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1.
Emerg Infect Dis ; 25(9): 1752-1753, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31441752

RESUMEN

Since its recent discovery, Bourbon virus has been isolated from a human and ticks. To assess exposure of potential vertebrate reservoirs, we assayed banked serum and plasma samples from wildlife and domestic animals in Missouri, USA, for Bourbon virus-neutralizing antibodies. We detected high seroprevalence in raccoons (50%) and white-tailed deer (86%).


Asunto(s)
Reservorios de Enfermedades , Thogotovirus/aislamiento & purificación , Animales , Animales Domésticos/virología , Animales Salvajes/virología , Missouri
2.
Biol Blood Marrow Transplant ; 24(4): 789-798, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29355721

RESUMEN

The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo) transplant is increasing worldwide. However, because multiple potential haplo donors are usually available, data-driven guidance is clearly needed to help transplant centers prioritize donors. To that end, we retrospectively analyzed 208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a single institution. Median recipient and donor age were 52 years (range, 19 to 75) and 38 years (range, 15 to 73), peripheral blood stem cell was the stem cell source in 66%, and myeloablative conditioning was used in 41%. Median follow-up for surviving patients was 33 months (range, 7 to 130). Donor variables analyzed included age, sex, relationship, cytomegalovirus (CMV) status, ABO compatibility, HLA disparity, and several natural killer (NK) alloreactivity models. Multivariate Cox analysis was used to adjust for known patient, disease, and transplant covariates. Donor characteristics independently associated with improved survival included presence of HLA-DR mismatch, HLA-DP nonpermissive mismatch, killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch, and KIR B/x haplotype with KIR2DS2. Donor characteristics associated with inferior survival included parental donor relationship and the use of a CMV-seronegative donor for a CMV-seropositive patient. Increased HLA disparity (≥4/10 HLA allelic mismatches [graft-versus-host direction]) resulted in relapse protection at the expense of increased nonrelapse mortality with no associated survival effect. We further propose a donor risk factor scoring system to permit a more evidence-based selection algorithm for potential haplo donors. This large, single-institution analysis demonstrates the importance of HLA-DR/HLA-DP disparity, NK alloreactivity, and other clinical variables in the haplo donor selection process and suggests that KIR and HLA-DP genotyping should be performed routinely for haplo donor selection.


Asunto(s)
Algoritmos , Selección de Donante/métodos , Antígenos HLA/genética , Trasplante de Células Madre de Sangre Periférica , Receptores KIR/genética , Donantes de Tejidos , Acondicionamiento Pretrasplante , Adulto , Anciano , Aloinjertos , Femenino , Estudios de Seguimiento , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
3.
medRxiv ; 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38370812

RESUMEN

Objectives: To ascertain if faculty and staff were the link between the two COVID-19 outbreaks in a rural university county, and if the local university's COVID-19 policies affected contact rates of their employees across all its campuses. Methods: We conducted two anonymous, voluntary online surveys for faculty and staff of a PAC-12 university on their contact patterns both within and outside the university during the COVID-19 pandemic. One was asked when classes were virtual, and another when classes were in-person but masking. Participants were asked about the individuals they encountered, the type and location of the interactions, what COVID-19 precautions were taken - if any, as well as general questions about their location and COVID-19. Results: We received 271 responses from the first survey and 124 responses from the second. The first survey had a median of 3 contacts/respondent, with the second having 7 contacts/respondent (p<0.001). During the first survey, most contacts were family contacts (Spouse, Children), with the second survey period having Strangers and Students having the most contact (p<0.001). Over 50% of the first survey contacts happened at their home, while the second survey had 40% at work and 35% at home. Both respondents and contacts masked 42% and 46% of the time for the two surveys respectively (p<0.01). Conclusion: For future pandemics, it would be wise to take employees into account when trying to plan for the safety of university students, employees, and surrounding communities. The main places to be aware of and potentially push infectious disease precautions would be on campus, especially confined spaces like offices or small classrooms, and the home, as these tend to be the largest areas of non-masked close contact.

