RESUMEN
The hematopoietic stem cell transplantation (HSCT) is performed for various hematological diseases. Chronic kidney disease (CKD) occurs relatively often after HSCT. Anemia after HSCT may be due to CKD and/or other reasons. The aim of this study is to assess the prevalence of anemia and its possible relationship to the presence of CKD in patients at least 3 months after HSCT. The study included 156 patients who underwent allogeneic HSCT treatment in our center in the years 1998 to 2021 due to different hematologic pathologies (acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma, and others). Anemia was diagnosed in 13% of women and 35% of men. Anemia was most common in people after HSCT due to a history of acute myeloid leukemia (55% women, 30% men). In 56% of women and 17% of men, anemia was associated with chronic kidney disease. In patients with anemia, age was related to the eGFR (r = -0.39, p < 0.001), in patients without anemia age was negatively related to eGFR (r = -0.56, p < 0.001), and hemoglobin was positively related to platelet count (r = 0.62, p < 0.001). Concluding, anemia, was relatively common in CKD after HSCT. In CKD, in particular with coexistent anemia, nephrology referral is to be taken into account to optimize therapy, including nephroprotection.
Asunto(s)
Anemia , Trasplante de Células Madre Hematopoyéticas , Nefrología , Insuficiencia Renal Crónica , Masculino , Humanos , Femenino , Prevalencia , Anemia/epidemiología , Anemia/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapiaRESUMEN
Acute graft-versus-host disease (aGvHD) remains a major threat to successful outcome following allogeneic hematopoietic cell transplantation though advances in prophylaxis and supportive care have been made. The aim of this study is to test whether the incidence and mortality of aGvHD have decreased over time. 102,557 patients with a median age of 47.6 years and with malignancies after first allogeneic sibling or unrelated donor (URD) transplant were studied in the following periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010 and 2011-2015. Findings: 100-day incidences of aGvHD grades II-IV decreased from 40% to 38%, 32%, 29% and 28%, respectively, over calendar time (P<0.001). In multivariate analysis URD, not in complete remission (CR) at transplant or untreated, and female donor for male recipient were factors associated with increased risk whereas the use of ATG/alemtuzumab decreased aGvHD incidence. Median follow-up was 214, 169, 127, 81 and 30 months, respectively, for the periods analyzed. Three-year-survival after aGvHD grades II-IV increased significantly from 38% to 40%, 43%, 44%, and 45%, respectively. In multivariate analysis URD, not in CR at transplant, peripheral blood as stem cell source, female donor for male recipient, and the use of ATG/alemtuzumab were associated with increased mortality whereas reduced-intensity conditioning was linked to lower mortality. Mortality increased with increasing patient age but decreased in the recent cohorts. Our analysis demonstrates that aGvHD has decreased over recent decades and also that the survival rates of patients affected with aGvHD has improved.
Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Alemtuzumab , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Donante no EmparentadoRESUMEN
Significant progress has been made in understanding the connection between intestinal barrier function and allogenic hematopoietic cell transplantation (allo-HCT) recipients' outcomes. The purpose of this study was to further evaluate gut barrier permeability and other potential intestinal barrier disruption markers in the allo-HCT setting. Fifty-one patients were enrolled in the study. Intestinal permeability was assessed with the sugar absorption test and faecal concentrations of the zonulin, calprotectin and beta-defensin-2 levels in the peri-transplantation period. Most patients undergoing allo-HCT in our department had a disrupted intestinal barrier at the baseline, which was associated with older age and higher Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Regardless of this, we observed a further increase in gut barrier permeability after allo-HCT in most patients. However, there was no association between permeability assay and other markers (zonulin, calprotectin and beta-defensin-2). Patients with acute GVHD had significantly higher median calprotectin concentrations after allo-HCT compared with the patients without this complication. Our findings indicate that gut barrier damage develops prior to allo-HCT with progression after the procedure and precedes further complications, but did not prove other markers to be useful surrogates of intestinal permeability.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , beta-Defensinas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Injerto contra Huésped/etiología , PermeabilidadRESUMEN
Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft-versus-host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.
