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AIM: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. METHODS: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. RESULTS: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. CONCLUSION: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos , Estudios Prospectivos , Estados Unidos , Adulto JovenRESUMEN
Eltrombopag (ELT), an oral thrombopoietin receptor agonist, has recently emerged as a promising new drug for the treatment of aplastic anemia (AA). How ELT is used outside of clinical trials in the real-world setting and results of this treatment are not known. We conducted therefore a retrospective survey on the use of ELT in AA among EBMT member centers. We analyzed the 134 patients reported in our survey together with 46 patients recently published by Lengline et al. The median follow-up from start of ELT treatment was 15.3 months, with 85.6% patients alive at last follow-up. Importantly, only 28.9% of our patients received ELT according to the FDA/EMA label as monotherapy in the relapsed/refractory setting, whereas 16.7% received ELT upfront. The overall response rate in our cohort was 62%, very similar to the results of the pivotal ELT trial. In multivariate analysis, combination therapy with ELT/cyclosporine/ATG and response to previous therapy were associated with response. Overall survival was favorable with a 1-year survival from ELT start of 87.4%. We identified age, AA severity before ELT start and response to ELT as variables significantly associated with OS. Two patients transformed to MDS; other adverse events were mostly benign. In sum, ELT is used widely in Europe to treat AA patients, mostly in the relapsed/refractory setting. Response to ELT is similar to the clinical trial data across different age groups, treatment lines, and treatment combinations and results in favorable survival.
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Anemia Aplásica/tratamiento farmacológico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Pirazoles/uso terapéutico , Adulto , Anciano , Anemia Aplásica/mortalidad , Evaluación de Medicamentos , Utilización de Medicamentos , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/epidemiología , Síndromes Mielodisplásicos/etiología , Modelos de Riesgos Proporcionales , Receptores de Trombopoyetina/agonistas , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Oral chronic graft-versus-host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD. STUDY DESIGN AND METHODS: PG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273-point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS). RESULTS: In five patients, 12 autologous blood collections were performed; median 3 (range 1-3) per patient, and 26 PG applications were performed; median 6 (range 2-8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%-47.3%), and median NIH OMS total score for 27.3% (range 20.0%-50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%-100%). No side effects were observed. CONCLUSION: Application of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment.
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Plaquetas , Geles/administración & dosificación , Enfermedad Injerto contra Huésped/terapia , Enfermedades de la Boca/terapia , Adulto , Autoinjertos , Femenino , Geles/uso terapéutico , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/patología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/diagnóstico , Úlceras Bucales/diagnóstico , Úlceras Bucales/terapia , Dolor/prevención & control , Resultado del TratamientoRESUMEN
AIM: To investigate the ability of two standard quality of life (QOL) questionnaires - The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria. METHODS: In this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT. RESULTS: The study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P<0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P=0.0007) and social functioning subscale of QLQ C30 (P=0.009). CONCLUSION: cGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients.
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Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Calidad de Vida , Encuestas y Cuestionarios , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Enfermedad Crónica , Estudios Transversales , Femenino , Enfermedad Injerto contra Huésped/psicología , Estado de Salud , Trasplante de Células Madre Hematopoyéticas/psicología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , Estados Unidos , Adulto JovenRESUMEN
AIM: To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). METHODS: 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. RESULTS: Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P=0.043), had lower Karnofsky performance status (P=0.028), and had a higher B-cell number (P=0.005), platelet count (P=0.022), and total protein (P=0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P=0.001), higher intensity of immunosuppressive treatment (P=0.020), and total body irradiation conditioning (P=0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). CONCLUSION: These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported.
