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1.
Fisioter. Bras ; 23(1): 73-79, Fev 11, 2022.
Article in Portuguese | LILACS | ID: biblio-1358411

ABSTRACT

Introdução: A anemia aplásica (AA) é uma condição clínica considerada rara que se desenvolve a partir da disfunção hematopoiética da medula óssea. O tratamento indicado é o transplante de células tronco hematopoiéticas (TCHP). Objetivo: Descrever o caso clínico e as estratégias utilizadas pela fisioterapia durante o processo de reabilitação física. Métodos: Trata-se de estudo de caso, realizado com paciente do sexo feminino, 34 anos de idade e diagnóstico de AA severa. Após avaliação clínica foi indicado o TCHP alogênico de um doador aparentado que apresentou compatibilidade histo-imunológica. O tempo total de internação hospitalar foi de 35 dias. Os objetivos da reabilitação física foram o de manter a ventilação pulmonar, prevenir o acúmulo de secreção, minimizar a progressão da fadiga, perda de força e resistência muscular. Resultados: A estratégia utilizada para contornar a extrema fragilidade hematológica e as implicações clínicas decorrentes evitou perda expressiva no desempenho no teste de caminhada de seis minutos (-10%) ao final da internação. Conclusão: Foi um verdadeiro desafio a implementação da reabilitação física durante o TCHP para o tratamento da AA, mas a estratégia adotada demonstrou-se segura, bem tolerada e suficiente para evitar maiores prejuízos no estado funcional. (AU)


Subject(s)
Female , Adult , Therapeutics , Bone Marrow , Physical Therapy Modalities , Health Strategies , Cell Transplantation , Fatigue , Walk Test , Frailty , Anemia, Aplastic
2.
Frontiers of Medicine ; (4): 718-727, 2021.
Article in English | WPRIM | ID: wpr-922504

ABSTRACT

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II-IV aGvHD, including two with grade III-IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4% ± 0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.


Subject(s)
Anemia, Aplastic/therapy , Bone Marrow Transplantation , Graft vs Host Disease , HLA Antigens , Hematopoietic Stem Cell Transplantation , Humans , Transplantation Conditioning
3.
Journal of Experimental Hematology ; (6): 1601-1605, 2021.
Article in Chinese | WPRIM | ID: wpr-922302

ABSTRACT

OBJECTIVE@#To analyze the clinical efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH), and preliminarily explore the role of an improved post-transplantation cyclophosphamide (PTCy) based conditioning regimen in PNH patients receiving transplantation.@*METHODS@#Clinical related data of PNH sufferers receiving allo-HSCT in Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected, and hematopoietic reconstitution, chimerism, PNH cloning, graft-versus-host disease (GVHD), infection, and survival were analyzed.@*RESULTS@#Totally five PNH patients receiving allo-HSCT were enrolled, including 1 case with classic PNH, 3 cases with aplastic anemia-PNH syndrome, 1 case with myelodysplastic syndrome, three of them (case 1-3) received the improved PTCy based conditioning regimen before HSCT. All sufferers engrafted successfully within 28 days, the median time of neutrophil and platelet engraftment was 11 days and 12 days, respectively, no patient occurred acute or chronic GVHD, after a median follow-up of 16 months, all recipients survived and completely eliminated PNH cloning.@*CONCLUSION@#Allo-HSCT can completely clear PNH cloning and restore hematopoietic function with controllable complications, and the improved PTCy based conditioning regimen is proved to be effective in PNH transplantation.


Subject(s)
Anemia, Aplastic/therapy , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hemoglobinuria, Paroxysmal/therapy , Humans , Transplantation Conditioning
4.
Journal of Experimental Hematology ; (6): 1548-1554, 2021.
Article in Chinese | WPRIM | ID: wpr-922293

