RESUMO
Introduction: Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Methods: Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Results: Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. Conclusion: The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. Clinical trial registration: http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.
Assuntos
Anemia Aplástica , Benzoatos , Pirazóis , Humanos , Masculino , Feminino , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/terapia , Adulto , Benzoatos/uso terapêutico , Benzoatos/efeitos adversos , Pessoa de Meia-Idade , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Adulto Jovem , Adolescente , Pirazolonas/uso terapêutico , Hidrazonas/uso terapêutico , Receptores de Trombopoetina/agonistas , Resultado do Tratamento , Estudos Prospectivos , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Idoso , Hidrazinas/uso terapêutico , Hidrazinas/efeitos adversos , Tiazóis , TiofenosRESUMO
Prior research has identified associations between immune cells and aplastic anaemia (AA); however, the causal relationships between them have not been conclusively established. A two-sample Mendelian randomisation analysis was conducted to investigate the causal link between 731 immune cell signatures and AA risk using publicly available genetic data. Four types of immune signatures, including relative cell, absolute cell (AC), median fluorescence intensities and morphological parameters, were considered sensitivity analyses were also performed to verify the robustness of the results and assess potential issues such as heterogeneity and horizontal pleiotropy. Following multiple test adjustments using the False Discovery Rate (FDR) method, no statistically significant impact of any immunophenotype on AA was observed. However, twelve immunophenotypes exhibited a significant correlation with AA without FDR correction (p of IVW < 0.01), of which eight were harmful to AA: CD127- CD8br %T cell (Treg panel), CD25 on IgD + CD38dim (B cell panel), CD38 on naive-mature B cell (B cell panel), CD39 + resting Treg % CD4 Treg (Treg panel), CD39 + secreting Treg AC (Treg panel), CD8 on CD28 + CD45RA- CD8br (Treg panel), HLA DR + NK AC (TBNK panel), Naive DN (CD4-CD8-) AC (Maturation stages of T cell panel); and four were protective to AA: CD86 on CD62L + myeloid DC (cDC panel), DC AC (cDC panel), DN (CD4-CD8-) NKT %T cell (TBNK panel), and TD CD4 + AC (Maturation stages of T cell panel). The results of this study demonstrate a close link between immune cells and AA by genetic means, thereby improving the current understanding of the interaction between immune cells and AA risk and providing guidance for future clinical research.
Assuntos
Anemia Aplástica , Análise da Randomização Mendeliana , Humanos , Anemia Aplástica/genética , Anemia Aplástica/imunologia , Imunofenotipagem , Predisposição Genética para Doença , Linfócitos B/imunologia , Linfócitos B/metabolismoRESUMO
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure syndrome whose development can be triggered by environmental, autoimmune, and/or genetic factors. The latter comprises germ line pathogenic variants in genes that bring about habitually predisposing syndromes as well as immune deficiencies that do so only occasionally. One of these disorders is the autosomal dominant form of chronic mucocutaneous candidiasis (CMC), which is defined by germ line STAT1 gain-of-function (GOF) pathogenic variants. The resultant overexpression and constitutive activation of STAT1 dysregulate the Janus kinase/signal transducer and activator of transcription 1 (STAT) signaling pathway, which normally organizes the development and proper interaction of different components of the immunologic and hematopoietic system. Although SAA is an extremely rare complication in this disorder, it gained a more widespread interest when it became clear that the underlying causative pathomechanism may, in a similar fashion, also be instrumental in at least some of the idiopathic SAA cases. Based on these premises, we present herein what is the historically most likely first cord blood-transplanted SAA case in a CMC family with a documented STAT1 GOF pathogenic variant. In addition, we recapitulate the characteristics of the six CMC SAA cases that have been reported so far and discuss the significance of STAT1 GOF pathogenic variants and other STAT1 signaling derangements in the context of these specific types of bone marrow failure syndromes. Because a constitutively activated STAT1 signaling, be it driven by STAT1 GOF germ line pathogenic variants or any other pathogenic variant-independent events, is apparently important for initiating and maintaining the SAA disease process, we propose to acknowledge that SAA is one of the definite disease manifestations in STAT1-mutated CMC cases. For the same reason, we deem it necessary to also incorporate molecular and functional analyses of STAT1 into the diagnostic work-up of SAA cases.
