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1.
Transfusion ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064638

RESUMO

BACKGROUND: Plerixafor should be administered 6 to 11 hours before starting leukocytapheresis. However, we have been using plerixafor followed by leukocytapheresis according to different time schedules since 2007. Our objective was to compare the CD34+ cell collection efficiency (CE1) of the first leukocytapheresis performed after using plerixafor at different time intervals. STUDY DESIGN AND METHODS: Same-day schedule refers to the administration of plerixafor at 10:00 AM and starting the leukocytapheresis on the same day at 4:00 PM (6 hours interval). Next-day schedule refers to the administration of plerixafor at 8:00 PM and starting the leukocytapheresis on the next day (10:00 AM or 4:00 PM; either a 14- or 20-hr interval). Variables that might influence the CE1 of CD34+ cells were analyzed by longitudinal linear regression with a random effects model derived by generalized estimating equations. RESULTS: The median CE1 of CD34+ cells was higher in the group of 30 patients who underwent leukocytapheresis on the same day when compared with the group of 62 patients who underwent leukocytapheresis on the next day (65.8% vs. 56.7%; p < 0.01). In the longitudinal linear regression analysis, only the time from plerixafor administration to leukocytapheresis start was associated with a statistically significant decrease in the CE1 of CD34+ cells (CE1 change -0.034%; p < 0.01). CONCLUSION: Higher CE1 of CD34+ cells was observed when patients underwent leukocytapheresis on the same day after receiving plerixafor in comparison with administering plerixafor and underwent leukocytapheresis on the next day. Larger studies are necessary to confirm present results.

2.
Haematologica ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949011

RESUMO

Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multi-center prospective non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult systemic sclerosis patients undergoing a first autologous hematopoietic stem cell transplantation between December 2012 and February 2016 were prospectively included in the study. Primary endpoint was progression free survival. Secondary endpoints were overall survival, non-relapse mortality, response and incidence of progression. Eighty systemic sclerosis patients were included. Median follow-up duration was 24 (6-57) months after stem cell transplantation using cyclophosphamide plus antithymocyte globulins conditioning for all, with CD34+ selection in 35 patients. At 2 years, progression free survival was 81.8%, overall survival was 90%, response was 88.7% and incidence of progression was 11.9%. The 100 days non-relapse mortality was 6.25% (n=5) with four deaths from cardiac event, including three due to cyclophosphamide toxicity. Modified Rodnan skin score and forced vital capacity improved with time (p< 0.001). By multivariate analysis, baseline skin score >24 and older age at transplant were associated with lower progression free survival (Hazard ration 3.32) and 1.77, respectively). CD34+-selection was associated with better response (Hazard ration: 0.46). This study confirms the efficacy of autologous stem cell transplantation in real-life practice for severe systemic sclerosis using non myeloablative conditioning. Careful cardio-pulmonary assessment to identify organ involvement at patient referral, reduced cyclophosphamide doses and CD34+ selection may improve outcomes. The study was registered at ClinicalTrials.gov: NCT02516124.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31932656

RESUMO

In 2015, we implemented an at-home allogeneic haematopoietic cell transplant (allo-HCT) program. Between 2015 and 2018, 252 patients underwent allo-HCT; 41 patients underwent allo-HCT in the at-home program (46% myeloablative; 63% unrelated donor; 32% posttransplant cyclophosphamide), and these patients were compared with 39 in-patients; safety, capacity to release beds for other programs, and economic efficiency cost were evaluated. We observed a lower incidence of febrile neutropenia in the at-home group compared with that in the in-patient group (32% versus 90%; p < 0.0001), whereas the incidence of aspergillosis was similar among groups (at-home 1% versus in-patient 3%; p = 0.5). The at-home patients showed a lower incidence of 1-year severe graft-versus-host disease (GVHD; 10% versus 29%; p = 0.03). There were no differences in 1-year transplant-related mortality, relapse, or overall survival among groups. The re-admission rate in the at-home group was 7%. The at-home setting was less expensive (9087 €/transplant), and its implementation increased capacity by 10.5 allo-HCTs/year. Moreover, a chimeric antigen receptor T-cell program could be established without increasing beds. Thus, our at-home allo-HCT program may be a safe modality to reduce febrile neutropenia and acute GVHD, resulting in lower re-admission rates.

