVID-19 event.
Cytotoxic chemotherapy administration was not significantly associated with a severe or critical COVID-19 event (HR, 1.10; 95% CI, 0.73 to 1.60). Hematologic malignancy was associated with increased COVID-19 severity (HR, 1.90; 95% CI, 1.30 to 2.80). Patients with lung cancer also demonstrated higher rates of severe or critical COVID-19 events (HR, 2.0; 95% CI, 1.20 to 3.30). Lymphopenia at COVID-19 diagnosis was associated with higher rates of severe or critical illness (HR, 2.10; 95% CI, 1.50 to 3.10). Patients with baseline neutropenia 14-90 days before COVID-19 diagnosis had worse outcomes (HR, 4.20; 95% CI, 1.70 to 11.00). Findings from these analyses remained consistent in a multivariable model and in multiple sensitivity analyses. The rate of adverse events was lower in a time-matched population of patients with cancer without COVID-19.
Recent cytotoxic chemotherapy treatment was not associated with adverse COVID-19 outcomes. Patients with active hematologic or lung malignancies, peri-COVID-19 lymphopenia, or baseline neutropenia had worse COVID-19 outcomes. Interactions among antineoplastic therapy, cancer type, and COVID-19 are complex and warrant further investigation.
The gut microbiota influences development
and homeostasis
of the mammalian immune system, and is associated with human inflammatory
and immune diseases
as well as responses to immunotherapy
. ...Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.
Omburtamab is a B7H3-specific murine monoclonal antibody. B7H3 (CD 276) is a member of the B7 family of immune checkpoint co-inhibitory receptors overexpressed on many human malignancies. ...Radioimmunotherapy with
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I- or
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I-omburtamab administered in the cerebrospinal fluid (CSF), intraperitoneal or intratumoral cavity is currently under investigation for the treatment of CNS malignancies. The immunologic effects of anti-B7H3 therapy are not fully elucidated. A 6-year-old male was diagnosed with metastates of neuroblastoma to the received intraventricular
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I-omburtamab on an IRB-approved protocol. A treatment cycle consisted of a 2 mCi dosimetry dose and a 50 mCi treatment dose. Dosimetry by serial imaging, pharmacokinetics and safety were investigated. Clinical status, magnetic resonance imaging, CSF cell count and cytology were evaluated pre- and post-
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I-omburtamab at 5 and 26 weeks. The patient did well with cycle 1. Three hours after the dosimetry dose of cycle 2, he developed a fever (39 °C), chills and headache. Blood and CSF samples were sent for culture. CSF was notable for nucleated cell pleocytosis with profound mast cell proliferation consistent with chemical meningitis. He was treated with supportive care; symptoms resolved over 48 h. Further therapy with
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I-omburtamab was electively discontinued. CSF cell count 5 weeks later demonstrated resolution of CSF pleocytosis. Local–regional administration of intraventricular
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I-omburtamab targeting B7H3 can result in a profound nucleated CSF pleocytosis with mastocytosis consistent with an acute allergic reaction.
BACKGROUND
Successful peripheral blood stem cell transplantation (PBSCT) depends on the collection and infusion of adequate numbers of peripheral blood progenitor cells (PBPCs). Several predictors of ...PBPC yield are used currently, including white blood cell (WBC) count and CD34 analysis. This study evaluated the utility of the new automated hematopoietic progenitor cell count available on Sysmex XN hematology analyzers (XN‐HPCs) in PBSCT.
STUDY DESIGN AND METHODS
The performance characteristics of XN‐HPC, CD34+, and WBC analysis were compared using 107 matched peripheral blood and apheresis samples.