Assuntos
Anemia Aplástica , Candidíase Mucocutânea Crônica , Fator de Transcrição STAT1 , Adulto , Feminino , Humanos , Masculino , Anemia Aplástica/genética , Candidíase Mucocutânea Crônica/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Linhagem , Estudos Retrospectivos , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismoRESUMO
Objective: To analyze the causes and demographic characteristics of pre-engraftment mortality in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and investigate the risk factors and measures for preventing pre-engraftment mortality. Methods: A retrospective case analysis, involving a total of 7 427 patients who underwent allo-HSCT at Peking University People's Hospital between January 2016 and July 2023, was conducted. Results: Among the 7 427 patients who underwent allo-HSCT, 56 cases (0.75% ) experienced pre-engraftment mortality. The median time to death for these 56 patients was +7 (-3 to +38) days after stem cell infusion. The median times to death for patients with acute leukemia (AL), severe aplastic anemia (SAA), and myelodysplastic syndrome (MDS) were +11 (-1 to +38), +3 (-1 to +34), and +16 (-1 to +38) days, respectively (P=0.013). The main causes of pre-engraftment mortality were infection (39.3% ), cardiac toxicity (28.6% ), and intracranial hemorrhage (26.8% ). Infection was the most common cause of pre-engraftment mortality in patients with AL and MDS (55.0% and 60.0% ), whereas cardiac toxicity was predominantly observed in patients with SAA (71.4% ), with no cases in patients with AL and only one case in patients with MDS. Among patients who died from intracranial hemorrhage, 53.3% had severe infections. The median times to death for infection, cardiac toxicity, and intracranial hemorrhage was +11 (-1 to +38), +2.5 (-1 to +17), and +8 (-3 to +37) days, respectively (P<0.001) . Conclusions: Infection is the primary cause of pre-engraftment mortality in allo-HSCT, and severe cardiac toxicity leading to pre-engraftment mortality should be closely monitored in patients with SAA.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Retrospectivos , Fatores de Risco , Síndromes Mielodisplásicas/terapia , Anemia Aplástica/terapia , Doença Enxerto-Hospedeiro/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Leucemia/terapia , Leucemia/mortalidade , AdultoRESUMO
To investigate the dynamic homing process and characteristics of macrophages in different organs of immune-mediated aplastic anemia (AA) model mice. Macrophages in donor lymph nodes were sorted by magnetic beads and labeled with PKH67. After modeling according to the preparation method of the AA model, peripheral blood rountine analysis, bone marrow biopsy and HE staining results were analyzed to verify the modeling effect. On days 4, 8, and 12 of modeling, the bone marrow, spleen, and lymph node mononuclear cells were collected, and dynamic changes of PKH67-labeled macrophages in donor mice were analyzed by flow cytometry. In this study, dynamic changes in PKH67-labeled macrophages in the pathogenesis of AA model mice were explored. Macrophages in donor mice homed to the lymph nodes, expanding and differentiating in the lymph nodes, and finally transported to the bone marrow and spleen. Through proteomics mass spectrometry analysis, the related immune inflammatory response pathway of macrophages involved in the activation of the AA bone marrow microenvironment was preliminarily revealed, which provides a basis for the pathological macrophages involved in the pathogenesis of AA model mice.
