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Allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative option for Fanconi anemia (FA) associated bone marrow failure (BMF)/aplastic anemia (AA) and hematological malignancy. We performed a retrospective multicenter study on 813 FA children undergoing first HSCT between 2010 and 2018. Median duration of follow-up was 3.7 years (interquartile range, 3.4-4.0). Median age at transplant was 8.8 years (6.5-18.1). Overall survival (OS), event-free survival (EFS) and GvHD-free, relapse-free survival (GRFS) at 5 years were 83% (80-86%), 78% (75-81%) and 70% (67-74%) respectively. OS was comparable between matched family donor (MFD, n=441, 88%) and matched unrelated donor (MUD, n=162, 86%) and was superior to that of mismatched family or unrelated donor (MMFD/MMUD, n=144, 72%) and haploidentical donor (HID) (n=66, 70%, p<0.001). In multivariable analysis, a transplant indication of acute myeloid leukaemia/myelodysplastic syndrome compared to AA/BMF, use of MMFD/MMUD and HID compared to MFD, Fludarabine-Cyclophosphamide (FluCy) + other conditioning compared to FluCy independently predicted inferior OS, while alemtuzumab compared to ATG was associated with better OS. Age ï³ 10 years was associated with worse EFS and GRFS. Cumulative incidences (CIN) of primary and secondary graft failure were 2% (1-3%) and 3% (2-4%) respectively. CIN of grade II-IV acute GvHD, grade III-IV acute GvHD and chronic GvHD were 23% (20-26%), 12% (10-15%) and 8% (6-10%) respectively. The 5-year CIN of secondary malignancy was 2% (1-3%). These data suggest that HSCT should be offered to Fanconi Anemia patients with AA/BMF at a younger age in the presence of a well-matched donor.
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BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.
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COVID-19 , Trasplante de Células Madre Hematopoyéticas , Humanos , COVID-19/epidemiología , COVID-19/terapia , COVID-19/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Niño , Masculino , Femenino , Estudios Retrospectivos , Adolescente , Turquía/epidemiología , Preescolar , Factores de Riesgo , SARS-CoV-2 , Lactante , Trasplante Homólogo , Índice de Severidad de la EnfermedadRESUMEN
Magnusiomyces clavatus is a rare yeast-like fungus that can cause opportunistic infections in immunocompromised patients. Here, we present a 14-year-old patient who was followed up with the diagnosis of acute lymphoblastic leukemia, developed skin rashes, and Magnusiomyces clavatus infection detected. The patient died shortly after the infection was diagnosed.
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Exantema , Leucemia-Linfoma Linfoblástico de Células Precursoras , Saccharomycetales , Niño , Humanos , Adolescente , Hongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Exantema/etiologíaRESUMEN
BACKGROUND: Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive combined immunodeficiency. The phenotype is profound T cell deficiency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the first year of life. Neurologic findings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP deficiency. METHODS: We report here six patients from five unrelated families with PNP deficiency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms "PNP" and "hematopoietic stem cell transplantation" to find all reported cases of PNP transplantation and compared to our cohort. RESULTS: Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21-48 months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor. DISCUSSION: In PNP deficiency, clinical manifestations are variable, and this disease should be considered in the presence of many different clinical findings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients.