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Alopecia Areata/complicaciones , Enfermedad Injerto contra Huésped , Vitíligo/complicaciones , Adolescente , Adulto , Anciano , Alopecia Areata/inducido químicamente , Niño , Estudios de Cohortes , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trasplante Homólogo , Vitíligo/inducido químicamente , Adulto JovenRESUMEN
PURPOSE: This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM). PATIENTS AND METHODS: Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD). All individuals were typed for HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci using Polymerase Chain Reaction-Sequence Specific Primers, PCR-Sequence Based Typing and Next-Generation Sequencing. All statistical analyses were done in the MedCalc software, version 19.2.6. RESULTS: Patients with MMs at HLA-B locus demonstrated worse OS (P â= â0.0440, HR â= â2.00, n â= â20). Absence of HLA-DRB5 was associated with a higher incidence of GvHD (P â= â0.0112, HR â= â1.93, n â= â67). A lower incidence of GvHD was observed in patients with HLA class II MMs compared to patients with HLA class I MMs (P â= â0.0166, HR â= â1.94, n â= â29). Finally, analysis of PIRCHE score (PS) impact revealed that patients with HLA class II PS â> â10 in GvH direction showed higher incidence of GvHD compared to patients with HLA class II PS â< â10 (P â= â0.0073, HR â= â2.01, n â= â55). CONCLUSION: Obtained results undisputedly indicate the necessity to further investigate this matter on a larger patient group, with focus on specific HLA alleles to define precisely priority criteria for selecting the best donor for all patients, thus improving the outcome of HSCT with an MMUD.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Estudios Retrospectivos , Prueba de Histocompatibilidad , Antígenos HLA/genética , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
AIM: To investigate the influence of tumor necrosis factor (TNF) microsatellite polymorphisms on patient survival following hematopoietic stem cell transplantation. METHODS: We analyzed TNFa, TNFb, and TNFd microsatellites among 100 patients who underwent allogeneic hematopoietic stem cell transplantation from a human leukocyte antigen (HLA)-identical sibling donor at the Internal Clinic of the University Hospital Center Zagreb in the period 2001-2009. The analysis was performed using polymerase chain reaction amplification and electrophoresis on a polyacrylamide gel in an automated sequencer. RESULTS: There was no significant difference in patient survival with respect to the allele length at a given microsatellite. However, a significantly lower survival rate was noticed among patients who were positive for TNFa8 allele (P<0.001) and a significantly higher survival rate among those who were positive for TNFa10 allele (P=0.0220). CONCLUSION: These results for the first time suggest an influence of TNFa microsatellite on patient survival following HSCT and indicate a need for further studies of this microsatellite.
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Trasplante de Células Madre Hematopoyéticas/mortalidad , Repeticiones de Microsatélite , Polimorfismo de Nucleótido Simple , Factores de Necrosis Tumoral/genética , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
INTRODUCTION: We investigated the association of HLA on clinical outcomes in our cohort of patients in the haplo-HSCT program using the HLAMatchmaker (EM) and PIRCHE score (PS) algorithms. METHODS: The group comprised 64 patients (male = 35-54.7%, female 29-45.3%; median age 43 years) and their related haplo-HSCT donors (male = 30-46.9%, female 34-53.1%). HLA-A/B/C/DRB1/DQB1/DPB1 loci were analyzed. RESULTS: Multivariate analysis of the association between different HLA or patient/donor-related parameters and clinical outcome revealed the following associations with statistical significance: GvHD and HLA class I PS in the GvH direction (p = .0420) and relapse with diagnosis (p = .0163). For OS, the only variable showing a tendency of association was the source of HSCT (p = .0965). CONCLUSION: Combined results of univariate and multivariate analysis suggest that the patients awaiting the selection of the best haplo-HSCT donor could benefit the most from the combination of all three approaches, in cases when a suitable donor can be chosen from a number of potential donors.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Femenino , Enfermedad Injerto contra Huésped/etiología , Antígenos HLA/genética , Humanos , Masculino , Recurrencia , Estudios RetrospectivosRESUMEN
Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin's lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach.