ABSTRACT

OBJECTIVE@#To observe the effects of Epimedium polysaccharides (EPS) on bone marrow hematopoietic function and Th17/Treg balance in aplastic anemia (AA) mice, and preliminarily explore its therapeutic mechanism.@*METHODS@#Forty BALB/C mice were randomly divided into control (control), model (model), stanozolol (stanozolol) and epimedium polysaccharide (EPS) group, with 10 mice in each group. Except for the control group, Acetophenazine, Gy irradiation and cyclophosphamide triple application were used to establish AA models for the other groups. After the model was established, the stanozolol group was intragastrically administered with 4 mg/kg stanozolol suspension, the EPS group was intragastrically administered with 100 mg/kg epimedium polysaccharide, while the control group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage once a day, for 14 consecutive days. The automatic animal blood analyzer was used to detect the changes in peripheral blood hemoglobin (Hb), red blood cells (RBC), white blood cells (WBC) and platelets (PLT), flow cytometry was used to detect the proportion of Treg and Th17 cells, the levels of interleukin 2 (IL-2), interleukin 11 (IL-11) and tumor necrosis factor α (TNF-α) were detected by ELISA, the number of nucleated bone marrow cells was counted, HE staining and immunohistochemical staining were used to detect the number, the proliferation and apoptosis of bone marrow cells, Western blot was used to detect the expression of signal transducer and activator of transcription 3 (STAT3), retinoic acid receptor-related orphan receptor γ (RORγt), transducer and activator of transcription 5 (STAT5) and fork head transcription factor 3 (Foxp3).@*RESULTS@#Compared with the model group, the levels of Hb, RBC, WBC and PLT in the peripheral blood of mice in stanozolol and EPS group significantly increased, the proportion of Th17 cells was significantly reduced, and the proportion of Treg cells significantly increased. The levels of IL-2 and TNF-α in serum were significantly reduced (P<0.05), the level of IL-11 significantly increased (P<0.05), the number of bone marrow nucleated cells significantly increased (P<0.05), the positive rate of Ki-67 significantly increased (P<0.05) and the positive rate of Caspase-3 was significantly reduced (P<0.05). At the same time, the protein expression of STAT3 and RORγt significantly decreased, and the protein expression of STAT5 and Foxp3 increased, the difference showed statistically significant (P<0.05).@*CONCLUSION@#EPS can promote the recovery of bone marrow hematopoietic function in AA mice and improve Th17/Treg imbalance, the mechanism may be related to the inhibition of STAT3/RORγt expression and promotion of STAT5/Foxp3 expression.


Subject(s)
Anemia, Aplastic , Animals , Bone Marrow , Epimedium , Mice , Mice, Inbred BALB C , Polysaccharides , T-Lymphocytes, Regulatory , Th17 Cells
5.
Journal of Experimental Hematology ; (6): 1896-1902, 2021.
Article in Chinese | WPRIM | ID: wpr-922220

ABSTRACT

OBJECTIVE@#To analyze the clinical characteristics and factors affecting prognosis in children with severe aplastic anemia (SAA).@*METHODS@#Two hundred and five children with SAA treated in our department from January 2008 to April 2018 were selected, and the clinical characteristics and factors affecting prognosis were retrospectively analyzed.@*RESULTS@#Among 205 SAA children, the effective rate (CR+PR) at 3, 6 and 12 months after immunosuppressive therapy (IST) treatment was 50.9%, 59.0% and 73.9%, respectively, and 5-year overall survival rate was 93.1%±2.0%. Univariate analysis showed that 5-year overall survival rate of SAA children of spontaneous delivery was higher than that of cesarean section (P=0.039), while multivariate analysis showed that birth way had no significant influence on 5-year overall survival rate (P>0.05). The response rate at 3 months after IST of children with a recent history of decoration before SAA onset was higher than those without history of decoration (P<0.05).@*CONCLUSION@#Most of the SAA children can achieve high response rate and overall survival rate. Patients with recent history of home/school decoration may be the factor affecting hematological response after 3 months of IST, but have no influence on long-term overall survival.


Subject(s)
Anemia, Aplastic , Cesarean Section , Child , Female , Humans , Immunosuppressive Agents , Pregnancy , Prognosis , Retrospective Studies , Treatment Outcome
6.
Article in Chinese | WPRIM | ID: wpr-921532

