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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.
Haematologica ; 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30076173

RESUMO

The randomized, phase 3 ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin added to standard front-line chemotherapy significantly improves event-free survival in adults with de novo acute myeloid leukemia. Here we report an independent review of event-free survival, final overall survival, and additional safety results from ALFA-0701. Patients (N=271) aged 50-70 years with de novo acute myeloid leukemia were randomized to receive conventional front-line induction chemotherapy (3+7 daunorubicin+cytarabine) with/without gemtuzumab ozogamicin 3 mg/m2 on days 1, 4, and 7 during induction. Patients in remission following induction therapy received 2 courses of consolidation therapy (daunorubicin+cytarabine) with/without gemtuzumab ozogamicin (3 mg/2;/day on day 1) according to their initial randomization. The primary endpoint was investigator-assessed event-free survival. Secondary endpoints included overall survival and safety. A blinded independent review confirmed the investigator-assessed event-free survival results (August 1, 2011; hazard ratio, 0.66 [95% CI, 0.49-0.89]; 2-sided p=0.006), corresponding to a 34% reduction in risk of events in the gemtuzumab ozogamicin versus control arm. Final overall survival (April 30, 2013) favored gemtuzumab ozogamicin but was not significant. No differences were observed between arms in early death rate. The main toxicity associated with gemtuzumab ozogamicin was prolonged thrombocytopenia. Veno-occlusive disease (including after transplant) was observed in 6 patients in the gemtuzumab ozogamicin arm and 2 in the control arm. In conclusion, gemtuzumab ozogamicin added to standard intensive chemotherapy has a favorable benefit/risk ratio. These results expand front-line treatment options for adult patients with previously untreated acute myeloid leukemia. (ClinicalTrials.gov identifier: NCT00927498).

4.
Eur J Clin Microbiol Infect Dis ; 37(10): 1931-1940, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30051357

RESUMO

Febrile neutropenia (FN) is the main reason for antibiotic prescription in hematology wards where, on the other hand, antibiotic stewardship (AS) is poorly explored. The objectives of the present study were to evaluate (1) the impact of an AS intervention on antibiotic consumption and (2) the applicability and acceptance rate of the intervention and its clinical impact. A persuasive AS intervention based on European Conference on Infection in Leukaemia (ECIL) guidelines for FN was implemented in a high-risk hematology ward in a tertiary referral public university hospital. This included the creation and diffusion of flow charts on de-escalation and discontinuation of antibiotics for FN, and the introduction in the team of a doctor dedicated to the implementation of flow charts and to antibiotic prescription revision. All consecutive patients receiving antibiotics during hospitalization were included. A segmented linear regression model was performed for the evaluation of antibiotic consumption, taking into account 1-year pre-intervention period and 6-month intervention period. Overall, 137 consecutive antibiotic prescriptions were re-evaluated, 100 prescriptions were for FN. A significant reduction of the level of carbapenem consumption was observed during the intervention period (level change (estimate coefficient ± standard error) = - 135.28 ± 59.49; p = 0.04). Applicability and acceptability of flow charts were high. No differences in terms of intensive care unit transfers, bacteremia incidence, and mortality were found. A persuasive AS intervention in hematology significantly reduced carbapenem consumption without affecting outcome and was well accepted. This should encourage further applications of ECIL guidelines for FN.

