RESUMO
BACKGROUND: It is well known that both acute and chronic graft-versus-host disease (GVHD) are associated with invasive fungal disease (IFD). Because the galactomannan antigen diagnostic test has low specificity and sensitivity outside of the neutropenic period, many institutions use posaconazole or voriconazole for IFD prophylaxis during GVHD treatment. Moreover, several factors, mainly hepatic impairment, can limit the use of extended spectrum azoles, both in prophylaxis or treatment. METHODS: We retrospectively analyzed 25 patients with allogeneic hematopoietic stem cell transplantation (HSCT) and GVHD - grade III-IV acute GHVD (n = 15), progressive chronic GVHD (n = 7), and "overlap" GVHD (n = 3) - who received intravenous anidulafungin (200 mg on day 1, followed by 100 mg once daily). If necessary, anidulafungin treatment was followed by oral administration of 200 mg voriconazole twice a day or 200 mg posaconazole 3 times daily until patients were considered not at risk for IFD. RESULTS: Twenty-one patients (85%) received anidulafungin as prophylaxis and 5 patients (15%) received it as treatment. Median duration of intravenous anidulafungin administration was 8 days (range 6-17). Seven patients (28%) presented mild adverse effects, with no significant interactions with calcineurin inhibitors. Sequentially, 4 patients received voriconazole and 6 posaconazole. Two patients (8%) developed IFD after anidulafungin withdrawal: 1 with Candida albicans and the other with Mucor, 8 and 5 days after withdrawal, respectively. CONCLUSIONS: Our results are of interest owing to the absence of data in the literature on anidulafungin use in HSCT patients with GVHD, and suggest that anidulafungin, because of its spectrum, pharmacological profile, low toxicity, and absence of interactions with immunosuppressants, could be a drug of choice in this setting.
Assuntos
Antifúngicos/uso terapêutico , Equinocandinas/uso terapêutico , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas , Micoses/prevenção & controle , Administração Oral , Adulto , Anidulafungina , Esquema de Medicação , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/etiologia , Micoses/imunologia , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Resultado do Tratamento , Adulto JovemRESUMO
Transfusion-related acute lung injury (TRALI) can be a life-threatening complication of transfusion and it is probably underdiagnosed. Human leucocyte antigen (HLA) and granulocyte antibodies are thought to play a major role, but preventive measures are difficult to implement. In our regional blood centre, we implemented a preventive strategy avoiding donor deferral. Previously, pregnant apheresis donors were screened for HLA antibodies, and those with positive results were assigned to a plasma-only protocol. Plasma from these donors and from all previously pregnant whole blood donors was diverted for protein fractionation. Plasma-poor red blood cells (in additive solution, buffy coat removed) and platelets (pools with additive solution) were prepared. Prestorage leucodepletion was also applied. We found HLA antibodies in 18.1% of previously pregnant apheresis donors, and our strategy caused a 6.0% loss of apheresis platelets, a 4.8% increase of apheresis fresh frozen plasma (FFP) and a 7.8% loss of transfusable apheresis FFP. The effect on FFP from whole blood donors could be compensated. The platelet preparation method reduced the mean volume of plasma from each donor to 24.4 mL. Fifteen months after the start of our strategy, no cases of TRALI have been reported. Our experience shows that a practical strategy to prevent TRALI is feasible.
Assuntos
Síndrome do Desconforto Respiratório/prevenção & controle , Reação Transfusional , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Remoção de Componentes Sanguíneos/métodos , Remoção de Componentes Sanguíneos/normas , Doadores de Sangue , Feminino , Granulócitos , Antígenos HLA/sangue , Teste de Histocompatibilidade , Humanos , Isoanticorpos/sangue , Isoantígenos/imunologia , Procedimentos de Redução de Leucócitos , Masculino , Pessoa de Meia-Idade , Gravidez , Programas Médicos RegionaisRESUMO
Toxoplasmosis appears to be a rare opportunistic protozoal infection following haematopoietic stem cell transplantation (HSCT). Most cases have been reported in allogeneic HSCT recipients, with only anecdotal reports of infection occurring after autologous transplantation. Reported here is the case of a patient who developed cerebral toxoplasmosis following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.