ABSTRACT

Objective To compare the efficacy and safety of cyclosporin A(CsA)and CsA combined with recombined human erythropoietin(rhEPO)in the treatment of patients with chronic aplastic anemia(CAA).Methods Data of 79 patients with CAA treated at Department of Hematology,PUMC Hospital between January 2016 and June 2018 were collected for retrospective analysis.Forty-five patients were treated with CsA+rhEPO,and the other 34 patients with CsA alone.All the enrolled patients were treated for at least 1.5-2.0 years and followed for at least 1.0 year.The efficacy,side effects,long-term outcomes were compared between the two groups,and factors that may influence the efficacy were analyzed.Results The patients treated with CsA+rhEPO included 14 males and 31 females,with a median age of 43(19,73)years old.The median treatment duration of CsA and rhEPO was 26(12,38)and 4(3,6)months,respectively,and the median followed-up time was 24(12,42)months.The patients treated with CsA alone included 16 males and 18 females,with a median age of 36(16,85)years old.The median CsA treatment duration was 24(12,40)months and the median follow-up time was 25(12,40)months.There was no statistical difference in baseline characteristics between the two groups(all


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Anemia, Aplastic/drug therapy , Cyclosporine/therapeutic use , Erythropoietin/therapeutic use , Female , Humans , Male , Middle Aged , Recombinant Proteins , Remission Induction , Retrospective Studies , Young Adult
7.
Journal of Experimental Hematology ; (6): 1257-1261, 2021.
Article in Chinese | WPRIM | ID: wpr-888548

ABSTRACT

OBJECTIVE@#To summarize the long-term efficacy of cyclosporine (CsA) in the treatment of non-severe aplastic anemia (NSAA) in children, and explore the early significant indicators.@*METHODS@#Data of 36 NSAA children in Department of Hematological Oncology, Wuhan Children's Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 2013 to December 2017 were analyzed retrospectively. All the children received oral CsA immunosuppressive therapy, and CsA trough concentration was checked to maintain at the rage of 200-250 μg/L after 2 weeks. The evaluation time points were at 3, 6, 12, 18 and 24 months, and assessment items were peripheral white blood cell differential count and reticulocyte's percentage and count.@*RESULTS@#The 36 NSAA cases were composed of 16 males and 20 females, whose median age was 5.46 (2.92-7.99) years old, and median follow-up time was 28.00 (10.00-38.25) months. After taking oral CsA for 24 months, the number of cumulative effective cases was 21. There were 4 cases of complete remission (CR), 17 cases of partial remission (PR), and 15 cases of non-remission (NR). The total effective rate was 58.33%, and median effect-acting time of CsA was 3.0 (0.5-10.0) months. Compared with ineffective group, neutrophil (NEU) and red blood cell (RBC) of effective group (CR+PR) began to increase significantly at the 3rd month, and hemoglobin (Hb), platelet (PLT) and white blood cell (WBC) increase significantly at the 6th month after oral CsA administration (P<0.05). Except for 2 cases who received component transfusion within 3-12 months after taking oral CsA for 3 months in effective group, the others did not need.@*CONCLUSION@#The overall effective rate of oral CsA in children with NSAA was 58.33%. Stopping blood transfusion after the 3 months of treatment may be considered as a turning point for disease outcomes, and levels of NEU, RBC at the 3rd month and Hb, PLT, WBC at the 6th month as indicators for predicting disease prognosis.


Subject(s)
Anemia, Aplastic/drug therapy , Child , Child, Preschool , Cyclosporine , Female , Humans , Immunosuppressive Agents , Male , Prognosis , Retrospective Studies , Treatment Outcome
8.
Journal of Experimental Hematology ; (6): 1251-1256, 2021.
Article in Chinese | WPRIM | ID: wpr-888547

