Diagnosis and treatment of 26 cases of adenovirus infection after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.

Correlation between Serum G-CSF Level and Immune Function in Children with Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To observe the occurrence of immune dysfunction in children with aplastic anemia (AA) and the factors that may lead to immune dysfunction, analyze the relationship between the expression of granulocyte colony stimulating factor (G-CSF) and immune dysfunction.@*METHODS@#A total of 34 children with AA treated in our hospital from December 2016 to September 2018 were selected. All the children received immunosuppressive therapy (IST) for 6 months. According to whether the children had immune dysfunction after 6 months of treatment, they were divided into occurrence group and non occurrence group. General information and laboratory indices were compared between the two groups, and serum G-CSF level was tested, the relationship between serum G-CSF level and immune dysfunction in AA children after treatment with IST was observed and analyzed.@*RESULTS@#After treatment with IST for 6 months, 12 cases developed immune dysfunction (35.29%). Serum interferon (IFN)-γ level of the occurrence group was higher but G-CSF level was lower than those of the non occurrence group (P<0.05), while the difference of other baseline data was not statistically significant (P>0.05). Multiple regression analysis showed that overexpression of serum IFN-γ and low expression of G-CSF were both the influencing factors of immune dysfunction in AA children after IST treatment (OR>1, P<0.05). ROC curve was drawn, and the result showed that the area under the curve (AUC) of serum G-CSF level predicted the risk of immune dysfunction after IST was 0.843>0.80, when the index cut-off value was set at 6.614 pg/ml, the predictive value was ideal.@*CONCLUSION@#AA children have a higher risk of immune dysfunction after IST, which may be related to the low expression of serum G-CSF. The detection of serum G-CSF expression can be considered to predict the risk of immune dysfunction in AA children after IST, so as to guide early clinical intervention.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Enfermedad de injerto contra huésped cutánea frente a necrólisis epidérmica tóxica en un receptor de trasplante de células madre hematopoyéticas / Cutaneous graft-versus-host disease versus toxic epidermal necrolysis in a hematopoietic stem cell transplant recipient

El diagnóstico diferencial entre la enfermedad de injerto contra huésped aguda grave (estadio IV) y la necrólisis epidérmica tóxica pude resultar difícil en el contexto de un paciente trasplantado, ya que ambas tienen presentaciones clínicas similares. Sin embargo, la distinción entre ellas es fundamental porque ocasionan una gran morbimortalidad, y su manejo y pronóstico difieren. Algunas pequeñas diferencias clínicas e histopatológicas son de gran ayuda para el diagnóstico diferencial y el dermatólogo deberá reconocerlas para tomar una conducta correcta y oportuna. Se comunica el caso de un paciente que presentó ampollas y epidermólisis después del trasplante de células hematopoyéticas y en el que se planteó la dificultad diagnóstica para diferenciar entre ambas afecciones.

The differental diagnosis between severe graft-versus-host disease (stage IV) and toxic epidermal necrolysis can be difficult in the context of a transplant patient, since both conditions have similar clinical presentations. However, the distinction between these two entities is critical because they produce great morbidity and mortality and their management and prognosis differ. Some small clinical and histopathological differences are of great help for the differential diagnosis, and the dermatologist must recognize them in order to take a correct and timely conduct. We present the case of a patient who developed blisters and epidermolysis after hematopoietic cell transplantation, and in whom the diagnostic difficulty to differentiate between the two entities was raised.

Trasplante de progenitores hematopoyéticos alogénico haploidéntico en aplasia medular, reporte del primer caso en Cuba / Allogenic hematopoietic stem-cell transplantation in marrow aplasia: the first case report in cuba

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)

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Differential impact of anti-thymocyte globulin dosing by disease risk index in alternative donor peripheral blood stem cell transplantation in patients with acute leukemia or myelodysplastic syndrome after reduced intensity conditioning

No abstract available.

