The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials

ТЕХНОЛОГИЧЕСКИЕ ОСНОВЫ СОЗДАНИЯ ИМПЛАНТАТОВ С ФАРМАЦЕВТИЧЕСКОЙ КОМПОЗИЦИЕЙ ЦИПРОФЛОКСАЦИНА И ИХ АНТИМИКРОБНАЯ АКТИВНОСТЬ В ЭКСПЕРИМЕНТАХ IN VITRO

The article is devoted to the investigation of the possibility of immobilized on the surface of the titanium implantable devices (model plates, “U-shaped” brackets) antimicrobial substances.Material and methods. The object of research were modeling titanium plates and titanium “U-shaped” brackets for implantation. Ciprofloxacin, hydroxypropylmethylcellulose and methylcellulose has been proposed as materials for the creation of antimicrobial pharmaceutical composition to immobilization. The antimicrobial properties of titanium implantable “U-shaped” brackets with ciprofloxacin was evaluated for potential antimicrobial activity against medically important bacterial (S. aureus, P. aeruginosa, E. coli, E. faecalis and S. pyogenes) using method of diffusion in agar. Results. The results showed the possibility of putting and holding а ciprofloxacin in grooves on the modified surface of titanium implants. In the course of the study was developed a pharmaceutical composition, comprising ciprofloxacin and hydroxypropylmethylcellulose. The results showed high antimicrobial activity of pharmaceutical composition with ciprofloxacin against the test organisms (S. aureus, P. aeruginosa, E. coli, E. faecalis and S. pyogenes).С целью снижения риска развития инфекционных осложнений в постимплантационный период и повышения эффективности хирургического лечения изучали возможность иммобилизации на поверхность титановых имплантируемых устройств (модельные пластинки, «п-образные» скобки) лекарственного вещества антимикробного действия. Материал и методы. Объектом исследований являлись модельные титановые пластинки и титановые «п-образные» скобки для инструмента сшивающего «ГЕРА-10» (ООО «НПО ТМИ», Томск) с модифицированной методом лазерной абляции поверхностью. В качестве действующего вещества разрабатываемой фармацевтической композиции использован ципрофлоксацин, в качестве вспомогательных компонентов – растворы метилцеллюлозы и гидроксипропилметилцеллюлозы. Антимикробную активность имплантируемых объектов с фармацевтической композицией определяли методом диффузии в агар на плотной питательной среде путем изучения размеров зон угнетения роста тест-штаммов микроорганизмов (S. aureus, P. аeruginosa, E. coli , E. faecalis и S. pyogenes). Результаты. В результате исследований показана возможность нанесения и удержания лекарственного вещества в пазах на модифицированной поверхности титановых имплантатов. Предложены фармацевтические композиции ципрофлоксацина с использованием в качестве связывающего и матрицеобразующего компонента гидроксипропилметилцеллюлозы. Установлено отсутствие зависимости между структурой поверхности рабочих элементов модельных пластинок со способностью связывания и удержания фармацевтической композиции на имплантатах. Выявлено, что кратность нанесения фармацевтической композиции непосредственно влияет на количественное содержание лекарственного вещества, а также на закрепление композиции на поверхности имплантата. Наиболее оптимально одноили двукратное нанесение в зависимости от требуемой дозы лекарственного вещества. В экспериментах in vitro выявлена выраженная антимикробная активность «п-образных» скобок с ципрофлоксацином в отношении S. aureus, P. аeruginosa, E. coli, E. faecalis и S. pyogenes, что свидетельствует о целесообразности использования скобок с иммобилизованным на их поверхности антимикробным веществом с целью снижения вероятности развития имплантат-ассоциированной инфекции в постоперационный период.

Application of Fresnel Prism in the Complex Treatment of Friendly Strabismus

Purpose: To analyze the effectiveness of Fresnel prism in the complex treatment of friendly strabismus.Patients and methods. The main group consisted of 428 patients with strabismus, who were assigned Fresnel prisms in combination with pleoptoorthoptic and surgical treatment. Indication for the appointment of Fresnel prism with a friendly strabismus was: angle of strabismus to 25 degrees, postoperative residual angles. The age of the patients ranged from 4 to 60 years. We evaluated the visual acuity without correction and with correction, refraction, character of vision, ability to bifoveal fusion evaluated with synoptophore. The results were compared with a control group treated without Fresnel prisms.Results. During initial selection of Fresnel prisms, doubling was revealed in 73% cases. With the constant wearing of glasses with Fresnel prisms, in which the state of orthotropy is achieved, in most patients doubling was cupped in the period from 2 weeks to 3 months. During the first month, doubling stopped in 72% of patients, and the minimum periods for arresting double vision were noted in preschool children. The absence of doubling served was an indication for surgical correction of strabismus. After the surgery, a good cosmetic effect was achieved in 392 persons (97%), and the state of orthotropy was in 330 of people (81.7%). Doubling after the operation was not observed, there was no relapse of strabismus. Comparative analysis of the main and control groups showed that in the main group of patients the use of prisms combined with pleoptoorthoptic and surgical treatment made it possible to restore binocular vision in 32.9% of cases.Conclusion. The use of Fresnel prism in the complex treatment of friendly strabismus in children allows to obtain not only a good cosmetic effect, but also to develop binocular vision in 32.9% of cases. The use of Fresnel prisms in the preoperative period in adults allows avoiding postoperative double vision, thereby reducing the risk of recurrence of strabismus because of the development of mechanisms for the formation of a single binocular image

TECHNOLOGICAL BASIS FOR THE CREATION OF IMPLANTS WITH A PHARMACEUTICAL COMPOSITION OF CIPROFLOXACIN AND THEIR ANTIMICROBIAL ACTIVITY IN EXPERIMENTS IN VITRO

The article is devoted to the investigation of the possibility of immobilized on the surface of the titanium implantable devices (model plates, “U-shaped” brackets) antimicrobial substances.Material and methods. The object of research were modeling titanium plates and titanium “U-shaped” brackets for implantation. Ciprofloxacin, hydroxypropylmethylcellulose and methylcellulose has been proposed as materials for the creation of antimicrobial pharmaceutical composition to immobilization. The antimicrobial properties of titanium implantable “U-shaped” brackets with ciprofloxacin was evaluated for potential antimicrobial activity against medically important bacterial (S. aureus, P. aeruginosa, E. coli, E. faecalis and S. pyogenes) using method of diffusion in agar. Results. The results showed the possibility of putting and holding а ciprofloxacin in grooves on the modified surface of titanium implants. In the course of the study was developed a pharmaceutical composition, comprising ciprofloxacin and hydroxypropylmethylcellulose. The results showed high antimicrobial activity of pharmaceutical composition with ciprofloxacin against the test organisms (S. aureus, P. aeruginosa, E. coli, E. faecalis and S. pyogenes)