5.
Hum Pathol ; 71: 100-108, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29107664

RESUMO

Eruption of lymphocyte recovery (ELR) may occur during bone marrow aplasia after chemotherapies. We reviewed the clinical and pathologic features of 12 patients (male-female ratio, 7:5; median age, 61 years) with an atypical ELR histologically mimicking a primary cutaneous T-cell lymphoma such as Sézary syndrome or CD30+ T-cell lymphoproliferative disorder. All the patients displayed an erythematous maculopapular eruption on the trunk and the limbs associated with fever. All but one had received a polychemotherapy for an acute myeloid leukemia (n=10) or a urothelial carcinoma (n=1) before the occurrence of the skin eruption. One had an autoimmune lymphoproliferative syndrome causing chronic agranulocytosis requiring granulocyte colony-stimulating factor injection. In all patients, the skin eruption was associated with a slight increase of white blood cell count followed by bone marrow recovery within the next weeks. All skin biopsies showed a dermal perivascular lymphocytic infiltrate containing atypical medium- to large-sized CD3+, CD4+ and CD8+, CD25+, ICOS+, PD1- lymphocytes with a strong CD30 expression in most instances (n=10), suggesting the recruitment of strongly activated T cells in the skin. In 6 patients, a diagnosis of CD30+ lymphoproliferative disorder or Sézary syndrome was proposed or suspected histopathologically, and only the clinical context allowed the diagnosis of ELR with a peculiar presentation with atypical lymphocytes. We describe a series of patients with an unusual form of ELR characterized by the presence of atypical activated T cells in the skin. On a practical ground, pathologists should be aware of this distinctive and misleading presentation.

6.
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
7.
Bull Cancer ; 104(12S): S84-S98, 2017 Dec.
Artigo em Francês | MEDLINE | ID: mdl-29179894

RESUMO

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory disease or with persistent molecular or radiological (PET-CT scan) residual disease. Within the frame of the 7th annual workshops of the francophone society for bone marrow transplantation and cellular therapy, the working group reviewed the literature in order to elaborate unified guidelines for the prevention and treatment of relapse after allo-HCT. For high risk AML and MDS, a post transplant maintenance strategy is possible, using hypomethylating agents or TKI anti-FLT3 when the target is present. For Philadelphia positive ALL, there was a consensus for the use of post-transplant TKI maintenance. For lymphomas, there are no strong data on the use of post-transplant maintenance, and hence a preemptive strategy is recommended based on modulation of immunosuppression, close follow-up of donor chimerism, and donor lymphocytes infusion. For multiple myeloma, even though the indication of allo-HCT is controversial, our recommendation is post transplant maintenance using bortezomib, due to its a good toxicity profile without increasing the risk of GVHD.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Prevenção Secundária/normas , Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Neoplasias do Sistema Nervoso Central/secundário , Marcadores Genéticos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/prevenção & controle , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/prevenção & controle , Linfoma/tratamento farmacológico , Quimioterapia de Manutenção/normas , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Recidiva , Retratamento/métodos , Retratamento/normas , Prevenção Secundária/métodos
8.
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.

9.
Medicine (Baltimore) ; 95(15): e3033, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27082547

RESUMO

Histiocytoid Sweet syndrome (H-SS) is a histological variant of Sweet syndrome (SS) differing from classical neutrophilic SS (N-SS) by a dermal infiltrate mainly composed of lymphocytes and histiocytoid myeloperoxidase-positive cells. We aimed to report a large series of H-SS and compare the frequency and type of hematological malignancies associated to H-SS and N-SS. We included 62 patients with a coding histopathologic diagnosis of SS prospectively registered between 2005 and 2014 in the database of our Department of Pathology. Overall, 22 (35.5%) and 40 (64.5%) patients had a histological diagnosis of H-SS and N-SS, respectively. Median age, sex ratio, and cutaneous lesions were similar in the 2 groups. The frequency of extra-cutaneous manifestations was similar (50% vs 37.5%, P = 0.42). Recurrent forms were significantly more frequent in H-SS than in N-SS patients (21% vs 2.5%, P = 0.01). A hematological malignancy was diagnosed in 22 patients, 12 (55.5%) with H-SS and 10 (25%) with N-SS (P = 0.019). Hematological malignancy was of myeloid origin in 8/22 (36.3%) H-SS and 5/40 (12.5%) N-SS patients (P = 0.02), and of lymphoid origin without myeloid component in 4/22 (18.1%) H-SS and 4/40 (10%) N-SS patients (P = 0.35), respectively. One N-SS patient had a hematological malignancy of mixed (myeloid and lymphoid) phenotype. A myelodysplastic syndrome (MDS) was diagnosed in 7/22 (31.8%) H-SS and 1/40 (2.5%) N-SS patients (P < 0.001). Hematological disease was diagnosed before (in 8 H-SS and 3 N-SS patients) or at the time of the occurrence of the cutaneous lesions (in 1 H-SS and 7 N-SS patients). However, in 3 H-SS patients, all with MDS, cutaneous lesions preceded the hematological disease by ≤6 months. In conclusion, H-SS was associated with MDS in one third of patients but also with lymphoid malignancies, and cutaneous lesions could precede the hematological diagnosis in patients with MDS. A complete hematological assessment is mandatory at diagnosis, and monitoring blood cell counts should be recommended for at least 6 months after the diagnosis of H-SS.


