Umbilical Cord Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease.

BACKGROUND: Steroid-refractory acute graft-vs.-host disease (SR-aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation with a dismal prognosis and for which there is no consensus-based second-line therapy. Ruxolitinib is not easily accessible in many countries. A possible therapy is the administration of mesenchymal stromal cells (MSCs). METHODS: In this retrospective study, 52 patients with severe SR-aGVHD were treated with MSCs from umbilical cord (UC-MSCs) in nine institutions. RESULTS: The median (range) age was 12.5 (0.3-65) years and the mean ± SD dose (×106/kg) was 4.73 ± 1.3 per infusion (median of four infusions). Overall (OR) and complete response (CR) rates on day 28 were 63.5% and 36.6%, respectively. Children (n = 35) had better OR (71.5% vs. 47.1%, p = 0.12), CR (48.6% vs. 11.8%, p = 0.03), overall survival (p = 0.0006), and relapse-free survival (p = 0.0014) than adults (n = 17). Acute adverse events (all of them mild or moderate) were detected in 32.7% of patients, with no significant difference in children and adult groups (p = 1.0). CONCLUSIONS: UC-MSCs are a feasible alternative therapy for SR-aGVHD, especially in children. The safety profile is favorable.

Applicability of the acute leukemia (AL) - EBMT score as a prognostic model for allogeneic hematopoietic stem cell transplantation: a single-center, prospective, cohort study at a reference transplant center in Brazil

Abstract Introduction The Acute Leukemia-European Society for Blood and Marrow Transplantation (AL-EBMT) risk score was recently developed and validated by Shouval et al. Objective To assess the ability of this score in predicting the 2-year overall survival (OS-2), leukemia-free survival (LFS-2) and transplant-related mortality (TRM) in acute leukemia (AL) adult patients undergoing a first allogeneic hematopoietic stem cell transplant (HSCT) at a transplant center in Brazil. Methods In this prospective, cohort study, we used the formula published by Shouval et al. to calculate the AL-EBMT score and stratify patients into three risk categories. Results A total of 79 patients transplanted between 2008 and 2018 were analyzed. The median age was 38 years. Acute myeloid leukemia was the most common diagnosis (68%). Almost a quarter of the cases were at an advanced stage. All hematopoietic stem cell transplantations (HSCTs) were human leukocyte antigen-matched (HLA-matched) and the majority used familial donors (77%). Myeloablative conditioning was used in 92% of the cases. Stratification according to the AL-EBMT score into low-, intermediate- and high-risk groups yielded the following results: 40%, 12% and 47% of the cases, respectively. The high scoring group was associated with a hazard ratio of 2.1 (p= 0.007), 2.1 (p= 0.009) and 2.47 (p= 0.01) for the 2-year OS, LFS and TRM, respectively. Conclusion This study supports the ability of the AL-EBMT score to reasonably predict the 2-year post-transplant OS, LFS and TRM and to discriminate between risk categories in adult patients with AL, thus confirming its usefulness in clinical decision-making in this setting. Larger, multicenter studies may further help confirm these findings.

Applicability of the acute leukemia (AL) - EBMT score as a prognostic model for allogeneic hematopoietic stem cell transplantation: a single-center, prospective, cohort study at a reference transplant center in Brazil.