Asunto(s)
Enteritis , Eosinofilia , Trasplante de Microbiota Fecal , Gastritis , Enfermedad Injerto contra Huésped , Humanos , NorovirusRESUMEN
Leukaemia cutis (LC) describes infiltration of the skin by leukaemia cells, resulting in clinically identifiable cutaneous lesions. LC has a wide range of clinical manifestations, which can make it difficult to distinguish LC from other skin changes. In a group of patients, LC can be the first manifestation of leukaemia, therefore skin biopsy is crucial for the diagnosis. In this mini review, we discuss various types of leukaemia most frequently represented in leukaemia cutis, in both children and adults and skin changes in multiple myeloma, focusing on the clinical presentation of LC and prognosis in patients.
RESUMEN
Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.
Asunto(s)
Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Antígenos CD19 , Médula Ósea , Tratamiento Basado en Trasplante de Células y Tejidos , Niño , Europa (Continente) , Humanos , Receptores de Antígenos de Linfocitos T/genética , Adulto JovenRESUMEN
Uric acid is a danger signal contributing to inflammation. Its relevance to allogeneic stem cell transplantation (alloSCT) derives from preclinical models where the depletion of uric acid led to improved survival and reduced graft-versus-host disease (GvHD). In a clinical pilot trial, peri-transplant uric acid depletion reduced acute GvHD incidence. This prospective international multicenter study aimed to investigate the association of uric acid serum levels before start of conditioning with alloSCT outcome. We included patients with acute leukemia, lymphoma or myelodysplastic syndrome receiving a first matched sibling alloSCT from peripheral blood, regardless of conditioning. We compared outcomes between patients with high and low uric acid levels with univariate- and multivariate analysis using a cause-specific Cox model. Twenty centers from 10 countries reported data on 366 alloSCT recipients. There were no significant differences in terms of baseline comorbidity and disease stage between the high- and low uric acid group. Patients with uric acid levels above median measured before start of conditioning did not significantly differ from the remaining in terms of acute GvHD grades II-IV incidence (Hazard ratio [HR] 1.5, 95% Confidence interval [CI]: 1.0-2.4, P=0.08). However, they had significantly shorter overall survival (HR 2.8, 95% CI: 1.7-4.7, P<0.0001) and progression free survival (HR 1.6, 95% CI: 1.1-2.4, P=0.025). Non-relapse mortality was significantly increased in alloSCT recipients with high uric acid levels (HR 2.7, 95% CI: 1.4-5.0, P=0.003). Finally, the incidence of relapse after alloSCT was increased in patients with higher uric acid levels (HR 1.6, 95% CI: 1.0-2.5, P=0.04). We conclude that high uric acid levels before the start of conditioning correlate with increased mortality after alloSCT.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Ácido ÚricoRESUMEN
Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (Pâ¯=â¯.02). Spontaneous menarche was more frequent after Treo than after Bu (P < .001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (Pâ¯=â¯.03 and Pâ¯=â¯.04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population.
Asunto(s)
Busulfano/análogos & derivados , Gónadas/metabolismo , Trasplante de Células Madre Hematopoyéticas , Pubertad Precoz , Adolescente , Adulto , Aloinjertos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Niño , Preescolar , Femenino , Gónadas/patología , Humanos , Masculino , Pubertad Precoz/inducido químicamente , Pubertad Precoz/metabolismo , Pubertad Precoz/patología , Estudios RetrospectivosRESUMEN
Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.
Asunto(s)
Oftalmopatías , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Médula Ósea , Europa (Continente) , Oftalmopatías/metabolismo , Oftalmopatías/patología , Oftalmopatías/fisiopatología , Oftalmopatías/prevención & control , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/fisiopatología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Factores de Riesgo , Sociedades Médicas , Trasplante HomólogoRESUMEN
Non-graft-versus-host disease (GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT) but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment and ocular toxicities associated with medications. We summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care.