Assuntos
Anemia Aplástica , Modelos Animais de Doenças , Macrófagos , Animais , Camundongos , Anemia Aplástica/imunologia , Macrófagos/imunologia , Masculino , Baço/citologia , Baço/imunologia , Linfonodos/imunologia , Linfonodos/citologia , Medula Óssea/patologiaRESUMO
This study aimed to investigate the effect of iron overload on the transplant outcomes of pediatric patients with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on the clinical data of 74 children with SAA who received allo-HSCT at the Hematology Department of Wuhan Children's Hospital between January 2018 and August 2022. Children with iron overload (serum ferritin >1 000 µg/L) before transplantation had a longer disease course, received more red blood cell transfusions, and had a higher number of CD34(+) cells infused. Moreover, iron overload significantly delayed the reconstitution of regulatory T cells after transplantation, increasing the incidence of hemorrhagic cystitis and grade â ¢-â £ acute graft-versus-host disease after transplantation. However, iron overload did not significantly affect the overall survival and failure-free survival rates of the children.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Sobrecarga de Ferro , Transplante Homólogo , Humanos , Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sobrecarga de Ferro/etiologia , Estudos Retrospectivos , Criança , Doença Enxerto-Hospedeiro/etiologia , Adolescente , Masculino , Feminino , Pré-Escolar , Taxa de SobrevidaRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acquired aplastic anemia (acquired AA) in young patients. The objective of the study was to compare patient outcomes after Cyclophosphamide and horse antithymocyte globulin (Cy-hATG) versus Fludarabine-cyclophosphamide and rabbit ATG (Flu-Cy-rATG) as part of conditioning regimen in allo-HSCT for acquired AA. RESEARCH DESIGN AND METHODS: Descriptive retrospective study conducted on patients with acquired AA who received allo-HSCT from HLA-matched sibling donors between January 2008 and August 2022 after conditioning regimen with Cy-hATG or Flu-Cy-rATG. RESULTS: A total of 121 patients were enrolled. Cumulative incidence of graft failure was 11.2% in Cy-hATG and 5.3% Flu-Cy-rATG group. There were no significant differences between the two groups in terms of acute GVHD, chronic GVHD, and transplant related mortality. Flu-Cy-rATG group was associated with significantly higher CMV and EBV reactivation(s) compared to Cy-hATG group (p = 0.008 and 0.035, respectively). After a median follow-up of 58 months, estimated overall survival, event-free survival, and graft rejection-free survival were not statistically different between the two groups. CONCLUSIONS: In high-risk population, Flu-Cy-rATG is associated with comparable outcomes to Cy-hATG in allo-HSCT from MSD. However, it seems to be associated with significant risk of viral infections.
Assuntos
Anemia Aplástica , Soro Antilinfocitário , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Irmãos , Condicionamento Pré-Transplante , Vidarabina , Humanos , Anemia Aplástica/terapia , Anemia Aplástica/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Condicionamento Pré-Transplante/métodos , Masculino , Feminino , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vidarabina/administração & dosagem , Animais , Adolescente , Estudos Retrospectivos , Adulto , Cavalos , Coelhos , Criança , Transplante Homólogo , Doadores de Tecidos , Adulto Jovem , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Pré-Escolar , Pessoa de Meia-IdadeAssuntos
Anemia Aplástica , Soro Antilinfocitário , Hemólise , Imunossupressores , Humanos , Soro Antilinfocitário/efeitos adversos , Soro Antilinfocitário/uso terapêutico , Anemia Aplástica/tratamento farmacológico , Anemia Aplástica/induzido quimicamente , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Hemólise/efeitos dos fármacos , Criança , Masculino , FemininoRESUMO
Hematopoietic stem cell transplantation is a curative treatment for many malignant and nonmalignant diseases in children and adults. It is performed with peripheral blood stem cells, bone marrow, and umbilical cord blood. Anaphylaxis may occur during hematopoietic stem cell transplantation, similar to that shown with blood transfusions. In children, although a few cases of anaphylaxis have been reported with cord blood transplantation, no cases of anaphylaxis have been reported with other hematopoietic stem cell transplantations. In this case report, we present the cases of 2 children, one diagnosed with thalassemia major and the other with aplastic anemia, both of whom developed anaphylaxis associated with bone marrow transplantation products cryopreserved with dimethyl sulfoxide and hydroxyethyl starch. Hematopoietic stem cell transplantation-induced anaphylaxis could be associated with cryoprotective agents, especially dimethyl sulfoxide, and alloantigens. In both anaphy-lactic reactions, dimethyl sulfoxide was thought to be the trigger, but it could not be excluded that it was related to stem cell components, plasma, or hydroxyethyl starch.
