Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

OBJECTIVES: Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. MATERIALS AND METHODS: This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. RESULTS: Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. CONCLUSION: Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Anti-Clogging Effect of Continuous Hemodiafiltration With Blood Recirculation.

Pediatric dialysis requires low flow from the body, but greater flow is needed to prevent clogging. As a solution, we developed a new continuous hemodiafiltration system with blood recirculation (CHDF-R), which enables separate settings for blood flow from the body and to the hemofilter. We compared CHDF-R with conventional continuous hemodiafiltration (CHDF) of bovine plasma and blood by monitoring the transmembrane pressure (TMP) and observing the hemofilter membrane surface. When using bovine plasma, the postdialysis TMP with CHDF-R was significantly lower than with CHDF (median CHDF, 23.7; median CHDF-R, 18.1; p = 0.029). Likewise, when using bovine blood, the postdialysis TMP was also significantly lower with CHDF-R than with CHDF (median CHDF, 150; median CHDF-R, 100; p = 0.029). Moreover, the area of clogged membrane was significantly smaller with CHDF-R than with CHDF, and the inner membrane surface showed less material deposition with CHDF-R than CHDF. CHDF-R thus appears to suppress accumulation of clogging substances by producing higher shear stress within hollow fiber membranes.

Synthesis of prostaglandin E(1) phosphate derivatives and their encapsulation in biodegradable nanoparticles.

PURPOSE: Prostaglandin E(1) (PGE(1)) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE(1) in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients. METHODS: In order to encapsulate PGE(1) in nanoparticles prepared with a poly(lactide) homopolymer (PLA) and monomethoxy poly(ethyleneglycol)-PLA block copolymer (PEG-PLA), we synthesized a series of PGE(1) phosphate derivatives and tested their efficacy. RESULTS: Among them, PGE(1) 2-(phosphonooxy)ethyl ester sodium salt (C2) showed the most efficient hydrolysis to yield PGE(1) in human serum. An in vitro platelet aggregation assay showed that C2 inhibited aggregation only after pre-incubation in serum, suggesting that C2 is a prodrug of PGE(1). In vivo, intravenous administration of C2 caused increase in cutaneous blood flow. In the presence of zinc ions, all of the synthesized PGE(1) phosphate derivatives could be encapsulated in PLA-nanoparticles. Use of L-PLA instead of D,L-PLA, and high molecular weight PLA resulted in a slower release of C2 from the nanoparticles. CONCLUSIONS: We consider that C2-encapsulated nanoparticles prepared with L-PLA and PEG-D,L-PLA have good sustained-release profile of PGE(1), which is useful clinically.