4.
bioRxiv ; 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38585826

RESUMEN

COVID-19 has presented hospitals with unique challenges. A SHEA Research Network survey showed that 40% reported "limited" or worse levels of personal protective equipment (PPE), and 13% were self-producing PPE to address those deficits, including 3D-printed items. However, we do not know how efficiently, if at all, 3D-printed materials can be disinfected. Additionally, two filaments, PLACTIVE and BIOGUARD, claim to be antimicrobial; they use copper nanocomposites and silver ions to reduce bacterial populations. We assess how PLACTIVE and BIOGUARD may be contaminated and how well they reduce contamination, and how readily Polylactic Acid (PLA), a standard 3D-printed material, may be disinfected. 3D-printed materials, including PLACTIVE and BIOGUARD, are readily contaminated with bacteria that are common in hospitals and can sustain that contamination. Our findings reveal that the levels of contamination on PLACTIVE and BIOGUARD can vary under specific conditions such as layer height or bacterial contact time, sometimes surpassing or falling short of PLA. However, disinfected disks had lower overall CFU averages than those that were not, but the level of disinfection was variable, and bacterial populations recovered hours after disinfection application. Proper disinfection and using appropriate 3D-printed materials are essential to limit bacterial contamination. 3D printers and their products can be invaluable for hospitals, especially when supplies are low, and healthcare worker safety is paramount. Environmental services should be made aware of the presence of antimicrobial 3D-printed materials, and patients should be discouraged from printing their own items for use in hospital environments.

5.
Transplant Cell Ther ; 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38879167

RESUMEN

Following conventional graft-versus-host disease (GVHD) prophylaxis, the development of acute and/or chronic GVHD is associated with lower relapse rates. However, the effects of GVHD on relapse and non-relapse mortality following post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis have not been well studied. To this end, we analyzed the impact of acute and chronic GVHD following PTCy-based haploidentical donor transplantation (HIDT). The analysis included 335 consecutive HIDT recipients transplanted at a single institution between 2005 and 2021. Landmark analysis (LA) and time-dependent multivariable analysis (MVA) were utilized to study the impact of GVHD development on transplant outcome. Landmarks were defined as Day +100 for acute GVHD and one-year for chronic GVHD. Recipient characteristics included a median age of 50 (19-80) years, most commonly transplanted for acute leukemia[/MDS [242]. PBSC was the graft source in 81%, and regimen intensity was myeloablative in 49%. Median follow-up was 65 (23-207) months. In landmark analysis, development of grade 3 to 4 acute GVHD (versus 0-1) was associated with inferior 3-year overall survival (OS 47% versus 64%, P = .041), due to higher NRM (25% versus 10%, P = .013). In contrast, development of grade 2 acute GVHD had no significant effect on NRM or survival. When restricted to acute leukemia/MDS patients, development of grade II acute GVHD was associated with improved OS (79% versus 58%, P = .027) and a trend towards lower relapse (24% versus 36%, P = .08). Development of moderate-to-severe chronic GVHD resulted in significantly higher NRM (15% versus 4%, P = .010), but had no impact on relapse, DFS or OS. In Cox multivariate analysis (MVA), grade 3 to 4 acute GVHD and moderate-to-severe chronic GVHD were both associated with significantly higher NRM (HR 3.38, P < .001 and HR3.35, P < .001, respectively). In addition, grade 3 to 4 acute GVHD predicted worse OS (HR 1.80, P = .007) and DFS (HR 1.55, P = .041). In contrast, relapse was not impacted by acute or chronic GVHD in MVA. Grade 2 acute GVHD was not associated with transplant outcome in MVA. In summary, both grade 3 to 4 acute and moderate-to-severe chronic GVHD were associated with higher NRM after PTCy-based HIDT, without an effect on relapse risk. Methods of early identification of such patients in order to augment GVHD prophylaxis are clearly needed.

