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BACKGROUND: Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD. METHODS: In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m2 twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing. FINDINGS: Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment discontinuation), one due to Aspergillus infection, one due to septic shock, and one due to acute respiratory distress syndrome; none were considered to be related to study drug. INTERPRETATION: Pending final analysis, this study suggests that ruxolitinib is active and well tolerated in both treatment-naive and corticosteroid-refractory patients aged 2 years to younger than 18 years with chronic GVHD, thereby supporting its use in this patient population. The safety profile of ruxolitinib in this patient population is consistent with that of adults. Final analysis of this study will provide further information on the long-term benefits of ruxolitinib in children with chronic GVHD. FUNDING: Novartis.
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Corticosteroides , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Nitrilas , Pirazóis , Pirimidinas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Corticosteroides/uso terapêutico , Doença Crônica , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Pirimidinas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Oral mucositis is one of the side effects developed post-hematopoietic stem cell transplant. This retrospective study aimed to assess the efficacy of a mouthwash mixture (lidocaine, sodium alginate, sucralfate, pheniramine) versus hyaluronic acid and a solution of sodium bicarbonate in terms of healing time and weight gain in the treatment of oral mucositis in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation with hemato-oncological malignancies. METHODS: A total of 171 patients that received chemotherapy for the hematopoietic stem cell transplant were divided into three groups; group 1, treated with a mixed mouthwash of lidocaine, sodium alginate, sucralfate, and pheniramine; group 2, treated with hyaluronic acid; and group 3, treated with an aqueous solution of 5% sodium bicarbonate. Weight and mucositis scale scores derived from medical records of patients. RESULTS: There was a statistically significant difference in the mucositis scale scores between the groups on the transplant day and days 5, 10, 15 and 20 after the transplantation. At these measurement points, Group 2 (receiving hyaluronic acid) had a lower score, and Group 3 (who received sodium bicarbonate) had a higher score, especially on days 5 and 10 after the transplantation. CONCLUSION: The results suggest that hyaluronic acid is a more effective treatment option than the other oral care solutions that are frequently used for prophylaxis and treatment of oral mucositis.
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Transplante de Células-Tronco Hematopoéticas , Estomatite , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Estomatite/prevenção & controle , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Adolescente , Pré-Escolar , Antissépticos Bucais/uso terapêutico , Ácido Hialurônico/uso terapêutico , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Bicarbonato de Sódio/uso terapêutico , Bicarbonato de Sódio/administração & dosagem , Higiene Bucal , Antineoplásicos/efeitos adversos , Neoplasias Hematológicas/terapia , Lidocaína/uso terapêutico , Sucralfato/uso terapêuticoRESUMO
ABSTRACT: Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871.
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Hemofilia A , Hemofilia B , Hemorragia , Humanos , Masculino , Hemofilia B/tratamento farmacológico , Hemofilia B/complicações , Adulto , Hemofilia A/tratamento farmacológico , Hemofilia A/complicações , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Criança , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/uso terapêutico , Fatores de Coagulação Sanguínea/uso terapêutico , Fatores de Coagulação Sanguínea/administração & dosagem , IdosoRESUMO
OBJECTIVES: Allogeneic hematopoietic stem cell transplant is the only curative treatment for patients with transfusion-dependent thalassemia major. In recent years, a number of novel approaches have improved patient outcomes and quality of life by minimizing the toxicity of conditioning regimens. The objective of this study was to compare the role of treosulfan- and busulfan-based conditioning in transfusion-dependent thalassemia. MATERIALS AND METHODS: Data were collected retrospectively on 121 children with beta thalassemia major who underwent hematopoietic stem cell transplant using treosulfan-based (n = 37) or busulfan-based (n = 84) conditioning regimens between 2012 and 2022. RESULTS: Two-year overall survival was 87.5% in the busulfan-based conditioning group and 91.1% in the treosulfan-based conditioning group.The group given the busulfan regimen compared with treosulfan regimen had significantly increased number of side effects (58.3% vs 21.6%, respectively; P < .001). When the busulfan-based regimen by level was evaluated, we observed no significant differences between the frequency of side effects according to drug serum levels. In addition, no significant differences were shown between the 2 regimen groups for cumulative incidence of acute and chronic graft-versus-host disease. CONCLUSIONS: The safety and effectiveness of a treosulfan-based myeloablative conditioning regimen has been confirmed by ourretrospective investigation of pediatric patients with beta thalassemia.