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Hematopoietic stem cell (HSC) transplantation is a standard approach in the treatment of hematological malignant diseases. For the last 15 years the main source of cells for transplantation have been peripheral blood stem cells (PBSC). With the availability of hematopoietic growth factors and understanding the advantages of treatment with PBSC, the application of bone marrow (BM) was supplanted. The aim of this survey was to explore the success of PBSC collection, the factors which influence the success of PBSC collection, the composition and the quality of graft and their influence on hematopoietic recovery and outcome after transplantation in patients with acute myeloid leukemia (AML). PBSC were collected by the method of leukapheresis after applying a combination of chemotherapy and growth factors or only growth factors. The quality of graft was determined with the clonogenic progenitor cell assay and with the flow cytometry analysis. Of the total 134 patients with AML, who were submitted to HSC mobilization, the collection was successful in 78 (58.2%) patients. The collection was more successful after the first than after the second attempt of HSC mobilization (49% vs. 11%). The criteria for effective mobilization were the number of leukocytes > 3 x 10(9)/L and the concentration of CD34+ cells > 20 x 10(3)/mL in the peripheral blood on the first day of leukapheresis. The number of CD34+ cells infused had the strongest impact on hematopoietic recovery. We noted significantly faster hematological recovery of neutrophils and platelets, fewer number of transfused units of red blood cells and platelets, shorter duration of the tranfusion support, shorter treatment with intravenous antibiotic therapy and shorter hospitalization after PBSC compared to BM transplantation. These advantages could provide their standard application in the treatment of patients with AML.
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Hematopoyesis , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Transfusión Sanguínea , Niño , Preescolar , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucaféresis , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Matching for HLA-A, -B, -C, -DRB1, -DQB1 alleles is the gold standard in hematopoietic stem cell transplantation (HSCT). However, this is often not enough to prevent postransplantational complications. The HLA mismatches (MM) have been associated with higher risk of acute graft versus host disease (GvHD). Gamma block (GB) is located in central HLA region, between HLA-B/C and HLA-DRB/DQB blocks and contains many inflammatory and immune regulatory genes. Single nucleotide polymorphisms (SNPs) within that block can be considered as markers for MHC haplotype matching. Aim of the research was to test whether MM in GB impact the outcome of HSCT in 51 patients transplanted with HLA 10/10 matched unrelated donor. The recipient-donor pairs were typed using PCR SSP kit that detects 25 SNPs within GB. Fifteen out of 51 (29.41%) pairs were GT matched (GT-M) while 36 out of 51 pairs (70.59%) were mismatched (GT-MM). In a univariate analysis, GT-MM was a significant risk factor associated with aGvHD (Pâ¯=â¯0.041), although this association was not seen in multivariate analysis. No significant difference in overall survival and relapse occurrence was seen. These results were obtained on a small sample, and it is necessary to further test the possible role of GT matching in unrelated HSCT.
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Enfermedad Injerto contra Huésped , Antígenos HLA/genética , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Polimorfismo de Nucleótido Simple , Sistema de Registros , Donante no Emparentado , Adolescente , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
PURPOSE: This study investigated the frequency and characteristics of sarcopenia among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a specific focus on the chronic graft-versus-host disease (cGVHD) population and its association with malnutrition, vitamin D and clinical characteristics. METHODS: We assessed sarcopenia, vitamin D levels, and nutritional status in 73 patients who underwent allo-HSCT, of which 45 were diagnosed with cGVHD. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. RESULTS: Sarcopenia was diagnosed in 19.2% of patients after allo-HSCT with statistically no significant difference between cGVHD and non-cGVHD patients. The risk factor for sarcopenia was the male gender. Sarcopenia in allo-HSCT patients correlated strongly with malnutrition and with current corticosteroid treatment (p < 0.005). Among cGVHD patients sarcopenia additionally correlated strongly with the number of prior systemic immunosuppressive therapy lines (p < 0.005) and moderately with the intensity of immunosuppression, cGVHD severity global rating assessed by both the health care provider and the patient and joint and fascia cGVHD involvement (p < 0.05). Vitamin D deficiency was found in more than 54.8% of patients, but the correlation to sarcopenia was not found. CONCLUSION: Sarcopenia was found to be common in long term survivors of allo-HSCT independently of the cGVHD diagnosis. Prospective longitudinal studies are needed for a better understanding of factors affecting the development of sarcopenia after allo-HSCT.