4.
J Neurol ; 267(2): 430-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31664549

RESUMO

We performed a prospective study to evaluate the types and characteristics of central nervous system (CNS) disorders in patients after hematopoietic stem cell transplantation. The study included 163 episodes of CNS disorders of which 58 (36%) were infections. Proven or probable infections were documented in 34 patients and included fungi (n = 10, 29%), viruses (n = 12, 35%), Toxoplasma spp. (n = 9, 27%) and bacteria (n = 3, 9%). Non-infectious neurological disorders (n = 105, 64%) frequently encompassed metabolic/drug-induced abnormalities (n = 28, 27%) or cerebral vascular events (n = 22, 21%). Median onset times were later for infectious (day + 101) vs non-infectious neurological disorders (day + 50, p = 0.009). An unremarkable cranial CT scan was found in 33% of infection episodes. Absence of cerebrospinal fluid pleocytosis despite a normal or increased peripheral blood white blood cell count occurred in 26% of infections. Day-30 mortality rates were significantly higher for fungal (87%) vs non-fungal infections (40%, p < 0.001). Significantly higher mortality rates were also documented for cerebral vascular events than for other non-infectious disorders (86% vs 34%, p < 0.001). Our prospective study shows that diagnostic findings in CNS infections might differ between hematopoietic stem cell transplant recipients and immunocompetent hosts. Special awareness and timely initiation of adequate diagnostics are crucial to improve the prognosis of these patients.

5.
Front Immunol ; 10: 2339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649666

RESUMO

Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Clinical data suggest that DF also reduces the incidence of aGVHD; however, the mechanisms of DF-mediated aGVHD regulation have not been examined. To investigate possible DF-mediated prophylactic and therapeutic mechanisms in aGVHD, we performed in vitro studies using endothelial cell (EC) lines. We found that DF significantly and dose-dependently suppressed EC proliferation and notably reduced their ability to form vascular tubes in Matrigel. To explore whether DF administered prophylactically or therapeutically has a significant effect on aGVHD endothelial dysfunction, ECs were exposed to media containing sera from patients with aGVHD (n = 22) in the absence or presence of DF and from patients that did not develop aGVHD (n = 13). ECs upregulated adhesion molecules (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), the adherence junction protein VE-cadherin, von Willebrand factor (VWF), and Akt phosphorylation in response to aGVHD sera. These responses were suppressed upon treatment with DF. In summary, DF inhibits vascular angiogenesis and endothelial activation induced by sera from aGVHD patients. Our results support the view that DF has notable positive effects on endothelial biology during aGVHD.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31570779

RESUMO

We aimed to describe epidemiology changes in bloodstream infections (BSI) episodes in hematopoietic stem cell transplant (HSCT) recipients throughout a 25-year period (1993-2017), comparing five-year time spans, and we evaluate their impact on inappropriate empirical antibiotic treatment (IEAT) and mortality. During the study period, 1164 BSI episodes were documented in patients undergoing HSCT (71.6% allogenic and 29% autologous). A significant decrease in gram-positive cocci (GPC) and increase in gram-negative bacilli (GNB) were observed (p < 0.001). Among GP, coagulase-negative staphylococci (CoNS) significantly decreased whereas rising E. faecium BSI was documented. Among GNB, E. coli, Pseudomonas aeruginosa and K. pneumoniae rates increased. Multidrug-resistant (MDR) GNB, especially ESBL-E. coli and MDR-P. aeruginosa, emerged in 2008 and has gradually increased. IEAT against MDR-P. aeruginosa, but not in other MDR-GNB, augmented throughout the study period. Overall, 30-day and related mortality rates were 12.7% and 7.7% respectively, both increasing over time (p < 0.001 and p = 0.025). In GNB, 30-day and related mortality were 18.5% and 12.8%, respectively, increasing over time (p < 0.001 and p = 0.004). To conclude, important BSI epidemiological changes were described in a 25-year period. Concerning increase in IEAT for P. aeruginosa infections and rising 30-day mortality rate were documented.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31558790

RESUMO

These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.