6.
Transplant Cell Ther ; 30(6): 608.e1-608.e10, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38561140

RESUMEN

The presence of an HLA-DPB1 nonpermissive mismatch (NPMM) by the TCE-3 model has been associated with improved survival following haploidentical donor transplantation (HIDT) using post-transplantation cyclophosphamide (PTCy). With the development of a revised model (TCE-Core) that further separates TCE-3 "group 3" alleles into "core" (C) and "noncore" (NC) alleles, a formerly permissive mismatch (PMM) resulting from group 3 alleles in both donor and recipient is now considered a C-NPMM if 1 or more of those alleles is NC. We aimed to study the additional effect of HLA-DPB1 C-NPMM according to the TCE-Core algorithm, as well as the directional vector of the mismatch, on outcomes following HIDT. To this end, we analyzed 242 consecutive HIDT recipients with acute leukemia or myelodysplastic syndrome who underwent transplantation between 2005 and 2021 (median age, 51 years; range, 19 to 80 years). The median follow-up was 62 months (range, 23 to 199 months). Of the 136 HIDTs classified as PMM by TCE-3, 73 were reclassified as a C-NPMM by the TCE-Core algorithm, of which 36 were in the graft-versus host (GVH) vector (37 were host-versus-graft [HVG] only). Given comparable survival between conventional NPMM and C-NPMM, GVH/bidirectional were analyzed together (nonpermissive). HVG-only C-NPMM were combined with HLA-DPB1-matched and PMM (permissive) because of similar outcomes. The presence of a TCE-Core-defined nonpermissive HLA-DP mismatch resulted in superior 5-year overall survival (OS) (66% versus 47%) and disease-free survival (DFS) (60% versus 43%). Compared to the conventional TCE-3 algorithm, TCE-Core identified a higher percentage of nonpermissive transplants (38% versus 23%) and better discriminated outcomes between nonpermissive and permissive status, with a larger difference in survival outcomes using TCE-Core compared to TCE-3 (OS Δ, 18.3% versus 12.7%; DFS Δ, 16.5% versus 8.5%). In multivariable analysis (MVA), a nonpermissive TCE-Core mismatch led to improved OS (hazard ratio [HR], .54; P = .003) and DFS (HR, .62; P = .013), largely due to decreased relapse risk (HR, .63; P = .049). In contrast, nonrelapse mortality (NRM) and graft-versus-host disease (GVHD) outcomes were not significantly impacted. In summary, the presence of nonpermissive TCE-Core HLA-DP mismatch strongly predicts survival following PTCy-based HIDT, owing to a reduction in relapse risk without a corresponding increase in GVHD or NRM. As a donor selection tool, TCE-Core appears to better discriminate HIDT outcomes while at the same time identifying a larger percentage of the potential donor pool.


Asunto(s)
Recurrencia , Trasplante Haploidéntico , Humanos , Persona de Mediana Edad , Adulto , Femenino , Masculino , Anciano , Adulto Joven , Cadenas beta de HLA-DP/genética , Cadenas beta de HLA-DP/metabolismo , Anciano de 80 o más Años , Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos/terapia , Síndromes Mielodisplásicos/mortalidad , Alelos , Enfermedad Injerto contra Huésped/inmunología
7.
Blood Adv ; 7(18): 5215-5224, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37379271

RESUMEN

Allogeneic transplant remains the best postremission therapy for patients with nonfavorable risk acute myeloid leukemia (AML). However, some patients are ineligible because of psychosocial barriers, such as lack of appropriate caregiver support. We hypothesized that immune checkpoint inhibition after autologous transplant might represent effective postremission therapy in such patients. We conducted a phase 2 study of autologous transplantation followed by administration of pembrolizumab (8 cycles starting day +1). Twenty patients with nonfavorable AML in complete remission were treated (median age, 64 years; CR1, 80%); 55% were non-White and adverse-risk AML was present in 40%. Treatment was well tolerated, with only 1 nonrelapse death. Immune-related adverse events occurred in 9 patients. After a median follow-up of 80 months, 14 patients remain alive, with 10 patients in continuous remission. The estimated 2-year LFS was 48.4%, which met the primary end point of 2-year LFS >25%; the 2-year overall survival (OS), nonrelapse mortality, and cumulative incidences of relapse were 68%, 5%, and 46%, respectively. In comparison with a propensity score-matched cohort group of patients with AML receiving allogeneic transplant, the 3-year OS was similar (73% vs 76%). Patients in the study had inferior LFS (51% vs 75%) but superior postrelapse survival (45% vs 14%). In conclusion, programmed cell death protein-1 blockade after autologous transplant is a safe and effective alternative postremission strategy in patients with nonfavorable risk AML who are ineligible for allogeneic transplant, a context in which there is significant unmet need. This trial was registered at www.clinicaltrials.gov as #NCT02771197.