ABSTRACT

OBJECTIVE@#To study the expression of B lymphocyte-induced mature protein-1 (BLIMP-1) in regulatory T cells (Tregs) of children with aplastic anemia (AA), and analyze its correlation with the number of Tregs and the levels of inhibitory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β in plasma.@*METHODS@#The peripheral blood samples of 10 newly diagnosed AA children and 10 healthy children were collected for experiment. qPCR was used to detect FOXP3 and PRDM1 mRNA expression levels. Flow cytometry was used to detect the proportion of Tregs, the expression of BLIMP-1 in Tregs, and the levels of cytokines such as IL-2, IL-17A, IL-6, interferon (IFN)-γ, IL-10 and TGF-β in plasma. Pearson correlation model was used to evaluate the relationship between the expression of BLIMP-1 in Treg and the number of Tregs, as well as the levels of IL-10 and TGF-β in plasma.@*RESULTS@#Compared with control group, the proportion of Tregs in peripheral blood of AA children was decreased significantly (P<0.001); The plasma levels of proinflammatory cytokines IL-2, IL-6 and IFN-γ in AA children were increased significantly (P=0.033, P=0.031, P=0.006), and IL-17A also was increased but the difference was not statistically significant (P=0.052), while anti-inflammatory cytokines IL-10 and TGF-β were significantly reduced (P=0.048, P=0.002). The relative expressions level of FOXP3 and PRDM1 mRNA in AA children were significantly lower than those in control group (P=0.037, P=0.016). The expression of BLIMP-1 protein in Tregs of AA children was significantly lower than that in control group (P<0.001). The expression level of BLIMP-1 protein in Tregs was positively correlated with the percentage of Tregs in lymphocytes (r=0.671, P=0.001), and was also positively correlated with the levels of IL-10 and TGF-β in plasma (r=0.500, P=0.029; r=0.486, P=0.030).@*CONCLUSION@#The expression of BLIMP-1 in Tregs of AA children is impaired, and the low expression of BLIMP-1 is related to the decrease of the number in Tregs and IL-10 and TGF-β expressions.


Subject(s)
Anemia, Aplastic , Child , Cytokines , Flow Cytometry , Forkhead Transcription Factors , Humans , Positive Regulatory Domain I-Binding Factor 1 , T-Lymphocytes, Regulatory , Transforming Growth Factor beta
9.
Article in English | WPRIM | ID: wpr-888493

ABSTRACT

Haploidentical hematopoietic stem cell transplantation is a recommended alternative therapy for children with severe aplastic anemia who lack a human leukocyte antigen (HLA)-identical sibling donor and do not respond well to immunosuppressive therapy; however, due to non-identical HLA, the patients may have donor-specific anti-HLA antibody, which may lead to a relatively high incidence rate of poor graft function. Compared with HLA-identical transplantation, conditioning regimen for haploidentical transplantation still needs to be explored. This article reviews the detection and treatment of donor-specific anti-HLA antibody, the selection of conditioning regimen, and the mechanism and treatment of poor graft function in haploidentical hematopoietic stem cell transplantation.


Subject(s)
Anemia, Aplastic/therapy , Child , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Transplantation Conditioning , Transplantation, Homologous
10.
Article in Chinese | WPRIM | ID: wpr-880173

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics and risk factors of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with severe aplastic anemia (SAA).@*METHODS@#Clinical data from 270 SAA patients with allo-HSCT were retrospectively analyzed, including 108 sib congruence patients and 162 substitute donors (68 unrelated donor congruence patients and 94 related haploid patients). Different pretreatment schemes were selected for different transplantation modes. The HLA-identical sibling and haploid grafts were all bone marrow and peripheral blood stem cells, and the grafts from unrelated donors were peripheral blood stem cells. After granulocyte implantation, blood CMV-DNA was regularly monitored. Flow cytometry was also used to determine the absolute number of CD3@*RESULTS@#CMV infection occurred in 229 of 270 patients with an incidence of 84.8%. Among them, 18 patients developed giant cell disease. Univariate analysis showed that alternative donors (unrelated total and haploid donors), mycophenolate mofetil and acute graft-versus-host disease were statistically significantly associated with CMV infection (P<0.05). Multivariate analysis showed that alternative donors were associated with CMV infection. The recovery of CD3@*CONCLUSION@#After allo-HSCT, substitute donors are more easily to develop CMV infection than full-sibling donors, and the reconstruction of immune function is delayed after transplantation.


Subject(s)
Anemia, Aplastic , Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Retrospective Studies
11.
Article in Chinese | WPRIM | ID: wpr-880113

ABSTRACT

METHODS@#To establish the acquired aplastic anemia mouse model through the X-ray irradiation in combination with lymphocytes injection. AA Group: the purified Pan T lymphocytes from the spleen of C57BL/6J mice were enriched and injected to the mice through tail vein(5×10@*RESULTS@#Compared with 4, 5 Gy irradiated mice in AA groups, the survival time of 3 Gy irradiated AA groups was significantly prolonged. 3, 4 and 5 Gy X-ray irradiation combined with Pan T lymphocyte injection could successfully induced severe reduction of red blood cells, blood neutrophils, and platelets, severe reduction of bone marrow nucleated cells, severe bone marrow hematopoietic failure, and the significant expansion of T lymphocytes ratio in the bone marrow. CD4@*CONCLUSION@#3, 4 and 5 Gy X-ray irradiation combined with 5×10


Subject(s)
Anemia, Aplastic , Animals , Bone Marrow , Bone Marrow Cells , CD8-Positive T-Lymphocytes , Humans , Mice , Mice, Inbred C57BL
12.
Article in Chinese | WPRIM | ID: wpr-880055

ABSTRACT

OBJECTIVE@#To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST.@*METHODS@#The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed.@*RESULTS@#There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3@*CONCLUSION@#The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.


