RESUMEN
ABSTRACT: Deleterious germ line RUNX1 variants cause the autosomal dominant familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, platelet dysfunction, and a predisposition to hematologic malignancies (HMs). We launched a FPDMM natural history study and, from January 2019 to December 2021, enrolled 214 participants, including 111 patients with 39 different RUNX1 variants from 45 unrelated families. Seventy of 77 patients had thrombocytopenia, 18 of 18 had abnormal platelet aggregometry, 16 of 35 had decreased platelet dense granules, and 28 of 55 had abnormal bleeding scores. Nonmalignant bone marrows showed increased numbers of megakaryocytes in 12 of 55 patients, dysmegakaryopoiesis in 42 of 55, and reduced cellularity for age in 30 of 55 adult and 17 of 21 pediatric cases. Of 111 patients, 19 were diagnosed with HMs, including myelodysplastic syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia, acute lymphoblastic leukemia, and smoldering myeloma. Of those 19, 18 were relapsed or refractory to upfront therapy and referred for stem cell transplantation. In addition, 28 of 45 families had at least 1 member with HM. Moreover, 42 of 45 patients had allergic symptoms, and 24 of 30 had gastrointestinal (GI) symptoms. Our results highlight the importance of a multidisciplinary approach, early malignancy detection, and wider awareness of inherited disorders. This actively accruing, longitudinal study will genotype and phenotype more patients with FPDMM, which may lead to a better understanding of the disease pathogenesis and clinical course, which may then inform preventive and therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT03854318.
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Neoplasias Hematológicas , Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Trombocitopenia , Adulto , Humanos , Niño , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Estudios Longitudinales , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicaciones , Trombocitopenia/genética , Trastornos Mieloproliferativos/complicaciones , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicacionesRESUMEN
Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors. We analyzed 83 patients with somatic pathogenic variants in UBA1 at p.Met41 (p.Met41Leu/Thr/Val), the start codon for translation of the cytoplasmic isoform of UBA1 (UBA1b). Patients with the p.Met41Val genotype were most likely to have an undifferentiated inflammatory syndrome. Multivariate analysis showed ear chondritis was associated with increased survival, whereas transfusion dependence and the p.Met41Val variant were independently associated with decreased survival. Using in vitro models and patient-derived cells, we demonstrate that p.Met41Val variant supports less UBA1b translation than either p.Met41Leu or p.Met41Thr, providing a molecular rationale for decreased survival. In addition, we show that these 3 canonical VEXAS variants produce more UBA1b than any of the 6 other possible single-nucleotide variants within this codon. Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A>T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G>C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis.
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Nucleótidos , Enzimas Activadoras de Ubiquitina , Codón Iniciador , Humanos , Mutación , Enzimas Activadoras de Ubiquitina/genética , UbiquitinaciónRESUMEN
Pediatric cutaneous T-cell lymphoma with γδ immunophenotype is extremely rare. Only a few cases of γδ T-cell neoplasm have been reported in the literature, and therefore little is known whether γδ T-cell neoplasms in children are distinct from their adult counterparts with respect to the clinicopathological presentation, behavior, and prognosis. In this study, we demonstrate three unique pediatric cutaneous T-cell neoplasm and mimics with increased γδ T cells. All cases showed an indolent clinical course.
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Linfoma Cutáneo de Células T , Neoplasias Cutáneas , Adulto , Humanos , Niño , Linfocitos T/patología , Neoplasias Cutáneas/patología , Piel/patología , PronósticoRESUMEN
Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 Federal Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of cGVHD. Part II discusses disease grading and therapeutic management.
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Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Calidad de Vida , Enfermedad Crónica , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.
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Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Calidad de Vida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Piel/patología , Enfermedad CrónicaRESUMEN
Dominant negative (DN) mutations in signal transducer and activator of transcription 3 (STAT3) are known to cause hyper-IgE syndrome, a rare primary immunodeficiency. STAT3 DN patients are prone to develop fungal infections, including chronic mucocutaneous candidiasis due to impaired IL-17-mediated immunity, and pulmonary aspergillosis. Despite having preserved phagocyte functions, STAT3 DN patients present connective tissue abnormalities and a defect in the immunological skin barrier. Fusarium species are ubiquitous molds, whose potential to infect humans depends on the host's innate and cellular immune status. Our aim was to describe four STAT3 DN patients with fusariosis confined to the skin. Medical records were reviewed and summarized. Four patients, aged 4, 11, 30, and 33 years, presented with chronic skin lesions which started in the extremities. Two patients had remote lesions, and none had systemic involvement. Skin biopsies showed mycelial threads with deep inflammatory-occasionally granulomatous-infiltrates, reaching the dermis; cultures grew Fusarium solani. Response to treatment was heterogeneous, often requiring multimodal therapies, including topical antifungal preparations. In this work, we describe primary invasive cutaneous fusariosis as a syndromic entity in four STAT3 DN patients.
