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Background: The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. Methods: In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Results: Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Conclusions: Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.
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Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare complication following hematopoietic stem cell transplantation (HSCT). Currently, there is a lack of consensus recommendations for the treatment of post-transplant HLH. This case report emphasizes the successful utilization of ruxolitinib as a salvage therapy for HLH post-HSCT. The aim is to provide valuable insights into the optimal management of this rare and complex complication. Case Description: We present a case study of an 11-year-old male patient diagnosed with severe aplastic anemia who received a haploidentical HSCT. On the 86th day post-transplantation, the patient developed recurrent fever, hepatomegaly, hypertriglyceridemia, severe pancytopenia, and elevated levels of inflammatory factors and ferritin. Hemophagocytosis was observed in the bone marrow, and subsequent DNA next-generation sequencing identified adenovirus type C infection, leading to a diagnosis of adenovirus-associated HLH. After unsuccessful treatment attempts with cidofovir, dexamethasone, immunoglobulin, plasmapheresis, and etoposide, ruxolitinib was administered. Remarkably, the patient's clinical symptoms rapidly improved, and his test results gradually normalized with ruxolitinib therapy. The adenovirus viral load became undetectable by the 180th day. With continuous remission, ruxolitinib was discontinued on the 137th day post-transplantation, and a 15-month follow-up examination showed no relapse. Conclusions: We present a case of adenovirus-related secondary HLH (sHLH) post-HSCT, which was effectively treated with ruxolitinib. Our case highlights the potential of ruxolitinib as a therapeutic option for patients with viral infections and sHLH. Nonetheless, the safety and efficacy of this innovative treatment should be evaluated in forthcoming large-scale clinical trials.
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The hematopoietic system constantly produces new blood cells through hematopoiesis, and maintaining this balance is vital for human health. This balance is maintained by self-renewing hematopoietic stem cells (HSCs) and various progenitor cells. Under typical circumstances, HSCs are not abundantly found in peripheral blood; hence, their mobilization from the bone marrow is vital. Hematopoietic growth factors achieve this effectively, enabling mobilization and thus allowing blood sample and thus HSC collection via apheresis. Securing a sufficient supply of HSCs is vital for successful hematopoietic reconstitution and the rapid integration of committed cells. Thus, isolation and expansion of HSCs are crucial for convenient extraction, production of transplantable quantities, genetic modifications for enhanced therapeutic efficacy, and as a source of increased/expanded/synthesized blood cells in vitro. In conclusion, the isolation and expansion of HSCs play pivotal roles in both regenerative medicine and hematology. This protocol describes the isolation of human HSCs by providing an overview of the primary method for isolating human hematopoietic stem cells from apheresis blood samples and sheds light on human HSC studies and developments in research and medicine.
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NMDP recognizes that despite advances in hematopoietic stem cell transplantation (HSCT) and other cell therapies, not all patients have equitable access to treatment, and disparities in outcomes remain. This paper explores the recent work of NMDP to accelerate progress and expand access to more patients through transformative clinical research, particularly in the use of mismatched unrelated donors for HSCT.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
[This corrects the article DOI: 10.3389/fonc.2024.1339605.].
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BACKGROUND: Infective endocarditis (IE) is a serious complication of bloodstream infections (BSIs) that occurs at variable rates depending on the pathogen and clinical setting. There is a paucity of data describing the risk of IE in patients with hematologic malignancy who develop bacteremia while neutropenic. METHODS: Adult patients on the hematology ward from January 2018 to December 2020 with hematologic malignancy and bacteremia were evaluated retrospectively for endocarditis by applying the 2023 Duke-ISCVID criteria. Charts of possible cases were evaluated 90 days after the initial BSI for new infectious complications that could indicate missed IE. Descriptive statistics compared patients admitted for hematopoietic stem cell transplantation (HSCT) to those admitted for alternative reasons (non-HSCT). RESULTS: Among the 1005 positive blood cultures initially identified, there were 66 episodes in 65 patients with hematologic malignancy and at least grade 3 neutropenia for a mean duration of 11.4 days during their admission. Transthoracic echocardiography (TTE) was performed in 34.8% of BSIs, and transesophageal echocardiography (TEE) in 6.1%. There were no new infectious complications in possible cases 90 days after their initial BSI. No cases of endocarditis were identified. CONCLUSIONS: Endocarditis is rare amongst patients with hematologic malignancy, bacteremia, and neutropenia, and no cases were identified in this cohort. The use of routine TTE in this setting seems unwarranted, and the addition of TEE is unlikely to improve patient-centered outcomes.