INTRODUCTION: The Acute Leukemia-European Society for Blood and Marrow Transplantation (AL-EBMT) risk score was recently developed and validated by Shouval et al. OBJECTIVE: To assess the ability of this score in predicting the 2-year overall survival (OS-2), leukemia-free survival (LFS-2) and transplant-related mortality (TRM) in acute leukemia (AL) adult patients undergoing a first allogeneic hematopoietic stem cell transplant (HSCT) at a transplant center in Brazil. METHODS: In this prospective, cohort study, we used the formula published by Shouval et al. to calculate the AL-EBMT score and stratify patients into three risk categories. RESULTS: A total of 79 patients transplanted between 2008 and 2018 were analyzed. The median age was 38 years. Acute myeloid leukemia was the most common diagnosis (68%). Almost a quarter of the cases were at an advanced stage. All hematopoietic stem cell transplantations (HSCTs) were human leukocyte antigen-matched (HLA-matched) and the majority used familial donors (77%). Myeloablative conditioning was used in 92% of the cases. Stratification according to the AL-EBMT score into low-, intermediate- and high-risk groups yielded the following results: 40%, 12% and 47% of the cases, respectively. The high scoring group was associated with a hazard ratio of 2.1 (p = 0.007), 2.1 (p = 0.009) and 2.47 (p = 0.01) for the 2-year OS, LFS and TRM, respectively. CONCLUSION: This study supports the ability of the AL-EBMT score to reasonably predict the 2-year post-transplant OS, LFS and TRM and to discriminate between risk categories in adult patients with AL, thus confirming its usefulness in clinical decision-making in this setting. Larger, multicenter studies may further help confirm these findings.

Causality assessment of adverse drug reactions by applying a global introspection method in a high complexity hospital.

Background: Causality assessment of adverse drug reactions (ADRs) is an essential approach in pharmacovigilance. The World Health Organization-Uppsala Monitoring Center (WHO-UMC) system has been considered one of the most adequate method for establishing causal relationship in hospitalized patients. Objective: To describe the causality of potential ADRs in hospitalized patients assessed by the WHO-UMC system and by different healthcare professionals. Methods: Three healthcare professionals, with different backgrounds, acted as judges to adjudicate the causality categories for potential ADRs according to WHO-UMC system, in a Brazilian high complexity hospital. Judges' agreement was evaluated by using Fleiss' and Cohen's kappa coefficients. Results: Ninety potential ADRs identified in 300 participants were adjudicated by each judge, comprising a total of 270 assessments. Most potential ADRs were classified as probable or possible (77.8%). Fleiss´ kappa revealed slight concordance among judges (k = 0.096;CI:95%;0.01-0.18). Conclusions: Diverse backgrounds may have influenced the results for causality assessment of ADRs by employing the WHO-UMC system. Despite the slight concordance found for the method, this result suggests potential opportunity to enrich the ADRs management by engaging multiprofessional teams in the process. Further studies should be considered to investigate the performance of methods for ADRs assessment in hospitalized patients in low- and middle-income countries.

Assessing the impact of ABO incompatibility on major allogeneic hematopoietic stem cell transplant outcomes: a prospective, single-center, cohort study

Abstract Background ABO blood group incompatibility between donor and recipient is associated with a number of immunohematological complications, but is not considered a major contraindication to allogeneic hematopoietic stem cell transplantation. However, available evidence from the literature seems to be conflicting as to the impact of incompatibility on overall survival, event-free survival, transplant-related mortality, graft-versus-host disease, and time to neutrophil and platelet engraftment. Methods This single-center, prospective, cohort study included patients with hematological malignancies who underwent a first allogeneic hematopoietic stem cell transplantation between 2008 and 2014. Patients receiving umbilical cord blood as the stem cell source were excluded from this analysis. The impact of ABO incompatibility was evaluated in respect to overall survival, event-free survival, transplant-related mortality, acute graft-versus-host disease and engraftment. Results A total of 130 patients were included of whom 78 (60%) were males. The median age at transplant was 36 (range: 2-65) years, 44 (33%) presented ABO incompatibility, 75 (58%) had acute leukemia, 111 (85%) had a related donor, 100 (77%) received peripheral blood hematopoietic stem cells as graft source and 99 (76%) underwent a myeloablative conditioning regimen. There was no statistically significant association between ABO incompatibility and overall survival, event-free survival, transplant-related mortality, grade II-IV acute graft-versus-host disease, neutrophil or platelet engraftment in multivariate analysis. Conclusion These results show that ABO incompatibility does not seem to influence these parameters in patients undergoing allogeneic hematopoietic stem cell transplantation.

Assessing the impact of ABO incompatibility on major allogeneic hematopoietic stem cell transplant outcomes: a prospective, single-center, cohort study.