Assuntos
Histiócitos/patologia , Síndromes Mielodisplásicas/epidemiologia , Neutrófilos/patologia , Síndrome de Sweet/epidemiologia , Síndrome de Sweet/fisiopatologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Feminino , Neoplasias Hematológicas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores Sexuais , Síndrome de Sweet/classificação , Adulto Jovem
12.
Haematologica ; 101(3): 328-35, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26635039

RESUMO

In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558).


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Proteínas do Citoesqueleto/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Células Sanguíneas/metabolismo , Células Sanguíneas/patologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 8 , Quimioterapia de Consolidação/métodos , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Proteínas do Citoesqueleto/metabolismo , Feminino , França , Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Neoplasia Residual , Estudos Prospectivos , Proteínas Proto-Oncogênicas/metabolismo , Proteína 1 Parceira de Translocação de RUNX1 , Reação em Cadeia da Polimerase em Tempo Real , Recidiva , Indução de Remissão , Análise de Sobrevida , Fatores de Transcrição/metabolismo , Translocação Genética
13.
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
14.
Blood ; 126(14): 1643-50, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26261239

RESUMO

Severe chronic primary neutropenia (CPN) is a rare entity, and long-term outcome and risk factors for infections in severe CPN adults have not been described to date. We report the characteristics and outcomes of 108 severe adult CPN patients enrolled in a multi-institutional observational study. Severe CPN adults were mostly female (78%), and median age at diagnosis was 28.3 years. Diagnosis was fortuitous in 62% of cases. The median absolute neutrophil count (ANC) at diagnosis was 0.4 × 10(9)/L, and median ANC without granulocyte colony-stimulating factor (G-CSF) during follow-up was 0.5 × 10(9)/L. Twenty-three of 66 (34.8%) evaluable patients had neutrophil autoantibodies, and 6 of 47 (12.8%) a T-cell clone. The presence of neutrophil autoantibodies or T-cell clone was not associated with any specific clinical or biological characteristics. No death or hematologic malignancies occurred, and 44 severe bacterial infections were reported in 27 patients with a median follow-up of 8.3 years. Fifty patients received G-CSF either sporadically (n = 24) or continuously (n = 26) and responded (96%). Nineteen patients received immunosuppressive therapies: overall response (OR) was 41%, and median duration of response was 3 months. At diagnosis, the only predictive factor for the occurrence of severe bacterial infections was an ANC count below 0.2 × 10(9)/L (OR, 0.76). Severe CPN in adults is characterized by a female predominance and a benign outcome with a low rate of severe bacterial infections and no secondary malignancies. G-CSF is efficient and well tolerated but is not required in a majority of patients.


Assuntos
Neutropenia/sangue , Neutropenia/patologia , Adulto , Autoanticorpos/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Neutropenia/tratamento farmacológico
15.
J Immunol ; 195(6): 2580-90, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26246143

RESUMO

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies that may be sensitive to the NK cell antitumor response. However, NK cells are frequently defective in AML. In this study, we found in an exploratory cohort (n = 46) that NK cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK cell profile, including reduced expression of some activating NK receptors (e.g., DNAX accessory molecule-1, NKp46, and NKG2D) and decreased IFN-γ production, had a significantly higher risk of relapse (p = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g., IL15, IFNGR1, IFNGR2, and CXCR4), Ag processing (e.g., HLA-DRA, HLA-DRB1, and CD74) and adhesion molecule pathways (e.g., PVR and ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.