Assuntos
Linfoma não Hodgkin/complicações , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/diagnóstico , Antifúngicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Seguimentos , Humanos , Hospedeiro Imunocomprometido , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/tratamento farmacológico , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Medição de Risco , Índice de Gravidade de Doença , Toxoplasmose Cerebral/tratamento farmacológico , Transplante Autólogo , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.
Assuntos
Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Doadores de Tecidos , Adolescente , Adulto , Idoso , Antígenos CD34/biossíntese , Criança , Pré-Escolar , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas , Humanos , Lactente , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , EspanhaRESUMO
Expression of the apoptosis inhibitory protein Bcl-x was studied in CD34+ hematopoietic precursor cells and in the promyelocytic leukemia cell line HL-60. The enriched population of CD34+ cells (more than 95%) was cultured in the presence of stem cell factor, interleukin-3 (IL-3), IL-6, and either granulocyte colony-stimulating factor or macrophage colony-stimulating factor to achieve granulocyte or monocyte/macrophage differentiation, respectively. The expression of Bcl-x increased in the early stages of both differentiation pathways. However, by day 21 of culture mature granulocytes were Bcl-x-negative, whereas monocytes/macrophages either maintained or increased the expression of Bcl-x. The pattern of Bcl-x expression in the differentiated CD34+ cells was similar to that observed in HL-60 cells differentiated along the granulocyte lineage (induced by incubation with retinoic acid), or along the monocyte/macrophage lineage (induced by incubation with phorbol diester). The bcl-x transcript predominant in HL-60 and CD34+ cells differentiated into monocytes/macrophages was bcl-xL. Although little is yet known regarding the functional significance of Bcl-x within the granulomonocytic compartment, marked changes in the pattern of its expression, as observed during granulomonocytic differentiation of HL-60 and CD34+ cells, are likely to alter the life span of mature granulocytes and monocytes/macrophages.
Assuntos
Fatores Estimuladores de Colônias/farmacologia , Granulócitos/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Macrófagos/citologia , Monócitos/citologia , Proteínas Proto-Oncogênicas/biossíntese , Transcrição Gênica/efeitos dos fármacos , Antígenos CD/análise , Antígenos CD34/análise , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Células HL-60 , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Interleucina-3/farmacologia , Interleucina-6/farmacologia , Fator Estimulador de Colônias de Macrófagos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , RNA Mensageiro/biossíntese , Fator de Células-Tronco/farmacologia , Proteína bcl-XRESUMO
PROBLEM: Subclinical microbial invasion of the amniotic cavity occurs in 18.8% of women with term labor and intact membranes and in 34% of patients with term PROM and is a risk factor for the development of puerperal infection related morbidity. Although amniotic fluid white blood cell count, interleukin-6 determination, and Gram stain examination have been used for the diagnosis of intrauterine infection in patients with preterm labor and preterm premature rupture of membranes, no information is available about the accuracy and specific cut-off values for these tests in patients at term. The purpose of this study was to compare the performance of the amniotic fluid Gram stain examination, white blood cell count, and interleukin-6 determination in the identification of microbial invasion of the amniotic cavity in patients at term with and without PROM. METHOD: Amniotic fluid was retrieved from 148 patients with term gestations (90 patients with spontaneous labor and intact membranes and 58 patients with PROM). Samples were cultured for bacteria and Mycoplasma species. Amniotic fluid Gram stain, white blood cell count, and interleukin-6 determinations (ELISA, sensitivity: 43 pg/ml) were performed in all samples. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture for microorganisms. Analysis was conducted using Mann-Whitney U test, Fisher's exact test, receiver operating characteristic curves and logistic regression. RESULTS: Patients with spontaneous labor and intact membranes: The prevalence of microbial invasion of amniotic cavity in this group was 15.6% (14/90). The most sensitive test for the detection of microbial invasion of the amniotic cavity was amniotic fluid interleukin-6 determination (sensitivity for: interleukin-6 > or = 5.7 ng/ml = 86%, white blood cell count > or = 20 cells/mm3 = 64%, Gram stain = 28%). The most specific test was the Gram stain of the amniotic fluid (specificity for: Gram stain = 84%, interleukin-6 = 79% and white blood cell count = 63%). Multiple logistic regression demonstrated that amniotic fluid interleukin-6 concentration was the only covariate that retained statistical significance when intrauterine infection was used as outcome variable. Patients with PROM: The prevalence of a positive amniotic fluid culture in this group was 39.7% (23/58). Logistic regression demonstrated that only interleukin-6 retained a significant relationship with the results of amniotic culture when all variables were entered simultaneously into a model to predict amniotic fluid culture results. The most sensitive tests for the detection of intrauterine infection were interleukin-6 determination and white blood cell count (sensitivity for interleukin-6 > or = 3.4 ng/ml and white blood cell count > or = 20 cells/mm3 = 69.6% for both). The most specific test was Gram stain (97.1%). CONCLUSIONS: Amniotic fluid interleukin-6 determination is the best rapid test for the detection of microbial invasion of the amniotic cavity in patients at term with and without PROM. When this test is not available, amniotic fluid Gram stain and white blood cell count represent valid diagnostic tools to assess the microbial state of amniotic cavity.