Subject(s)
Anemia, Aplastic , Humans , Immunosuppression , Immunosuppressive Agents/therapeutic use , Lymphocyte Subsets , Retrospective Studies
13.
Article in Portuguese | LILACS | ID: biblio-1355169

ABSTRACT

RESUMO: Estudo analítico, transversal, retrospectivo. Objetivos: Verificar a relação entre reações transfusionais imediatas, características demográficas e clínicas dos pacientes e características das hemotransfusões em um hemocentro universitário. Metodologia: O estudo foi realizado com dados de transfusões realizadas em 2016 no hemocentro da Universidade Federal de São Paulo. Foram coletados dados demográficos dos pacientes, características das hemotransfusões e ocorrência de reações transfusionais imediatas. Possíveis associações foram avaliadas usando os Testes de Fisher, Mann-Whitney, Qui-quadrado e t de Student. Associações com valores de p<0,05 foram consideradas significativas. Resultados: Foram analisados dados de 320 fichas de pacientes, totalizando 938 transfusões. Dos produtos sanguíneos transfundidos, 90,3% eram concentrados de hemácias, administrados por auxiliares de enfermagem em 43,8% das situações. As reações transfusionais ocorreram em 4,3% das situações (n=40). O sinal de reações mais frequente foi a febre (47,5%), seguido de prurido (22,5%). As reações foram mais prevalentes em pacientes com maior idade média (p= 0,0037), que receberam duas transfusões sanguíneas em comparação a uma (p<0,0001), consequentemente mais bolsas de transfusões (p=0,0002), maior volume total transfundido (p<0,0001) e maior tempo de administração (p=0,0017). Pacientes com anemia aplásica, leucemia mieloide aguda e neoplasias de órgãos sólidos tiveram reações transfusionais imediatas mais frequentemente do que pacientes com outros diagnósticos (p≤0,05). Conclusões: A ocorrência de reações transfusionais imediatas teve relação com a idade, diagnóstico médico, número de hemotransfusões, número de bolsas transfundidas, volume total transfundido e tempo de transfusão. O conhecimento desses fatores pode subsidiar treinamentos específicos voltados para a vigilância quanto às reações transfusionais imediatas. (AU)


ABSTRACT An analytical, cross-sectional, retrospective study. Objectives: To investigate the relationship among immediate transfusion reactions, patient's demographic and clinical characteristics, and transfusion-related characteristics in a university blood center. Methodology: The study was performed with data regarding blood transfusions of the blood center at Universidade Federal de São Paulo in 2016. Patient's demographic and clinical characteristics and the characteristics of the immediate trans-fusion reactions were collected. Possible associations were evaluated using Fisher's exact test, Mann-Whitney, Chi-square, and Student's t-test. Associations with p≤0.05 were considered statistically significant. Results: Data from 320 patient records were analyzed, totaling 938 blood transfusions. Of the blood products transfused, 90.3% were packed red blood cells administered by nursing assistants in 43.8% of the situations. Immediate transfusion reactions occurred in 4.3% of the situations (n=40). The most common transfusion reaction was fever (47.5%), followed by pruritus (22.5%). The transfusion reactions were more frequent in older patients (p=0.0037) who received two blood transfusions compared to one (p<0.0001), consequently more transfusion bags (p=0.0002), greater total transfused volume (p <0.0001), and longer length of administration (p=0.0017). Patients with aplastic anemia, acute myeloid leukemia, and solid organ neoplasms had immediate transfusion reactions more frequently than patients with other diagnoses (p <0.05). Conclusion: The occurrence of immediate transfusion reactions was related to age, medical diagnosis, number of blood transfusions, number of transfused bags, total transfused volume, and length of administration. Knowledge of these factors may support specific training for immediate transfusion reactions surveillance.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Blood Transfusion , Leukemia, Myeloid, Acute , Retrospective Studies , Hemotherapy Service , Transfusion Reaction , Anemia, Aplastic
14.
Rev. cuba. hematol. inmunol. hemoter ; 36(3): e1277, jul.-set. 2020. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1156444

