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1.
Support Care Cancer ; 32(1): 63, 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38150035

RESUMO

PURPOSE: Support groups might help survivors of allogeneic hematopoietic cell transplantations (HCT) to cope with medical, psychological, and social challenges. The aim of this project was (1) to establish a facilitated post-HCT support group and (2) to assess the participation behaviour. METHODS: From 11/2013 until 7/2017, all adult patients who had received a HCT at our centre were invited to participate in a professionally facilitated support group. The format of the group was unstructured without any rules regarding regular attendance. The attendance was prospectively minuted by the facilitator. Reasons for non-attendance were assessed by a survey. RESULTS: During the observation period, 53 group meetings were scheduled. Nine meetings were cancelled because of low attendance. Altogether 23 different patients (F: n=10; M: n=13) and 10 spouses (F: n=9; M: n=1) participated. Median participation was 5 [range 2-11]. With respect to all HCT patients who had the theoretical opportunity to attend, the mean participation rate was 7%. Thirteen patients and four spouses attended more than one meeting. The median count of participations among those participants was 8 [2-32]. The median interval from the first until the last participation was 16 months. The main reason reported for non-participation was the effort to get to the venue of the support group. CONCLUSIONS: To our knowledge, this is the first analysis on the attendance behaviour of the participants of a support group for HCT survivors. The results provide guidance for the organization of future support groups and indicate what participation rates can be expected and how they might be increased.


Assuntos
Serviços de Saúde , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Conhecimento , Pacientes , Grupos de Autoajuda , Masculino , Feminino
2.
Leukemia ; 37(9): 1860-1867, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37454239

RESUMO

In a registry-based analysis of 135 patients with "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions" (MLN-TK; FIP1L1::PDGFRA, n = 78; PDGFRB, diverse fusions, n = 26; FGFR1, diverse, n = 9; JAK2, diverse, n = 11; ETV6::ABL1, n = 11), we sought to evaluate the disease-defining characteristics. In 81/135 (60%) evaluable patients, hypereosinophilia (>1.5 × 109/l) was observed in 40/44 (91%) FIP1L1::PDGFRA and 7/7 (100%) ETV6::ABL1 positive patients but only in 13/30 (43%) patients with PDGFRB, FGFR1, and JAK2 fusion genes while 9/30 (30%) patients had no eosinophilia. Monocytosis >1 × 109/l was identified in 27/81 (33%) patients, most frequently in association with hypereosinophilia (23/27, 85%). Overall, a blast phase (BP) was diagnosed in 38/135 (28%) patients (myeloid, 61%; lymphoid, 39%), which was at extramedullary sites in 18 (47%) patients. The comparison between patients with PDGFRA/PDGFRB vs. FGFR1, JAK2, and ETV6::ABL1 fusion genes revealed a similar occurrence of primary BP (17/104, 16% vs. 8/31 26%, p = 0.32), a lower frequency (5/87, 6% vs. 8/23, 35%, p = 0.003) of and a later progression (median 87 vs. 19 months, p = 0.053) into secondary BP, and a better overall survival from diagnosis of BP (17.1 vs. 1.7 years, p < 0.0008). We conclude that hypereosinophilia with or without monocytosis and various phenotypes of BP occur at variable frequencies in MLN-TK.


Assuntos
Eosinofilia , Linfoma , Transtornos Mieloproliferativos , Humanos , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Proteínas de Fusão Oncogênica/genética , Transtornos Mieloproliferativos/complicações , Eosinofilia/genética , Eosinofilia/complicações , Fusão Gênica
3.
Ann Hematol ; 102(8): 2077-2085, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37012462