Assuntos
Anafilaxia , Dimetil Sulfóxido , Transplante de Células-Tronco Hematopoéticas , Humanos , Anafilaxia/diagnóstico , Anafilaxia/terapia , Anafilaxia/etiologia , Anafilaxia/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Dimetil Sulfóxido/efeitos adversos , Feminino , Anemia Aplástica/terapia , Anemia Aplástica/imunologia , Anemia Aplástica/diagnóstico , Talassemia beta/terapia , Talassemia beta/imunologia , Talassemia beta/complicações , Talassemia beta/diagnóstico , Crioprotetores/efeitos adversos , Criopreservação , Resultado do Tratamento , Transplante Homólogo , Criança , Derivados de Hidroxietil Amido/efeitos adversos , Pré-EscolarRESUMO
BACKGROUND: Observational studies have found a link between lipid metabolism disorders and aplastic anemia (AA). However, due to confounding variables and reverse causation, it is difficult to conclude such a causal link. The precise mechanism and potential implications of lipid metabolism disorder in AA remain unclear, necessitating further studies in this area. METHOD: This study aimed to examine the causal relationship between 38 different subtypes of triacylglycerols and AA using two-sample Mendelian randomization (MR). Additionally, two-step MR analyses were conducted to investigate the mediating effects of vitamin A to oleoyl-linoleoyl-glycerol (18:1-18:2) ratio. RESULTS: MR analysis showed that triacylglycerol (53:3) levels were positively associated with the risk of AA [inverse variance weighting (IVW): odds ratio (OR) = 1.131,95% confidence interval (CI):1.029-1.243, P = 0.011; Bayesian weighted MR (BWMR): OR = 1.137,95% CI:1.031-1.254, P = 0.010]. Triacylglycerol (53:3) level showed no inverse causality with AA (IVW:P = 0.834; BWMR:P = 0.349). Mediation analyses showed that increasing the vitamin A to oleoyl-linoleoyl-glycerol (18:1-18:2) ratio can decrease the risk of AA. CONCLUSION: This study revealed the association between vitamin A to oleoyl-linoleoyl-glycerol (18:1-18:2) ratio, triacylglycerol (53:3) levels and AA, and indicated that lowering triacylglycerol (53:3) levels can reduce the risk of AA.
Assuntos
Anemia Aplástica , Triglicerídeos , Humanos , Triglicerídeos/metabolismo , Triglicerídeos/sangue , Anemia Aplástica/metabolismo , Análise da Randomização MendelianaRESUMO
Aplastic anemia is a lethal bone marrow disease with a heterogeneous etiological background. Interleukin-6 (IL-6) and IL-8 were shown to affect the proliferation and differentiation of primitive hematopoietic cells. They may serve as potential markers for the assessment of severity/prognosis of aplastic anemia. The study aimed to evaluate the levels of IL-6 and IL-8-in patients with aplastic anemia and their relation to disease severity. This study included a total of 35 cases of aplastic anemia, and 27 normal subjects as controls. Levels of IL-6 and IL-8 were quantitatively measured by ELISA. The median serum IL-6 and IL-8 levels in aplastic anemia cases were 125.2 ng/l and 320 ng/l, respectively. These levels were significantly increased in the aplastic anemia patients than in the controls, as the median serum IL-6 was 29.7 ng/l and the median serum IL-8 97ng/l in the controls (p < 0.001). A significant correlation was observed between levels of both IL-6 and IL-8 and the severity of the disease (p <0.001). In conclusion, IL-6 and IL-8 serum levels are higher in patients with aplastic anemia and have a correlation to the severity of the disease.
Assuntos
Anemia Aplástica , Interleucina-6 , Interleucina-8 , Índice de Gravidade de Doença , Humanos , Anemia Aplástica/sangue , Anemia Aplástica/diagnóstico , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores/sangue , AdolescenteRESUMO
Immune check point inhibitors (ICIs) have durable antitumor effects. However, autoimmune toxicities, termed immune-related adverse events, occur in some patients. We report a case of severe immune aplastic anemia (AA) in a patient with non-small cell lung cancer who was receiving atezolizumab with bevacizumab/carboplatin/paclitaxel. Although the cancer has not recurred, his bone marrow is depleted and he did not respond to immunosuppressive therapy. He has survived for 1.5 years with blood transfusions and infection control. Immune AA associated with ICIs is rare, and a treatment has not yet been established. This case report provides information on the management and treatment response of patients with AA caused by ICIs. Further studies should investigate the mechanism and pathogenesis of immune AA caused by ICIs.
