31 research outputs found
Инвазивный микоз с поражением центральной нервной системы, обусловленный редкими дрожжевыми грибами Malassezia spp., у пациентов с острым лейкозом: описание клинических случаев и обзор литературы
Malassezia spp. is a commensal yeast that represents normal microflora in humans and some animals. However, Malassezia spp. can cause life-threatening invasive mycosis. Evidence on Malassezia spp. infections is limited mostly to a case reports describing disease in newborns and premature infants, because lipid infusions (total parenteral nutrition) given through central venous catheter is a major risk factor. Here, we report two cases of CNS infection caused by Malassezia species in non-neonates with acute leukemia.Malassezia spp. — дрожжевые грибы, которые представлены в составе нормальной микрофлоры кожи человека и как симбионт препятствуют развитию инфекций, обусловленных опасными патогенами. Однако Malassezia spp. также может стать причиной тяжелого инвазивного микоза и привести к летальному исходу. Данные литературы ограничены, представлены преимущественно публикациями об инфекциях у новорожденных и недоношенных детей, что, в первую очередь, связывают с известным фактором риска — применение парентерального питания, включающего в себя жировую эмульсию, с использованием центрального венозного катетера. Мы представляем клинические случаи инфекции центральной нервной системы, обусловленной редкими возбудителями, дрожжевыми грибами рода Malassezia, у детей с острым лейкозом
Busulfan-fludarabine- or treosulfan-fludarabine-based myeloablative conditioning for children with thalassemia major
Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan-fludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.Transplantation and immunomodulatio
СРАВНЕНИЕ ЭФФЕКТИВНОСТИ ХИМИОТЕРАПИИ И АЛЛОГЕННОЙ ТРАНСПЛАНТАЦИИ ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК ПРИ ОСТРОМ МИЕЛОБЛАСТНОМ ЛЕЙКОЗЕ В ПЕРВОЙ РЕМИССИИ У ВЗРОСЛЫХ
The aim of the study was to compare the efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) and chemotherapy (CT) of acute myeloid leukemia (AML) in first remission (CR1), to identify factors influencing the results. We compare the efficacy alloHSCT in CR1 (n = 70) and CT (n = 52). Patients were stratified by age, the level of leucocytes, the origin of AML, cytogenetic risk group and response to induction CT. Five-years overall and disease-free survival (OS and DFS) were higher in the group alloHSCT (67 and 65 % vs 46 and 30 % (p = 0.02 and p = 0.001)). Benefits of DFS after alloHSCT was in standard and high-risk cytogenetic groups (78 % versus 29 % (p = 0.001), and 34 % vs 17 % (p = 0.007)). The risk of relapse (RR) was 24 % in patients after alloHSCT vs. 57 % for CT (p = 0.003). Comparing the RR after alloHSCT and CT depending on the cytogenetic risk groups: standard (HR0.2(CI95 %0.07 - 0.56) p = 0.002), and high (HR0.27(CI95 %0.08-0.86) p = 0.03). Additional factors affect the RR were the origin of AML (de novo) (HR0.47 (CI95 %0.3-0.74) p = 0.001), the hyperleukocytosis (HR1.91 (CI95 %1.09 - 3.32) p = 0.02), and no remission after the first course CT (HR3.32(CI95 %1.57-7.0) p = 0.002). The efficacy of alloHSCT compared with CT is higher both in standard and high-risk cytogenetic group.