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Trasplante de Células Madre Hematopoyéticas , Enfermedades de Inmunodeficiencia Primaria , Errores Innatos del Metabolismo de la Purina-Pirimidina , Humanos , Purina-Nucleósido Fosforilasa/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedades de Inmunodeficiencia Primaria/diagnóstico , Enfermedades de Inmunodeficiencia Primaria/terapia , Enfermedades de Inmunodeficiencia Primaria/etiología , Errores Innatos del Metabolismo de la Purina-Pirimidina/terapiaRESUMEN
BACKGROUND: Respiratory viral infections (RVIs) are important complications in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT); however, risk factors for lower respiratory tract infections (LRTIs) are not well characterized. The aim of this study was to determine risk factors for the progression to LRTIs in pediatric patients with respiratory symptoms who underwent HSCT. PATIENTS AND METHODS: This retrospective study included 87 pediatric patients with respiratory symptoms who underwent HSCT. Respiratory viral polymerase chain reaction samples were obtained from all patients. The evaluated data included risk factors to progression to LRTIs, long-term pulmonary complications, transplantation-related mortality, and overall survival. RESULTS: Viral pathogens were detected in 31 (48.4%) patients with upper respiratory tract infections and 13 (56.5%) patients with LRTIs. There was a statistically significant difference between the groups in engraftment delay and lymphocytopenia. Also it was determined that engraftment delay (odds ratio: 7.46 [95% CI, 1.99 to 27.86]; P = 0.003) and COVID-19 infection had statistically significant effects on overall survival in general (odds ratio: 8.06 [95% CI, 2.63 to 24.64]; P <0.001]). CONCLUSION: Not only host and transplant-related factors but also viral agent type were found to be effective in progression to LRTIs. As the available therapy for respiratory viral infections remains limited, the focus should be on the prevention of infection.
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COVID-19 , Trasplante de Células Madre Hematopoyéticas , Infecciones del Sistema Respiratorio , Humanos , Niño , Estudios Retrospectivos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/etiología , Infecciones del Sistema Respiratorio/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de RiesgoRESUMEN
OBJECTIVES: Sinusoidal obstruction syndrome/venoocclusive disease is a significant complication of hematopoietic stem cell transplantation. Due to high mortality rates, new treatment strategies have been investigated. Here, we have presented outcomes of therapeutic plasma exchange performed on patients with sinusoidal obstruction syndrome/veno-occlusive disease. MATERIAL AND METHODS: Our study included 70 pediatric patients diagnosed with sinusoidal obstruction syndrome/veno-occlusive disease. Therapeutic plasma exchange procedures in patients were evaluated retrospectively. RESULTS: There were 9 mild (12.9%), 9 moderate (12.9%), 21 severe (30%), and 31 very severe (44.2%) cases of sinusoidal obstruction syndrome/venoocclusive disease. Therapeutic plasma exchange was performed in 31 of the 70 study patients (59.6%). Moreover, 10/21 patients with severe (47.6%) and 21/31 patients with very severe (67.7%) disease underwent plasma exchange. Mean time from diagnosis of sinusoidal obstruction syndrome/venoocclusive disease to therapeutic plasma exchange initiation was 2.3 days. The 31 patients who received therapeutic plasma exchange had a total of 146 sessions. Overall survival rates at 100 days were 87.1% and 92.3% for patients who did and did not undergo therapeutic plasma exchange, respectively. When patients with mild and moderate disease who were not expected to undergo plasma exchange were excluded (n = 52), 100-day overall survival rates were 87.1% and 90.5% for those who did and did not undergo plasma exchange, respectively. When we compared severe versus very severe groups, no significant difference was found. CONCLUSIONS: Plasmapheresis had no positive effect on survival. However, overall survival in all groups was higher than that in the literature, despite the high number of patients with severe and very severe disease. Interpretation of the results is limited by the retrospective nature of the study. Thus, prospective, randomized controlled trials with larger numbers of patients are necessary to investigate the role of therapeutic plasma exchange in patients with sinusoidal obstruction syndrome/veno-occlusive disease.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Niño , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/diagnóstico , Enfermedad Veno-Oclusiva Hepática/etiología , Enfermedad Veno-Oclusiva Hepática/terapia , Humanos , Intercambio Plasmático/efectos adversos , Plasmaféresis/efectos adversos , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Human Inborn Errors of Immunity (IEIs) are clinically and genetically heterogeneous group of diseases, with relatively mild clinical course or severe types that can be life-threatening. Severe combined immunodeficiency (SCID) is the most severe form of IEIs, which is caused by monogenic defects that impair the proliferation and function of T, B, and NK cells. According to the most recent report by the International Union of Immunological Societies (IUIS), SCID is caused by mutations in IL2RG, JAK3, FOXN1, CORO1A, PTPRC, CD3D, CD3E, CD247, ADA, AK2, NHEJ1, LIG4, PRKDC, DCLRE1C, RAG1 and RAG2 genes. The targeted next-generation sequencing (TNGS) workflow based on Ion AmpliSeq™ Primary Immune Deficiency Research Panel was designed for sequencing 264 IEI-related genes on Ion S5™ Sequencer. Herein, we present 21 disease-causing variants (12 novel) which were identified in 22 patients in eight different SCID genes. Next-generation sequencing allowed a rapid and an accurate diagnosis SCID patients.