RESUMO

We sought to evaluate the efficacy of the purine analogue cladribine in 79 patients with advanced systemic mastocytosis (AdvSM) using data from the 'German Registry on Disorders of Eosinophils and Mast Cells (GREM)'. The overall response rate according to modified Valent criteria (46 evaluable patients) for first- (1L) and second-line (2L) cladribine treatment was 41% (12/29) and 35% (6/17, P = 0.690), respectively, and the median overall survival (OS, all patients evaluable) was 1.9 years (n = 48) and 1.2 years (n = 31; P = 0.311). Univariate and multivariable analyses of baseline and on-treatment parameters identified diagnosis of mast cell leukemia (hazard ratio [HR] 3.5, 95% confidence interval [CI, 1.3-9.1], P = 0.012), eosinophilia ≥ 1.5 × 109/L (HR 2.9 [CI 1.4-6.2], P = 0.006) and < 3 cycles of cladribine (HR 0.4 [CI 0.2-0.8], P = 0.008) as independent adverse prognostic parameters for OS. There was no impact of other laboratory (anemia, thrombocytopenia, serum tryptase) or genetic markers (mutations in SRSF2, ASXL1 or RUNX1) on OS. In consequence, none of the recently established prognostic scoring systems (MARS, IPSM, MAPS or GPSM) was predictive for OS. Modified Valent criteria were superior to a single factor-based response assessment (HR 2.9 [CI 1.3-6.6], P = 0.026). In conclusion, cladribine is effective in 1L and 2L treatment of AdvSM. Mast cell leukemia, eosinophilia, application of < 3 cycles and a lack of response are adverse prognostic markers.


Assuntos
Leucemia de Mastócitos , Mastocitose Sistêmica , Humanos , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/genética , Cladribina/uso terapêutico , Leucemia de Mastócitos/tratamento farmacológico , Leucemia de Mastócitos/genética , Prognóstico , Sistema de Registros
5.
Sci Rep ; 12(1): 14228, 2022 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987779

RESUMO

Systemic mastocytosis (SM) is characterized by multifocal accumulation of neoplastic mast cells (MCs), predominately affecting the bone marrow (BM). Imaging with computed tomography (CT) is used for assessment of bone mineral density and structure. However, the value of functional imaging with dual-energy CT (DECT) and the assessment of virtual-non-calcium attenuation values (VNCa-AV) for visualization of BM disease burden in SM has not yet been assessed. DECT of the axial skeleton was performed in 18 patients with SM (indolent SM [ISM], n = 6; smoldering SM [SSM]/advanced SM [AdvSM], n = 12) and 18 control subjects. VNCa-AV were obtained in 5 representative vertebraes per patient and correlated with laboratory, morphologic and molecular parameters. VNCa-AV strongly correlated with quantitative BM MC infiltration (r = 0.7, R2 = 0.49, P = 0.001) and serum tryptase levels (r = 0.7, R2 = 0.54, P < 0.001). Mean VNCa-AV were significantly higher in SSM/AdvSM as compared to ISM (- 9HU vs. - 54HU, P < 0.005) and controls (- 38HU, P < 0.005). Nine of 10 (90%) patients with a VNCa-AV > - 30HU and 7/7 (100%) patients with a VNCa-AV > - 10HU had SSM or AdVSM. BM VNCa-AV provide information about the MC burden of SM patients and correlate with SM subtypes. DECT may therefore serve as a supplementary tool for SM diagnosis, subclassification and monitoring in a one-stop-shop session.


Assuntos
Doenças da Medula Óssea , Mastocitose Sistêmica , Medula Óssea/diagnóstico por imagem , Humanos , Mastócitos , Mastocitose Sistêmica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
6.
Ann Hematol ; 101(8): 1825-1834, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35597847

RESUMO

COVID-19 in patients with hematological diseases is associated with a high mortality. Moreover, preventive vaccination demonstrated reduced efficacy and the knowledge on influencing factors is limited. In this single-center study, antibody levels of the SARS-CoV-2 spike protein were measured ≥ 2 weeks after 2nd COVID-19 vaccination with a concentration ≥ 0.8 U/mL considered positive. Between July and October 2021, in a total of 373 patients (median age 64 years, 44% women) with myeloid neoplasms (n = 214, 57%), lymphoid neoplasms (n = 124, n = 33%), and other diseases (n = 35, 10%), vaccination was performed with BNT162b2 (BioNTech), mRNA-1273 (Moderna), ChADOx1 (AstraZeneca), or a combination. A total of 229 patients (61%) were on active therapy within 3 months prior vaccination and 144 patients (39%) were previously treated or treatment naïve. Vaccination-related antibody response was negative in 56/373 patients (15%): in 39/124 patients with lymphoid neoplasms, 13/214 with myeloid neoplasms, and 4/35 with other diseases. Active treatment per se was not correlated with negative response. However, rituximab and BTK inhibitor treatment were correlated significantly with a negative vaccination response, whereas younger age and chronic myeloid leukemia (CML) disease were associated with positive response. In addition, 5 of 6 patients with myeloproliferative neoplasm (MPN) and negative vaccination response were on active treatment with ruxolitinib. In conclusion, a remarkable percentage of patients with hematological diseases had no response after 2nd COVID-19 vaccination. Multivariable analysis revealed important factors associated with response to vaccination. The results may serve as a guide for better protection and surveillance in this vulnerable patient cohort.