Assuntos
Anemia Aplástica , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Paclitaxel , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Anemia Aplástica/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Bevacizumab/efeitos adversos , Bevacizumab/administração & dosagem , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Resultado do Tratamento , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Aplastic anemia is a rare and heterogeneous disease that causes pancytopenia and aplasia of the bone marrow. It is characterized by a failure of hematopoiesis. It is believed that approximately 65% of cases of acquired aplastic anemia are idiopathic. In a subset of cases, a drug or infection is the cause of bone marrow failure. This case report presents a 38-year-old patient with axial spondylarthritis who developed pancytopenia and was diagnosed with aplastic anemia during anti-TNF-α treatment.
Assuntos
Anemia Aplástica , Pancitopenia , Fator de Necrose Tumoral alfa , Humanos , Adulto , Pancitopenia/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anemia Aplástica/induzido quimicamente , Masculino , Espondilartrite/tratamento farmacológico , Espondilartrite/complicações , Antirreumáticos/efeitos adversos , Espondiloartrite Axial/induzido quimicamente , Infliximab/efeitos adversos , Infliximab/uso terapêuticoRESUMO
Aplastic anemia is a syndrome characterized by reduced hematopoietic stem cells, bone marrow hypoplasia, and pancytopenia, and is often considered a T-cell-mediated autoimmune disease. It is predominantly treated with hematopoietic stem cell transplantation and immunosuppressive therapy with anti-human thymocyte immunoglobulin (ATG) and cyclosporine. Only rabbit ATG was previously available in Japan, but equine ATG was recently approved for use in 2023. Thrombopoietin receptor agonists available in Japan are oral eltrombopag and injectable romiplostim. In hematopoietic stem cell transplantation for aplastic anemia, a conditioning regimen of reduced-dose cyclophosphamide and fludarabine has been used to reduce cardiotoxicity. Human leukocyte antigen haploidentical stem cell transplants have also been developed, and their use in patients without a donor is increasingly reported. Future advancements in novel drugs and transplantation therapies could revolutionize the management of aplastic anemia.
Assuntos
Anemia Aplástica , Anemia Aplástica/terapia , Humanos , Transplante de Células-Tronco Hematopoéticas , AnimaisRESUMO
Thrombopoietin (TPO) is the critical regulator of platelet production. However, the role of TPO in pediatric patients with thrombocytopenic disorders has not been fully elucidated. In the present study, we attempted to investigate serum TPO levels in patients with acquired aplastic anemia (aAA) and immune thrombocytopenia (ITP). We analyzed the endogenous plasma concentration of TPO and platelet count at the time of TPO measurement in 166 patients with aAA and 280 patients with ITP retrospectively. We further observed a correlation between platelet counts and TPO. Serum TPO levels were significantly higher in aAA compared with ITP (1142 vs. 77.99 pg/mL, P <0.001). In patients with aAA, an elevation for TPO levels in very severe AA (VSAA) was seen when compared with non-severe AA (NSAA) (1360 vs. 984.4 pg/mL, P <0.05). In contrast, the circulating TPO levels with chronic ITP (CITP) showed a decrease than newly diagnosed ITP (NITP) and persistent ITP (PITP) (62.28 vs. 81.56 pg/mL, P <0.01, 62.28 vs. 87.82 pg/mL, P <0.05, respectively). There was a negative correlation between platelet counts and TPO levels in aAA (r s =-0.3325, P <0.001) as well as ITP (r s =-0.2570, P <0.001). Especially, TPO levels were inversely correlated with platelet counts in NSAA (r s =-0.3672, P <0.001) and NITP (r s =-0.3316, P <0.001). After grouping by age or sex, there were no statistical differences in aAA or ITP. Serum TPO levels were markedly elevated in pediatric patients with aAA compared with ITP. It was higher in VSAA and lower in CITP, suggesting that serum TPO level could play a role in classifying disease severity or clinical course in aAA and ITP.