Aplasia medular adquirida, experiencia en un hospital público de referencia / Acquired aplastic anemia: experience in a public hospital

Background: The first line treatment for patients < 40 years old with aplastic anemia (AA) is allogeneic HLA-identical sibling donor transplantation (SCT). Immunosuppressive therapy (IST) with a combination of Thymoglobuline (ATG) and cyclosporine is used for older patients or those without a donor. Five year overall survival (OS) for both therapies is > 70%. Aim: To report the experience with SCT and ATG for AA in a public hospital. Patients and Methods: AA was diagnosed in 42 patients between 1998 and 2016, according to Camitta criteria. Thirty eight (90%) received treatment, 7 (18%) under 40 years old received SCT, and 31 (82%) IST. The rest were not treated. OS was calculated from date of diagnosis until last control, death or loss from follow up. Results: Complete or partial hematologic response, was obtained in 71% and 58% of cases with SCT and IS, respectively. Five year OS was 71% and 55% with SCT and IST, respectively. No difference in response was observed between horse and rabbit ATG. Conclusions: SCT from an HLA-identical sibling donor had a high response rate and survival. IST instead, had a lower response and survival, due to an initial high mortality rate.

Proposal of a Selective Prophylaxis Strategy Based on Risk Factors to Prevent Early and Late Pneumocystis jirovecii Pneumonia after Renal Transplantation / 대한이식학회지

BACKGROUND: Currently, trimethoprim-sulfamethoxazole is used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, but it is associated with frequent adverse effects. This study evaluated the efficacy and safety of the current protocol and proposes an individualized risk-based prophylaxis protocol. METHODS: The PJP incidence and risk factors during the first 6 months (early PJP) and afterwards (late PJP) was assessed in renal transplant recipients with (prophylaxis group) and without (no-prophylaxis group) 6-month PJP prophylaxis. RESULTS: In 578 patients, there were 39 cases of PJP during a median follow-up of 51 months. Renal adverse events were encountered frequently during trimethoprim-sulfamethoxazole prophylaxis, leading to premature discontinuation. Patients without the prophylaxis had a significantly higher incidence of early PJP (n=27, 6.6%) compared to patients with the prophylaxis (n=0). The incidence of late PJP was 2.2%, without between-group differences. The factors associated with early PJP were preoperative desensitization and acute rejection within 1 month, whereas late PJP was associated with age, deceased donor transplant, and acute rejection requiring antithymocyte globulin treatment. CONCLUSIONS: Based on the simulation results of several risk-based scenarios, the authors recommend universal prophylaxis up to 6 months post-transplant and extended selective prophylaxis in patients aged ≥57 years and those with a transplant from deceased donors.

Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia

PURPOSE: To investigate the efficacy and safety of umbilical cord blood (UCB) infusion (UCBI) plus immunosuppressive therapy (IST) treatment in comparison to IST treatment, as well as predictive factors for clinical responses, in severe aplastic anemia (SAA) patients. MATERIALS AND METHODS: Totally, 93 patients with SAA were enrolled in this cohort study. In the IST group, rabbit antithymocyte globulin (r-ATG) combined with cyclosporine A (CsA) was administered, while in the IST+UBCI group, r-ATG, CsA, and UCB were used. RESULTS: After 6 months of treatment, UCBI+IST achieved a higher complete response (CR) rate (p=0.002) and an elevated overall response rate (ORR) (p=0.004), compared to IST. Regarding hematopoietic recovery at month 6, platelet responses in the UCBI+IST group were better than those in the IST group (p=0.002), and UCBI+IST treatment facilitated increasing trends in absolute neutrophil count (ANC) response (p=0.056). Kaplan-Meier curves illuminated UCBI+IST achieved faster ANC response (p < 0.001) and platelet response (p < 0.001), compared with IST therapy. There was no difference in overall survival (OS) between the two groups (p=0.620). Furthermore, logistic regression analysis demonstrated that UCBI+IST was an independent predicting factor for both CR (p=0.001) and ORR (p < 0.001), compared to IST; meanwhile, very severe aplastic anemia (VSAA) and ANC could predict clinical responses as well. However, Cox proportional hazard regression indicated that VSAA (p=0.003), but not UCBI+IST, affected OS. Safety profiles showed that UCBI+IST therapy did not elevate adverse events, compared with IST treatment. CONCLUSION: UCBI+IST achieved better clinical responses and hematopoietic recovery than IST, and was well tolerated in SAA patients.