Assuntos
Líquido Amniótico/microbiologia , Ruptura Prematura de Membranas Fetais/microbiologia , Trabalho de Parto/fisiologia , Líquido Amniótico/citologia , Líquido Amniótico/imunologia , Técnicas Bacteriológicas , Feminino , Ruptura Prematura de Membranas Fetais/imunologia , Humanos , Interleucina-6/análise , Trabalho de Parto/imunologia , Contagem de Leucócitos , Gravidez , Sensibilidade e Especificidade , Coloração e RotulagemRESUMO
Isotonic solution was administered extraamniotically to 41 pregnant patients with dead fetus of 24 to 40 weeks of gestational age. Vaginal deliveries occurred in 90% and 9,7% had complications.
Assuntos
Morte Fetal , Soluções Isotônicas/administração & dosagem , Trabalho de Parto Induzido/métodos , Administração Intravaginal , Adolescente , Adulto , Cateterismo/métodos , Feminino , Viabilidade Fetal , Humanos , Ocitocina/administração & dosagem , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da GravidezRESUMO
Eight patients with acute leukemia (AL) and invasive pulmonary aspergillosis (IPA) developing during previous antileukemic therapy underwent BMT (autologous in 6 cases and allogeneic 2). IPA was treated prior to BMT with full doses of amphotericin B, associated with surgical resection in three cases. One patient was treated with amphotericin B and itraconazole. Prior to BMT, seven patients had minimal residual pulmonary lesions. All patients received amphotericin B (0.5 mg/kg/day) during the aplastic period prior to engraftment. One patient died of Gram-negative septic shock before engraftment. Seven patients achieved complete hematological engraftment without any evidence of IPA reactivation. Amphotericin B was well tolerated with only minimal transient renal dysfunction in three patients. Later pulmonary complications related to IPA were observed in only one patient who developed a self-limited episode of hemoptysis. One patient died of CMV pneumonitis and two of leukemia relapse. Four patients survive disease-free and without complications related to IPA. We conclude that the reactivation of correctly treated IPA can be successfully prevented in BMT patients by use of prophylactic amphotericin B. With this approach, prior IPA is not a contraindication to BMT.
Assuntos
Aspergilose/complicações , Transplante de Medula Óssea , Leucemia Mieloide Aguda/complicações , Pneumopatias Fúngicas/complicações , Adolescente , Adulto , Anfotericina B/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Feminino , Sobrevivência de Enxerto , Humanos , Hospedeiro Imunocomprometido , Incidência , Itraconazol/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/epidemiologia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Indução de Remissão , Análise de Sobrevida , Resultado do TratamentoRESUMO
The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity during spontaneous parturition at term. Amniotic fluid was retrieved by transabdominal amniocentesis from 90 women in spontaneous term labor with intact membranes. Fluid was cultured for aerobic and anaerobic bacteria, including Mycoplasma. The prevalence of positive amniotic fluid cultures was 18.8% (17/90). The most common microbial isolates were Ureaplasma urealyticum, Streptococcus agalactiae, Lactobacillus species and Mycoplasma hominis. Clinical signs of chorioamnionitis were present in three patients, and only one of them had a positive amniotic fluid culture. Five patients (5.5%) had puerperal endometritis; three of them had an amniotic fluid culture positive for microorganisms. All neonates were free of clinical signs of infection. The data indicate that microbial invasion of the amniotic cavity occurs frequently during spontaneous labor at term, and it may be both the cause and the consequence of labor.