Assuntos
Formação de Anticorpos , Vacinas contra COVID-19 , COVID-19 , Doenças Hematológicas , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Feminino , Doenças Hematológicas/complicações , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Falha de Tratamento , Vacinação
7.
J Clin Oncol ; 40(16): 1783-1794, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235417

RESUMO

PURPOSE: On the basis of data from the German Registry on Disorders of Eosinophils and Mast Cells, we compared the efficacy of midostaurin and cladribine in patients with advanced systemic mastocytosis (AdvSM). PATIENTS AND METHODS: Patients with AdvSM (n = 139) were treated with midostaurin only (n = 63, 45%), cladribine only (n = 23, 17%), or sequentially (midostaurin-cladribine, n = 30, 57%; cladribine-midostaurin, n = 23, 43%). Prognosis was assessed through the Mutation-Adjusted Risk Score (MARS). Besides the comparison of efficacy between midostaurin and cladribine on response (eg, organ dysfunction, bone marrow mast cell [MC] infiltration, and tryptase), overall survival (OS), and leukemia-free survival, we focused on the impact of treatment on involved non-MC lineages, for example, monocytes or eosinophils, and the KIT D816V expressed allele burden. RESULTS: Midostaurin only was superior to cladribine only with effects from responses on MC and non-MC lineages conferring on a significantly improved OS (median 4.2 v 1.9 years, P = .033) and leukemia-free survival (2.7 v 1.3 years, P = .044) on the basis of a propensity score-weighted analysis of parameters included in MARS. Midostaurin compensated the inferior efficacy of cladribine in first- and second-line treatment. On midostaurin in any line, response of eosinophilia did not improve its baseline adverse prognostic impact, whereas response of monocytosis proved to be a positive on-treatment parameter. Multivariable analysis allowed to establish three risk categories (low/intermediate/high) through the combination of MARS and the reduction of the KIT D816V expressed allele burden of ≥ 25% at month 6 (median OS not reached v 3.0 years v 1.0 year; P < .001). CONCLUSION: In this registry-based analysis, midostaurin revealed superior efficacy over cladribine in patients with AdvSM. In midostaurin-treated patients, the combination of baseline MARS and molecular response provided a compelling three-tier risk categorization (MARSv2.0) for OS.


Assuntos
Mastocitose Sistêmica , Cladribina/uso terapêutico , Humanos , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Sistema de Registros , Estaurosporina/efeitos adversos , Estaurosporina/análogos & derivados
8.
Am J Hematol ; 97(3): 303-310, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34978721

RESUMO

Central venous catheters (CVC) placed either via the internal jugular vein (IJV) or the subclavian vein (SCV) are routinely used in patients with hematologic malignancies. In this retrospective study, we systematically compared CVC-associated complications for both insertion sites, IJV and SCV. Between January 2011 and June 2013, all consecutive patients (n = 87) were included with at least one CVC (n = 153; n = 94 IJV; n = 59 SCV) at our institution due to induction/consolidation for AML/ALL or autologous hematopoietic cell transplantation (HCT). Primary study endpoints were central line-associated (CLABSI), catheter-related (CRBSI) blood stream infections and local inflammation (LI) at the insertion site. CRBSI occurred earlier and more frequently in the IJV- versus the SCV-group with an incidence rate of CRBSI at day 15 of 10% versus 0% (p = .04) and a rate of CRBSI per 1000 CVC days of 5.7 versus 1.2. In addition, CLABSI was detected more often in IJV- compared to SCV-CVC (26% vs. 8%, p = .009). Conversely, LI occurred more frequently and earlier in SCV- versus IJV-CVC (88% vs. 56%, p < .0001) with a median time to LI of 9 versus 14 days (p < .0001). The strongest risk factor for the endpoints CRBSI, CLABSI, and LI was the insertion site. However, SCV insertion was a risk factor for LI (p = .001, HR: 2.0), insertion in the IJV a risk factor for CLABSI (p = .044, HR: 2.7) and CRBSI (p = .036, HR: 5.4). These results demonstrate a differential effect of the insertion site of CVC in neutropenic patients with a significantly reduced frequency of CVC-related blood stream infections in SCV-CVC.