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Inmunodeficiencia Combinada Grave , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Células Asesinas Naturales , Mutación , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/genética , TurquíaRESUMEN
We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Talasemia , Talasemia beta , Niño , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Talasemia/complicaciones , Talasemia/terapia , Acondicionamiento Pretrasplante/efectos adversos , Turquía/epidemiología , Talasemia beta/complicaciones , Talasemia beta/terapiaRESUMEN
INTRODUCTION: In highly sensitized patients who have panel reactive antibodies (PRAs) before hematopoietic stem cell transplantation, primary graft failure risk may increase. In this study, we aimed to determine the association of PRA with engraftment, and graft versus host disease (GVHD) in pediatric patients. MATERIALS AND METHODS: Forty-three PRA-positive and 42 PRA-negative patients were taken into study. Both groups were compared in terms of graft failure, acute GVHD, viral infection and survival rates. PRA-positive group was also divided into 2 according to treatment modality (steroid-only group/combination therapy) and compared for the same parameters. RESULTS: There was no difference in PRA-positive and negative patients in terms of graft failure, acute GVHD and viral infections. Analysis of the PRA-positive group in itself showed that there was also no difference in terms of graft failure and viral infection frequency. The only difference is that acute grade 3 to 4 GVHD was higher in the steroid-only group. The 100-day overall survival was 90.2% and 90.4% for the PRA-positive and negative groups, respectively. CONCLUSIONS: Different treatment strategies like plasmapheresis, steroid, rituximab, or combination therapies can be used for the desensitization of PRA-positive patients before hematopoietic stem cell transplantation. Patient-specific treatment modality for sensitized patients before transplant can increase the success rate.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA , Prueba de Histocompatibilidad , HumanosRESUMEN
OBJECTIVES: The mostimportant problems thatlimitthe effectiveness of allogeneic hematopoietic stem cell transplantation in patients with severe aplastic anemia are graft failure and graft-versus-host disease. Mesenchymal stem cells can support normal hematopoiesis and prevent graft-versus-host disease. We aimed to analyze the effects of combined transplant of human umbilical cord-derived mesenchymal stem cells and matched donor allogeneic hematopoietic stem cells in children with severe aplastic anemia. MATERIALS AND METHODS: We retrospectively examined 15 pediatric patients with severe aplastic anemia who received fludarabine-based reduced intensity conditioning regimen and intravenously infused human umbilical cord-derived mesenchymal stem cells at a dose of 1 × 106/kg recipient body weight within 12 to 18 hours before hematopoietic stem cells infusion. We evaluated the engraftment rate, the frequency and severity of graft-versus-host disease, and the overall survival rate. RESULTS: No patients had adverse events related to intravenously human umbilical cord-derived mesenchymal stem cells infusion. All patients achieved successful engraftment and sustained donor chimerism. The median time for neutrophil and platelet engraftment was 14 and 25 days,respectively. The frequency was 20% for grade III/IV acute graftversus- host disease and 15.3% for chronic graftversus-host disease. Patients were followed-up for a median of 33 months (range, 2-89 months). The 5-year overall survival rate was 80%. CONCLUSIONS: Combined transplant of matched donor hematopoietic stem cells with human umbilical cord-derived mesenchymal stem cells is safe in pediatric patients with severe aplastic anemia. The achievement of engraftment in all of our patients and the acceptable frequency of acute and chronic graft-versus-host disease and survival rate are encouraging.