Allogeneic hematopoietic stem cell transplantation in congenital hemoglobinopathies with myeloablative conditioning and rabbit anti-thymocyte globulin

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for β-thalassemia major (TM) and sickle cell disease (SCD) in children. Graft-versus-host disease (GVHD) and treatment-related mortality (TRM) remain significant challenges to improving survival after HSCT. Here, we analyzed the outcome of TM and SCD patients, who received allogeneic HSCT with myeloablative conditioning at our institution. METHODS: Twenty-two patients (15 TM, 7 SCD), with a median age of 9 years (range, 1.6–16.9), underwent allogeneic HSCT using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin-based conditioning. Cells were derived from either the bone marrow (8 patients), or peripheral blood stem cells (14 patients). The majority of patients received HSCT from a matched sibling donor (N=18). GVHD prophylaxis included cyclosporine and short course methotrexate. RESULTS: All patients achieved donor engraftment. Two SCD patients died from TRM-related grade IV gut GVHD (N=1) or severe bronchiolitis obliterans (BO) (N=1). Cumulative incidence of acute and chronic GVHD was 36.4% and 32.7%, respectively. Veno-occlusive disease (VOD) occurred in 8 patients (36.4%), but resolved in all instances. Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disease (PTLD) occurred in 1 patient. The overall survival (OS) was 90.9% (TM 100%, SCD 71.4%), with all patients achieving transfusion independence, while 8 achieved complete donor chimerism. CONCLUSION: Busulfan, cyclophosphamide, and ATG-based conditioning for HSCT of TM and SCD patients did not result in graft failure, although modifications may be required to reduce VOD incidence. Further changes to donor type and cell source prioritization are necessary to minimize TRM and morbidity caused by GVHD.

Prevalência de doença por citomegalovírus em transplantados renais em unidade de terapia intensiva / Prevalence of cytomegalovirus disease in kidney transplant patients in an intensive care unit

RESUMO Objetivos: Definir frequência de doença por citomegalovírus dentre pacientes transplantados renais na unidade de terapia intensiva nos quais houve a suspeita desta complicação; identificar fatores predisponentes e possível impacto na evolução clínica. Métodos: Estudo retrospectivo observacional, no qual foram incluídos pacientes transplantados renais acima de 18 anos, internados por quaisquer motivos em uma unidade de terapia intensiva, com pelo menos uma coleta de antigenemia ou reação em cadeia da polimerase para citomegalovírus durante internação. Doença por citomegalovírus foi definida por antigenemia positiva ou reação em cadeia da polimerase acima de 500 cópias/mL, na presença de sintomas, no contexto clínico apropriado, conforme julgamento do médico assistente. Resultados: Foram incluídos 99 pacientes (idade: 53,4 ± 12,8 anos, 71,6% homens). A doença por citomegalovírus foi diagnosticada em 39 pacientes (39,4%). Sintomas respiratórios (51%), piora clínica inespecífica (20%) ou sintomas gastrintestinais (14%) foram os principais motivos para coleta de exames. O tempo de transplante foi menor naqueles com doença por citomegalovírus em relação àqueles sem este diagnóstico (6,5 meses e 31,2 meses; p = 0,001), bem como uso de pulsoterapia nos últimos 6 meses (41% e 16,9%; p = 0,008) e uso prévio de timoglobulina no último ano (35,9% e 6,8%; p < 0,001). No modelo de regressão logística, somente o tempo de transplante e o uso de timoglobulina associaram-se à maior frequência de citomegalovírus. Não houve diferença na evolução clínica entre pacientes com ou sem doença por citomegalovírus. Conclusão: Em pacientes transplantados renais com suspeita de doença por citomegalovírus, a prevalência foi alta. O tempo de transplante menor que 6 meses e o uso de timoglobulina no último ano devem aumentar a suspeita do intensivista para esta complicação.