Asunto(s)
Leucemia Mieloide Aguda , Receptor de Muerte Celular Programada 1 , Humanos , Persona de Mediana Edad , Trasplante Autólogo , Leucemia Mieloide Aguda/terapia , Inducción de Remisión , Trasplante Homólogo
8.
PLoS One ; 17(2): e0260580, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35113884

RESUMEN

Healthcare-associated infections (HAIs) remain a serious public health problem. In previous work, two models of an intensive care unit (ICU) showed that differing population structures had markedly different rates of Staphylococcus aureus (MRSA) transmission. One explanation for this difference is the models having differing long-term equilbrium dynamics, resulting from different basic reproductive numbers, R0. We find in this system however that this is not the case, and that both models had the same value for R0. Instead, short-term, transient dynamics, characterizing a series of small, self-limiting outbreaks caused by pathogen reintroduction were responsible for the differences. These results show the importance of these short-term factors for disease systems where reintroduction events are frequent, even if they are below the epidemic threshold. Further, we examine how subtle changes in how a hospital is organized-or how a model assumes a hospital is organized-in terms of the admission of new patients may impact transmission rates. This has implications for both novel pathogens introduced into ICUs, such as Ebola, MERS or COVID-19, as well as existing healthcare-associated infections such as carbapenem-resistant Enterobacteriaceae.


Asunto(s)
Infección Hospitalaria/transmisión , Brotes de Enfermedades , Unidades de Cuidados Intensivos , Staphylococcus aureus Resistente a Meticilina , Modelos Estadísticos , Admisión del Paciente , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/transmisión , Humanos , Enfermeras y Enfermeros , Médicos , Infecciones Estafilocócicas/microbiología , Procesos Estocásticos
9.
Transplant Cell Ther ; 28(8): 486.e1-486.e7, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35598842

RESUMEN

Single-agent high-dose melphalan (Mel) followed by autologous stem cell transplantation (ASCT) remains a standard of care in eligible patients with multiple myeloma (MM), and efforts to improve transplant outcomes by intensifying transplant conditioning have mostly failed. Bendamustine combines both alkylating and antimetabolite properties, can induce responses in MM resistant to other alkylators and represents a promising agent to combine with Mel prior to ASCT. We performed a phase II study to test the safety and efficacy of the high-dose chemotherapy combination of bendamustine, etoposide, cytarabine, and melphalan (BeEAM) in newly diagnosed MM patients up to 70 years of age. The primary study endpoint was the day 100 complete response rate. Sixty-five patients with a median (range) age of 59 (40-69) years underwent transplantation from 2015 to 2020. Other characteristics included Karnofsky performance status <80%, hematopoietic cell transplantation-comorbidity index ≥3, International Staging System III, and high-risk fluorescein in situ hybridization (FISH) in 35%, 46%, 26%, and 44%, respectively. ASCT after BeEAM was well tolerated, and there were no non-relapse deaths through 1 year after transplantation. Although at least 1 nonhematologic grade 3 toxicity was reported in 58 (89%) patients (including grade 3 febrile neutropenia in 48% and stomatitis/esophagitis in 28%), there were no grade ≥3 renal or hepatic toxicity and no grade ≥4 non-hematologic toxicity. The day 100 response rate was ≥CR1 and ≥ very good partial response (VGPR1) in 40% and 89%, respectively. With a median follow-up of 44 (13-70) months, the 3-year overall survival was 92%, 96%, and 90% for all patients and those with standard- and high-risk FISH, respectively. The corresponding values for 3-year progression-free survival was 57%, 72%, and 40%, respectively. When BeEAM-conditioned patients were compared to historical Mel-conditioned cohort, no significant differences were noted in relapse or survival outcomes in univariate or multivariable analysis. In summary, BeEAM was shown to be a safe and effective conditioning regimen before up-front autologous transplant for MM. Although the BeEAM regimen does not appear to offer a significant advantage over single-agent Mel, further studies combining bendamustine and melphalan in the front-line setting may be warranted.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Clorhidrato de Bendamustina/uso terapéutico , Citarabina/uso terapéutico , Quimioterapia Combinada/efectos adversos , Etopósido/uso terapéutico , Humanos , Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia , Trasplante Autólogo
10.
Transplant Cell Ther ; 28(9): 601.e1-601.e8, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35788088