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Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Sarcopenia/epidemiología , Adulto , Anciano , Aloinjertos , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Sarcopenia/etiología , Vitamina D/sangre , Adulto JovenRESUMEN
Chimerism status evaluation is a routine test performed in post-hematopoietic stem cell transplantation (HSCT) period. The aim of the study was to evaluate a quantitative polymerase chain reaction (qPCR) method (GenDx, Utrecht, the Netherlands) applicability for this purpose. The study included 74 recipient/donor pairs tested for informative markers: median of four and six informative markers was found for patients (related and unrelated donor, respectively). Higher sensitivity of qPCR method was confirmed by analysis of recipient post-HSCT samples (N = 800) among which microchimerism (0.1%-1% recipient DNA) was detected in 21.8% of cases. The ability to detect less than 1% of minor population, as opposed to the short tandem repeat (STR) method for which 1% is the limit, translated into earlier identification of a disease relapse for four patients in our study sample.
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Quimerismo , Trasplante de Células Madre Hematopoyéticas , Monitoreo Fisiológico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Quimera por Trasplante/genética , Familia , Marcadores Genéticos , Técnicas de Genotipaje/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Quimera por Trasplante/sangre , Inmunología del Trasplante/genética , Donante no EmparentadoRESUMEN
INTRODUCTION: Thrombosis is the most common complication in Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms patients. PATIENTS AND METHODS: In a cohort of 258 Ph- myeloproliferative neoplasm patients, the difference between patients with and without thrombosis was analyzed according to genetic thrombophilia factors, JAK2 V617F status and burden allele, blood count, cardiovascular risk factors and age. Patients were also divided in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) subgroups as well as by the type of thrombosis. RESULTS: Analysis of cardiovascular risk factors regarding arterial thrombosis showed that PV patients with thrombosis had higher incidence of diabetes (P = .030), ET patients more often had hypertension (P = .003) and hyperlipidemia (P = .005), while PMF patients had hyperlipidemia (P = .046) and at least one cardiovascular risk factor (P = .044). Moreover, leukocytes > 18 × 109/L and V617F burden allele > 25.7% were statistically significantly different in PV patients (P = .019 and borderline significant at P = .055, respectively), while in ET patients leukocytes > 9.2 × 109/L (P < .001) and age at diagnosis of > 55 years were statistically significantly different (P = .002). PMF patients with V617F burden allele ≤ 34.8% were more prone to thrombosis (P = .032). When comparing patients with and without venous thrombosis, cutoff value of V617F burden allele > 90.4% was significant for PV patients with thrombosis (P = .036), as was > 56.7% for PMF patients with thrombosis (P = .046). Platelets ≤ 536 × 109/L and age at diagnosis > 54 years showed statistically significant difference for ET patients with thrombosis (P = .015 and P = .041, respectively). CONCLUSION: On the basis of our results, a new scoring system for thrombosis risk in PV could be made, while PMF prognostic model may be expanded for better recognition of potential thrombotic risk factors.
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Recuento de Células Sanguíneas/métodos , Enfermedades Cardiovasculares/genética , Janus Quinasa 2/genética , Trastornos Mieloproliferativos/genética , Trombofilia/genética , Trombosis/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
Current classification of acute leukemia is based on morphology, immunophenotyping, cytogenetic and molecular abnormalities of leukemic cells. All these techniques have a diagnostic and prognostic value. Molecular abnormalities in many cases suggest the pathogenesis of acute leukemia, but also point to the key site of genetic abnormalities that may be targeted with the therapy. Treatment approach in acute leukemia is still chemotherapy. The probability of long-term disease-free survival after intensive chemotherapy for younger patients with acute lymphoblastic leukemia and acute myeloid leukemia is 30%-40% and 40%-50%, respectively. Allogeneic stem cell transplantation is associated with better disease-free survival compared to other cytotoxic regimens. In recent years, targeted therapy seems to improve the chemotherapy outcome. This therapy targets only leukemic cells while sparing normal cells. Immunotherapy, differential agents and especially drugs acting on the key molecular abnormalities are currently being used together with chemotherapy as a treatment approach for acute leukemia. It is expected that techniques such as gene expression profiling will identify genetic abnormalities and their proteins as a targeted site for new drugs. This might increase the efficacy of leukemia treatment and control.