ABSTRACT Objectives: To define the frequency of cytomegalovirus disease among kidney transplant patients in an intensive care unit in which this complication was suspected and to identify predisposing factors and their possible impact on clinical outcome. Methods: Retrospective observational study in which kidney transplant patients over the age of 18 years were hospitalized for any reason in an intensive care unit with at least one collection of samples to test for the presence of antigenemia or cytomegalovirus via polymerase chain reaction during hospitalization. Cytomegalovirus disease was defined as positive antigenemia or polymerase chain reaction above 500 copies/mL in the presence of symptoms and in the appropriate clinical setting, as judged by the attending physician. Results: A total of 99 patients were included (age: 53.4 ± 12.8 years, 71.6% male). Cytomegalovirus disease was diagnosed in 39 patients (39.4%). Respiratory symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal symptoms (14%) were the main reasons for exam collection. Transplant time was lower in those with cytomegalovirus disease than in those without this diagnosis (6.5 months and 31.2 months, p = 0.001), along with pulse therapy in the last 6 months (41% and 16.9%, p = 0.008) and previous use of thymoglobulin in the last year (35.9% and 6.8%, p < 0.001). In the logistic regression model, only the transplant time and the use of thymoglobulin were associated with a higher frequency of cytomegalovirus. There was no difference in clinical evolution between patients with and without cytomegalovirus disease. Conclusion: In kidney transplant patients suspected of cytomegalovirus disease, the prevalence was high. Transplant time less than 6 months, and the use of thymoglobulin in the last year should increase the intensivist's suspicion for this complication.

Caracterización de pacientes con mordedura de serpiente atendidos en Hospital Tela, Atlantida / Characterization of patients with snake bite treated in Tela, Atlántida Hospital

Según la Organización Mundial de la Salud, se estima que anualmente suceden unos 5 millones de accidentes por mordedura de serpiente con 100 000 fallecimientos y cerca del triple de casos de amputación y discapacidad permanente. En el departamento de Atlántida, Honduras, la mordedura de serpiente se ha relacionado con la actividad agrícola, específicamente, con el cultivo de palma africana. Objetivo: Describir las características epidemiológicas y demográficas de pacientes que sufrieron mordedura de serpiente atendidos en el Hospital Tela, Atlántida. Material y Métodos: Estudio descriptivo, retrospectivo y transversal realizado durante el periodo comprendido del año 2013 al 2015 en el Hospital Tela. Universo, 92 casos con diagnóstico de mordedura de serpiente, de los cuales se excluyeron 8 casos por no cumplir criterios de inclusión, se obtuvo una muestra de 84 casos. La recolección de datos se obtuvo de los expedientes clínicos. Resultados: Del total de casos estudiados, la incidencia fue de 32(38.1%) casos en el 2015, 20(23.8%) en el 2014 y 32(38.1%) en el 2013. El rango de edad de los pacientes oscilaba entre los 2 a 75 años, con edad media de 28 años. De los 84 casos estudiados, 25(29.8%) eran menores de 18, 53(63.1%) se encontraban entre los 18-60 y 6(7.1%) eran mayores de 60 años. Se encontró 40(47.6%) casos del sexo femenino y 44(52.4%) masculino. 82(97.6%) eran del departamento de Atlántida y 2 eran procedentes del departamento de Yoro. 52(61.9%) pacientes afirmaron haber sido mordido por serpiente de la especie Bothrops asper (Barba Amarilla), los pies fueron los sitios anatómicos de mayor frecuencia afectados 55(65.5%), con predominio del pie izquierdo. Conclusión: La frecuencia de mordeduras de serpiente fue de 84 casos entre los años 2013-2015, siendo la población del municipio de Tela la más afectada, con 68% de los casos...(AU)

Cut-off value for absolute lymphocytes as an alternative for the immunophenotypic analysis of CD3+ T cells in the monitoring of immunosuppressive therapy with thymoglobulin / Valor de corte para linfócitos absolutos como alternativa para análise imunofenotípica de células T CD3+ no monitoramento de terapia imunossupressora com timoglobulina