8.
Biol Blood Marrow Transplant ; 25(11): 2281-2286, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31325586

RESUMO

Diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease relies on the presence of GI symptoms and detection of CMV, mainly by immunohistochemistry (IHC), in GI biopsy specimens. Thus, in a symptomatic patient, a positive CMV-IHC result is accepted as a diagnosis of CMV disease. However, a positive CMV-PCR in GI tissue is considered "possible" CMV disease. Therefore, it would be very useful if, in practice, both techniques showed equal sensitivity and reliability. This is because PCR has many practical advantages over IHC for detecting CMV. The aim of this study was to compare quantitative PCR with IHC for the diagnosis of GI CMV disease. A total of 186 endoscopic GI biopsy specimens from 123 patients with GI symptoms after an allogeneic stem cell transplantation (allo-SCT; 2004-2017) were analyzed by IHC and PCR on 113 paraffin-embedded and 73 fresh samples. The results were then compared. Of the patients with macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, "proven" CMV disease, n = 28), all but 1 were CMV-PCR positive. Of the patients without macroscopic lesions in the mucosa and CMV-IHC-positive biopsy specimens (eg, probable CMV disease, n = 4), only 1 was CMV-PCR positive. Eight patients had CMV-IHC-negative/CMV-PCR-positive gut biopsy specimens. These cases fall within the current definition of possible CMV disease. In 6 of these 8 cases (75%), the viral load in GI tissue was very high (>10,000 copies/µg). Taken together, the results from the proven and probable cases revealed that CMV-PCR shows the same sensitivity (100%), specificity (98%), and positive (93%) and negative predictive value (100%) as CMV-IHC. Detection of CMV in fresh GI mucosa by quantitative PCR is as useful as IHC for the diagnosis of GI CMV disease. The results show that quantitative PCR has the same sensitivity, specificity, and positive/negative predictive value as IHC.

9.
Biol Blood Marrow Transplant ; 25(9): 1703-1712, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31054983

RESUMO

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.

10.
Transfusion ; 59(8): 2636-2642, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31135994

RESUMO

BACKGROUND: Extracorporeal photopheresis (ECP) has been increasingly used as a second-line therapy for graft-versus-host disease (GVHD) but there is no consensus regarding the best therapeutic schedule. STUDY DESIGN AND METHODS: Our offline ECP schedule for treating patients with GVHD was retrospectively reviewed. Patients with acute GVHD were treated on 2 days per week for the first 2 weeks, followed by 1 day per week for 2 more weeks. After the first month of treatment, patients received treatment 1 day every 2 weeks for a minimum of 16 ECP procedures. Patients with chronic GVHD were treated on 1 day per week for 4 weeks followed by 1 day every 2 weeks for a minimum of 14 ECP procedures. RESULTS: Our series comprises 21 (45%) patients with acute GVHD and 26 (55%) patients with chronic GVHD who received 667 ECP procedures. A median (interquartile range [IQR]) of 1.0 (1.0-1.12) total blood volume was processed. Patients with acute and chronic GVHD received ECP procedures during a median of 49 (IQR, 14-103) and 180 (IQR, 111-274) days, respectively. Mild citrate-induced symptoms were present in 98 (46%) and 232 (51%) procedures in patients with acute and chronic GVHD, respectively. Overall response rate (ORR) and overall survival (OS) were 57 and 38% (95% confidence interval [CI], 17%-59%), respectively, for patients with acute GVHD. For patients with chronic GVHD, ORR and OS were 77 and 61% (95% CI, 18%-87%), respectively. CONCLUSION: Our new offline ECP schedule for treating patients with acute and chronic GVHD was efficacious and safe.

