ABSTRACT
In acute promyelocytic leukemia (APL), hemorrhage, particularly intracranial hemorrhage, is the most common cause of early death. A central venous catheter (CVC) may provide a greater guarantee of safety and comfort to APL patients. However, CVCs have seldom been attempted in APL patients during induction therapy because of concerns about increasing the risk of hemorrhagic complications after this invasive procedure. To evaluate the hemorrhagic risk after CVC placement in APL patients during induction therapy, we retrospectively analyzed 95 newly diagnosed patients with APL from January 2010 to December 2022. Among these patients, 39 patients in the CVC group and 56 patients in the non-CVC group were included. Laboratory and clinical parameters of the two groups were collected and compared. There were no significant differences in median platelet, fibrinogen (Fbg), D-dimer, prothrombin time (PT), white blood count (WBC) and hemoglobin (Hb) between the CVC and non-CVC groups on the first day of the visit (day 0) and the following days (day 4, day 7, day 11, day 14, day 18 and day 21) (p = 0.382, p = 0.805, p = 0.456, p = 0.902, p = 0.901 and p = 0.097, respectively). The consumption of transfused platelets and Fbg was not significantly different between the CVC group and non-CVC group (5.0 vs. 4.5 units, p = 0.34, and 6.8 vs. 6.0, p = 0.36, respectively). The last day of platelet and Fbg transfusion was also not significantly different (21 vs. 19, p = 0.238 and 7.5 vs. 8.5, p = 0.684, respectively). The incidences of total hemorrhagic events and hemorrhagic death were lower in the CVC group than in the non-CVC group (17.9% vs. 37.5%, p = 0.04 and 0% vs. 16.1%, p = 0.01, respectively). The 30-day survival rate was not significantly different (92.3% vs. 82.1%, respectively, p = 0.145) for the CVC group compared with the non-CVC group. Our study suggested that CVCs did not increase the hemorrhagic risk in APL patients during induction therapy and that a CVC should be considered in this type of clinical situation.
ABSTRACT
As an indispensable, even lifesaving practice, red blood cell (RBC) transfusion is challenging due to several issues, including supply shortage, immune incompatibility, and blood-borne infections since donated blood is the only source of RBCs. Although large-scale in vitro production of functional RBCs from human stem cells is a promising alternative, so far, no such system has been reported to produce clinically transfusable RBCs due to the poor understanding of mechanisms of human erythropoiesis, which is essential for the optimization of in vitro erythrocyte generation system. We previously reported that inhibition of mammalian target of rapamycin (mTOR) signaling significantly decreased the percentage of erythroid progenitor cells in the bone marrow of wild-type mice. In contrast, rapamycin treatment remarkably improved terminal maturation of erythroblasts and anemia in a mouse model of ß-thalassemia. In the present study, we investigated the effect of mTOR inhibition with rapamycin from different time points on human umbilical cord blood-derived CD34+ cell erythropoiesis in vitro and the underlying mechanisms. Our data showed that rapamycin treatment significantly suppressed erythroid colony formation in the commitment/proliferation phase of erythropoiesis through inhibition of cell-cycle progression and proliferation. In contrast, during the maturation phase of erythropoiesis, mTOR inhibition dramatically promoted enucleation and mitochondrial clearance by enhancing autophagy. Collectively, our results suggest contrasting roles for mTOR in regulating different phases of human erythropoiesis.