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Bacteriemia , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Neutropenia , Humanos , Neutropenia/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Hematológicas/complicaciones , Estudios Retrospectivos , Bacteriemia/microbiología , Bacteriemia/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Endocarditis/microbiología , Endocarditis/complicaciones , Anciano , Ecocardiografía , Ecocardiografía TransesofágicaRESUMEN
BACKGROUND: Air-leak syndrome (ALS) is considered as an independent risk factor for poor prognosis in adult patients who had received hematopoietic stem cell transplantation (HSCT), and the 5-year overall survival (OS) of ALS is less than 30%. However, the clinical features of ALS among post-transplant pediatric patients have rarely been explored. PROCEDURES: We retrospectively reviewed 2206 pediatric patients who had received an allo-HSCT between January 2013 and December 2019 at the Hebei Yanda Lu Daopei Hospital, and analyzed the role of ALS in prognosis following HSCT. RESULTS: In our research, ALS was divided into two categories: 15 cases of bronchiolitis obliterans syndrome (BOS) and 13 cases of idiopathic pneumonia syndrome (IPS). Following treatment of the ALS, 18 patients survived (18/28, 64.3%), and 10 patients died of respiratory failure or infection (10/28, 35.7%). CONCLUSIONS: The OS of ALS in Hebei Yanda Lu Daopei Hospital is significantly higher than others, and they were cited to be related to early diagnosis and timely FAM treatment in previous reports.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Niño , Preescolar , Adolescente , Lactante , Pronóstico , Tasa de Supervivencia , Estudios de Seguimiento , Trasplante Homólogo , Bronquiolitis Obliterante/etiología , Bronquiolitis Obliterante/mortalidad , Bronquiolitis Obliterante/terapia , Neumonía/etiología , Neumonía/mortalidadRESUMEN
Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.
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Introduction: Donor choosing remains to play a pivotal role in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Numerous criteria beyond HLA compatibility impact the selection of a suitable donor. Methods: We evaluated the effect of donor parity on transplant outcomes in a large homogeneously treated population that received an HLA-matched allo-HSCT between 2010 and 2021 at our center. All patients were transplanted from a peripheral blood stem cell source following a myeloablative Busulfan-based conditioning and an identical protocol for graftversus-host disease (GVHD) prophylaxis regimen. Results: A total of 1103 allo-HSCT recipients were included. 188 (17%) had transplants from parous female donors, whereas 621 (56.30%) and 294 (26.70%) received transplants from male and nulliparous female donors, respectively. HSCTs from parous female donors compared to male and nulliparous females were associated with a significantly higher incidence of grade III-IV acute (a) GVHD (55.27% vs. 11.34 and 10.84%) and extensive chronic (c) GVHD (64.32% vs. 15.52 and 13.65%), as well as lower relapse incidence (RI). Discussion: This study finds that while parous female donors are associated with higher incidences of grade III-IV aGVHD and extensive cGVHD post-allo-HSCT, the advantages, such as a lower RI, outweigh the risks. The results of our study provide valuable insights for donor selection.