Цель - сравнить эффективность аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК) и химиотерапии (ХТ) при остром миелобластном лейкозе (ОМЛ) в первой ремиссии и выявить факторы, влияющие на результаты лечения. Сравнивалась эффективность в первой ремиссии ОМЛ алло ТГСК (n = 70) и ХТ (n = 52). Пациенты были разделены по возрасту, уровню лейкоцитов, происхождению ОМЛ, цитогенетическим группам риска и ответу на индукционную ХТ. Пятилетняя общая и бессобытийная выживаемость (ОВ и БСВ) были выше в группе аллоТГСК (67 и 65 % против 46 и 30 % (р = 0,02 и р = 0,001)). При анализе БСВ от цитогенетических групп риска выявлены преимущества аллоТГСК в стандартной и высокой группах риска (78 % против 29 % (р = 0,001) и 34 % против 17 % (р = 0,007)). Совокупный риск рецидива (РР) составил 24 % у пациентов после аллоТГСК против 57 % при ХТ (р = 0,003). При сравнении РР после аллоТГСК и ХТ от цитогенетических групп риска: стандартная (HR,0,2(CI95 %0,07-0,56) p = 0,002) и высокая (HR,0,27(CI95 %0,08-0,86) p = 0,03). Дополнительными факторами, оказывающими влияние на РР, были: происхождение ОМЛ (de novo) (HR,0,47(CI95 %0,3-0,74) p = 0,001), гиперлейкоцитоз в дебюте заболевания (HR,1,91(CI95 %1,09-3,32) p = 0,02) и отсутствие ремиссии после одного курса индукции (HR,3,32(CI95 %1,57 - 7,0) p = 0,002). Эффективность алло ТГСК по сравнению с ХТ выше при стандартной и высокой цитогенетических группах риска
Бактериальные инфекции у пациентов детского и подросткового возраста после трансплантации аллогенных гемопоэтических стволовых клеток: этиология, структура, факторы риска
155 children and adolescents who had been diagnosed oncohematological diseases and had undergone allogeneic hemapoetic stem cell transplantation were examined. In post-transplant period 80% of patients developed different bacterial complications. Main risk factors of bacterial infections were acute leukemia (73%), acute «graft versus host disease» (61%), severe infectious complications before HSCT (30%), cytomegaloviral reactivation (51%). Main causative agents were Kl. pneumoniae (15%), Escherichia coli (8%), Enterobacter sp. (7%), Pseudomonas sp. (6,5%), Enterococcus sp. (16,5%), S.еpidermidis (13,5%). Most frequent involved sites are urinary tract (30,6%), lungs (22,5%) and bacteriemia (38,7%). Rise in ciprofloxacin resistans among Entorobactri, aerobic and Gram-positive cocci. General survival rate of patients with bacterial complications was 36,3% (p<0,001). Number of infectious episodes and their severity were statistically significant (both p<0,001) deteriorating factor for general surviral rate.Обследовано 155 пациентов детского и подросткового возраста со злокачественными заболеваниями системы крови после трансплантации аллогенных гемопоэтических стволовых клеток (алло-ТГСК). У 80% больных на разных этапах после алло-ТГСК развились бактериальные осложнения различной степени тяжести. Основными факторами риска бактериальных инфекций были диагноз острого лейкоза (73%), развитие острой «реакции трансплантат против хозяина» (61%), тяжелые инфекционные осложнения в анамнезе до трансплантации (30%), реактивация цитомегаловирусной инфекции (51%). Основные возбудители: Kl. pneumoniae (15%), Escherichia coli (8%), Enterobacter sp. (7%), Pseudomonas sp. (6,5%), Enterococcus sp. (16,5%), S. еpidermidis (13,5%). Наиболее часто возникает поражение мочевыводящих путей (30,6%), легких (22,5%) и бактериемия (38,7%). Отмечен рост резистентности к ципрофлоксацину среди энтеробактерий, аэробной и грам-положительной кокковой флоры. Общая выживаемость больных с развившимися бактериальными осложнениями составила 36,3% (p<0,001). Статистически значимо ухудшает показатели общей выживаемости больных с бактериальными инфекциями количество инфекционных эпизодов (p<0,001) и их тяжесть (p<0,001)
СОСТОЯНИЕ ИММУННОГО СТАТУСА У ГЕМАТОЛОГИЧЕСКИХ ПАЦИЕНТОВ С ИНВАЗИВНЫМ АСПЕРГИЛЛЕЗОМ