Assuntos
Anemia Aplástica , Púrpura Trombocitopênica Idiopática , Trombopoetina , Humanos , Trombopoetina/sangue , Feminino , Masculino , Anemia Aplástica/sangue , Criança , Púrpura Trombocitopênica Idiopática/sangue , Pré-Escolar , Adolescente , Estudos Retrospectivos , Contagem de Plaquetas , LactenteRESUMO
Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Anemia Aplástica/diagnóstico , Anemia Aplástica/etiologia , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Itália , COVID-19/diagnóstico , Imunossupressores/uso terapêutico , SARS-CoV-2RESUMO
OBJECTIVE: To investigate the expression level and clinical correlation of microRNA-144/451 gene cluster (miR-144/451) in different types of anemia. METHODS: The peripheral blood of patients with aplastic anemia (AA), myelodysplastic syndrome (MDS) and diffuse large B-cell lymphoma (DLBCL) who had been diagnosed with anemia for the first time and after chemotherapy were collected. The expression levels of miR-144 and miR-451 were measured by RT-qPCR, and the correlation between the expression levels of miR-144 and miR-451 and routine laboratory indexes was analyzed by Spearman correlation analysis. RESULTS: The expression levels of miR-144 and miR-451 in the peripheral blood of AA and MDS patients were significantly lower than those in normal controls (all P < 0.01). No statistical differences were observed in the expression level of miR-144 in three subgroups of DLBCL patients (P >0.05), while the expression level of miR-451 in peripheral blood of three subgroups of DLBCL patients were significantly higher than those in normal controls (all P < 0.05). Correlation analysis showed that the expression levels of miR-144 and miR-451 in AA patients were positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) (r =0.629, 0.574). There were no significant correlations between the expression levels of miR-144 and miR-451 and laboratory parameters in MDS and DLBCL patients. CONCLUSION: Different types of anemia disorders have varying levels of miR-144 and miR-451 expression, which is anticipated to develop into a secondary diagnostic and differential diagnostic indicator for clinical anemia diseases.
Assuntos
MicroRNAs , Síndromes Mielodisplásicas , Humanos , MicroRNAs/genética , Síndromes Mielodisplásicas/genética , Linfoma Difuso de Grandes Células B/genética , Anemia Aplástica/genética , Anemia , Família MultigênicaRESUMO
Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more prone to relapse, the lower the overall survival rate, and the higher the probability of clonal evolution. The regulation of telomere length is affected by many factors, including telomerase activity, telomerase-related genes, telomere regulatory proteins and other related factors. Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia. This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.
Assuntos
Anemia Aplástica , Homeostase do Telômero , Anemia Aplástica/genética , Anemia Aplástica/patologia , Encurtamento do Telômero , Evolução Clonal , Taxa de Sobrevida , Recidiva , Homeostase do Telômero/genética , Telomerase/genética , Telomerase/metabolismo , Instabilidade Genômica/genética , HumanosRESUMO
An area-under-the-curve (AUC24)-based approach is recommended to guide vancomycin therapeutic drug monitoring (TDM), yet trough concentrations are still commonly used despite associated risks. A definitive toxicity target is lacking, which is important for hematology patients who have a higher risk of nephrotoxicity. The aims were to (1) assess the impact of trough-based TDM on acute kidney injury (AKI) incidence, (2) establish a vancomycin nephrotoxicity threshold, and (3) evaluate the proportion of hematology patients achieving vancomycin therapeutic targets. Retrospective data was collected from 100 adult patients with a hematological malignancy or aplastic anemia who received vancomycin between April 2020 and January 2021. AKI occurrence was determined based on serum creatinine concentrations, and individual pharmacokinetic parameters were estimated using a Bayesian approach. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pharmacokinetic indices to predict AKI occurrence. The proportion of patients who achieved target vancomycin exposure was evaluated based on an AUC24/MIC ≥400 and the determined toxicity threshold. The incidence of AKI was 37%. ROC curve analysis indicated a maximum AUC24 of 644 mg.h/L over the treatment period was an important predictor of AKI. By Day 4 of treatment, 29% of treatment courses had supratherapeutic vancomycin exposure, with only 62% of courses achieving AUC24 targets. The identified toxicity threshold supports an AUC24 target range of 400-650 mg.h/L, assuming an MIC of 1 mg/L, to optimize vancomycin efficacy and minimize toxicity. This study highlights high rates of AKI in this population and emphasizes the importance of transitioning from trough-based TDM to an AUC-based approach to improve clinical outcomes.