Assuntos
Líquido Amniótico/microbiologia , Corioamnionite/microbiologia , Trabalho de Parto , Complicações Infecciosas na Gravidez/microbiologia , Adolescente , Adulto , Corioamnionite/epidemiologia , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Estudos RetrospectivosRESUMO
A case of Potter syndrome secondary to renal agenesia and duodenal atresia with anular pancreas is presented. The karyotype was 47 XY-21. We discuss the antenatal diagnosis and the perinatal management.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Síndrome de Down/complicações , Obstrução Duodenal/congênito , Atresia Intestinal/diagnóstico por imagem , Rim/anormalidades , Ultrassonografia Pré-Natal , Adulto , Obstrução Duodenal/diagnóstico por imagem , Feminino , Humanos , Rim/diagnóstico por imagem , Oligo-Hidrâmnio/diagnóstico por imagem , Gravidez , SíndromeRESUMO
OBJECTIVE: The purpose of this study was to determine the frequency, microbiologic characteristics, and clinical significance of microbial invasion of the amniotic cavity in women with premature rupture of membranes at term. STUDY DESIGN: Amniocentesis was performed in 32 women with term premature rupture of membranes and amniotic fluid cultured for aerobic and anaerobic bacteria and Mycoplasmas. RESULTS: The prevalence of positive amniotic fluid cultures was 34.3% (11/32). The most common isolates were Ureaplasma urealyticum, Peptostreptococcus sp., Lactobacillus sp., Bacteroides fragilis, and Fusobacterium sp. Clinical chorioamnionitis occurred only in one patient with a positive amniotic fluid culture. Her neonate had ophthalmitis. Three patients (9.4%) had endometritis. Among women who were delivered vaginally, those with a positive amniotic fluid culture had a significantly higher rate of endometritis than those with a negative culture (33% [3/9] vs 0% [0/20], respectively, p = 0.023). CONCLUSIONS: These data indicate that microbial invasion of the amniotic cavity occurs in approximately one third of patients with preterm premature rupture of membranes. Microbial invasion of the amniotic cavity is a risk factor for endometritis in women with term premature rupture of membranes.
Assuntos
Âmnio/microbiologia , Ruptura Prematura de Membranas Fetais/microbiologia , Líquido Amniótico/microbiologia , Bacteroides fragilis/isolamento & purificação , Corioamnionite/microbiologia , Endometrite/microbiologia , Feminino , Fusobacterium/isolamento & purificação , Humanos , Lactobacillus/isolamento & purificação , Peptostreptococcus/isolamento & purificação , Gravidez , Ureaplasma urealyticum/isolamento & purificaçãoRESUMO
Ectopic implantation of the embryo in the tube opposite to the ovary containing the corpus luteum constitutes evidence of peritoneal or uterine transmigration of the egg. The frequency of this phenomenon was reinvestigated utilizing histopathologic confirmation of the side of the corpus luteum. A tubal pregnancy contralateral to the ovulating ovary was found in 28% of 67 cases, indicating that either the oocyte, the zygote or the embryo had entered the tube in which implantation took place from a medial site such as the peritoneal or the uterine cavity rather than directly from the ovulating ovary. Assuming that once in the medial site there is equal chance of entering either tube, it follows that in 56% of tubal pregnancies the egg has entered the tube from a midline location. Attempts to recover the oocyte from the tubes in normal women were successful in fewer than 5% of cases contralateral to the corpus luteum. It is concluded that tubal pregnancy is associated with a significant increase in the occurrence of transmigration of the egg.