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Neoplasias Hematológicas/terapia , Adulto , Idoso , Infecções Relacionadas a Cateter/etiologia , Feminino , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Inflamação/epidemiologia , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Br J Haematol ; 194(2): 344-354, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34060083

RESUMO

We report on 45 patients with myeloid neoplasms and concurrent Janus kinase 2 (JAK2) V617F and KIT proto-oncogene, receptor tyrosine kinase (KIT) D816V (JAK2pos. /KITpos. ) mutations, which are individually identified in >60% of patients with classical myeloproliferative neoplasms (MPN) and >90% of patients with systemic mastocytosis (SM) respectively. In SM, the concurrent presence of a clonal non-mast cell neoplasm [SM with associated haematological neoplasm (SM-AHN)] usually constitutes a distinct subtype associated with poor survival. All 45 patients presented with a heterogeneous combination of clinical/morphological features typical of the individual disorders (e.g. leuco-/erythro-/thrombocytosis and elevated lactate dehydrogenase for MPN; elevated serum tryptase and alkaline phosphatase for SM). Overlapping features identified in 70% of patients included splenomegaly, cytopenia(s), bone marrow fibrosis and additional somatic mutations. Molecular dissection revealed discordant development of variant allele frequency for both mutations and absence of concurrently positive single-cell derived colonies, indicating disease evolution in two independent clones rather than monoclonal disease in >60% of patients examined. Overall survival of JAK2pos. /KITpos. patients without additional somatic high-risk mutations [HRM, e.g. in serine and arginine-rich splicing factor 2 (SRSF2), additional sex combs like-1 (ASXL1) or Runt-related transcription factor 1 (RUNX1)] at 5 years was 77%, indicating that the mutual impact of JAK2 V617F and KIT D816V on prognosis is fundamentally different from the adverse impact of additional HRM in the individual disorders.


Assuntos
Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Mutação Puntual , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/patologia , Humanos , Masculino , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/patologia , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/patologia
10.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806359

RESUMO

In systemic mastocytosis (SM), qualitative and serial quantitative assessment of the KIT D816V mutation is of diagnostic and prognostic relevance. We investigated peripheral blood and bone marrow samples of 161 patients (indolent SM (ISM), n = 40; advanced SM, AdvSM, n = 121) at referral and during follow-up for the KIT D816V variant allele frequency (VAF) at the DNA-level and the KIT D816V expressed allele burden (EAB) at the RNA-level. A round robin test with four participating laboratories revealed an excellent correlation (r > 0.99, R2 > 0.98) between three different DNA-assays. VAF and EAB strongly correlated in ISM (r = 0.91, coefficient of determination, R2 = 0.84) but only to a lesser extent in AdvSM (r = 0.71; R2 = 0.5). However, as compared to an EAB/VAF ratio ≤2 (cohort A, 77/121 patients, 64%) receiver operating characteristic (ROC) analysis identified an EAB/VAF ratio of >2 (cohort B, 44/121 patients, 36%) as predictive for an advanced phenotype and a significantly inferior median survival (3.3 vs. 11.7 years; p = 0.005). In terms of overall survival, Cox-regression analysis was only significant for the EAB/VAF ratio >2 (p = 0.006) but not for VAF or EAB individually. This study demonstrates for the first time that the transcriptional activity of KIT D816V may play an important role in the pathophysiology of SM.


Assuntos
Mastocitose Sistêmica/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Medula Óssea/metabolismo , DNA/sangue , DNA/genética , DNA/metabolismo , Feminino , Frequência do Gene , Humanos , Masculino , Mastocitose Sistêmica/sangue , Mastocitose Sistêmica/metabolismo , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Proteínas Proto-Oncogênicas c-kit/metabolismo , RNA/sangue , RNA/genética , RNA/metabolismo , Transcrição Gênica
11.
Haematologica ; 106(2): 363-374, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31879324

RESUMO

Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at www.clinicaltrials.gov as #NCT02156479.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Medição de Risco , Ativação Viral
12.
Oncol Res Treat ; 43(12): 672-678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33070144