BACKGROUND: ABO blood group incompatibility between donor and recipient is associated with a number of immunohematological complications, but is not considered a major contraindication to allogeneic hematopoietic stem cell transplantation. However, available evidence from the literature seems to be conflicting as to the impact of incompatibility on overall survival, event-free survival, transplant-related mortality, graft-versus-host disease, and time to neutrophil and platelet engraftment. METHODS: This single-center, prospective, cohort study included patients with hematological malignancies who underwent a first allogeneic hematopoietic stem cell transplantation between 2008 and 2014. Patients receiving umbilical cord blood as the stem cell source were excluded from this analysis. The impact of ABO incompatibility was evaluated in respect to overall survival, event-free survival, transplant-related mortality, acute graft-versus-host disease and engraftment. RESULTS: A total of 130 patients were included of whom 78 (60%) were males. The median age at transplant was 36 (range: 2-65) years, 44 (33%) presented ABO incompatibility, 75 (58%) had acute leukemia, 111 (85%) had a related donor, 100 (77%) received peripheral blood hematopoietic stem cells as graft source and 99 (76%) underwent a myeloablative conditioning regimen. There was no statistically significant association between ABO incompatibility and overall survival, event-free survival, transplant-related mortality, grade II-IV acute graft-versus-host disease, neutrophil or platelet engraftment in multivariate analysis. CONCLUSION: These results show that ABO incompatibility does not seem to influence these parameters in patients undergoing allogeneic hematopoietic stem cell transplantation.

Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country.

Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) has enabled better prediction of transplant-related mortality (TRM) in allogeneic hematopoietic stem cell transplants (AHSCT), data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27), in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM) and peripheral blood stem cells (PBSC) as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18-65 years); HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3) in this Brazilian population might justify these results.

Neutropenic patients and their infectious complications at a University Hospital.

OBJECTIVE: The aim of this study was to analyze the characteristics and infectious complications of neutropenic patients in a referral hospital. METHODS: A cross-sectional study was carried out between April and September 2008, which enrolled all neutropenic patients identified by daily blood counts in the Universidade Federal de Minas Gerais. Demographic data and information on infections were obtained from the Hospital Infection Control Committee. Statistical analysis was performed using the Statistical Package for Social Sciences. RESULTS: One hundred and sixteen patients were followed up during 129 hospitalizations. The patients had a mean age of 48.7 years old. Sixty-four (55.2%) patients were male and 25 (21.6%) died during the follow-up. In 97 (75.2%) of the hospitalizations, patients had episodes of febrile neutropenia. Patients classified as low-risk had a mortality rate of 16.2% (n = 12) vs. 39.1% (n = 9) among high-risk patients (p-value = 0.02). The death rate of the patients who had been submitted to hematopoietic stem cell transplantation was 13.5% (n = 5) vs. 26.7% (n = 16) among patients not submitted to transplantation (p-value = 0.13). Of the 155 infections diagnosed, 45.5% were defined as clinically documented. The etiological agent most frequently isolated was Escherichia coli and the main topography reported was bloodstream infections. The most used antimicrobial agents were cefepime, vancomycin and fluconazole. Approximately 24% of patients evolved with impaired renal function during hospitalization. CONCLUSION: Most reported infections in neutropenic patients were defined as clinically documented, which shows the importance of suspicion in patients without specific signs and symptoms for early diagnosis and the need for the classification of risk for timely interventions.

Infectious complications associated with the use of central venous catheters in patients undergoing hematopoietic stem cell transplantation.

In this prospective, observational study, we sought to investigate the incidence, risk factors, and outcomes of central venous catheter-associated infection in 56 patients admitted for hematopoietic stem cell transplantation. In multivariate analysis, we found a 7-fold higher risk of central line-associated bloodstream infection with central venous catheter insertion in the internal jugular vein as compared with the subclavian access. Patients with central line-associated bloodstream infection had a higher incidence of acute renal failure.