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia beta , Humanos , Criança , Bussulfano/efeitos adversos , Talassemia beta/diagnóstico , Talassemia beta/terapia , Talassemia beta/complicações , Estudos Retrospectivos , Qualidade de Vida , Turquia , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , VidarabinaRESUMO
BACKGROUND: Pneumatosis cystoides intestinalis (PI) is a rare but important condition in which widespread air sacs are found in the submucosa, and subserosa of the bowel wall. Although it has several etiologies, children receiving chemotherapy are at risk for PI. Preferred imaging tools for the diagnosis are abdominal direct radiography and computed tomography. In patients with PI, rupture of intramural air sacs is the source of benign pneumoperitoneum, causing free air without true intestinal perforation. Intestinal perforation or obstruction are indications for surgical intervention. CASE: Here, we present a 4-year-old patient diagnosed with acute myeloblastic leukemia (AML), who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) and developed PI after HSCT. The patient was consulted to the pediatric surgery department, and her oral feeding was stopped. Broad spectrum antibiotics (teicoplanin, metronidazol and vancomycin) were initiated. Her fever increased during the 24-hour monitoring, there was no stool passage, CRP ( > 25 mg/dL, normal value < 1 mg/dL) and abdominal distension increased and there was prolonged neutropenia and radiologic investigations could not rule out intestinal perforation, so the patient underwent exploratory laparotomy. No intestinal perforation was found. There was no sign in the intestinal wall and numerous gas-filled cysts of various sizes. CONCLUSIONS: PI is an uncommon complication, and direct radiography/computed tomography scans are very helpful in making the diagnosis in suspicious cases. PI, should be kept in mind, especially in transplanted or relapsed leukemia patients receiving intensive chemotherapy.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Pneumatose Cistoide Intestinal , Animais , Feminino , Humanos , Criança , Pré-Escolar , Pneumatose Cistoide Intestinal/induzido quimicamente , Pneumatose Cistoide Intestinal/diagnóstico por imagem , Leucemia Mieloide Aguda/terapia , Doadores de Tecidos , AntibacterianosRESUMO
BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.
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Infecções Fúngicas do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Leucemia , Criança , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/etiologia , Infecções Fúngicas do Sistema Nervoso Central/diagnóstico , Infecções Fúngicas do Sistema Nervoso Central/terapia , Antifúngicos/uso terapêutico , Leucemia/tratamento farmacológicoRESUMO
Haemophilia is an X-linked lifelong congenital bleeding disorder that is caused by insufficient levels of factor VIII (FVIII; haemophilia A) or factor IX (FIX; haemophilia B) and characterized by spontaneous and trauma-related bleeding episodes. The cornerstone of the treatment, factor replacement, constitutes several difficulties, including frequent injections due to the short half-life of recombinant factors, intravenous administration and the risk of inhibitor development. While extended half-life factors and subcutaneous novel molecules enhanced the quality of life, initial successes with gene therapy offer a significant hope for cure. Although adeno-associated viral (AAV)-based gene therapy is one of the most emerging approaches for treatment of haemophilia, there are still challenges in vector immunogenicity, potency and efficacy, genotoxicity and persistence. As the approval for the first gene therapy product is coming closer, eligibility criteria for patient selection, multidisciplinary approach for optimal delivery and follow-up and development of new pricing policies and reimbursement models should be concerned. Therefore, this review addresses the unmet needs of current haemophilia treatment and explains the rationale and principles of gene therapy. Limitations and challenges are discussed from a global and national perspective and recommendations are provided to adopt the gene therapies faster and more sufficient for the haemophilia patients in developing countries like Turkey.