RESUMO

INTRODUCTION: We report on patients who developed severe acyclovir-resistant (ACVr) herpes simplex virus 1 (HSV-1) stomatitis after allogeneic hematopoietic cell transplantation (HCT). PATIENTS: HCT patients suffering from HSV-1 stomatitis without response after 1 week of high-dose acyclovir (ACV) were tested for ACV resistance. Patients with proven ACV resistance were treated either topically with cidofovir solution and gel or with topical foscavir cream or with intravenous foscavir. RESULTS: Among 214 consecutive HCT patients, 6 developed severe ACVr HSV-1 stomatitis (WHO grade III n = 1, WHO grade IV n = 5). All 6 patients suffered from relapse of acute myeloid leukemia (AML) after HCT. ACVr stomatitis was treated topically with first-line (n = 4) or second-line (n = 2) cidofovir. Topical foscavir cream was applied as first-line (n = 1) or second-line (n = 1) therapy. Intravenous foscavir was used in 3 patients (first-line therapy, n = 1; second-line therapy, n = 2). Complete remission was reached by topical cidofovir (n = 3), topical foscavir (n = 1), and intravenous foscavir (n = 1), respectively. Five of the 6 patients died due to progression of leukemia. Only 1 patient survived. CONCLUSIONS: ACVr HSV-1 stomatitis is a severe complication in AML patients relapsing after HCT. It reflects the seriously impaired general condition of these patients. This analysis shows that topical treatment with cidofovir or foscavir might be a sufficient first-line therapy approach in ACVr HSV-1 stomatitis. It might serve as a less toxic alternative to intravenous foscavir.


Assuntos
Antivirais/administração & dosagem , Cidofovir/administração & dosagem , Foscarnet/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Simples/tratamento farmacológico , Estomatite/tratamento farmacológico , Aciclovir/administração & dosagem , Aciclovir/farmacologia , Administração Tópica , Adulto , Idoso , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Herpes Simples/etiologia , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estomatite/virologia , Resultado do Tratamento
13.
Biol Blood Marrow Transplant ; 26(6): 1189-1194, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32084541

RESUMO

Central venous catheters (CVCs) are extensively used in patients undergoing allogeneic hematopoietic cell transplantation (HCT). In these patients CVC are placed routinely either via the internal jugular vein (IJV) or the subclavian vein (SCV). Purpose of this study was to systematically analyze complications of CVC at different insertion sites in HCT recipients. In this retrospective analysis, all consecutive patients (n = 56) who received a CVC (n = 101) due to allogeneic HCT at our institution between January 2011 and June 2013 were included. Three-lumen standard, nontunneled CVCs were placed via either the IJV (n = 60; 59%) or the SCV (n = 41; 41%). Study endpoints were time to local inflammation at the insertion site, time to fever, time to a combined endpoint of inflammation and fever, central line-associated bloodstream infection (CLABSI), duration of catheterization, catheter lumen obstruction, deep-vein thrombosis, pneumothorax, and catheter-related death. The median duration of catheterization per CVC was almost identical for the IJV and SCV sites (18 days versus 17 days; P not significant). There were no differences in the frequency of CLABSI, deep-vein thrombosis, pneumothorax, and catheter lumen obstruction between IJV and SCV CVC insertion sites. None of the patients died due to a CVC-related cause. Local inflammation occurred less frequently (48% versus 71%; P = .025) and later (median time to local inflammation, 25 days versus 12 days; P = .01) in IJV CVCs versus SCV CVCs. There was a trend toward a median longer time to the occurrence of fever for IJV CVCs compared with SCV CVCs (20 days versus 13 days; P = .07). In the multivariate analysis, diagnosis of acute leukemia (hazard ratio [HR], 1.696; P = .036), SCV CVC (HR, 1.617; P  = .039), and neutropenic CVC-days (HR, 2.477; P = .01) were identified as risk factors for the occurrence of local inflammation or fever. In contrast to earlier studies in patients without hematologic malignancies, these data demonstrate that CVCs placed in the SCV are not superior over IJV CVCs. Moreover, local inflammation occurred earlier and more frequently in patients with an SCV CVC.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Transplante de Células-Tronco Hematopoéticas , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Veia Subclávia
14.
Leukemia ; 33(5): 1124-1134, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30635631