ABSTRACT

Introducción: La aplasia medular adquirida grave es una enfermedad hematológica infrecuente caracterizada por una disminución o ausencia de precursores hematopoyéticos en la médula ósea, lo cual se expresa con distintos grados de citopenias. Varios factores, infecciosos o no, pueden incidir en su origen. Su manejo es complejo y puede incluir tratamiento inmunosupresor y trasplante de progenitores hematopoyéticos alogénico. Objetivo: Demostrar la utilidad de la realización del trasplante de progenitores hematopoyéticos alogénico haploidéntico en pacientes con aplasia medular grave. Caso clínico: Paciente masculino de 21 años de edad, con antecedentes de salud, que en octubre del 2018 debutó con íctero, pancitopenia, lesiones purpúrico hemorrágicas en piel y mucosas, en el curso de una hepatitis aguda seronegativa. La biopsia de médula ósea mostró aplasia medular severa. Se inició tratamiento inmunosupresor con globulina antitimocίtica, ciclosporina A y metilprednisolona. Al cabo de los 6 meses mantenía trombocitopenia severa con necesidades transfusionales y en octubre de 2019 se decide realizar trasplante de progenitores hematopoyéticos alogénico con donante haploidéntico y empleando como tratamiento acondicionante globulina antitimocίtica, fludarabina, ciclofosfamida y bajas dosis de irradiación corporal total. En evaluación clίnica de julio de 2020 (dίa + 280 del trasplante) el paciente estaba asintomático y con parámetros hematológicos normales. Conclusiones: Se demostró que el trasplante de progenitores hematopoyéticos alogénico haploidéntico es un proceder realizable y útil en pacientes con aplasia medular grave, lo cual corrobora el beneficio clínico que puede aportar su ejecución en pacientes con esta enfermedad(AU)


Introduction: Acquired severe marrow aplasia is a rare hematological disease characterized by decrease or absence of hematopoietic precursors in bone marrow, which is expressed with different degrees of cytopenias. Several factors, infectious or not, can influence its origin. Its management is complex and may include immunosuppressive treatment and allogeneic hematopoietic stem-cell transplantation. Objective: To demonstrate the usefulness of performing haploidentical allogeneic hematopoietic stem-cell transplantation in patients with severe medullary aplasia. Clinical case: A 21-year-old male patient, with medical history, who first presented, in October 2018, with icterus, pancytopenia, as well as purpuric hemorrhagic lesions on the skin and mucosa, in the course of acute seronegative hepatitis. The bone marrow biopsy showed severe marrow aplasia. Immunosuppressive treatment was started with antithymocytic globulin, cyclosporine A, and methylprednisolone. After six months, he maintained severe thrombocytopenia under transfusion requirements and, in October 2019, the decision was to perform allogeneic hematopoietic stem-cell transplantation with a haploidentical donor and using antithymocyte globulin, fludarabine, cyclophosphamide, and low doses of total body irradiation as conditioning treatment. In the clinical assessment carried out in July 2020 (day +280 after transplantation), the patient was asymptomatic and with normal hematological parameters. Conclusions: Transplantation of haploidentic allogeneic hematopoietic progenitors was shown to be a feasible and useful procedure in patients with severe marrow aplasia, which corroborates the clinical benefit that its execution can bring in patients with this disease(AU)


Subject(s)
Humans , Male , Young Adult , Tissue Donors/ethics , Methylprednisolone/therapeutic use , Whole-Body Irradiation/methods , Microscopy, Electron, Scanning Transmission/methods , Hematologic Diseases , Hematopoietic Stem Cell Transplantation/methods , Cuba , Transplantation, Haploidentical/methods , Anemia, Aplastic/therapy , Antilymphocyte Serum
15.
Article in English | WPRIM | ID: wpr-810958