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Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most severe and life-threatening complications after hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is approved for adult and pediatric patients with VOD/SOS with renal or pulmonary dysfunction after HSCT in the United States, and for severe VOD/SOS post-HSCT in patients above 1 month of age in the European Union. Several studies have examined whether DF prophylaxis can reduce the incidence of VOD/SOS in high-risk patients. A total of 334 pediatric allogeneic HSCT were included in this study. All patients received DF at the dose of 25 mg/kg/d, from the first day of the conditioning regimen to the 30th day after transplantation for VOD/SOS prophylaxis. Seventeen patients (5.08%) developed VOD/SOS; 4 of these had moderate, while 13 had mild VOD/SOS. None of the patients were developed severe or very severe VOD/SOS. In conclusion, we showed that prophylactic intervention with DF lowered the incidence of VOD/SOS in high-risk pediatric patients.
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Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Polidesoxirribonucleotídeos/administração & dosagem , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/prevenção & controle , Humanos , Incidência , Lactente , Masculino , Polidesoxirribonucleotídeos/efeitos adversos , Estudos Retrospectivos , Estados UnidosRESUMO
OBJECTIVE: Hemophilia A is the second most common bleeding disorder causing patients to have lifelong follow-up and treatment. Despite being a rare disease, hemophilia A has a high economic burden on individuals and the public. The purpose of this study was to estimate the total disease cost of hemophilia A in Turkey. MATERIALS AND METHODS: Data used in this analysis were collected through literature review, including studies conducted in Turkey in December 2018. A disease burden analysis was performed by modeling hemophilia A-related costs among patients, their relatives, and the social security system. Two expert panels were held to evaluate real-world data sources and to provide further information. All direct medical and non-medical costs were calculated annually from the Social Security Institution of the Republic of Turkey perspective, while indirect costs were estimated from the patient and community perspective. RESULTS: For the calendar year of 2018, the number of hemophilia A patients in Turkey were estimated to be 5,055, with an average weight of 64.7 kg. The average annual direct medical, direct non-medical, and indirect costs of hemophilia A were calculated as 93,268 ($109,286; âº502,717), 2,533 ($2,968; âº13,655), and 7,957 ($9,323; âº42,888) per patient, respectively, with a total annual cost of 103,759 ($121,578; âº559,259). For the management of patients with inhibitors (4.9%), the average annual total cost was calculated to be 325,439 ($381,330; âº1,754,117) per patient. The total annual disease burden of hemophilia A in 2018 was estimated to be about 524 million ($614 million; âº2.82 billion), which corresponded to 1.6% of the total health expenditure in Turkey. CONCLUSION: The most important reason hemophilia A has a significant economic burden in Turkey is that replacement therapy is expensive. The major cost contributor was identified as factor replacement therapy. With inhibitor development, the average annual cost increased more than 3-fold.
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Efeitos Psicossociais da Doença , Hemofilia A , Custos de Cuidados de Saúde , Gastos em Saúde , Hemofilia A/tratamento farmacológico , Hemofilia A/epidemiologia , Humanos , Turquia/epidemiologiaRESUMO
Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Humanos , Cinética , Leucemia Mieloide Aguda/terapia , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: BK virus-associated hemorrhagic cystitis is a common complication of allogeneic hematopoietic stem cell transplant. It is known to be associated with cyclophosphamide therapy and the intensity of the conditioning regimen as well as infection with the BK virus. Data are limited for BK virus-associated hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Therefore, we aimed to identify the risk factors and etiology of BK virus-associated hemorrhagic cystitis and determine the factors that may improve the treatment efficacy. MATERIALS AND METHODS: Data from recipients of allogeneic hematopoietic stem cell transplant were retrospectively analyzed. These data included information about age, sex, underlying disease, the details of ablative conditioning, graft-versus-host disease prophylaxis, donor type, stem cell source, history of acute graft-versus-host disease, and cytomegalovirus reactivation. RESULTS: A total of 50 patients developed BK virusassociated hemorrhagic cystitis among 334 patients. Symptoms associated with BK virus-associated hemorrhagic cystitis manifested an average of 45.3 days after transplant. Most of the patients had grade 2 and grade 3 hemorrhagic cystitis. Risk factor analysis revealed that haploidentical donor type, treatment with busulfan and cyclophosphamide as part of conditioning regimen, and history of total body irradiation increased the risk of BK virus-associated hemorrhagic cystitis in the pediatric recipient population. CONCLUSIONS: We found that, despite current conditioning regimens, BK virus-associated infection still leads to a considerable incidence rate of hemorrhagic cystitis in pediatric recipients of allogeneic hematopoietic stem cell transplant. Patients with a haploidentical donor and a history of busulfan and cyclophosphamide treatment or total body irradiation had a higher risk of BK virus-associated hemorrhagic cystitis. Thus, we suggest that patients with these factors should be followed closely after allogeneic hematopoietic stem cell transplant.