Abstract Introduction: Immunosuppression of T lymphocytes is required for preventing acute rejection after transplantation and for the treatment of chronic autoimmune and inflammatory diseases. The laboratory monitoring for this therapy is the measurement of T cells by immunophenotyping, aiming the target value of less than 20 cells per µL. Objective: To establish a cut-off point for the total number of lymphocytes in the automated blood cell count that reflects less than twenty T cells µL by immunophenotyping. Methods: We studied and evaluated 242 kidney transplant patients that had results of automated blood cell count and quantification of T cells by immunophenotyping technique. The patients were divided into two groups, depending on the T lymphocyte immunophenotyping rates established by lower and higher than 20 cells per µL. After, we evaluated the cut-off point for lymphocytes in the blood cell count with a specificity of 100% to exclude patients with high levels of T lymphocytes. Results: We found that the cut-off point of 70 lymphocytes per µL obtained by automated blood cell count showed 100% of specificity to exclude patients with T-cell counts higher than 20 cells per µL by immunophenotyping. Conclusion: The results found in this study may be helpful to monitor the immunosuppressive therapy in kidney transplant patients in places where a flow cytometer is not available, or when this equipment is not present in the full routine.

Resumo Introdução: A imunossupressão de linfócitos T é necessária para a prevenção da rejeição aguda em transplantes e no tratamento de doenças autoimunes e inflamatórias crônicas. O seu monitoramento laboratorial consiste na quantificação dos linfócitos T realizada pela técnica de imunofenotipagem, na qual o valor preconizado é manter inferior a 20 células/µL. Objetivo: Estabelecer um ponto de corte para o número de linfócitos totais no hemograma automatizado que reflita uma contagem de linfócitos T inferior a 20 células/µL por imunofenotipagem. Métodos: Foram avaliados 242 pacientes transplantados renais que continham resultados do hemograma automatizado e quantificação de linfócitos T por imunofenotipagem. Os pacientes foram divididos em dois grupos, conforme os valores de linfócitos T estabelecidos pela imunofenotipagem: inferiores e superiores a 20 células/µL. A partir disto, foi avaliado o ponto de corte de linfócitos no hemograma com especificidade de 100% para excluir os pacientes com valores elevados de linfócitos T. Resultados: Este estudo evidenciou que o ponto de corte de 70 linfócitos/µL obtidos pelo hemograma automatizado apresentou especificidade de 100% para excluir os pacientes com contagens de linfócitos T superiores a 20 células/µL na imunofenotipagem. Conclusão: Esta pesquisa poderá auxiliar no monitoramento da terapia imunossupressora em pacientes transplantados renais em locais que não possuem um citômetro de fluxo disponível, ou ainda quando este equipamento não se faz presente na rotina integral.

Fatal Invasive Pulmonary Aspergillosis after Combined Induction with Rituximab and Antithymocyte Globulin for Kidney Transplantation in a Sensitized Recipient, and Early Rejection Therapy with Plasmapheresis and Low-dose Immunoglobulin / 대한이식학회지

A high degree of sensitization to human leukocyte antigen requires more intensive induction therapy; however, this increases vulnerability to opportunistic infections following kidney transplantation. Although recent studies have suggested that combined induction therapy with antithymocyte globulin and rituximab would be more effective in highly sensitized kidney recipients, we experienced a case of near-fatal invasive pulmonary aspergillosis 2 months after combined induction and early rejection therapy for graft dysfunction. Fortunately, the patient recovered with intensive antifungal treatment and lung lobectomy for a necrotic cavity. Antifungal prophylaxis should be considered in cases undergoing intensive induction therapy.