ABSTRACT

BACKGROUND: This study aimed to assess the outcome of stem cell transplantation (SCT), including overall survival (OS), failure-free survival (FFS) and graft-versus-host disease (GvHD)-free/failure-free survival (GFFS), and to analyze prognostic factors in children with aplastic anemia (AA).METHODS: From 1991 to 2018, 43 allogeneic SCT recipients were enrolled in the study to investigate the demographic characteristics, survival outcomes and prognostic factors.RESULTS: With the median follow-up of 7.1 years, the estimated 10-year OS, FFS, GFFS were 86.0%, 60.5%, and 51.2%, respectively. Matched related donors (MRD, n = 28) showed better 10-year OS than unrelated donors (n = 15) (96.4% vs. 66.7%; P = 0.006). Engraftment failure was seen in 13 patients (30.2%). Donor-type aplasia was seen in 13.8% (4/29) after fludarabine (Flu)-based conditioning (Flu-group), while in 42.6% (6/14) after cyclophosphamide (Cy)-based regimen (Cy-group) (P = 0.035). Six patients died. The 10-year OS in Cy-group was 92.9% (n = 14, all MRD), while that of Flu-group was 82.1% (n = 29; P = 0.367). But Flu-group tended to have better FFS and GFFS than Cy-group, although Flu-group had less MRDs (41.4% vs. 100%; P = 0.019), and higher proportion of previous immunosuppressive treatment (IST; 62% vs. 21.4%, P = 0.012). In MRD transplants, OS was similar between Flu-group (100%, n = 14) and Cy-group (92.9%, n = 14), while FFS (100.0% vs. 42.9%; P = 0.001) and GFFS (85.7% vs. 35.7%; P = 0.006) were significantly better in Flu-group. Stem cell sources, irradiation in the conditioning, and method of GvHD prophylaxis did not significantly influence the outcome.CONCLUSION: This study reviewed SCT outcomes for pediatric AA with changes of transplant strategies over the last 25 years. The FFS and GFFS were higher in Flu-group than in Cy-group, especially in matched related transplantation. Graft failure including donor-type aplasia remains troublesome even with Flu-based conditioning. Further refinement of transplant strategies to ensure better quality-of-life should be pursued.


Subject(s)
Anemia, Aplastic , Child , Cyclophosphamide , Follow-Up Studies , Graft vs Host Disease , Humans , Methods , Stem Cell Transplantation , Stem Cells , Tissue Donors , Transplants , Unrelated Donors
16.
Article in Chinese | WPRIM | ID: wpr-827186

ABSTRACT

OBJECTIVE@#To explore the effect of miR-335-5p/ADCY3 interaction on the lymphocyte function in the patients with aplastic anemia (AA).@*METHODS@#Blood samples were collected from 22 healthy volunteers (HC) and 50 AA patients including 38 severe AA (SAA) and 12 non-severe AA (NSAA). Peripheral blood mononuclear cells (PBMNC) were isolated. The expression of miR-335-5p and ADCY3 mRNA was detected by using RT-PCR. Negative control miR-335-5p (NC group) and miR-335-5p mimic (mimic group) were transfected to AA-PBMNC by using RNAimax reagent, respectively. The proliferative ability, activation and cytokines of CD4 T and CD8 T cells were measured by flow cytometry. Dual-luciferase reporter assay was used to verify the targeted relationship between miR-335-5p and target gene.@*RESULTS@#The expression of miR-335-5p was significantly downregulated in SAA-PBMNC and NSAA-PBMNC compared with HC-PBMNC (0.08±0.01 vs 0.74±0.10, P<0.01; 0.17±0.02 vs 0.74±0.10, P<0.01). Meanwhile, the expression of miR-335-5p in SAA-PBMNC was very statistically significantly lower than that in NSAA-PBMNC (P<0.01). Compared with NC group, upregulation of miR-335-5p in vitro could significantly inhibited the proliferation of CD4 T and CD8 T cells in AA-PBMNC (P<0.05 and P<0.05, respectively). And, upregulating miR-335-5p in AA-PBMNC could significantly inhibited the activation of CD4 and CD8 T cells (P<0.01 and P<0.01, respectively). The ratio of CD4TNFα T, CD8IFNγ+T and CD8TNFα T cell by up-regulating the expression of miR-335-5p from AA-PBMNC in vitro was also significantly lower (P<0.01, P<0.05 and P<0.05, respectively). In addition, the expression of ADCY3 was higher in AA-PBMNC than that in HC-PBMNC (1.70±0.15 vs 0.76±0.12, P<0.01). Furthermore, by means of dual-luciferase reporter assay, the luciferase activity of ADCY3'UTR wildtype could be inhibited by miR-335-5p.@*CONCLUSIONS@#The expression of miR-335-5p was significantly downregulated in AA, and that correlates with disease severity. Up-regulating miR-335-5p can correct the hyperimmune status in AA patients by targeting ADCY3. These changes may relates with the strengthen of inhibition for targeted gene ADCY3.