11.
Bone Marrow Transplant ; 54(7): 933-942, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30705338

RESUMO

Over the last 20 years, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with severe autoimmune and inflammatory diseases whose response to standard treatment options has been limited, resulting in a poor long-term prognosis in terms of survival or disability. The vast majority of patients have received autologous HSCT where an increasing evidence-base supports its use in a wide range of autoimmune diseases, particularly relapsing remitting MS, systemic sclerosis and Crohn's disease. Compared with standard treatments for autoimmune diseases, HSCT is associated with greater short-term risks, including a risk of treatment-related mortality and long-term complications. There is a need for a careful appraisal of potential benefits and risks by disease and transplant specialists working closely together with patients and carers to determine individual suitability for HSCT. HSCT should be conducted in accredited transplant centres with robust arrangements for long-term follow-up with both disease and transplant specialists. The aim of this open-access position statement is to provide plainly worded guidance for patients and non-specialist clinicians considering HSCT for an autoimmune disease, especially when treatment abroad is being considered. Recent technical publications in the field have been referenced to support the statement and provide more detail for clinicians advising patients.

13.
Bone Marrow Transplant ; 54(8): 1295-1303, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30664727

RESUMO

Autologous stem cell transplant (ASCT) has demonstrated to be an effective treatment for patients with light-chain (AL) amyloidosis. However, a high transplant-related mortality (TRM) rate was reported in previous series of patients and questioned the role of transplant in this disease. Recently, experienced groups have shown a significant TRM decrease that has been attributed to an accurate selection of patients. Moreover, application of several supportive measures has decreased toxicity over amyloid-involved organs. We analyzed a series of 66 patients with AL amyloidosis, who underwent ASCT at a single institution and evaluated the impact of these measures beyond patient selection. Four temporary groups were established: group-A (non-selection plus post-transplant G-CSF use) with 29 patients, group-B (selection) with 13, group-C (selection and G-CSF avoidance) with 14, and group-D (selection, G-CSF avoidance and corticosteroid's prophylaxis) with 10. A decreasing TRM was observed over time from group-A (38%), to group-D (0%); p = 0.02. We also observed a progressive increase of three-year OS from 62% in group-A to 100% in group-D; p = 0.049. On the multivariate analysis, cardiac involvement was the only independent predictor of survival. Therefore, tailored selection policy together with transplant supportive measures have allowed ASCT to be a safe procedure in AL amyloidosis.

14.
Eur J Cancer ; 106: 212-219, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30528805

RESUMO

BACKGROUND: Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). METHODS: In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen-matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included. ATG was used in 429/575 (75%) and 121/595 (20%) patients transplanted from unrelated or sibling donors, respectively. RESULTS: The incidence of chronic GVHD was 35% for patients treated with ATG compared with 52% in those not receiving ATG (p < 0.001), while the rate of extensive chronic GVHD was 16% and 36%, respectively (p < 0.001). The probability of survival free from GVHD and relapse (GRFS) was 42% and 32%, respectively (p = 0.002). In a multivariate model, the use of ATG was associated with reduced risk of overall chronic GVHD (hazard ratio [HR] = 0.52, p < 0.001) and extensive chronic GVHD (HR = 0.46, p < 0.001). It was also associated with better GRFS (HR = 0.77, p = 0.007), despite increased risk of relapse (HR = 1.41, p = 0.02). No significant effect was found with regard to the risk of non-relapse mortality and overall mortality. CONCLUSIONS: The use of ATG for patients with Ph+ ALL undergoing alloPBSCT is associated with reduced risk of chronic GVHD without impact on survival and therefore, could be considered. However, increased risk of relapse suggests the need for strict monitoring of minimal residual diseases and appropriate interventions after transplantation.