Efeito da terapia de indução em pacientes sensibilizados: análise dos riscos e benefícios / Effect of induction therapy in kidney transplantation in sensitive patients: analysis of risks and benefits

Resumo Introdução: A sensibilização está associada a piores desfechos clínicos após o transplante renal (TxR), incluindo maior incidência de função tardia, rejeição aguda e perda do enxerto. Objetivos: Avaliar os desfechos de eficácia e segurança de 1 ano de receptores de TxR com doador falecido sensibilizados induzidos com globulina antitimócito (ATG) e compará-las aos de pacientes não sensibilizados. Métodos: Receptores de TxR com doador falecido entre janeiro de 1998 e dezembro de 2009 foram divididos em 5 grupos: grupo controle 1 - n = 89, PRA negativo, sem indução; grupo controle 2 - n = 94, PRA negativo, indução com basiliximabe; grupo controle 3 - n = 81, PRA negativo, indução com ATG; grupo teste 4 - n = 64, PRA 1-49%, indução com ATG; grupo teste 5 - n = 118, PRA ≥ 50%, indução com ATG. Resultados: Não houve diferença na incidência de rejeição entre pacientes sensibilizados e não sensibilizados, exceto pelo grupo 1, que apresentou a maior incidência de rejeição aguda comprovada por biópsia (20,2%, p = 0,006 vs. grupo 4 ep = 0,001 vs. grupo 5). Os pacientes sensibilizados induzidos com ATG apresentaram maior incidência de infecção por citomegalovírus quando comparados aos pacientes do grupo 2 (26,6% e 14,4% vs. 2,1%). Não houve diferença nas sobrevidas do enxerto e do paciente. Na análise multivariada, PRA > 50% e uso de ATG não foram associados à perda, perda com óbito censorado ou óbito. Conclusão: Os pacientes sensibilizados induzidos com ATG apresentaram incidência de rejeição semelhante ou inferior à de pacientes não sensibilizados não induzidos. Estes pacientes apresentaram sobrevidas do enxerto e do paciente semelhantes em 1 ano e comparável perfil de segurança.

Abstract Introduction: Sensitization is associated with worse clinical outcomes after kidney transplantation (KT), including increased incidence of delayed graft function, acute rejection (AR) and graft loss. Objectives: To evaluate 1-year efficacy and safety outcomes in sensitized KT recipients receiving antithymocyte globulin (ATG) induction and compare them to non-sensitized patients. Methods: Deceased donors KT recipients transplanted between January 1998 and December 2009 were divided into 5 groups: control group 1 -n = 89, PRA negative, without induction therapy; control group 2 - n = 94, PRA negative, basiliximab induction; control group 3 - n = 81, PRA negative, ATG induction; test group 4 - n = 64, PRA 1-49%, ATG induction; test group 5 -n = 118, PRA ≥ 50%, ATG induction. Results: There was no difference in the incidence of AR among patients sensitized and non-sensitized, except for group 1, with highest incidence of AR (20.2%,p = 0.006 vs. Group 4 andp = 0.001 vs. group 5). Sensitized patients induced with ATG had higher incidence of citomegalovirus infection when compared with group 2 (26.6% and 14.4% vs. 2.1%). There were no differences in graft and patient survivals. In multivariable analysis, PRA > 50% and ATG induction were not associated with graft loss, death or death-censored graft loss. Conclusion: Sensitized patients induced with ATG presented similar or lower incidence of AR when compared with non-sensitized patients not induced. Besides, these patients had similar safety profile and graft and patient survivals at 1 year.

Successful Allogeneic Hematopoietic Stem Cell Transplantation for a Patient with Very Severe Aplastic Anemia During Active Invasive Fungal Infection / 임상소아혈액종양

Allogeneic hematopoietic stem cell transplantation (HSCT) may not be considered feasible in a patient with active fungal infection due to transplant-related mortality. We report a case of HSCT performed on a 6-month-old girl, who was diagnosed with very severe aplastic anemia (vSAA) at the age of 2 months, during active invasive pulmonary aspergillosis (IPA). Despite receiving continuous antifungal treatment and multiple granulocyte infusions, her IPA was aggravated. She underwent allogeneic HSCT from a matched sibling donor using conditioning regimen of fludarabine, reduced dose of cyclophosphamide, and anti-thymocyte globulin (ATG) during IPA. After neutrophil engraftment, fever subsided and IPA improved. She was continued on voriconazole for 7 months after HSCT. She is alive with normal hematopoiesis 4 years post-transplant. Our report suggests that allogeneic HSCT using conditioning regimen of fludarabine, reduced dose of cyclophosphamide, and ATG can be a feasible option for the patients with vSAA even during active fungal infection.