RESUMEN

The role of NK cell alloreactivity on outcomes after T cell-replete haploidentical donor transplantation (HIDT) remains uncertain. After transplantation, newly formed NK cells are licensed through interactions of donor inhibitory KIR (iKIR) and NKG2A receptors with their cognate ligands on recipient cells. Donor NKG2A recognizes HLA-E bound by recipient HLA class I leader peptides, a process requiring methionine (M) at position -21 of the leader sequence. An rs1050458C/T dimorphism results in approximately 40% of individuals expressing at least one copy of -21M HLA-B (M/M or M/T [M+]), allowing ligand expression. We assessed the impact of recipient HLA-B-leader genotype (M+ versus M- [T/T]) and HLA-C-group iKIR missing ligand (ML, C1C1/C2C2 versus C1C2) on relapse and disease-free survival (DFS) in recipients of post-transplantation cyclophosphamide (PTCy)-based HIDT. Based on preclinical data, we hypothesized that the relative impact of each variable may depend on disease lineage (lymphoid versus myeloid). To this end, we analyzed outcomes of 322 consecutive PTCy-based HIDT recipients with hematologic malignancy who underwent transplantation at a single institution using standardized supportive care measures with mature follow-up (median 45 months). Primary endpoints were relapse and DFS of patients based on HLA-B-leader genotype and HLA-C-group iKIR ML. Planned subgroup analysis included patient with lymphoid versus myeloid malignancy. M+ HLA-B-leader genotype and HLA-C-group iKIR ML were seen in 42% and 49% of recipients, respectively. The presence of a recipient M+ B-leader (versus M-) improved overall survival (OS) and DFS and lowered cumulative incidence of relapse (CIR), an effect primarily seen in lymphoid malignancies (80% versus 51%, 72% versus 41%, 16% versus 42%, respectively). In contrast, myeloid malignancy patients benefited most from HLA-C-group iKIR ML with better OS and DFS and lower CIR (67% versus 51%, 64% versus 44%, 25% versus 45%, respectively). Multivariate analysis confirmed the disease-specific associations of improved relapse/DFS with M+ HLA-B-leader in lymphoid malignancy (hazard ratio [HR] 0.20, P < .001/HR 0.34, P <.001) and HLA-C-group iKIR ML in myeloid malignancy (HR 0.44, P = .004/HR 0.54, P = .009). Neither HLA-B-leader nor iKIR ML was associated with the incidence of non-relapse mortality or acute or chronic graft-versus-host disease. Two distinct NK cell education pathways predict relapse and DFS after HIDT-PTCy in a disease-specific manner: the presence of recipient M+ HLA-B-leader genotype improves outcome in patients with lymphoid malignancies, whereas HLA-C-group iKIR ML improves outcome in patients with myeloid malignancies. These findings strengthen the essential role of NK cells for optimal GVL in the context of HIDT-PTCy and may suggest different approaches to improving transplant outcome depending on disease type.


Asunto(s)
Antígenos HLA-B , Antígenos HLA-C , Recurrencia Local de Neoplasia , Trasplante Haploidéntico , Ciclofosfamida/uso terapéutico , Genotipo , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Ligandos , Recurrencia Local de Neoplasia/diagnóstico , Receptores KIR
11.
Artículo en Inglés | MEDLINE | ID: mdl-34444008