15.
Enferm Infecc Microbiol Clin ; 37(8): 535-541, 2019 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29960829

RESUMO

Aspergillus infection is a significant cause of morbi-mortality in an at-risk population. The Study Group of Fungal Infections (GEMICOMED) from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has reviewed announcements made in invasive aspergillosis management. We have organized our recommendations in such a way as to provide a guide in resolving different clinical situations concerning the entire spectrum of invasive diseases caused by Aspergillus in various populations. Diagnostic approach, treatment and preventions strategies are outlined. It is not our aim that these guidelines supplant clinical judgment with respect to specific patients; however, it is our objective to perform a comprehensive summary of quality of care evidence for invasive aspergillosis management in different settings.

16.
J Crohns Colitis ; 13(5): 634-647, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30521002

RESUMO

BACKGROUND AND AIMS: Recent studies have shown the efficacy of autologous haematopoietic stem cell transplantation [HSCT] in severely refractory Crohn's disease [CD] patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. METHODS: We followed a group of CD patients [n = 18] receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanisms driving efficacy, we monitored changes after HSCT in blood and intestine immune-cell composition. CD patients [n = 22] receiving anti-tumour necrosis factor [TNF]-α were included for comparison. RESULTS: Severe immune ablation followed by HSCT induced dramatic changes in both peripheral blood T and B cells in all patients regardless of the efficacy of the treatment. Endoscopic remission at week 52 following HSCT was associated with significant intestinal transcriptional changes. A comparison of the remission signature with that of anti-TNFα identified both common and unique genes in the HSCT-induced response. Based on deconvolution analysis of intestinal biopsy transcriptome data, we show that response to HSCT, but not to anti-TNFα, is associated with an expansion of naïve B-cells, as seen in blood, and a decrease in the memory resting T-cell content. As expected, endoscopic remission, in response to both HSCT and anti-TNFα, led to a significant reduction in intestinal neutrophil and M1 macrophage content. CONCLUSIONS: Peripheral blood immune remodelling after HSCT does not predict efficacy. In contrast, a profound intestinal T-cell depletion that is maintained long after transplant is associated with mucosal healing following HSCT, but not anti-TNFα.


Assuntos
Doença de Crohn/terapia , Transplante de Células-Tronco Hematopoéticas , Contagem de Linfócitos , Adulto , Linfócitos B , Doença de Crohn/imunologia , Feminino , Humanos , Macrófagos , Masculino , Neutrófilos , Linfócitos T , Resultado do Tratamento
17.
Rev Iberoam Micol ; 35(3): 162-166, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30274955

RESUMO

BACKGROUND: The most common presentation of mucormycosis in the past was the nasosinusal involvement in patients with diabetic ketoacidosis. However, in the last few years, new groups of patients with risk of mucormycosis have emerged. AIMS AND METHODS: Retrospective analysis of the characteristics, treatment and evolution of patients with mucormycosis in a tertiary hospital in the years 2012-2016. RESULTS: Of the 12 patients included in the study, 7 had a haematological disease as a predisposing factor, most of them (6 patients) related to transplantation of haematopoietic progenitors. Only one patient had diabetic ketoacidosis. Seven out of the twelve patients were receiving an antifungal treatment at the onset of symptoms, and 9 patients had received them three months before. The clinical presentation was rhinosinusal (16.6%), localised lung disease (33.3%), and musculoskeletal (25%) and disseminated disease (25%). Surgical debridement was performed on 8 patients. Combination therapy with amphotericin B and posaconazole was received by 6 patients (16% mortality), and 4 patients were treated with amphotericin B alone (50% mortality), with an overall mortality of 41%. The mortality of patients with pulmonary involvement was 71%, increasing to 100% in the case of disseminated disease. None of the patients with only musculoskeletal involvement died. CONCLUSIONS: Mucormycosis has a high mortality rate, especially the pulmonary forms. Musculoskeletal involvement had a better prognosis. The main group at risk was that of patients with haematopoietic stem cell transplantation. Combination therapy had better results than monotherapy, although more experience is needed to define the most appropriate treatment.