Asunto(s)
Oftalmopatías/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Oftalmopatías/diagnóstico , Oftalmopatías/prevención & control , Oftalmopatías/terapia , Humanos , Incidencia , Tamizaje Masivo , Grupo de Atención al Paciente , Factores de RiesgoRESUMEN
Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs 44.8%; p < 0.0001). Outcome of bacterial infections was better in children (95.5% vs 91.4%; p = 0.0011). The IFD incidence (25.3% vs 6.3%; p < 0.0001) and outcome (88.0% vs 74.9%; p < 0.0001) were higher in children. The incidence of viral infections was higher in children after allo-HCT (56.3% vs 29.3%; p < 0.0001), and auto-HCT (6.6% vs 0.8%; p < 0.0001). Outcome of viral infections was better in children (98.6% vs 92.3%; p = 0.0096). Infection-related mortality was 7.8% in children and 18.4% in adults (p < 0.0001). No child after auto-HCT died of infection. Adult age, mismatched transplants, acute leukemia, chronic GVHD, CMV reactivation, infection with Gram-negatives, and duration of infection > 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.
Asunto(s)
Infecciones Bacterianas/epidemiología , Infecciones por Citomegalovirus/epidemiología , Enfermedad Injerto contra Huésped/epidemiología , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras/epidemiología , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Infecciones Bacterianas/etiología , Niño , Preescolar , Enfermedad Crónica , Estudios Transversales , Infecciones por Citomegalovirus/etiología , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Incidencia , Lactante , Recién Nacido , Infecciones Fúngicas Invasoras/etiología , Leucemia , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND The most common etiological agents of infections in onco-hematological patients are Gram-negative rods resistant to many antimicrobials, including carbapenems. Recently, ceftolozane combined with tazobactam became a novel therapeutic option. The aim of the present study was to analyze the susceptibility to ceftolozane/tazobactam of the clinical strains of these bacteria. MATERIAL AND METHODS Material comprised rectal swabs, urine, and bronchoalveolar lavage fluid obtained from onco-hematological patients hospitalized in a clinical hospital (1050 beds) in Poland. Identification of the isolated bacteria was done by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using the MALDI Biotyper (Bruker). Ceftolozane/tazobactam susceptibility of the isolates was assessed using antimicrobial gradient strips (E-test, BioMérieux). Antimicrobial susceptibility testing and interpretation of the results was done according to the current recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). RESULTS In total, 281 rectal swabs and 116 urine samples were tested for the presence of Gram-negative rods producing ESBL, and 531 rectal swabs and 8 bronchoalveolar lavage fluid samples were tested for the presence of Gram-negative rods resistant to carbapenems. In the analyzed period, 69 non-repetitive strains of bacteria were isolated that were in the spectrum of activity of ceftolozane/tazobactam. Among 44 clinical strains of ESBL(+) Enterobacteriaceae rods, 76% were susceptible to ceftolozane/tazobactam. All 9 strains of non-carbapenemase-producing P. aeruginosa resistant or with decreased susceptibility to carbapenems were susceptible to ceftolozane/tazobactam. CONCLUSIONS Ceftolozane/tazobactam may be an option in the therapy of infections caused by ESBL(+) strains of Enterobacteriaceae as well as non-carbapenemase-producing carbapenem-resistant strains of P. aeruginosa.