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Anemia Aplásica , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Células Madre Mesenquimatosas , Humanos , Niño , Anemia Aplásica/diagnóstico , Anemia Aplásica/cirugía , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Aguda , Cordón UmbilicalRESUMEN
BACKGROUND: Haploidentical HSCT is a good option for children with PIDs lacking an HLA-matched donor. Co-transplantation of MSCs during haploidentical HSCT in patients with PIDs may enhance engraftment, decrease the risk of GVHD, and ensure stable donor chimerism. METHODS: Twenty-seven pediatric patients (median age, 1.4 years; range, .3-10.9) with PIDs undergoing thirty haploidentical HSCT with TCR αß depletion and co-transplantation of MSCs were enrolled to study. Most patients (73.3%) received myeloablative conditioning consisting of treosulfan or busulfan, fludarabine, and thiotepa. The median duration of follow-up was 14.3 months (range, 1-69 months). RESULTS: Acute GVHD occurred in 7 patients (grade I-II n = 5, grade III-IV n = 2). Chronic GVHD was observed in only one patient. Twenty-one patients (70.2%) had 100% donor chimerism in all cell lines including T-cell and B-cell lineages. Primary graft failure was observed in 7 patients (25.9%). The cumulative incidences of TRM were 20% at day 100, and 26.7% at one year and five years. Probabilities of OS were 80% at day 100, and 71.9% at 1 year and 5 years. Infants transplanted younger than 6 months of age had the highest 5-year survival rate (85.7%). CONCLUSION: We conclude that use of TCR αß depleted haploidentical transplantation with MSCs may ensure a rapid engraftment rate, low incidence of significant acute and chronic GVHD, and acceptable post-transplantation morbidity, especially in patients diagnosed with SCID and may be considered in children with PIDs. In younger patients (≤6 months), survival is comparable between HLA-matched graft and CD3+ TCRαß depleted HLA-mismatched graft recipients.
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Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Enfermedades de Inmunodeficiencia Primaria/terapia , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Acondicionamiento Pretrasplante/métodos , Niño , Preescolar , Femenino , Rechazo de Injerto , Humanos , Lactante , MasculinoRESUMEN
Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA). Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h. Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05). Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.
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Terapia Trombolítica , Trombosis , Activador de Tejido Plasminógeno , Adolescente , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Trombosis/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
BACKGROUND: Anti-human T-lymphocyte immunoglobulin is commonly used as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors. The studies according to optimum dose of ATLG especially in pediatric patients are limited. PATIENTS AND METHODS: Outcomes of 99 pediatric patients diagnosed with nonmalignant diseases, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2), and 30 mg/kg (group 3), were analyzed retrospectively. RESULTS: The incidences of acute and chronic GVHD were statistically not different between three groups (p = .20 and p = .13), but we did not observe chronic GVHD in group 3 patients. Cox regression analysis showed that ATLG dose of 10 mg/kg (p = .007) and severe acute GVHD (p = .001) were significant prognostic factors for inferior overall survival. Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention, TRM and overall survival were superior in ATLG doses ≥20 mg/kg (p = .04 and p = .037) with no difference between 20 and 30 mg/kg. CONCLUSION: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection, TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 and 30 mg/kg. These observations should be supported with other multicenter prospective studies including larger patient population.