Neutropenic patients and their infectious complications at a University Hospital

OBJECTIVE: The aim of this study was to analyze the characteristics and infectious complications of neutropenic patients in a referral hospital. METHODS: A cross-sectional study was carried out between April and September 2008, which enrolled all neutropenic patients identified by daily blood counts in the Universidade Federal de Minas Gerais. Demographic data and information on infections were obtained from the Hospital Infection Control Committee. Statistical analysis was performed using the Statistical Package for Social Sciences. RESULTS: One hundred and sixteen patients were followed up during 129 hospitalizations. The patients had a mean age of 48.7 years old. Sixty-four (55.2%) patients were male and 25 (21.6%) died during the follow-up. In 97 (75.2%) of the hospitalizations, patients had episodes of febrile neutropenia. Patients classified as low-riskhad a mortality rate of 16.2% (n = 12) vs. 39.1% (n = 9) among high-risk patients (p-value = 0.02). The death rate of the patients who had been submitted to hematopoietic stem cell transplantation was 13.5% (n = 5)vs. 26.7% (n = 16) among patients not submitted to transplantation (p-value = 0.13). Of the 155 infections diagnosed, 45.5% were defined as clinically documented. The etiological agent most frequently isolated was Escherichia coli and the main topography reported was bloodstream infections. The most used antimicrobial agents were cefepime, vancomycin and fluconazole. Approximately 24% of patients evolved with impaired renal function during hospitalization. CONCLUSION: Most reported infections in neutropenic patients were defined as clinically documented, which shows the importance of suspicion in patients without specific signs and symptoms for early diagnosis and the need for the classification of risk for timely interventions.

Notificação de infecções hospitalares de pacientes submetidos a transplante hepático: casuística de cinco anos do Hospital das Clínicas da UFMG / Notification of nosocomial infections of liver transplanted patients: five years of follow up at Hospital das Clínicas - UFMG

Objetivos: o objetivo do presente estudo é estabelecer notificação de infecções hospitalares (IH) de pacientes submetidos ao transplante hepático (TH), pois as complicações infecciosas são importante causa de morbimortalidade dessa população.Métodos: trata-se de estudo observacional prospectivo, para notificação de IH de pacientes submetidos ao TH, no período de 2000-2005, no Hospital das Clínicas/UFMG. Todos os pacientes foram incluídos a partir do procedimento e seguidos durante um ano. A notificação das IHs baseou-se no National Nosocomial Infection Surveillance System (NNISS). Os dados foram analisados pelos programas EpiInfo e Excel. Resultados: no período do estudo, foram realizados 311 transplantes e notificadas 276 infecções, correspondendo a uma taxa de IH de 88,7 infecções por 100 transplantes. O tempo médio de ocorrência da primeira IH foi de 9,5 dias. As principais infecções foram: olhos/ouvidos/nariz/garganta (24,3 por cento), infecções de sítio cirúrgico (12,7 por cento), infecções de corrente sangüínea (21,4 por cento) e pneumonias (13,8 por cento). Das culturas realizadas, 177 (64,1 por cento) foram positivas, sendo principalmente de sítio cirúrgico (66 casos). Os principais microrganismos foram: Staphylococcus coagulase negativo (18,6 por cento), Staphylococcus aureus (15,2 por cento) e Pseudomonas aeruginosa (15,2 por cento). Conclusões: a aplicação dos critérios de IH definidos pelo NNISS nesses pacientes permitiu avaliação temporal das taxas de infecção nessa população e comparação com outros serviços, direcionando medidas de controle e prevenção de IH.

Infecção hospitalar e resistência bacteriana em pacientes de um Centro de Terapia Intensiva de um Hospital Universitário / Nosocomial infections and bacterial resistance in patients from a Teaching Hospital Intensive Care Unit

