depleted of both of them (Figure C). NNK-SMZL expressed significantly higher levels of genes belonging to NOTCH2 pathway and of genes that are activated by non-canonical NF-κB transcription factors. Conversely, DMT-SMZL had a signature of TP53 and apoptosis impairment (Figure D). Digital cytometry and in situ profiling segregated two basic types of SMZL immune microenvironment termed inflamed SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and noninflamed SMZL (50% of cases) (Figure E and F). The combination of molecular and phenotypic profiling allowed to sort out a high risk clinical subset of patients whose tumor was characterized by having both NNK genotype and ''inflamed'' microenvironment (Figure G). Conclusions: Our study highlights the complexity of SMZL. The molecular framework provides an evolving understanding of the pathogenesis of SMZL, and can be regarded as a building block for further refining the classification of B-cell tumors of the spleen, and for aiding the development of rationally targeted treatments.
The impact of pre‐transplant anti‐severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine in 20 recipients of allogeneic hematopoietic stem cell transplantation (Allo‐HSCT) and/or their donors is reported here, showing that the persistence of anti‐SARS‐CoV‐2 antibodies can be detected in almost all patients, whatever the type of vaccine used, and up to 9 months post transplant. Also, an anti‐SARS‐CoV‐2 spike glycoprotein CD3+ T‐cell response could be detected in six (35%) of 17 evaluable patients. This study provides a rationale to consider anti‐SARS‐CoV‐2 vaccination of both recipients and donors before Allo‐HSCT.
The absorption of pazopanib depends on gastric pH. PPIs are frequently prescribed for cancer patients to modify gastric acidity, decreasing pazopanib absorption. The aim of our study was, retrospectively, to investigate the impact of PPIs on the clinical efficacy and safety of pazopanib in a cohort of patients treated in our health center. Of the 147 patients who were included retrospectively, 79 (54%) did not take PPIs concomitantly with pazopanib (cohort 1), while 68 (46%) patients did take PPIs concomitantly with pazopanib (cohort 2). The efficacy parameters were lower in patients taking pazopanib and PPIs: the i/tumor response was statistically different between the two cohorts (p = 0.008), in particular, with 19% vs. 3% of the objective response and 24% vs. 43% of progression in cohorts 1 and 2, respectively; ii/median overall survival was 17.6 (95% CI: 12.5–32.8) months in cohort 1 and 8.6 months (95% CI: 5.9–18.6) in cohort 2 (HR = 1.7 [95% CI: 1.2–2.5]; p < 0.006); on multivariable analysis, overall survival was associated with performance status, PPI intake, tumor location, hemoglobin, and PMN/lymphocyte ratio. In contrast, the dose reduction for toxicity and severe adverse events were (non-significantly) less frequent in cohort 1. To conclude, our study shows that combining PPIs with pazopanib has an adverse effect on overall survival. The clinical modifications that were observed are in line with a decrease in pazopanib absorption due to PPIs. This co-medication should be avoided.
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