RESUMEN

BACKGROUND: One of the consequences of COVID-19 has been the cancelation of collegiate sporting events. We explore the impact of sports on COVID-19 transmission on a college campus. METHODS: Using a compartmental model representing the university, we model the impact of influxes of 10,000 visitors attending events and ancillary activities (dining out, visiting family, shopping, etc.) on 20,000 students. We vary the extent visitors interact with the campus, the number of infectious visitors, and the extent to which the campus has controlled COVID-19 absent events. We also conduct a global sensitivity analysis. RESULTS: Events caused an increase in the number of cases ranging from a 25% increase when the campus already had an uncontrolled COVID-19 outbreak and visitors had a low prevalence of COVID-19 and mixed lightly with the campus community to an 822% increase where the campus had controlled their COVID-19 outbreak and visitors had both a high prevalence of COVID-19 and mixed heavily with the campus community. The model was insensitive to parameter uncertainty, save for the duration a symptomatic individual was infectious. CONCLUSION: Sporting events represent a threat to the health of the campus community. This is the case even in circumstances where COVID-19 seems controlled both on-campus and among the general population.


Asunto(s)
COVID-19 , Aglomeración , Deportes , Universidades , COVID-19/epidemiología , Brotes de Enfermedades , Humanos , Estudiantes
12.
Blood Adv ; 4(15): 3669-3676, 2020 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-32777064

RESUMEN

Proteasome inhibition results in extensive immunomodulatory effects that augment natural killer cell cytotoxicity and inhibit aspects of T-cell, B-cell, and dendritic cell function. We performed a phase 2 study that examined the effects of ixazomib for graft-versus-host disease (GVHD) prophylaxis (up to 12 cycles) with posttransplant cyclophosphamide and tacrolimus after standard nonmyeloablative haploidentical donor transplantation (HIDT). Ixazomib was started on day +5 (4 mg on days 1, 8, and 15 of a 28-day cycle), with dose reductions allowed in future cycles for toxicity. All patients received peripheral blood stem cells. Twenty-five patients were enrolled with a median age of 62 years (range, 35-77 years) who had acute leukemia (4), myelodysplastic syndrome (7), non-Hodgkin lymphoma/Hodgkin lymphoma/chronic lymphocytic leukemia (8), and myeloma (6). The hematopoietic cell transplant comorbidity index was ≥3 in 68% of the patients. After a median follow-up of 33.5 months, the cumulative incidence of relapse/progression at 1 year was 24% and 44% at 3 years, which failed to meet the statistically predefined goal of decreasing 1-year risk of relapse. Engraftment occurred in all patients with no secondary graft failure, and 3-year nonrelapse mortality (NRM) was 12%. Cumulative incidence of grade 3 to 4 acute GVHD was 8%, whereas moderate-to-severe chronic GVHD occurred in 19%. Nineteen patients survive with an estimated 1-year overall survival (OS) of 84% and 3-year OS of 74%. Hematologic and cutaneous toxicities were common but manageable. The substitution of ixazomib for mycophenolate mofetil (MMF) post-HIDT results in reliable engraftment, comparable rates of clinically significant GVHD, relapse and NRM, and favorable OS. This trial was registered at www.clinicaltrials.gov as # NCT02169791.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Adulto , Anciano , Compuestos de Boro , Glicina/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Prospectivos
13.
Bone Marrow Transplant ; 55(1): 189-198, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31527818

RESUMEN

Due to perceived intolerance, many elderly AML patients do not receive therapy, and few are considered for hematopoietic cell transplantation (HCT). To better understand "real-world" outcomes, 323 consecutive AML patients ≥ 60 years referred from 2009 to 2017 were evaluated (median age 70 [60-88] years); favorable (fav) in 48 (15%), intermediate (int) in 112 (35%) and poor risk in 161 (50%). Remission induction therapy, either intensive chemotherapy (IC, n = 205) or hypomethylating agents (HMA, n = 57), was given to all but 61 (19%) patients. With median f/u of 34 months, 2-year overall survival (OS) for the whole cohort was 31%; 40 and 33% for IC- and HMA-treated vs. 0% for untreated patients. Early mortality was 14%. Remission (CR/CRi) was achieved in 60% of patients, with approximately half of these surviving 2 years. In transplant-eligible patients (60-75-year-old, int/poor risk, achieving remission), 54 (46%) of 118 received HCT. Transplanted patients had improved 2- and 3-year post-remission survival of 59% and 40% compared to 26% and 18% in similar patients not receiving HCT (HR = 0.59, 95% CI 0.37-0.93, p = 0.023). These results suggest that survival of elderly AML patients may be improved through a coordinated approach of remission induction therapy for most patients followed by HCT when feasible.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Anciano , Estudios de Cohortes , Humanos , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Trasplante Homólogo
14.
Blood Adv ; 4(20): 5311-5321, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-33108457