Assuntos
Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
18.
Rev. iberoam. micol ; 35(3): 162-166, jul.-sept. 2018. ilus
Artigo em Espanhol | IBECS | ID: ibc-179579

RESUMO

Antecedentes: La descripción antiguamente más frecuente de la mucormicosis era la afectación nasosinusal en pacientes con cetoacidosis diabética. Sin embargo, en los últimos años han surgido nuevos grupos de pacientes con riesgo de mucormicosis. Objetivos y métodos: Se realizó un análisis retrospectivo de las características, tratamiento y evolución de los pacientes con mucormicosis en nuestro hospital (años 2012-2016). Resultados: De los 12 pacientes del estudio, siete padecían alguna enfermedad hematológica como factor predisponente, la mayoría (6 pacientes) por trasplante de progenitores hematopoyéticos. Solamente un paciente estaba en cetoacidosis diabética. Siete pacientes del total estaban recibiendo antifúngicos al inicio de los síntomas, y 9 pacientes los habían recibido los tres meses previos. La afectación fue rinosinusal (16,6%), pulmonar localizada (33,3%), musculoesquelética (25%) y diseminada (25%). En 8 pacientes se realizó desbridamiento quirúrgico. Seis pacientes recibieron tratamiento combinado con anfotericina B y posaconazol (mortalidad de grupo 16%), y 4 pacientes fueron tratados con anfotericina B en monoterapia (mortalidad 50%), con una mortalidad global del 41%. La mortalidad de los pacientes con afectación pulmonar fue del 71%, y en el caso de enfermedad diseminada del 100%. Ningún paciente con afectación únicamente musculoesquelética falleció. Conclusiones: La mucormicosis sigue teniendo una elevada mortalidad, especialmente las formas pulmonares. Las formas musculoesqueléticas tuvieron mejor pronóstico. El grupo de riesgo principal fue el de los pacientes con trasplante de médula ósea. El tratamiento combinado obtuvo mejores resultados que la monoterapia, aunque se necesita más experiencia para definir el tratamiento más adecuado


Background: The most common presentation of mucormycosis in the past was the nasosinusal involvement in patients with diabetic ketoacidosis. However, in the last few years, new groups of patients with risk of mucormycosis have emerged. Aims and methods: Retrospective analysis of the characteristics, treatment and evolution of patients with mucormycosis in a tertiary hospital in the years 2012-2016. Results: Of the 12 patients included in the study, 7 had a haematological disease as a predisposing factor, most of them (6 patients) related to transplantation of haematopoietic progenitors. Only one patient had diabetic ketoacidosis. Seven out of the twelve patients were receiving an antifungal treatment at the onset of symptoms, and 9 patients had received them three months before. The clinical presentation was rhinosinusal (16.6%), localised lung disease (33.3%), and musculoskeletal (25%) and disseminated disease (25%). Surgical debridement was performed on 8 patients. Combination therapy with amphotericin B and posaconazole was received by 6 patients (16% mortality), and 4 patients were treated with amphotericin B alone (50% mortality), with an overall mortality of 41%. The mortality of patients with pulmonary involvement was 71%, increasing to 100% in the case of disseminated disease. None of the patients with only musculoskeletal involvement died. Conclusions: Mucormycosis has a high mortality rate, especially the pulmonary forms. Musculoskeletal involvement had a better prognosis. The main group at risk was that of patients with haematopoietic stem cell transplantation. Combination therapy had better results than monotherapy, although more experience is needed to define the most appropriate treatment