Assuntos
Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/imunologia , Receptores de Células Matadoras Naturais/metabolismo , Evasão Tumoral/imunologia , Adulto , Idoso , Antígenos CD/imunologia , Moléculas de Adesão Celular/imunologia , Feminino , Cadeias alfa de HLA-DR/imunologia , Cadeias HLA-DRB1/imunologia , Humanos , Interferon gama/biossíntese , Interleucina-15/biossíntese , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Receptores CXCR4/biossíntese , Receptores de Interferon/biossíntese , Sialiltransferases/imunologia , Evasão Tumoral/genética , Adulto Jovem
16.
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
17.
Br J Haematol ; 170(2): 192-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25920561

RESUMO

The virological diagnosis of Parvovirus B19 (PvB19) infection is currently based on sero-diagnosis, molecular methods or both, yet without clear recommendations. We retrospectively identified patients with polymerase chain reaction-positive PvB19 and/or positive serological assay between 2007 and 2013. Eighty-two adults with at least one diagnostic criterion of recent PvB19 infection (IgM antibodies, viral DNA in blood and/or in marrow) were included and classified into three homogeneous groups: 30 patients had no underlying predisposing condition, 25 a hereditary haemolytic anaemia, 27 an underlying immunodeficiency. The classical PvB19-related manifestations were less frequent in immunocompromised than in immunocompetent patients (arthromyalgia: 5 vs. 14; erythema: 4 vs. 17, respectively). Only 41·4% of patients with no underlying disease were anaemic. Bicytopenia and pancytopenia were observed mainly in immunocompromised patients. Classical pure red cell aplasia was observed in only 9 of the 27 marrow smears performed. Specific IgM were found in 93% of immunocompetent patients, whereas only 58% had detectable viral DNA in blood. IgM and DNA were present alone or together in all patients with hereditary haemolytic anaemia. In immunocompromised patients, the diagnosis was confirmed by marrow analysis in 91% of cases. We make some proposals based on this large series of PvB19-infected patients.


Assuntos
Eritema Infeccioso/diagnóstico , Eritema Infeccioso/virologia , Parvovirus B19 Humano/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Congênita/complicações , Biópsia , Medula Óssea/patologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Eritema Infeccioso/complicações , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
18.
Haematologica ; 100(6): 780-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25715404

RESUMO

Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18-60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12).


Assuntos
Antineoplásicos/uso terapêutico , Fatores de Ligação ao Core , Dasatinibe/uso terapêutico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Estudos de Coortes , Feminino , Seguimentos , França/epidemiologia , Humanos , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Fatores de Risco , Adulto Jovem
20.
Blood ; 124(8): 1312-9, 2014 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-25006122

RESUMO

Although core-binding factor-acute myeloid leukemia (CBF-AML) (t[8;21] or inv[16]/t[16;16]) represents a favorable cytogenetic AML subgroup, 30% to 40% of these patients relapse after standard intensive chemotherapy. The encouraging results of gemtuzumab ozogamicin (GO) in newly diagnosed AML, and particularly in CBF-AML, incited us to retrospectively investigate the impact of GO-based salvage in these patients. We retrospectively analyzed the outcome of 145 patients with CBF-AML (59 t[8;21], 86 inv[16]/t[16;16]) in first relapse. As salvage, 48 patients received GO-based chemotherapy and 97 patients received conventional chemotherapy. Median age was 43 years (range, 16-76). Median first complete remission duration was 12.1 months (range, 2.1-93.6). Overall, second complete remission (CR2) rate was 88%. With a median follow-up from relapse of 3.5 years, the estimated 5-year disease-free survival (DFS) was 50% and 5-year overall survival (OS) was 51%. Older age and shorter first complete remission duration was associated with a shorter OS. Patients treated with GO had similar CR2 rate but significantly higher 5-year DFS (68% vs 42%; P = .05) and OS (65% vs 44%; P = .02). In multivariate analysis, GO salvage was still associated with a significant benefit in DFS and OS. In the 78 patients who received allogeneic hematopoietic stem cell transplantation in CR2, GO before transplant significantly improved posttransplant DFS and OS without excess of treatment-related mortality.


Assuntos
Inversão Cromossômica , Cromossomos Humanos/genética , Fatores de Ligação ao Core , Fatores de Crescimento de Células Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , França , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida
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