RESUMEN

HLA disparity is the major predictor of outcome following unrelated donor (UD) transplantation, where a single mismatch (mm) at the HLA-A, HLA-B, HLA-C, or HLA-DRB1 locus leads to increased mortality, and mismatching at multiple loci compounds this effect. In contrast, HLA disparity has not been shown to increase mortality in the context of haploidentical transplant using posttransplant cyclophosphamide (PTCy). To better define the consequences of loci-specific HLA mm, we analyzed 208 consecutive patients undergoing haploidentical transplantation for hematologic malignancy using PTCy at our institution (median age, 52 years [range, 19-75 years]; peripheral blood stem cell, 66%; reduced-intensity conditioning, 59%). Median follow-up was 65.4 months (range, 34.3-157.2 months). In univariate analysis, a single class II HLA mm at HLA-DR, HLA-DQ or a nonpermissive (np) HLA-DP mm had a protective effect on disease-free and overall survival (OS), primarily a result of reduced relapse risk. Furthermore, this survival effect was cumulative, so that patients with 3 class II mm (HLA-DR, HLA-DQ, and np HLA-DP) had the best OS. In multivariate analysis, HLA-DR mm and np HLA-DP mm were both independently associated with improved OS (hazard ratio [HR], 0.43; P =.001; and HR, 0.47; P =.011, respectively). In contrast, single or multiple mm at HLA-A, HLA-B, or HLA-C loci had no effect on acute graft-versus-host disease (GVHD), nonrelapse mortality (NRM), relapse, or survival, although the presence of an HLA-A mm was associated with increased chronic GVHD incidence. The association of class II mm with lower relapse occurred without a corresponding increase in NRM or acute or chronic GVHD. These findings will require validation in larger registry studies.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante Haploidéntico , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Acondicionamiento Pretrasplante
15.
J Med Entomol ; 56(3): 603-608, 2019 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-30668743

RESUMEN

St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) have recently emerged in the southwestern United States. Surveillance for arboviruses in Las Vegas, NV, detected a surge of SLEV activity in the southern house mosquito (Culex quinquefasciatus Say) during 2016. To identify candidate avian amplifiers, we assessed the identification, viral infection, and immune status of vertebrate hosts for 195 blood-engorged Cx. quinquefasciatus mosquitoes collected in August and September 2016. Bloodmeals were identified from 164 engorged abdomens, representing 19 species of birds and three species of mammals. No SLEV or WNV viremia was detected, but one mosquito tested positive for Culex flavivirus. House finch (Haemorhous mexicanus) (Muller) was the most common bloodmeal, followed by domestic chicken (Gallus gallus) (Linnaeus), American robin (Turdus migratorius) L., house sparrow (Passer domesticus) (L.), great-tailed grackle (Quiscalus mexicanus) (Gmelin), northern mockingbird (Mimus polyglottos) (L.) and mourning dove (Zenaida macroura) (L.). SLEV-reactive antibodies were detected in six identified bloodmeals and WNV-reactive antibodies were detected in 33. House sparrow and house finch were the most likely hosts to show previous exposure to SLEV and WNV, respectively. Over-utilization by Cx. quinquefasciatus for bloodmeal hosts was observed primarily among robin, finch and sparrow, all species that roost communally. House finch stands out as a candidate important amplifier for both SLEV and WNV because of its preference by mosquito vectors, and high competence for closely related virus strains. While implicated in previous outbreaks as an important mosquito vector, Cx. quinquefasciatus feeds infrequently on mammals in Las Vegas, indicating a low risk for bridge transmission to humans.


Asunto(s)
Aves , Culex/fisiología , Virus de la Encefalitis de San Luis/aislamiento & purificación , Cadena Alimentaria , Mamíferos , Virus del Nilo Occidental/aislamiento & purificación , Animales , Culex/virología , Conducta Alimentaria , Femenino , Nevada
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