This paper reports the syntheses and properties of the coordination compounds of CoCl2 with dibenzo-24-crown-8, dibcnzo-30-crown-10, 4'-iodobcnzo-15-crown-5 and 4'-bromobenzo-15-crown and the coordination compounds of Co(NO3)2 with benzo-15-crown-5,4'-iodobenzo-15-crown-5 and 4'-bromobcnzo-15-crown-5. The complexes have been characterized by elemental analysis, IR, UV, DTA-TG and X-ray powder diffraction analysis as well as the molar conductance measurements.
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents, accounting for ~75% of all childhood leukemia. 1Despite the advancement in treating newly diagnosed ALL, patients with refractory or relapsed (R/R) disease have poor outcome, and combinational chemotherapies induce complete response in about 35-42% of the children under this condition. 2Thus, new antileukemic agents are urgently needed.Clofarabine is a second-generation purine nucleoside analog, which requires intracellular phosphorylation by deoxycytidine kinase to be metabolized to the triphosphate form necessary for cytotoxic effect. 3It has been approved for treating pediatric R/R ALL patients based on several phase II studies, with a response rate of ~26-30% in the Western population. 4,5The most common adverse events (AEs) reported in phase I trial were transient liver dysfunction, skin rashes, palmoplantar erythrodysesthesia and mucositis. 6Despite its antileukemic activities and acceptable toxicity in the Western population, 7-10 little data are available on Asian patients with R/R ALL.Therefore, we performed this multicenter, phase II study in China to evaluate the activity, safety and pharmacokinetics of clofarabine monotherapy in pediatric patients with R/R ALL.Eligible patients were pediatric patients (younger than 21 years old) with R/R ALL confirmed by histology.Relapsed ALL was defined as ALL that relapsed after at least two times of antileukemia therapy.Normal cardiac, hepatic and renal function and Eastern Cooperative Oncology Group performance status (0-2) were also needed.Patients with AEs who had not recovered from prior therapy within 3 months after allogeneic or autologous stem cell transplantation and with central nervous involvement or active infection were excluded.The detailed inclusion and exclusion criteria are listed in Supplementary Information Method section.The primary end point was overall response rate (ORR), comprised of complete remission (CR) and CR with incomplete recovery of courts (CRi), according to the NCCN guidelines for ALL.This trial was reviewed by the institutional ethics committees and was conducted according to the Declaration of Helsinki.Written informed consent was obtained from each patient or their legal guardians.This study was registered as NCT02544789.Clofarabine was administered intravenously at 52 mg/m 2 over 2 h daily for five consecutive days.During the first two induction cycles, patients without objective response were taken off the study, and responsive patients continued to receive consolidation for a maximum 11 cycles if their nonhematological toxicity were below grade 3. A 25% dose reduction was required when grade 3 or higher non-hematological, non-infectious events occurred and recovered within 14 days.The response was determined using the NCCN guidelines for ALL.The methods for response assessment are detailed in the Supplementary Information Method section.
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