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Transplantation-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although survival has improved significantly with the introduction of eculizumab, the need for improvement remains, especially in high-risk patients. This study aimed to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment. We designed a national multicenter retrospective study of children treated with eculizumab for high-risk TA-TMA. The study cohort comprised 29 patients who had undergone a first (n = 28) or second (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for malignant (n = 17) or nonmalignant (n = 12) disease. The median time from HSCT to TA-TMA diagnosis was 154 days (interquartile range [IQR], 103 to 263 days). Eleven patients (38%) who were initially diagnosed with low- to intermediate-risk TA-TMA progressed to high-risk TA-TMA (hrTA-TMA), within a median time of 4 days (IQR, 1 to 33 days). SC5b-9 was increased in 90% of 20 patients in whom it was measured. Renal (n = 12), pulmonary (n = 1), and intestinal (n = 1) biopsy confirmed the diagnosis in 12 of 14 patients (85%). Seventeen patients (58%) had extrarenal involvement with serositis (n = 13; 44,8%), pulmonary (n = 12; 41,4%), gastrointestinal (n = 8; 27.6%), cardiovascular (n = 7; 24.1%), or central nervous system (CNS) (n = 2; 6.9%) involvement. The median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR, 1 to 8 days). Overall, 19 patients (65.5%) responded to eculizumab, of whom 17 (58.6%) achieved a complete response and 2 (6.9%) achieved a partial response. The remaining 10 patients (34.5%) did not show any of response. The overall response rate to eculizumab for TA-TMA was 27.59% (95% confidence interval [CI], 14.87% to 47.66%) at 1 month, 55.17% (95% CI, 38.43% to 73.48%) at 3 months, and 62.07% (95% CI, 45.10% to 79.13%) at 6 months after eculizumab initiation. In multivariate analysis, the pulmonary involvement decreased the probability of response (hazard ratio [HR], .18; P = .0298). The 1-year overall survival (OS) was 55.2% (95% CI, 35.6% to 71.0%) for the whole cohort and 83.3% (95% CI, 56.7% to 94.3%) for patients who responded to eculizumab. Pulmonary involvement (HR, 14.93; P = .0043) and CNS involvement (HR, 8.63; P = .0497) were associated with a statistically significant decrease in survival. We found that patients diagnosed with hrTA-TMA with pulmonary involvement had a poor response to eculizumab, and that patients with pulmonary and CNS involvement had significantly decreased survival. Given these results, we hypothesize that providing eculizumab therapy at an early stage of the disease before organ damage is established might significantly improve the response and, consequently, survival.
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Anticuerpos Monoclonales Humanizados , Trasplante de Células Madre Hematopoyéticas , Microangiopatías Trombóticas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios Retrospectivos , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Niño , Factores de Riesgo , Preescolar , Adolescente , Resultado del Tratamiento , Lactante , España/epidemiología , Inactivadores del Complemento/uso terapéuticoRESUMEN
The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system.
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Hematopoietic stem cell transplantation (HSCT) has benefited an increasing number of patients with hematological disease in the clinic. It is a curative therapy for malignant and nonmalignant hematological diseases. With the advancement and further clinical application of HSCT in recent years, the life expectancy of patients has increased, but complications have become more common. The occurrence of ocular complications is receiving increasing attention because they can seriously affect the quality of life of patients. Ocular complications require increased attention from clinicians because of their negative impact on patients and increasing incidence. Most of recent reports on posttransplant ocular complications involve ocular manifestations of graft-versus-host disease (GVHD), and a few ocular complications that do not originate from GVHD have also been reported. This review summarizes the diagnosis, scoring criteria, pathophysiology, and clinical manifestations of and common therapies for ocular graft-versus-host disease(oGVHD) after HSCT, and includes a description of some rare cases and novel therapies.
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BACKGROUND: Hematopoietic stem cell transplantation (HSCT) was associated with potentially life-threatening complications. Among patients supported by extracorporeal membrane oxygenation (ECMO), those who underwent HSCT had a worse prognosis than those who did not. Advances in HSCT and critical care management have improved the prognosis of ECMO-supported HSCT patients. CASE: The patient in the remission stage of lymphoma after 22 months of allogeneic hematopoietic stem cell transplantation, suffered from ARDS, severe neutropenia, thrombocytopenia, and long-term COVID-19. We evaluated the benefits and risks of ECMO for the patient, including the possibility of being free from ECMO, the status of malignancy, the interval from HSCT to ARDS, the function of the graft, the amount of organ failure, and the comorbidities. ECMO was ultimately used to save his life. CONCLUSIONS: We did not advocate for the general use of ECMO in HSCT patients and we believed that highly selected patients, with well-controlled tumors, few comorbidities, and fewer risk factors for death, tended to benefit from ECMO with well ICU management.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Trasplante de Células Madre Hematopoyéticas , Neoplasias , Neutropenia , Síndrome de Dificultad Respiratoria , Trombocitopenia , Humanos , Oxigenación por Membrana Extracorpórea/efectos adversos , COVID-19/terapia , COVID-19/complicaciones , Síndrome de Dificultad Respiratoria/etiología , Trombocitopenia/terapia , Trombocitopenia/complicaciones , Neutropenia/complicaciones , Neutropenia/terapia , Neoplasias/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