Subject(s)
Anemia, Aplastic , Genetics , CD8-Positive T-Lymphocytes , Humans , Leukocytes, Mononuclear , Lymphocyte Count , MicroRNAs , Genetics
17.
Article in Chinese | WPRIM | ID: wpr-827184

ABSTRACT

OBJECTIVE@#To establish a stable and rapidly rat model acquired aplastic anemia.@*METHODS@#The SD rats were exposed to Csγ-ray at 3.5 and 4.0 Gy ( 91 cGy/min), and intraperitoneally injected with CTX at 35 mg/( kg·d) and CHL at 45 mg/( kg·d) in d 4, 6 and 8 after irradiation; the WBC, platelet and reticulocyte counts in peripheral blood, the smears and nucleated cells counts of bone marrow were observed.@*RESULTS@#The levels of peripheral blood 3-lineage cells of SD rats treated with Csγ-irradiation combined with cyclophosphamide and chloramphenicol were significantly reduced, among which white blood cells, platelets and reticulocytes decreased rapidly, and the number of bone marrow nucleated cells decreased significantly; bone marrow pathological sections showed severe reduction of hematopoietic cells, and the non-hematopoietic cells such as fat cells increased, and a serve or lightly reduction of bone marrow cells were found.@*CONCLUSION@#The rat model established by Csγ-ray irradiation combined with cyclophosphamide and chloramphenicol meets the clinical characteristics of aplastic anemia, and this study provides a stable rat model for the study of new therapeutic drugs for acquired aplastic anemia.


Subject(s)
Anemia, Aplastic , Animals , Bone Marrow , Bone Marrow Cells , Cyclophosphamide , Rats , Rats, Sprague-Dawley
18.
Article in Chinese | WPRIM | ID: wpr-827182

ABSTRACT

OBJECTIVE@#To investigate the effects of different routes in placental mesenchymal stem cells (PMSC) on serum expression levels of IL-4, IL-17, TNF-α and IFN-γ in aplastic anemia (AA) rats.@*METHODS@#The rat model of aplastic anemia (AA rats) was established by 5-fluorouracil combined with busulfan. The rats was divided into four groups: control, experimental, PMSC-injected into the tail vein, and PMSC-injected into the medullary cavity. The general state of rats in each group was observed in detail before and after treatment. The serum levels of interleukin-4 (IL-4) , interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) at week 1, 3 and 5 after treatment.@*RESULTS@#The serum levels of TNF-α, IFN-γ and IL-17 in the experimental group were significantly higher than those in the control group, while the level of IL-4 was significantly decreased (P<0.05). The levels of TNF-α, IFN-γ and IL-17 gradually decreased after treatment while the level of IL-4 increased. By the fifth week, the above indexes were closed to the control group (P>0.05), and the levels of TNF-α, IFN-γ and IL-17 in the group with PMSCs injected via the medullary cavity decrease more significantly than those group with PMSC injected via the tail vein, but level of IL-4 was not significantly different between two groups.@*CONCLUSION@#The level of serum hematopoietic negative regulators increase significantly, and the level of hematopoietic promoting factors decreases significantly in aplastic anemia rats. PMSC can down-regulate the level of hematopoietic negative regulators and up-regulate the level of hematopoietic promoting factors in the rats with aplastic anemia, and the inhibition of hematopoietic negative regulators by intramedullary injection is more significant than that by caudal vein injection.


Subject(s)
Anemia, Aplastic , Animals , Female , Hematopoietic Stem Cell Transplantation , Interferon-gamma , Mesenchymal Stem Cells , Placenta , Pregnancy , Rats , Tumor Necrosis Factor-alpha
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