Modified R-CODOX-M/IVAC chemotherapy regimens in Chinese patients with untreated sporadic Burkitt lymphoma

Objective:To characterize modified R-CODOX-M/IVAC-based chemotherapy to lower the severe adverse events in Chinese adult patients with sporadic Burkitt lymphoma.Methods:We enrolled a retrospective cohort including 123 adult patients with untreated sporadic Burkitt lymphoma from August 2008 to September 2019 at Sun Yat-sen University Cancer Center.We studied a dose-modified and long-course R-CODOX-M/IVAC regimen utilizing a low dose of 1.0 g/m2/cycle cyclophosphamide,2 g/m2/cycle methotrexate,4,500 mg/m2/cycle ifosfamide,and 4.0 g/m2/cycle cytarabine.Forty-nine patients with low risk disease underwent 4–6 cycles of dose-modified R-CODOX-M-based chemotherapy.Seventy-four patients with high risk disease underwent 6–8 cycles of dose-modified alternating R-CODOX-M/IVAC regimens.Results:The objective remission was 87.0%.The event-free survival rate and overall survival at 3 years were 81.2%and 92.1%,respectively.Major grade 3–4 adverse events included leukopenia(91.9%),anemia(58.5%),thrombocytopenia(73.2%),and febrile neutropenia(48.8%).A total of 26.0%and 37.4%of patients received red blood cell and platelet transfusions,respectively.We observed 4 cases(3.3%)of septic shock after chemotherapy.Two treatment-related deaths occurred from severe infection.Conclusions:The modified R-CODOX-M/IVAC chemotherapy regimen was effective for sporadic Burkitt lymphoma in the Chinese population,with a lower toxicity than standard regimens.

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis.Long non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear.The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis.We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis.In cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation.The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown.Moreover,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation.The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice.We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation.To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in mice.The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice.The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.