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1.
Artigo em Inglês | MEDLINE | ID: mdl-31381996

RESUMO

Among 419 consecutive allogeneic hematopoietic cell transplant recipients, we observed 17 (4.0%) cases of toxoplasmosis at a median time of day 45 (range, 6 to 322) after transplant. Seven of these 17 cases occurred before day 30 after transplant. Because of the lack of PCR screening and trimethoprim-sulfamethoxazole prophylaxis before engraftment, the diagnosis of toxoplasmosis was late, and 5 of these 7 patients died. Analyzing these cases, early Toxoplasma blood PCR screening, starting from transplant, is crucial.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30413810

RESUMO

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening disease in allogeneic hematopoietic cell transplantation (HCT) recipients. Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylaxis but has significant toxicity. We assessed 139 consecutive HCT patients for PCP prophylaxis in our center. According to our procedures, TMP-SMX should be given as first-line prophylaxis from engraftment. In case of intolerance, atovaquone (ATO) or aerosolized pentamidine may be given. Thirteen (9.3%) patients did not receive prophylaxis because they early died. Of the 126 prophylaxed patients, 113 (90%) received TMP-SMX and 13 (10%) received ATO as first-line regimen. However, only 51/113 (45%) patients received TMP-SMX as the sole prophylaxis: 60 patients were switched to ATO because of side effect. There were 18 PCP cases: 3 occurred before engraftment, 7 occurred under ATO, 3 occurred while prophylaxis was pending the resolution of side effects, and 5 occurred after stopping prophylaxis. No cases occurred under TMP-SMX while 7 (9.6%) cases occurred under first-(n = 13) or second (n = 60)-line ATO. There are many concerns about PCP prophylaxis after HCT: patients may develop PCP before engraftment or several months after stopping immunosuppressors, and half of them do not receive TMP-SMX all along the at-risk periods. New prophylactic drugs and strategies should be evaluated.

3.
BMC Infect Dis ; 17(1): 747, 2017 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-29207952

RESUMO

BACKGROUND: Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach. METHODS: We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant. RESULTS: CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7-334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25-30% (p < 0.0001). CONCLUSION: Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs.


Assuntos
Infecções por Citomegalovirus/economia , Transplante de Células-Tronco Hematopoéticas/economia , Adulto , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Transplante Homólogo
4.
J Antimicrob Chemother ; 72(9): 2602-2606, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28651341

RESUMO

Objectives: Atovaquone is one of the alternatives to trimethoprim/sulfamethoxazole for prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients. In volunteers, there was wide inter-individual variability in atovaquone bioavailability. The aim of this study was to assess the plasma concentrations of atovaquone in immunocompromised patients under PCP prophylaxis. Methods: Adult haematology or HIV-positive patients receiving atovaquone (750 mg oral suspension twice a day) for PCP prophylaxis were included. Plasma concentrations were assessed using UV-HPLC, around 12 h after the evening dose (Cmin) and 1-5 h after the morning dose (Cmax). Results: A total of 82 measurements were performed in 33 patients. This included 19 HSCT recipients, 7 haematology non-transplant patients and 7 HIV-positive patients. The median Cmin (IQR) was 11.3 µg/mL (6.2-27.8) and the median Cmax was 13.4 µg/mL (6.0-28.3). The Cmin and Cmax of atovaquone were not different between HIV-negative and HIV-positive patients, or between HSCT and non-HSCT patients. Atovaquone concentrations were not influenced by the co-administration of valaciclovir (n = 20) or ciclosporin (n = 11), by gut graft-versus-host disease (n = 7) or by the intake of atovaquone with food. Nineteen of the 33 (58%) patients had Cmin <15 µg/mL, a threshold associated with a low rate of clinical response in PCP treatment. Conclusions: Atovaquone is poorly absorbed in more than half of immunocompromised patients and its bioavailability varies between individuals. These unpredictable variations raise the question of therapeutic drug monitoring, in order to identify patients with low concentrations and those who could benefit from regimen adaptation or from alternatives.


Assuntos
Antifúngicos/sangue , Atovaquona/sangue , Hospedeiro Imunocomprometido , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/prevenção & controle , Idoso , Antifúngicos/administração & dosagem , Atovaquona/administração & dosagem , Atovaquona/farmacocinética , Disponibilidade Biológica , Feminino , Infecções por HIV/complicações , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/microbiologia
5.
Front Microbiol ; 8: 700, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28484441

RESUMO

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in hematology. Although occasionally reported, the role of interhuman transmission of P. jirovecii in PCP, compared to that of reactivation, remains an unresolved question; the recommendation to isolate PCP patients in the hematology ward are not well evidence-based. Following an unexpected increase in the number of febrile pneumonia patients with P. jirovecii DNA detected in respiratory samples in our hematology ward, we explored 12 consecutive patients from November 2015 to May 2016. Genotyping of P jirovecii was performed using microsatellite markers. The frequency of simultaneous occupancy of these 12 patients in the same unit on the same day from 4 months prior to the first diagnosis was recorded. In three patients, the P. jirovecii genotype could not be determined because DNA was insufficient. One rare single genotype (Gt2) was found in four of the other nine, all allogeneic stem cell transplant recipients. The transmission map showed that these 4 patients had multiple opportunities to meet on the same day (median, 6.5; range, 4-10) at the daycare center. It was much less among the eight non-Gt2 patients (median, 1; range, 0-9; P = 0.048). This study, based on modern molecular technics, strongly suggests that interhuman transmission of P. jirovecii between allogeneic stem cell transplant recipients is possible. P. jirovecii DNA detected in respiratory specimens supports that isolation and respiratory precautions be recommended in such cases in the hematology ward.