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Mucormicose/epidemiologia , Mucorales/isolamento & purificação , Doenças Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucorales/patogenicidade , Atenção Terciária à Saúde/estatística & dados numéricos , Fatores de Risco , Estudos Retrospectivos , Antifúngicos/uso terapêutico
19.
Biol Blood Marrow Transplant ; 24(10): 2088-2093, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29753162

RESUMO

This study examined the impact of prednisone (PDN) on cytomegalovirus (CMV) infection after allogeneic stem cell transplantation (allo-SCT) according to donor and recipient CMV serostatus. Seventy-five patients underwent allo-SCT from June 2010 to July 2012. The risk of CMV infection according to donor and recipient serostatus was defined as follows: high risk (HR; D-/R+), intermediate risk (IR; D+/R+ and D+/R-), and low risk (D-/R-). Forty-five patients (60%) developed CMV infection, and 46 patients (61%) received steroids (PDN ≥ 1 mg/kg/day) to treat acute graft-versus-host disease. CMV infection was more common in those treated with steroids than in those not treated with steroids (70% versus 44%, respectively, P < .05). Overall, 40% of patients had recurrent CMV infection (50% PDN versus 24% no PDN, P < .05). Steroids had no impact on the incidence of CMV infection or its recurrence in HR patients; however, steroids did prolong the need for antiviral treatment. The incidence of CMV infection in IR patients was higher in those receiving PDN (80% PDN versus 41% no PDN, P = .01); recurrence rates were also higher (55% PDN versus 18% no PDN, P = .02). We analyzed CMV-specific immune reconstitution in the first 22 patients of the series and observed that patients on steroids had lower levels of CMV-specific lymphocytes TCD8 (P < .05 on days +60, +100, and +180) and that CMV-specific immune reconstitution (defined as lymphocytes CD8/IFN ≥ 1 cell/µL) was achieved later (after day +100 post-SCT) in the steroid group.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus , Citomegalovirus , Doença Enxerto-Hospedeiro , Esteroides/efeitos adversos , Doadores de Tecidos , Adolescente , Adulto , Idoso , Aloenxertos , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/induzido quimicamente , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Esteroides/administração & dosagem
20.
J Crohns Colitis ; 12(9): 1097-1103, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-29788233

RESUMO

BACKGROUND AND AIMS: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with severe, treatment-refractory Crohn's disease [CD]. The evidence base for AHSCT for CD is limited, with one randomised trial [ASTIC] suggesting benefit. The aim of this study was to evaluate safety and efficacy for patients undergoing AHSCT for CD in Europe, outside the ASTIC trial. METHODS: We identified 99 patients in the European Society for Blood and Marrow Transplantation [EBMT] registry, who were eligible for inclusion. Transplant and clinical outcomes were obtained for 82 patients from 19 centres in seven countries. RESULTS: Median patient age was 30 years [range 20-65]. Patients had failed or been intolerant to a median of six lines of drug therapy; 61/82 [74%] had had surgery. Following AHSCT, 53/78 [68%] experienced complete remission or significant improvement in symptoms at a median follow-up of 41 months [range 6-174]; 22/82 [27%] required no medical therapy at any point post-AHSCT. In patients who had re-started medical therapy at latest follow-up, 57% [24/42] achieved remission or significant symptomatic improvement with therapies to which they had previously lost response or been non-responsive. Treatment-free survival at 1 year was 54%. On multivariate analysis, perianal disease was associated with adverse treatment-free survival (hazard ratio 2.34, 95% confidence interval [CI] 1.14-4.83, p = 0.02). One patient died due to infectious complications [cytomegalovirus disease] at Day +56. CONCLUSIONS: In this multicentre retrospective analysis of European centres, AHSCT was relatively safe and appeared to be effective in controlling otherwise treatment-resistant Crohn's disease. Further prospective randomised controlled trials against standard of care are warranted.

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