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BACKGROUND AND OBJECTIVES: We aimed to evaluate joint health in children with hemophilia (CwH) and to investigate the effects of hemarthrosis on the musculoskeletal system. METHOD: Forty-one CwH aged between 6-18 years participated in the study. Joint health status was evaluated according to Hemophilia Joint Health Score (HJHS). Pain intensity level was assessed in resting and in activity using Visual Analog Scale. Range of motion was measured with goniometer and muscle strength was assessed with digital dynamometer. Arthropathic joints were examined in three groups named knee, elbow and ankle. RESULTS: Physical examination revealed arthropathy findings to be found in 29 knee, 19 elbow and 18 ankle joints. The median of flexion angle of the affected side were 120°, 122° and 12° for the knee, elbow and ankle and extension losses of these joints were 5°, 7° and 0, respectively. In CwH having knee and elbow arthropathy, index joint HJHS was found to be significantly higher than those with ankle arthropathy (p < 0.01). The flexor and extensor muscle strength significantly decreased in 11 CwH with unilateral elbow arthropathy compared to the non-arthropatic side (p < 0.05). In 15 CwH with unilateral ankle arthropathy decreased in the extensor muscle strength (plantarflexors) (p < 0.05). Extension loss showed a good correlation with index HJHS of elbow, knee and ankle joints, respectively. (rs= 0.599, 0.576, 0.606, p < 0.01). We observed that the muscle strength of elbow flexors/extensors and ankle extensors were significantly decreased compared to the non-arthropathic side. However this situation was not detected in knee joint despite having highest index HJHS. CONCLUSION: Our findings indicate that hemarthrosis may cause more muscle strength loss in the upper extremity than the lower extremity. Furthermore, extension loss was found to be an important parameter in physical examination of hemophilic arthropathy. Musculoskeletal system should be evaluated comprehensively at regular intervals and when necessary rehabilitative treatment should be planned.
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Hemofilia A , Adolescente , Articulação do Tornozelo , Criança , Estudos Transversais , Hemartrose/diagnóstico , Hemartrose/epidemiologia , Hemartrose/etiologia , Hemofilia A/complicações , Humanos , Força MuscularRESUMO
INTRODUCTION: Among children with haemophilia and their caregivers; problems arising from the teeth and the surrounding tissues have an important role in the treatment of this disease and it affects the quality of life of children and their parents. AIM: Aim of this study is to evaluate the oral health-related quality of life of children with haemophilia from the perspective of their parents. METHODS: Paediatric oral health-related quality of life (POQL) instrument was used in this cross-sectional study for quality of life measurement. The research data collected by the questionnaire form were coded for scale items and personal information questions and transferred to SPSS, a multivariate statistical analysis program for social sciences. SPSS 23.0 (IBM Corp, Armonk, NY) package program was used for statistical analysis of the data. RESULTS: Primary dentition dmft scores of patients with haemophilia are higher than the control group; mean value of haemophilic group is 3.5 vs control group are 2.6, respectively (P = 0.034). In spite of higher dmft scores, the haemophilia and control groups have shown no significant difference in oral health-related quality of life scores; median scores were 63.9 in haemophilic group and 85.3 in control group (P = 0.336), respectively. CONCLUSION: In spite of lower oral health measures, children with haemophilia and their parents reported no difference in oral health-related quality of life from their healthy counterparts.
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Transtornos Herdados da Coagulação Sanguínea/patologia , Cuidadores/psicologia , Saúde Bucal , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Emoções , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.