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Suero Antilinfocítico/administración & dosificación , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Donante no EmparentadoRESUMEN
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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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Niño , Humanos , Cinética , Leucemia Mieloide Aguda/terapia , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Type I and III leukocyte adhesion deficiencies (LADs) are primary immunodeficiency disorders resulting in early death due to infections and additional bleeding tendency in LAD-III. The curative treatment of LAD-I and LAD-III is allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective multicenter study, data were collected using the European Society for Blood and Marrow Transplantation registry; we analyzed data from 84 LAD patients from 33 centers, all receiving an allo-HSCT from 2007 to 2017. The 3-year overall survival estimate (95% confidence interval [CI]) was 83% (74-92) for the entire cohort: 84% (75-94) and 75% (50-100) for LAD-I and LAD-III, respectively. We observed cumulative incidences (95% CI) of graft failure (GF) at 3 years of 17% (9%-26%) and grade II to IV acute graft-versus-host disease (aGVHD) at 100 days of 24% (15%-34%). The estimate (95% CI) at 3 years for GF- and GVHD-II to IV-free survival as event-free survival (EFS) was 56% (46-69) for the entire cohort; 58% (46-72) and 56% (23-88) for LAD-I and LAD-III, respectively. Grade II to IV acute GVHD was a relevant risk factor for death (hazard ratio 3.6; 95% CI 1.4-9.1; P = .006). Patients' age at transplant ≥13 months, transplantation from a nonsibling donor, and any serological cytomegalovirus mismatch in donor-recipient pairs were significantly associated with severe acute GVHD and inferior EFS. The choice of busulfan- or treosulfan-based conditioning, type of GVHD prophylaxis, and serotherapy did not impact overall survival, EFS, or aGVHD. An intrinsic inflammatory component of LAD may contribute to inflammatory complications during allo-HSCT, thus providing the rationale for considering anti-inflammatory therapy pretreatment.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndrome de Deficiencia de Adhesión del Leucocito , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Síndrome de Deficiencia de Adhesión del Leucocito/terapia , Leucocitos , Estudios RetrospectivosAsunto(s)
COVID-19/complicaciones , Neoplasias/complicaciones , Trasplante de Células Madre , Adolescente , Antivirales/uso terapéutico , COVID-19/epidemiología , COVID-19/terapia , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Neoplasias/epidemiología , Neoplasias/terapia , Estudios Retrospectivos , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/aislamiento & purificación , Resultado del Tratamiento , Turquía/epidemiologíaRESUMEN
PURPOSE: Patients with heterozygous gain-of-function (GOF) mutations in STAT1 frequently exhibit chronic mucocutaneous candidiasis (CMC), immunodeficiency and autoimmune manifestations. Several treatment options including targeted therapies and hematopoietic stem cell transplantation (HSCT) are available for STAT1 GOF patients but modalities and outcomes are not well established. Herein, we aimed to unravel the effect of ruxolitinib as a bridge therapy in a patient with sporadic STAT1 T385M mutation to manage infections and other disease manifestations. METHODS: Peripheral blood mononuclear cells were isolated from the patient prior to, during ruxolitinib treatment and 6 months after HSCT. IFN-ß-induced STAT1 phosphorylation/dephosphorylation levels and PMA/ionomycin-stimulated intracellular IL-17A/IFN-γ production in CD4+ T cells were evaluated. Differentially expressed genes between healthy controls and the patient prior to, during ruxolitinib treatment and post-transplantation were investigated using Nanostring nCounter Profiling Panel. RESULTS: Ruxolitinib provided favorable responses by controlling candidiasis and autoimmune hemolytic anemia in the patient. Dysregulation in STAT1 phosphorylation kinetics improved with ruxolitinib treatment and was completely normalized after transplantation. TH17 deficiency persisted after ruxolitinib treatment, but normalized following HSCT. Consistent with the impairment in JAK/STAT signaling, multiple immune related pathways were found to be dysregulated in the patient. At baseline, genes related to type I IFN-related pathways, antigen processing, T-cell and B-cell functions were upregulated, while NK-cell function and cytotoxicity related genes were downregulated. Dysregulated gene expression was partially improved with ruxolitinib treatment and normalized after transplantation. CONCLUSION: Our findings suggest that improved disease management and immune dysregulatory profile can be achieved with ruxolitinib treatment before transplantation and this would be beneficial to reduce the risk of adverse outcome of HSCT.