Os Centros de Terapia Intensiva representam uma importante e indispensável parte da medicina moderna, por prestar atendimento a pacientes criticamente enfermos utilizando recursos humanos especializados e tecnologia avançada. Objetivou-se neste estudo determinar a incidência da infecção hospitalar, sua possível relação com a ocorrência da colonização por microrganismos resistentes, os principais agentes dessa colonização e a taxa de mortalidade nesta unidade. Tratou-se de um estudo prospectivo e descritivo entre agosto de 2005 a julho de 2006. Para a coleta de dados realizou-se a leitura de prontuários e consulta ao banco de dados microbiológicos, entre outros. A taxa global de infecção foi de 23,8%, a colonização por microrganismos resistentes contribuiu para o desenvolvimento de infecção (RR=6,8 [4,8-9,6], p<0,05), cujos patógenos resistentes mais prevalentes foram Pseudomonas aeruginosa e Acinetobacter baumannii. A taxa de mortalidade foi de 10,8% e destes, 23 pacientes (37,1%) faleceram após o diagnóstico de infecção hospitalar. Tais resultados reafirmam a necessidade de esforços direcionados ao controle da infecção e da resistência bacteriana subsidiando reflexões frente à adoção de medidas tais como uso de equipamentos de proteção individual, procedimentos invasivos, higienização das mãos e educação permanente da equipe assistencial multiprofissional.

[Comparative study of surgical wound infection diagnosed in-hospital and post discharge]. / Estudo comparativo do diagnóstico da infecção do sítio cirúrgico durante e após a internação.

OBJECTIVE: Surgical wound infection (SWI) is a serious hospital infection due to its incidence, morbidity and mortality. Because of the short hospital stay, the majority of SWI appears post-discharge, and its incidence is often underreported when there is no follow-up of the surgical patient post discharge. The need of a surveillance system for surgical patient after discharge is critical for infection control. The study objective was to determine the incidence of SWI in surgical patients and to compare the frequency of SWI diagnosed in-hospital and after discharge. METHODS: A prospective cohort study was carried out in a university hospital. Patients admitted to the general surgery unit (504) and underwent digestive tract surgery in the first semester of the year 2000 were followed up during their hospital stay and after discharge. RESULTS: Of 504 surgical patients, 398 (79.0%) returned to follow up in the post discharge outpatient clinic. Of the total surgical wound infections diagnosed, most (62.9%) was detected in the post discharge outpatient clinic, and 88% of SWI diagnosed were classified as superficial, and 67% reported up to day 7 after discharge. CONCLUSIONS: This study showed the importance of following up surgical patients after discharge to achieve reliable incidence data on surgical wound infection because of the late occurrence of infection in the majority of cases, which results in underreporting when the patient is followed up only during the hospital stay.

Estudo comparativo do diagnóstico da infecçäo do sítio cirúrgico durante e após a internaçäo / Comparative study of surgical wound infection diagnosed in-hospital and post discharge

OBJETIVO: A infecçäo do sítio cirúrgico constitui um grave problema dentre as infecçöes hospitalares por sua incidência, morbidade e mortalidade. Devido ao curto período de internaçäo, a maioria dessas infecçöes se manifesta após a alta hospitalar, sendo subnotificada quando näo há o seguimento do paciente cirúrgico. Programas de vigilância específicos do paciente após a alta säo considerados fundamentais para controlar as infecçöes. O objetivo do estudo foi determinar a incidência de infecçäo do sítio cirúrgico e comparar sua freqüência durante a internaçäo e após a alta. MÉTODOS: Realizou-se um estudo epidemiológico, tipo coorte, em um hospital universitário, com acompanhamento durante o período de internaçäo e no seguimento pós-alta hospitalar, de 504 pacientes que se submeteram à cirurgia do aparelho digestivo no primeiro semestre de 2000. RESULTADOS: Das 504 cirurgias realizadas no período do estudo, 398 (79,0 por cento) dos pacientes retornaram ao ambulatório de egressos. Do total de infecçöes do sítio cirúrgico diagnosticadas, a maioria (62,9 por cento) foi notificada no ambulatório de egressos, sendo 88,0 por cento superficiais, e 67,0 por cento notificadas até o sétimo dia após a alta. CONCLUSÖES: Comprovou-se a importância do seguimento pós-alta para a obtençäo de dados fidedignos sobre as infecçöes do sítio cirúrgico devido à manifestaçäo tardia na maioria dos casos, levando a subnotificaçäo quando o seguimento do paciente é realizado somente durante a internaçäo