The technique of αß T cell depletion (αßTCD) is a well-established method of hematopoietic stem cell transplantation (HSCT) for children with acute leukemia owing to the low rates of graft-versus-host disease and nonrelapse mortality (NRM). The graft-versus-leukemia effect is generally ascribed to natural killer (NK) cells conserved within the graft. It is not known whether NK-related factors affect the outcome of αßTCD HSCT, however. The aim of this retrospective study was to explore the impact of NK alloreactivity (based on donor-recipient killer immunoglobulin-like receptor [KIR] mismatch), graft NK cell dose, and blood NK cell recovery on day +30 post-HSCT on the incidences of leukemia relapse and NRM. The pediatric acute leukemia cohort comprised 295 patients who underwent their first HSCT from a haploidentical donor in complete remission. During post hoc analysis, the total cohort was divided into subcohorts by diagnosis (acute lymphoblastic leukemia [ALL]/acute myeloid leukemia [AML]), NK alloreactivity prediction (KIR match/KIR mismatch), graft NK cell dose (less than versus greater than the median value), and blood NK cell recovery on day +30 post-HSCT (less than versus greater than the median value). We also investigated the influence of serotherapy (antithymocyte globulin [ATG] group) versus abatacept + tocilizumab combination [aba+toci] group) on relapse risk in the context of KIR mismatch. The risks of relapse and NRM were calculated by the cumulative risk method, and groups were compared using the Gray test. Multivariate analysis revealed no apparent impact of predicted NK alloreactivity or any other studied NK cell-related factors for the entire cohort. For patients with AML, a significantly higher relapse risk associated with high NK cell graft content on the background of no predicted KIR mismatch (P = .002) was shown. Multivariate analysis confirmed this finding (P = .018); on the other hand, for the KIR-mismatched patients, there was a trend toward a lower risk of relapse associated with high NK cell dose. The use of ATG was associated with a trend toward reduced relapse risk (P = .074) in the AML patients. There was no significant impact of NK-related factors in the ALL patients. Overall, the evaluated NK-related factors did not show a clear and straightforward correlation with the key outcomes of HSCT in our cohort of children with acute leukemia. In practice, the data support prioritization of KIR-mismatched donors for patients with AML. Importantly, a potential interaction of KIR ligand mismatch and NK cell content in the graft was identified. Indirect evidence suggests that additional cellular constituents of the graft could influence the function of NK cells after HSCT and affect their role as graft-versus-leukemia effectors.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Niño , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/terapia , Células Asesinas Naturales , Receptores KIR , Suero Antilinfocítico , Linfocitos T , RecurrenciaRESUMEN
AIMS: To explore whether music intervention improves the quality of life (QOL) of patients undergoing hematopoietic stem cell transplantation (HSCT) and to evaluate its impact on patients' symptoms of depression/anxiety and fatigue. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Cochrane CENTRAL, and EMBASE were searched from inception to September 30, 2022. The search strategy used a combination of the keywords "music" and "hematopoietic stem cell transplantation" or "HSCT." The outcomes assessed were QOL, depression and anxiety, and fatigue. Pooled standardized mean differences with 95% confidence intervals were calculated to compare the outcomes between the music intervention and control groups. Heterogeneity across the studies was assessed using a chi-square-based test, and the I2 and Q statistics. RESULTS: Meta-analysis of the included study population showed that music intervention for patients undergoing HSCT was associated with patients' improved QOL, and resulted in reduced depression/anxiety and fatigue compared to patients without music intervention. CONCLUSION: Music intervention benefits HSCT outcomes, including better QOL, less depression/anxiety, and less fatigue postoperatively. Future trials with larger samples are still warranted to strengthen the evidence supporting the benefits of music intervention in this patient population.
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Trasplante de Células Madre Hematopoyéticas , Musicoterapia , Música , Humanos , Musicoterapia/métodos , Calidad de Vida , Ansiedad/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , FatigaRESUMEN
The typical pleuroparenchymal fibroelastosis (PPFE) after hematopoietic stem cell transplantation (HSCT) is characterized by late-onset progressive pulmonary complication within 5 years. PPFE shows a poor prognosis without definitive standard care other than lung transplantation. Our case indicated an over 20 years late-onset and aggressively exacerbating PPFE.