Invasive aspergillosis – is severe mycotic infection that often occurs in hematological patients and is characterized by high mortality. We examined the immunological parameters of hematological patients with invasive aspergillosis developed after cytostatic chemotherapy. Was founded, disruption of all parts of the immune respons: reduction in the absolute number of T-helper cells (CD4 +), natural killer cells (CD16 +), lowering of IFN-γ and IL-10 production, reduction in the number of B-lymphocytes and immunoglobulin levels of all classes, suppression killer ability of neutrophils are features of immune status in hematological patients with invasive aspergillosis receiving cytostatic chemotherapy.Инвазивный аспергиллез – тяжелая микотическая инфекция, которая наиболее часто возникает у гематологических больных и характеризуется высокой летальностью. Мы впервые изучили иммунологические показатели гематологических больных, у которых инвазивный аспергиллез развился после цитостатической полихимиотерапии. Установлено, что особенностью иммунного статуса у гематологических пациентов с инвазивным аспергиллезом, получающих цитостатическую полихимиотерапию, является нарушение всех звеньев иммунного ответа: снижение абсолютного числа Т-хелперов (CD4+), естественных киллеров (CD16+), продукцисов, угнетение киллерной способности нейтрофилов
Анализ факторов риска и эффективности Дефибротида для лечения синдрома обструкции синусоидов/веноокклюзионной болезни печени после аллогенной трансплантации гемопоэтических стволовых клеток у детей и взрослых
Introduction. Sinusoidal obstructive syndrome (SOS)/veno-occlusive liver disease (VOD) is one of the most dangerous complication of allogeneic hematopoietic stem cell transplantation (alloHSCT).The objective of our study was to analyze risk factors associated with SOS/VOD in children and adults after alloHSCT.Methods and materials. The study included 76 patients who were diagnosed with the development of SOS/VOD after alloHSCT performed in Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation between 2001 and 2019. 25 patients (32.9 %) were younger than 18 years, 51 patients (68.1 %) — 18 years and older. Among them, 17 patients were treated with defibrotide at a dose of 25 mg/kg per day, median therapy duration — 21 day.Results. One-year overall survival (OS) was significantly higher when partial and complete response to the therapy was achieved — 45 %, than when there was no response — 0 % in the general group (p = 0.001). According to the results of multivariate analysis of unrelated alloHSCT HR 2.040 (95 %CI 1.112-3.744, р = 0.021), acute GVHD HR 0.496 (95 % CI 0.272-0.903, р = 0.022), moderate/severe SOS/VOD HR 2.423 (95 % CI 1.298-4.524, p = 0.005) statistically significantly influenced the 1-year OS. Defibrotide and accompanying therapy did not significantly influence the 1-year OS in children and adults (n=76) - 53 % and 54 % (p=0.86), respectively. In a multivariate analysis. unrelated alloHSCT HR 8.172 (95 %CI 2.176-30.696, р=0.002) and moderate and severe SOS/VOD HR 9.077 (95 % CI 2.425-33.978, р=0.001) significantly influenced the 1-year OS in the pediatric group.Conclusion. The understanding of risk factors of adverse prognosis in patients SOS/VOD facilitates selection of patients who will benefit the most from therapy with defibrotide. Early administration of defibrotide in the course of VOD/SOS is crucial to achieve response.Введение. Синдром обструкции синусоидов (СОС)/веноокклюзионная болезнь печени (ВОБ) — одно из фатальных осложнений аллогенной трансплантации гемопоэтических стволовых клеток (аллоТГСК).Целью исследования является оценка факторов риска и эффективности применения Дефибротида при СОС/ ВОБ у детей и взрослых после аллоТГСК.Методы и материалы. В исследование включены 76 пациентов НИИДОГИТ им. Р. М. Горбачёвой после аллоТГСК, у которых в период с 2001 по 2019 г. было выявлено развитие СОС/ВОБ печени. В возрасте до 18 лет наблюдали 25 (32,9 %) пациентов, 51 (68,1 %) пациент — 18 лет и старше. Из них 17 пациентов получили Дефибротид в дозе 25 мг/кг в сутки, медиана длительности терапии составила 21 день.