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Anemia Falciforme/complicações , Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Talassemia/complicações , Adolescente , Anemia Falciforme/terapia , Biomarcadores , Transfusão de Sangue , Criança , Pré-Escolar , Estudos de Coortes , Deferasirox/administração & dosagem , Deferasirox/efeitos adversos , Feminino , Ferritinas/sangue , Ferritinas/metabolismo , Humanos , Ferro/sangue , Ferro/metabolismo , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/metabolismo , Masculino , Talassemia/terapia , Resultado do Tratamento , TurquiaRESUMO
GI perforation after stem cell transplantation is extremely rare and is associated with poor prognosis. In addition, the clinical limitations of MMF are associated with GI intolerance and hematologic suppression. However, the exact mechanism whereby MMF induces changes in GI mucosa is unknown. Currently, there is no definite method to distinguish between GI toxicity associated with MMF and GVHD. It is important to recognize association between MMF and the histologic changes mimicking GVHD, given that GVHD is a significant differential diagnosis in stem cell transplant patients. MMF-induced colitis and GI perforation are extremely rare but should be considered in patients presenting with diarrhea and abdominal pain. Histology and clinical features are helpful to distinguish this condition from ischemic colitis. Early recognition of GI perforation is necessary for proper diagnosis and subsequent intervention. Emergency medical treatment and laparotomy have been shown to reduce the risk of fatal complications in patients presenting with GI symptoms suspected of GI perforation.
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FK506 (tacrolimus) is an immunosuppressive drug and more potent than cyclosporine. FK506 is widely used for immunosuppression in the prevention and treatment of graft-versus-host disease after allogeneic bone marrow transplantation and solid organ transplantation. Neurotoxicity is a recognized complication of FK506 therapy, but ptosis and weakness of eye abduction unilaterally has not been reported in association with FK506 administration to date. We discuss a 13-year-old male patient who developed ptosis and weakness of eye abduction unilaterally 90 days after transplantation with bone marrow from an unrelated donor, for acute lymphoblastic leukemia in this case report. FK506 therapy was administered for graft-versus-host disease prophylaxis and CMV infection was treated with ganciclovir. The physical examination findings completely resolved 72 to 96 hours after concomitant FK506 and ganciclovir treatment were terminated.
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Transplante de Medula Óssea/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Transtornos da Motilidade Ocular/induzido quimicamente , Adolescente , Antivirais/uso terapêutico , Blefaroptose/induzido quimicamente , Transplante de Medula Óssea/métodos , Ganciclovir/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Transtornos da Motilidade Ocular/etiologia , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).
Assuntos
Anticorpos Neutralizantes/sangue , Fator VIII/imunologia , Hemofilia A/tratamento farmacológico , Isoanticorpos/análise , Fator de von Willebrand/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Fator VIII/antagonistas & inibidores , Fator VIII/uso terapêutico , Hemofilia A/complicações , Hemofilia A/imunologia , Hemorragia/etiologia , Humanos , Incidência , Lactente , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
Following joint hemorrhages, intramuscular hemorrhages are the second most prevalent bleeding pattern in hemophiliac patients. Hematomas of the iliopsoas muscle are a well-known complication of hemophilia; however, obturator muscle hematomas are rare. We herein report a case of spontaneous bleeding of the bilateral external obturator muscles, which occured three times within a period of 9 months in a hemophilia patient with factor VIII inhibitors. To the best of our knowledge, this is the first published case of an obturator externus muscle hematoma in hemophilia. In addition to hip hemarthrosis, iliopsoas hematomas and acute appendicitis, obturator muscle hematoma should be considered as one of the diagnostic alternatives for pelvic pain in hemophiliaψ patients. Magnetic resonance imaging enables rapid diagnosis of obturator muscle hematoma.
RESUMO
OBJECTIVE: The role of cord milking as an alternative to delayed cord clamping is an area that requires more research. Purpose of this clinical trial was to investigate the impact of umbilical cord milking on the absolute neutrophil counts (ANCs) and the neutropenia frequency of preterm infants. METHODS: Fifty-eight pregnant women were randomly assigned to one of the umbilical cord milking and control groups. A total of 54 preterm infants (gestational age ≤ 32 weeks) were enrolled into the study. The umbilical cords of 25 infants were clamped immediately after birth, and in 29 infants, umbilical cord milking was performed first. RESULTS: The ANCs were statistically significantly lower in the cord milking group compared with the control group on days 1, 3 and 7. The frequency of neutropenia was higher in the cord milking group compared with the control group. CONCLUSION: In our study, ANCs were lower in the cord milking group and the frequency of neutropenia was higher. Umbilical cord milking plays a role on the ANCs of preterm infants.