Bone marrow biopsy can be omitted in the diagnostic workup of CNS lymphoma of DLBCL origin: a population-based retrospective study in the PET-CT era.

Currently, bone marrow (BM) biopsy (BMB) is recommended in the initial staging of patients with the presumed primary central nervous system (CNS) lymphoma (PCNSL). However, the added value of BMB in the era of positron emission tomography (PET-CT) has been challenged in other lymphoma subtypes. We analyzed BM findings in patients with biopsy-proven CNS lymphoma and a negative PET-CT scan for disease outside CNS. A comprehensive Danish population-based registry search was performed to identify all patients with CNS lymphoma of diffuse large B cell lymphoma (DLBCL) histology with available BMB results and staging PET-CT without systemic lymphoma. A total of 300 patients fulfilled the inclusion criteria. Of them, 16% had a previous history of lymphoma, while 84% were diagnosed with PCNSL. None of the patients had DLBCL in the BM. A minority (8.3%) had discordant BMB findings, mainly low-grade histologies that did not influence treatment choice in any case. In conclusion, the risk of overlooking concordant BM infiltration in patients with CNS lymphoma of DLBCL histology and negative PET-CT scan is negligible. As we did not find any patient with DLBCL in the BMB, our results suggest that BMB can be safely omitted in the diagnostic workup in patients with CNS lymphoma and a negative PET-CT.

Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

Different modulation by Ca2+-activated K+ channel blockers and herbimycin of acetylcholine- and flow-evoked vasodilatation in rat mesenteric small arteries.

1. The present study addressed whether endothelium-dependent vasodilatation evoked by acetylcholine and flow are mediated by the same mechanisms in isolated rat mesenteric small arteries, suspended in a pressure myograph for the measurement of internal diameter. 2. In pressurized arterial segments contracted with U46619 in the presence of indomethacin, shear stress generated by the flow evoked relaxation. Thus, in endothelium-intact segments low (5.1+/-0.6 dyn cm(-2)) and high (19+/-2 dyn cm(-2)) shear stress evoked vasodilatations that were reduced by, respectively, 68+/-11 and 68+/-8% (P<0.05, n=7) by endothelial cell removal. Acetylcholine (0.01-1 microM) evoked concentration-dependent vasodilatation that was abolished by endothelial cell removal. 3. Incubation with indomethacin alone did not change acetylcholine and shear stress-evoked vasodilatation, while the combination of indomethacin with the nitric oxide (NO) synthase inhibitor, N(G),N(G)-asymmetric dimethyl-L-arginine (ADMA 1 mM), reduced low and high shear stress-evoked vasodilatation with, respectively, 52+/-15 and 58+/-10% (P<0.05, n=9), but it did not change acetylcholine-evoked vasodilatation. 4. Inhibition of Ca(2+)-activated K(+) channels with a combination of apamin (0.5 microM) and charybdotoxin (ChTX) (0.1 microM) did not change shear stress- and acetylcholine-evoked vasodilatation. In the presence of indomethacin and ADMA, the combination of apamin (0.5 microM) and ChTx (0.1 microM) increased contraction induced by U46619, but these blockers did not change the vasodilatation evoked by shear stress. In contrast, acetylcholine-evoked vasodilatation was abolished by the combination of apamin and charybdotoxin. 5. In the presence of indomethacin, the tyrosine kinase inhibitor, herbimycin A (1 microM), inhibited low and high shear stress-evoked vasodilatation with, respectively, 32+/-12 and 68+/-14% (P<0.05, n=8), but it did not change vasodilatation induced by acetylcholine. In the presence of indomethacin and ADMA, herbimycin A neither changed shear stress nor acetylcholine-evoked vasodilatation. 6. The present study suggests that Ca(2+)-activated K(+) channels sensitive for the combination of apamin and ChTx are involved in acetylcholine-evoked, mainly non-NO nonprostanoid factor-mediated, vasodilatation, while an Src tyrosine kinase plays a role for flow-evoked NO-mediated vasodilatation in rat mesenteric small arteries.