RESULTS
Good correlation was observed between XN‐HPC and CD34+ cell counts in peripheral blood (r = 0.88; slope, 0.81) and apheresis collections (r = 0.91; slope, 0.89). Moreover, peripheral blood XN‐HPC and CD34 analysis showed comparable ability to predict successful PBPC harvests (≥2 × 106 CD34+ cells/kg). At a cutoff of 20 × 106 progenitor cells/L, peripheral blood XN‐ HPC and CD34 analysis both showed negative predictive values (NPVs) of 100% and positive predictive values (PPVs) of 55.4 and 63%, respectively. Using an optimized cutoff of 38 × 106 progenitor cells/L, derived from receiver operating characteristic analysis, the PPV for XN‐HPC and CD34 analysis increased to 71.4 and 78.9%, respectively, with relatively unchanged NPVs (XN‐HPC 97.7%, CD34+ 98.0%). In contrast, the correlation between peripheral blood WBC and CD34 analysis was poor (r = 0.48; slope, 669.85), and the peripheral blood WBC count (cutoff, 10 × 109/L) was a poor predictor of PBPC harvest (NPV 60%, PPV 43.1%).
CONCLUSION
XN‐HPC compares favorably with CD34 analysis and may be a surrogate for CD34 analysis to predict optimal timing of PBPC collections.
Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and ...decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10
) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10
). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.
BACKGROUND
Adoptive immunotherapy using engineered lymphocytes has shown promising results in treating cancers even in patients who have failed other treatments. As the first essential step, the ...number of peripheral mononuclear cell (MNC) collection procedures is rapidly increasing. In this retrospective study, we reviewed the collection results to determine factors that affect MNC collection.
STUDY DESIGN AND METHODS
We reviewed 184 collections that were performed on 169 adult allogenic donors and patients with acute lymphoid leukemia, chronic lymphoid leukemia, lymphoma, multiple myeloma, or solid‐organ tumors. All the leukapheresis procedures were performed after a complete cell count with differential was obtained. Total blood volume (TBV) was defined as processed blood volume divided by patient blood volume.
RESULTS
There was a significant association between the precollection MNC count (pre‐MNC) and the MNC yields normalized by TBV (r = 0.926; p < 0.001) and a regression formula was created to predict MNC yields. Multiple regression analyses showed that pre‐MNC, TBV, and precollection hemoglobin were strongly associated with MNC yield (R
2 = 0.866; F (3180) = 388.472; p < 0.001), and pre‐MNC had the greatest influence on MNC yield (β = 0.960; p < 0.001) followed by TBV (β = 0.302; p < 0.001), and Hgb (β = 0.136; p < 0.001).
CONCLUSION
Our results suggest that the optimal time for MNC collection can be determined based on pre‐MNC and that processing volume should be determined based on collection goal and pre‐MNC to optimize and personalize the harvesting procedure.
•Turbulent flow chromatography–MS/MS was used for the determination of MTX, 7-OH MTX and DAMPA in human serum.•The assay is applicable for therapeutic drug monitoring and pharmacokinetic ...studies.•TFLC–MS/MS for MTX evaluated against DHFR inhibition and FPIA assays for MTX.•The method is fast, reliable, convenient and sensitive.
A rapid and simple turbulent flow liquid chromatography (TFC–LC) method implementing positive heated electrospray ionization (HESI) for the accurate and precise determination of methotrexate (MTX), 7-hydroxy methotrexate (7-OH MTX), and 4-amino-4-deoxy-N10-methylpteroic acid (DAMPA) concentrations in serum was developed. MTX was isolated from serum samples (100μL) after protein precipitation with methanol containing formic acid and internal standard (MTX-D3) followed by centrifugation. The supernatant was injected into the turbulent flow liquid chromatography which is followed by electrospray positive ionization tandem mass spectrometry (TFC–LC–MS/MS) and quantified using a six-point calibration curve. For MTX and DAMPA the assays were linear from 10 to 1000nmol/L and for 7-OH MTX from 20 to 2000nmol/L. Dilutions of 10, 100 and 1000-fold were validated giving a clinically reportable range of 10nmol/L to 5×105nmol/L. Within-day and between-day precisions at concentrations spanning the analytical measurement ranges were less than 10% for all three analytes. MTX, DAMPA and 7-OH MTX were sufficiently stable under all relevant analytical conditions. No significant matrix effect was observed during the method validation. The TFC–LC-MS/MS MTX method was also compared with three other clinically validated MTX assays: a dihydrofolate reductase (DHFR) inhibition assay, an immunoassay based on fluorescence polarization and a previously developed LC–MS/MS assay.
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