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Leucemia/diagnóstico , Leucemia/terapia , Enfermedad Aguda , Adulto , Supervivencia sin Enfermedad , Humanos , Leucemia/mortalidad , Pronóstico , Tasa de SupervivenciaRESUMEN
Conflicting results have been reported regarding the association between early cytomegalovirus (CMV) reactivation and relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This prompted us to evaluate the impact of CMV reactivation on outcomes of 155 consecutive adult patients transplanted in our institution. In our study, CMV reactivation did not affect cumulative incidence (CI) of relapse in patients with lymphoproliferative disorders. However, the CI of relapse in patients with myeloproliferative disorders (AML and MPN) was 37% (95% CI, 21-53) in patients without CMV reactivation as opposed to 17% (95% CI, 9-28) in patients with CMV reactivation (p = 0.03). An important correlation between CMV reactivation and relapse was found in patients with MPN; the CI of relapse was 50% (95% CI, 12-80) in patients without CMV reactivation as opposed to only 7% (95% CI, 0-27) in patients with CMV reactivation (p = 0.02). A substantial reduction of relapse in myeloproliferative disorders associated with CMV reactivation was confirmed by multivariate analysis (HR 2.73; 95% CI, 1.09-6.82, p = 0.03) using time-dependent covariates for high-risk disease, older age, RIC conditioning, ATG, grade II-IV acute, and chronic GVHD. To our knowledge, we are the first to show an association of CMV reactivation with relapse reduction in MPN patients. This putative virus vs myeloproliferation effect warrants further research.
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Citomegalovirus/patogenicidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo/efectos adversos , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Trastornos Mieloproliferativos , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo/métodos , Adulto JovenAsunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Linfoma de Burkitt/tratamiento farmacológico , Metotrexato/administración & dosificación , Adolescente , Adulto , Protocolos Antineoplásicos , Linfoma de Burkitt/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , RituximabRESUMEN
The impact of patient/donor matching for HLA-A, -B, -C, -DRB1 and -DQB1 genes in hematopoietic stem cell transplantation (HSCT) is well-recognized, but typing for additional genes, such as HLA-DPB1, is still controversial. Based on defined T-cell epitope (TCE) groups, all HLA-DPB1 mismatches can be classified as permissive or non-permissive. In this retrospective study we analysed 82 patient-matched unrelated donor (MUD) pairs who underwent HSCT, and explored the impact of HLA-DPB1 matches, permissive and non-permissive mismatches on transplantation outcomes. Patient-MUD pairs matched for HLA-DPB1 alleles in univariate analysis were associated with a significantly higher incidence of disease relapse compared to pairs who were permissive/non-permissive HLA-DPB1 mismatched according to the TCE3 and TCE4 algorithms (P=0.025 and P=0.026, respectively), although the significance was lost in multivariate analysis. The analysis did not reveal any significant influence of HLA-DPB1 alleles on overall survival (OS), non-relapse mortality (NRM) or graft-versus-host disease (GvHD) incidence. In conclusion, our study presents evidence that HLA-DPB1 matching influenced the relapse rate in patients after HSCT so the HLA-DPB1 alleles should be implemented in the MUD search algorithm as a transplantation determinant.
Asunto(s)
Enfermedad Injerto contra Huésped/genética , Cadenas beta de HLA-DP/genética , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Epítopos de Linfocito T/metabolismo , Femenino , Genotipo , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/mortalidad , Histocompatibilidad , Prueba de Histocompatibilidad , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
Killer cell immunoglobulin-like receptors (KIR) are a family of inhibitory/activating receptors expressed on NK cells. Interactions of KIR receptors with KIR ligands have been shown to modify hematopoietic stem cell transplantation (HSCT) outcome. The aim of this research was to determine the KIR2DS4 allele variants distribution among 111 patients with different hematological malignancy who underwent HSCT and their donors, and to evaluate KIR2DS4 alleles' impact on HSCT outcome. The KIR gene frequency analysis showed a significantly higher incidence of full-length KIR2DS4 alleles among patients. The impact of KIR2DS4 alleles on transplantation outcomes revealed that donors' full-length KIR2DS4 alleles is associated with lower overall survival rates, higher risk of GVHD and higher relapse incidence. The expression of full-length KIR2DS4 allele variants may contribute to a worse clinical outcome after HSCT. KIR typing for KIR2DS4 could be used as an additional criterion for selecting suitable donors in cases when more than one HLA identical donor is identified for a specific patient.