Результаты. Однолетняя общая выживаемость (ОВ) была значимо выше при достижении частичного и полного ответа на терапию — 45 %, чем при отсутствии ответа — 0 % в общей группе (р = 0,001). По результатам многофакторного анализа аллоТГСК от неродственного донора ОР 2,040 (95 % ДИ 1,112 — 3,744, р = 0,021), наличие острой реакции «трансплантат против хозяина» (оРТПХ) ОР 0,496 (95 % ДИ 0,272 — 0,903, р = 0,022), степень СОС/ВОБ ОР 2,423 (95 % ДИ 1,298 — 4,524, р = 0,005) статистически значимо влияли на 1-летнюю ОВ. При применении Дефибротида и сопроводительной терапии 1-летняя ОВ не различалась в группе взрослых и детей (n=76) и составила 53 и 54 % соответственно (Р = 0,86). В многофакторном анализе аллоТГСК от неродственного донора — ОР 8,172 (95 % ДИ 2,176 — 30,696, р = 0,002) и СОС/ВОБ 2 — 3-й степени — ОР 9,077 (95 % ДИ 2,425 — 33,978, р = 0,001) — статистически значимо влияли на 1-летнюю ОВ в педиатрической группе.Заключение. Обнаружение неблагоприятных факторов риска позволит сделать диагностику СОС/ВОБ более своевременной и безотлагательно начать терапию, что имеет ключевое значение для эффективного лечения данного осложнения аллоТГСК
Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children: a Randomised, Controlled, Phase 3 Trial
Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11–1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51–6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding: Bayer AG and Janssen Research & Development. © 2020 Elsevier Ltd
CHEMOTHERAPY-BASED CONDITIONING FOR CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA AS PREPARATIVE REGIMEN FOR ALLOGENEIC HEMATOPOETIC STEM CELL TRANSPLANTATION: AN EBMT PAEDIATRIC DISEASES WORKING PARTY STUDY
Transplantation and immunomodulatio
Application experience of extracorporeal photopheresis for treatment of acute “graft-versus-host” disease after allogeneic hematopoietic stem cell transplantation
Extracorporeal photopheresis (ECP) has been used as a component of combined immunosuppressive therapy in 53 patients with steroid-refractoryacute “graft-versus-host” disease. Overall response was observed in 35 patients (66 %; 95 % CI 52.6–77.3): complete response (CR) in 15 pts (28.3 %; 95 % CI 18–41.6) and partial response (PR) in 20 pts (37.7 %; 95 % CI 25.9–51.2). 3-year OS was 39 % in patients with clinical response (CR or PR); in the absence of clinical response OS was 8 % during the first year (p < 0.0001). Median methylprednisolone dose before ECP was 2 mg/kg/day, and at the end of ECP course – 0.7 mg/kg/day (p < 0.0001).</p
ACTIVATION OF T. GONDII INFECTION AFTER ALLOGENEIC TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS: DEPENDENCE ON TIME OF TRANSPLANTATION AND SEROLOGICAL STATUS OF THE PATIENTS
The article focuses on aspects of T. gondii reactivation/reinfection in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). We have observed 297 patients who received conditioning therapy and allogeneic grafts due to different oncohematological or lymphoproliferative diseases (1 to 60 years old, at a mediane of 19 years). Conditioning regimens were either myeloablative (35%), or non-myeloablative (65%). DNA diagnostics of T. gondii was performed on a regular basis at 0 to 6 months post-HSCT. IgG and IgM antibodies against T. gondii were determined in 78 patients before HSCT, as well as in their donors. T. gondii DNA post-transplant proved to be positive in 13% of blood specimens, 9% of cerebrospinal liquor samples, 11% of bronchoalveolar cell lavages, and in 5% of urine sediments. In adolescent patients (10 to 14 years old), an increased prevalence of T. gondii was found in patients who received myeloablative treatment (p = 0.01). When assessing posttransplant dynamics of T. gondii, we have revealed distinct increase in the pathogen excretion within 1st month after HSCT (p = 0.03). Finally, initial presence of IgG antibodies against T. gondii in the patients was associated with lower incidence of the pathogen reactivation post-transplant