RESUMO

KIT D816 mutations (KIT D816mut) are strongly associated with systemic mastocytosis (SM) but are also detectable in acute myeloid leukemia (AML), where they represent an adverse prognostic factor in combination with core binding factor (CBF) fusion genes. Here, we evaluated the clinical and molecular features of KIT D816mut/CBF-negative (CBFneg) AML, a previously uncharacterized combination. All KIT D816mut/CBFneg cases (n = 40) had histologically proven SM with associated AML (SM-AML). Molecular analyses revealed at least one additional somatic mutation (median, n = 3) beside KIT D816 (e.g., SRSF2, 38%; ASXL1, 31%; RUNX1, 34%) in 32/32 (100%) patients. Secondary AML evolved in 29/40 (73%) patients from SM ± associated myeloid neoplasm. Longitudinal molecular and cytogenetic analyses revealed the acquisition of new mutations and/or karyotype evolution in 15/16 (94%) patients at the time of SM-AML. Median overall survival (OS) was 5.4 months. A screen of two independent AML databases (AMLdatabases) revealed remarkable similarities between KIT D816mut/CBFneg SM-AML and KIT D816mut/CBFneg AMLdatabases (n = 69) with regard to KIT D816mut variant allele frequency, mutation profile, aberrant karyotype, and OS suggesting underlying SM in a significant proportion of AMLdatabases patients. Bone marrow histology and reclassification as SM-AML has important clinical implications regarding prognosis and potential inclusion of KIT inhibitors in treatment concepts.


Assuntos
Alelos , Fatores de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Medula Óssea/patologia , Análise Citogenética , Feminino , Frequência do Gene , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Mastocitose Sistêmica/genética , Mastocitose Sistêmica/metabolismo , Mastocitose Sistêmica/patologia , Pessoa de Meia-Idade
15.
Eur J Haematol ; 98(5): 485-492, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28135011

RESUMO

OBJECTIVE: Multidrug-resistant organisms (MDRO) are a challenge in allogeneic hematopoietic cell transplantation (HCT). However, in the literature there is no comprehensive analysis on MDRO in HCT. In this retrospective, single-center analysis, we appraised prevalence and clinical impact of MDRO in 98 consecutive allogeneic HCT patients. METHOD: Prior to the conditioning (baseline) and whenever clinically indicated patients underwent a full screening for MDRO (stool and urine cultures, swabs from several body regions). RESULTS: It turned out that 26 patients were colonized by 33 MDRO, either at baseline (n=16) or at any other time until day 100 post-transplantation. Of these 26 patients, eight developed an infection with MDRO, four of them by 4MRGN Pseudomonas aeruginosa, and three of them died MDRO-related. However, there was no significant difference between MDRO-colonized and non-colonized patients regarding overall survival (OS) and non-relapse-mortality (NRM). There was only a trend toward a higher NRM in patients already colonized by MDRO at baseline. This was due to the high NRM in multidrug-resistant P. aeruginosa-colonized patients. CONCLUSION: In summary, colonization with MDRO other than P. aeruginosa had no negative impact on NRM and OS. Patients colonized by multidrug-resistant P. aeruginosa had a dismal outcome. HCT of these patients should be considered with care. Screening for MDRO in the pretransplant work-up is suggested.


Assuntos
Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções/epidemiologia , Infecções/etiologia , Adulto , Idoso , Anti-Infecciosos/farmacologia , Gerenciamento Clínico , Neutropenia Febril/diagnóstico , Neutropenia Febril/etiologia , Neutropenia Febril/terapia , Feminino , Humanos , Infecções/diagnóstico , Infecções/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mortalidade , Prevalência , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto Jovem
16.
J Clin Oncol ; 32(29): 3264-74, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25154823

RESUMO

PURPOSE: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown. PATIENTS AND METHODS: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC). RESULTS: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response. CONCLUSION: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mastocitose Sistêmica/terapia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento
17.
Eur Radiol ; 24(8): 1835-44, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24863887