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PURPOSE: We aimed to assess the role of liver stiffness measurement (LSM), evaluated using transient elastography (TE), for the diagnosis of sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD), a complication of hematopoietic stem cell transplantation (HSCT). METHODS: In this retrospective study, ultrasonography (US) and LSM were performed on 86 adult patients (55 men and 31 women) undergoing HSCT between January 2016 and December 2022. Characteristics and changes in liver stiffness (LS) were compared between patients with and without SOS/VOD. RESULTS: Of the 86 patients, 14 were diagnosed with SOS/VOD. A significant increase in LS (ranging from 12.6 to 55.1 kPa, median 23.8 kPa) compared to pre-HSCT values was observed in all patients who developed SOS/VOD. The area under the receiver operating characteristic curve (AUROC) for the diagnosis of SOS/VOD was 0.9663 (0.933-0.995) for LS ≥ 17.4 kPa after HSCT. Post-transplant LS exceeded 17.4 kPa in all 14 patients in the SOS/VOD group (100%) and in seven patients in the non-SOS/VOD group (9.7%). The sensitivity and specificity were 100% and 90.3%, respectively. AUROC for the diagnosis of SOS/VOD was 0.973 (0.943-1.000) for LS increase ≥ + 12.6 kPa from baseline after HSCT. The change of ≥ + 12.6 kPa from baseline was observed in all 14 patients in the SOS/VOD group (100%) and in four patients in the non-SOS/VOD group (5.6%). The sensitivity and specificity were 100% and 94.4%, respectively. CONCLUSION: LSM using TE may contribute to establishing the diagnosis of SOS/VOD after HSCT.
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Diagnóstico por Imagen de Elasticidad , Trasplante de Células Madre Hematopoyéticas , Enfermedad Veno-Oclusiva Hepática , Hígado , Humanos , Enfermedad Veno-Oclusiva Hepática/diagnóstico por imagen , Enfermedad Veno-Oclusiva Hepática/etiología , Masculino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Estudios Retrospectivos , Diagnóstico por Imagen de Elasticidad/métodos , Adulto , Persona de Mediana Edad , Hígado/diagnóstico por imagen , Adulto Joven , Adolescente , Anciano , Curva ROCRESUMEN
Acute myeloid leukemia (AML) is the second most common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management, and prognosis prediction is much more important than before. Disease classifications and risk group classifications, such as the WHO classification, the international consensus classification (ICC), and the European LeukemiaNet (ELN) classification, were revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different; therefore, in this review, we emphasize well-known genetic subtypes in childhood AML, including core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotype AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML, and acute promyelocytic leukemia (APL). Current risk group classification, the management algorithm in childhood AML, and novel treatment modalities such as targeted therapy, immune therapy, and chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.
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Severe combined immunodeficiency (SCID) is an inborn error of immunity invariably resulting in mortality in infancy until managed by hematopoietic stem cell transplant (HSCT). We present an unusual case of SCID with a rare mutation involving the non-homologous end-joining 1 (NHEJ1) gene, where a haploidentical HSCT was carried out with modified conditioning and graft versus host prophylaxis regimen using proteasome inhibitor bortezomib with a successful outcome.
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PURPOSE OF REVIEW: Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset, acquired, muscle disease that can be associated with monoclonal gammopathy or HIV infection. The pathological hallmark of SLONM is the accumulation of nemaline rods in muscle fibers. We review here current knowledge about its presentation, pathophysiology, and management. RECENT FINDINGS: SLONM usually manifests with subacutely progressive proximal and axial weakness, but it can also present with chronic progressive weakness mimicking muscular dystrophy. The pathophysiology of the disease remains poorly understood, with evidence pointing to both autoimmune mechanisms and hematological neoplasia. Recent studies have identified histological, proteomic, and transcriptomic alterations that shed light on disease mechanisms and distinguish SLONM from inherited nemaline myopathies. A majority of SLONM patients respond to intravenous immunoglobulins, chemotherapy, or hematopoietic stem cell transplant. SLONM is a treatable myopathy, although its underlying etiology and pathomechanisms remain unclear. A high degree of suspicion should be maintained for this disease to reduce diagnostic delay and treatment in SLONM and facilitate its distinction from inherited nemaline myopathies.