7.
Biol Blood Marrow Transplant ; 22(2): 292-299, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26453972

RESUMO

The sensitization to HLA antigens is caused mainly by pregnancy and transfusions; however, anti-HLA antibodies also may be detected in nulliparous females and nontransfused males, and thus specifically in hematopoietic stem cell transplantation (HSCT) donors. In such cases, the impact on HSCT outcome is known only for platelet transfusion refractoriness. This study addresses the impact on graft-versus-host disease (GVHD) of anti-HLA antibodies detected in voluntary unrelated donors. Among 100 donor/recipient (D/R) pairs, 33 and 82 showed at least 1 HLA class I and class II mismatch, respectively. Because class II mismatches were more frequent, we focused our detection on anti-class II antibodies, using the Luminex assay. Among 82 HLA class II mismatched D/R pairs, 26 donors (32%) had at least 1 anti-HLA class II antibody detected in peripheral blood. Recipients of a graft from an anti-class II immunized donor had a higher cumulative incidence for a first episode of either acute or chronic GVHD (2- year cumulative incidence, 88% versus 67%; P = .03), which was confirmed in multivariate analysis (hazard ratio, 1.7; P = .04). In particular, according to the National Institutes of Health classification scheme, the cumulative incidence of chronic GVHD was higher in recipients of immunized donors (multivariate hazard ratio, 2.5; P = .02). Identifying specificities of anti-class II antibodies revealed that 13 of 26 alloimmunized donors had recipient-specific antibodies, directed mainly against mismatched HLA-DPB1 alleles. Donor-derived anti-HLA antibodies could be detected in recipients up to at least 6 months post-HSCT, supporting their association with chronic GVHD. Donor immunization against foreign HLA antigens is a new parameter to predict the occurrence of GVHD after HSCT from HLA-mismatched unrelated donors.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA-D/efeitos adversos , Imunização/métodos , Feminino , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA-D/imunologia , Humanos , Masculino , Fatores de Risco , Doadores de Tecidos
8.
Biomed Res Int ; 2015: 945769, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26075276

RESUMO

OBJECTIVES: Bacterial resistance is of growing concern in haematology wards. As the inappropriate administration of empirical antibacterial may alter survival, we studied risk factors for resistance to our usual empirical first-line antibacterial therapy, cefepime. METHODS: We retrospectively studied 103 first episodes of bacteraemia recorded in our haematology department over 2.5 years. Risk factors for cefepime-resistance were identified by multivariate logistic regression with backward selection (P < 0.05). A scoring system for predicting cefepime-resistance was built on independent factor, with an internal validation by the bootstrap resampling technique. RESULTS: 38 (37%) episodes were due to Gram-negative bacteria. Fifty (49%) were due to bacteria resistant to cefepime. Cefepime resistance was significantly associated with a decreased survival at day 30 (P < 0.05). Three risk factors were independently associated with cefepime-resistance: acute lymphoblastic leukaemia; ≥18 days since hospital admission; and receipt of any ß-lactam in the last month. Patients with ≥2 of these risk factors had a probability of 86% (CI 95%, 25 to 100%) to carry a cefepime-resistant strain. CONCLUSION: Using our scoring system should reduce the indication of very broad antibacterial regimens in the empirical, first-line treatment of febrile hematology patients in more than 80% of the cases.


Assuntos
Bacteriemia , Cefalosporinas/administração & dosagem , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Negativas , Adulto , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Cefepima , Feminino , Departamentos Hospitalares , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade
9.
Eur J Haematol ; 94(3): 265-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25130897

RESUMO

T-prolymphocytic leukemia (T-PLL), a rare aggressive mature T-cell disorder, remains frequently resistant to conventional chemotherapy. Studies have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) might possibly serve to consolidate the response to initial chemotherapy. The current report summarizes the outcome of 27 T-PLL cases identified in the registry in French Society for stem cell transplantation (SFGM-TC). Prior to HSCT, 14 patients were in complete remission (CR), 10 in partial response, three refractory, or in progression. Following HSCT, 21 patients achieved CR as best response. With a median follow-up for surviving patients of 33 (range, 6-103) months, 10 patients are still alive in continuous CR. Overall survival and progression-free survival estimates at 3 yr were 36% (95% CI: 17-54%) and 26% (95% CI: 14-45%), respectively. The relapse incidence after HSCT was 47% occurring at a median of 11.7 (range, 2-24) months. Overall cumulative incidence of transplant-related mortality was 31% at 3 yr. These results suggest that HSCT may allow long-term survival in patients with T-PLL following induction treatment; however, it is associated with a significant rate of toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Raios gama/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Prolinfocítica de Células T/terapia , Sistema de Registros , Adulto , Idoso , Feminino , Seguimentos , França , Humanos , Leucemia Prolinfocítica de Células T/mortalidade , Leucemia Prolinfocítica de Células T/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Sociedades Médicas , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
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