RESUMO

OBJECTIVES: After allogeneic stem cell transplantation (SCT), a reliable diagnosis of acute graft versus host disease (aGvHD) is essential for an early and successful treatment. It is the aim of this analysis to assess intestinal aGvHD by magnetic resonance imaging (MRI). METHODS: Prior to allogeneic SCT, 64 consecutive patients underwent abdominal MRI examination on a 3 T MR system, including axial and coronal T2w sequences and a three-dimensional dynamic T1w, contrast enhanced sequence. After SCT, 20 patients with suspected aGvHD received a second MRI as well as an endoscopic examination. RESULTS: Nine patients suffered from histologically proven intestinal aGvHD. In eleven patients intestinal aGvHD was excluded. In all aGvHD patients typical MRI findings with long-segment bowel wall thickening--always involving the terminal ileum--with profound submucosal oedema, were detected. The bowel wall was significantly thickened in patients with intestinal aGvHD. Bowel contrast enhancement spared the submucosa while demonstrating strong mucosal hyperemia. CONCLUSIONS: In intestinal aGvHD, a characteristic MR-appearance can be detected. This MRI pattern might facilitate an early and non-invasive diagnosis of intestinal aGvHD. MRI might thus be used as a sensitive tool to rule out or support the clinical diagnosis of aGvHD. KEY POINTS: • Acute intestinal graft versus host disease (aGvHD) can be assessed by MRI. • The aGvHD of the bowel demonstrates a characteristic MR imaging pattern. • Bowel wall shows extensive long-segment wall thickening with profound submucosal oedema. • Terminal ileum seems invariably affected; other bowel segments show variable involvement. • Colonoscopy in suspected aGvHD should include inspection of terminal ileum.


Assuntos
Neoplasias Gastrointestinais/terapia , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Imageamento por Ressonância Magnética/métodos , Doença Aguda , Adulto , Idoso , Diagnóstico Diferencial , Endoscopia Gastrointestinal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-24109904

RESUMO

Sleep plays a fundamental role in the life of every human. The prevalence of sleep disorders has increased significantly, now affecting up to 50% of the general population. Sleep is usually analyzed by extracting a hypnogram containing sleep stages. The gold standard method polysomnography (PSG) requires subjects to stay overnight in a sleep laboratory and to wear a series of obtrusive devices. This work presents an easy to use method to perform somnography at home using unobtrusive motion sensors. Ten healthy male subjects were recorded during two consecutive nights. Sensors from the Shimmer platform were placed in the bed to record accelerometer data, while reference hypnograms were collected using a SOMNOwatch system. A series of filters were used to extract a motion feature in 30 second epochs from the accelerometer signals. The feature was used together with the ground truth information to train a Naive Bayes classifiers that distinguished wakefulness, REM and non-REM sleep. Additionally the algorithm was implemented on an Android mobile phone. Averaged over all subjects, the classifier had a mean accuracy of 79.0 % (SD 9.2%) for the three classes. The mobile phone implementation was able to run in realtime during all experiments. In future this will lead to a method for simple and unobtrusive somnography using mobile phones.


Assuntos
Telefone Celular , Movimento , Polissonografia/instrumentação , Polissonografia/métodos , Adulto , Algoritmos , Humanos , Masculino , Sono REM/fisiologia , Vigília/fisiologia
19.
J ECT ; 28(3): e37-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22914638

RESUMO

Little is known about homocysteine and related changes in serum levels in patients receiving ECT. This study examined relationships between levels of homocysteine and seizure duration in 11 patients with depression receiving electroconvulsive therapy. Elevated homocysteine levels, such as have been associated in other studies with cellular damage, were not observed.


Assuntos
Eletroconvulsoterapia , Homocisteína/sangue , Convulsões/fisiopatologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/terapia , Eletroencefalografia , Feminino , Humanos , Masculino , Estudos Prospectivos , Vitaminas/sangue
20.
J Nerv Ment Dis ; 200(5): 423-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22551796

RESUMO

The incidence of mental and somatic sequelae has been shown to be very high in people who survived the Holocaust. In the current study, 80 Holocaust survivors with posttraumatic stress disorder were examined based on evaluation of their complete record (medical reports, clinical history, medical statements, and handwritten declarations of patients under oath). These survivors were compared with subjects with posttraumatic stress disorder caused by traumata other than the Holocaust. The data were analyzed for the presence of cardiovascular, gastrointestinal, and orthopedic diseases that developed in the time between the earliest medical report (expert opinion) and the latest expert opinion. Analysis revealed an increase in myocardial infarction, chronic degenerative diseases, and cancerous changes in the second expert opinion. No differences between the groups were seen with regard to sex, age at traumatization, or age at examination. Several implications of the data are discussed, including the implication that the survivors examined in this study may comprise a highly resilient group, inasmuch as they had reached an advanced age.


Assuntos
Holocausto/psicologia , Transtornos de Estresse Pós-Traumáticos/complicações , Sobreviventes/psicologia , Fatores Etários , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Gastroenteropatias/epidemiologia , Gastroenteropatias/etiologia , Holocausto/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/etiologia , Fatores Sexuais , Sobreviventes/estatística & dados numéricos , Fatores de Tempo
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