Asunto(s)
Cefalosporinas/uso terapéutico , Enterobacteriaceae/efectos de los fármacos , Pseudomonas/efectos de los fármacos , Tazobactam/uso terapéutico , Antibacterianos/farmacología , Antiinfecciosos/uso terapéutico , Cefalosporinas/farmacología , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Quimioterapia Combinada , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Pacientes , Polonia , Infecciones por Pseudomonas/tratamiento farmacológico , Tazobactam/farmacologíaRESUMEN
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trastornos Neurocognitivos/etiología , Biomarcadores , Humanos , Trastornos Neurocognitivos/diagnóstico , Trastornos Neurocognitivos/prevención & control , Trastornos Neurocognitivos/terapia , Prevalencia , Factores de RiesgoRESUMEN
A cute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Dipéptidos/farmacología , Inhibidores Enzimáticos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Metacrilatos/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteína Disulfuro Isomerasas/antagonistas & inhibidores , Femenino , Células HL-60 , Humanos , Leucemia Mieloide Aguda/enzimología , Leucemia Mieloide Aguda/patología , Masculino , Proteínas de Neoplasias/metabolismo , Proteína Disulfuro Isomerasas/metabolismoRESUMEN
Background: Patients with blood disorders colonized with antibiotic-resistant bacteria (ARB) are prone to systemic infections that are difficult to treat. Reintroduction of commensal bacteria in a murine model of enterococcal colonization of the gut can lead to eradication of enterococci. We hypothesized that fecal microbiota transplantation (FMT) could be used to eradicate ARB in humans. Methods: Participants colonized with ARB were treated with intraduodenal FMT according to a prospective protocol (NCT02461199). The primary endpoint was complete ARB decolonization at 1 month after FMT. Secondary endpoints included safety assessment and partial ARB decolonization. Microbiome sequencing was performed to investigate the influence of microbial composition of the transplanted material on the outcome of FMT. Results: Twenty-five FMTs were performed in 20 participants (including 40% who had neutropenia) who were colonized by a median of 2 (range, 1-4) strains of ARB. The primary endpoint was reached in 15/25 (60%) of the FMTs and more frequently in cases in which there was no periprocedural use of antibiotics (79% vs 36%, P < .05). Among participants, 15/20 (75%) experienced complete ARB decolonization. There were no severe adverse events, and partial ARB decolonization was observed in 20/25 (80%) of the FMTs. The microbiota composition analysis revealed higher abundance of Barnesiella spp., Bacteroides, and Butyricimonas and greater bacterial richness in the fecal material, resulting in eradication of Klebsiella pneumoniae compared with nonresponders. Conclusions: FMT in patients with blood disorders is safe and promotes eradication of ARB from the gastrointestinal tract. Clinical Trials Registration: NCT02461199.
Asunto(s)
Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiología , Enfermedades Hematológicas/terapia , Adulto , Anciano , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana , Trasplante de Microbiota Fecal/efectos adversos , Trasplante de Microbiota Fecal/estadística & datos numéricos , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported. RESULTS: After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]). CONCLUSIONS: Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875-80. © 2017 American Cancer Society.
Asunto(s)
Antineoplásicos/uso terapéutico , Crisis Blástica/terapia , Imidazoles/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Piridazinas/uso terapéutico , Trasplante de Células Madre/métodos , Adulto , Anciano , Crisis Blástica/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Homólogo , Resultado del TratamientoRESUMEN
Gut colonization by antibiotic-resistant bacteria may underlie hard-to-treat systemic infections. There is also accumulating evidence on the immunomodulatory function of gut microbiota after allogeneic stem cell transplantation (alloSCT) and its impact on graft-versus-host disease (GVHD). We investigated the epidemiology and clinical impact of gut colonization after alloSCT and retrospectively analyzed data on 107 alloSCTs performed at a single transplant center. Pretransplant microbiology screening identified colonization in 31% of cases. Colonization had a negative impact on overall survival after alloSCT in univariate (34% versus 74% at 24 months, P < .001) and multivariate (hazard ratio, 3.53; 95% confidence interval, 1.71 to 7.28; P < .001) analyses. Nonrelapse mortality was significantly higher in colonized than in noncolonized patients (42% versus 11% at 24 months, P = .001). Colonized patients more frequently experienced bacteremia (48% versus 24%, P = .01), and more deaths were attributable to infectious causes in the colonized group (42% versus 11% of patients and 67% versus 29% of deaths, P < .05). We observed a significantly higher incidence of grades II to IV acute GVHD in colonized than in noncolonized patients (42% versus 23%, P < .05), especially involving the gastrointestinal system (33% versus 13.5%, P = .07). In summary, we determined that gut colonization by antibiotic-resistant bacteria decreases the overall survival of patients undergoing alloSCT by increasing nonrelapse mortality and the incidences of systemic infection and acute GVHD.