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Mutación con Ganancia de Función , Trasplante de Células Madre Hematopoyéticas , Enfermedades del Sistema Inmune/etiología , Enfermedades del Sistema Inmune/terapia , Inhibidores de las Cinasas Janus/uso terapéutico , Nitrilos/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Factor de Transcripción STAT1/genética , Alelos , Preescolar , Terapia Combinada , Citocinas/metabolismo , Diagnóstico Diferencial , Femenino , Genotipo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Enfermedades del Sistema Inmune/diagnóstico , Inmunofenotipificación , Fenotipo , Fosforilación , Factor de Transcripción STAT1/metabolismo , Resultado del TratamientoRESUMEN
Mesenchymal stem cells (MSCs) have been used systemically or locally in many chronic and nonhealing skin lesions in recent years. In this study, umbilical cord-derived MSCs (UC-MSCs)-seeded fibrin matrix was used as a wound dressing in pediatric patients with stage 4 acute graft-versus-host disease (aGVHD)-induced desquamated skin lesions. This is the first study in which the UC-MSCs-seeded fibrin matrix was used as a wound dressing in aGVHD. A total of 14 times the MSCs-seeded fibrin matrix were applied to 9 patients as a wound dressing. On the seventh day, epithelialization and clinical response were evaluated. According to the size of the skin defect min: 1, max: 6 pieces were applied at a time. After 48 to 72 hours, it was observed that all of the MSCs-seeded fibrin matrixes adhered to the skin and the crustation started in 6 (43%) applications, whereas liquefaction was detected under all of them in 7 (50%) applications. Complete response was obtained in 6 applications (43%), partial response in 1 (7%), and no response in 7 applications (50%). This study showed that the MSCs-seeded fibrin matrix can be used effectively and safely in the matrix in the local treatment of aGVHD-induced skin wounds in pediatric patients.
Asunto(s)
Fibrina/química , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Andamios del Tejido/química , Cordón Umbilical/citología , Adolescente , Vendajes , Células Cultivadas , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Masculino , Células Madre Mesenquimatosas/citología , Estudios Prospectivos , Piel/patología , Cicatrización de HeridasRESUMEN
BACKGROUND: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. PROCEDURE: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. RESULTS: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. CONCLUSION: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia/mortalidad , Leucemia/terapia , Enfermedad Aguda , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Lactante , Recién Nacido , Leucemia/diagnóstico , Masculino , Pronóstico , Recurrencia , Estudios Retrospectivos , Terapia Recuperativa , Análisis de Supervivencia , Trasplante Homólogo , Turquía/epidemiología , Adulto JovenRESUMEN
BACKGROUND: RhD typing has remained of primary importance, as being the leading cause of hemolytic disease of the newborn. Among Rh system's 55 blood group antigens, RhD is the most immunogenic. We aimed with this study to determine weak D/partial D variant frequency in blood donors who were admitted to our blood center and have serologically designated blood group weak D. MATERIALS AND METHODS: We screened blood donors who admitted between 2011 and 2017 to our blood center. Sixty-seven serologically weak D phenotyped donors have participated in the study. These donors' samples were studied further by Polymerase Chain Reaction Sequence- Specific Primers (PCR-SSP) for determining D variants. RESULTS: Weak D phenotype was detected in 228(0.12 %) out of 177,554 donors. Sixty-seven of them agreed to take part in the study. The frequency of weak D and partial D was 68.7 % (n = 46), and 22.4 % (n = 15), in order. The most encountered weak D and partial D variant was type 15 and DFR type, respectively. CONCLUSIONS: The prevalence of serologically weak D phenotypes varies by race and ethnicity. Turkey is a country covering a mixture of European and Asian DNA with different ethnic groups. Thus, our research as giving the overall distribution of RHD variants from the largest city of Turkey, which may reflect the general ethnic background of the country, would help to the establishment of a databank for blood banking. This paper is the first molecular study on RHD variants in Turkey. New molecular research would be more reliable and precise.