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Fusariosis , Síndrome de Job , Humanos , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Síndrome de Job/genética , Factor de Transcripción STAT3/genética , Piel/microbiología , Antifúngicos/uso terapéuticoRESUMEN
Steroid-refractory chronic graft-versus-host disease (cGVHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase 2 clinical trial (#NCT01688466) to determine the safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGVHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide 0.5 mg per day orally (n = 17; low-dose cohort) or 2 mg per day at a starting dose of 0.5 mg per day increasing to 2 mg per day over 6 weeks (n = 17; high-dose cohort). The primary endpoint was overall response rate (ORR) at 6 months according to the 2005 National Institutes of Health cGVHD Response Criteria. Thirty-two patients had severe sclerotic skin and received a median of 5 (range, 2-10) previous systemic therapies. ORR was 47% (95% confidence interval, 30-65) in the intention-to-treat analyses. All were partial responses, with no difference in ORR between the cohorts. ORR was 67% (45%-84%) in the 24 evaluable subjects at 6 months. Nine had improvement in National Institutes of Health joint/fascia scores (P = .018). Median change from the baseline in body surface area involvement of skin cGVHD was -7.5% (-10% to 35%; P = .002). The most frequent adverse events were lymphopenia, infection, and fatigue. Eight subjects in the high-dose cohort had dose decreases because of adverse events. There was 1 death in the low-dose cohort from bacterial pneumonia. Our data indicate antifibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and interleukin-2. Pomalidomide 0.5 mg per day is a safe and effective therapy for advanced corticosteroid-refractory cGVHD.
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Enfermedad Injerto contra Huésped/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Terapia Recuperativa/métodos , Talidomida/análogos & derivados , Adolescente , Adulto , Anciano , Aloinjertos , Susceptibilidad a Enfermedades , Relación Dosis-Respuesta a Droga , Resistencia a Medicamentos , Fatiga/etiología , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Infecciones , Articulaciones/patología , Estimación de Kaplan-Meier , Recuento de Linfocitos , Subgrupos Linfocitarios/efectos de los fármacos , Subgrupos Linfocitarios/inmunología , Linfopenia/etiología , Masculino , Persona de Mediana Edad , Calidad de Vida , Piel/patología , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/farmacocinética , Talidomida/uso terapéutico , Adulto JovenRESUMEN
We report a series of four unrelated adults with Smith-Magenis syndrome (SMS) and concomitant features of Birt-Hogg-Dubé (BHD) syndrome based upon haploinsufficiency for FLCN and characteristic renal cell carcinomas and/or evidence of cutaneous fibrofolliculomas. Three of the cases constitute the first known association of histopathologically verified characteristic BHD-associated renal tumors in adults with SMS; the fourth was identified to have histologically confirmed skin fibrofolliculomas. Molecular analysis documented second-hit FLCN mutations in two of the three cases with confirmed BHD renal pathology. These cases suggest the need to expand management recommendations for SMS to include kidney cancer surveillance starting at 20 years of age, as per the screening recommendations for BHD syndrome.
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Síndrome de Birt-Hogg-Dubé , Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Cutáneas , Síndrome de Smith-Magenis , Adulto , Humanos , Síndrome de Birt-Hogg-Dubé/complicaciones , Síndrome de Birt-Hogg-Dubé/diagnóstico , Síndrome de Birt-Hogg-Dubé/genética , Síndrome de Smith-Magenis/complicaciones , Detección Precoz del Cáncer , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Neoplasias Renales/genética , Carcinoma de Células Renales/genética , Neoplasias Cutáneas/genéticaRESUMEN
BACKGROUND: Singleton-Merten syndrome (SGMRT) is a rare immunogenetic disorder that variably features juvenile open-angle glaucoma (JOAG), psoriasiform skin rash, aortic calcifications and skeletal and dental dysplasia. Few families have been described and the genotypic and phenotypic spectrum is poorly defined, with variants in DDX58 (DExD/H-box helicase 58) being one of two identified causes, classified as SGMRT2. METHODS: Families underwent deep systemic phenotyping and exome sequencing. Functional characterisation with in vitro luciferase assays and in vivo interferon signature using bulk and single cell RNA sequencing was performed. RESULTS: We have identified a novel DDX58 variant c.1529A>T p.(Glu510Val) that segregates with disease in two families with SGMRT2. Patients in these families have widely variable phenotypic features and different ethnic background, with some being severely affected by systemic features and others solely with glaucoma. JOAG was present in all individuals affected with the syndrome. Furthermore, detailed evaluation of skin rash in one patient revealed sparse inflammatory infiltrates in a unique distribution. Functional analysis showed that the DDX58 variant is a dominant gain-of-function activator of interferon pathways in the absence of exogenous RNA ligands. Single cell RNA sequencing of patient lesional skin revealed a cellular activation of interferon-stimulated gene expression in keratinocytes and fibroblasts but not in neighbouring healthy skin. CONCLUSIONS: These results expand the genotypic spectrum of DDX58-associated disease, provide the first detailed description of ocular and dermatological phenotypes, expand our understanding of the molecular pathogenesis of this condition and provide a platform for testing response to therapy.
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Exantema , Glaucoma de Ángulo Abierto , Odontodisplasia , Proteína 58 DEAD Box/genética , Exantema/patología , Glaucoma de Ángulo Abierto/patología , Humanos , Interferones/genética , Metacarpo/patología , Odontodisplasia/genética , Odontodisplasia/patología , Receptores InmunológicosRESUMEN
OBJECTIVES: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in ALPK1, is an autoinflammatory disease. METHODS: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of ALPK1 mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored. Exome sequencing was used to identify a new pathogenic variant. Cytokine profiling, transcriptomics, immunoblotting and knock-in mice were used to assess the impact of ALPK1 mutations on protein function and immune signalling. RESULTS: The majority of the cohort carried the p.Thr237Met mutation but we also identified a new ROSAH-associated mutation, p.Tyr254Cys.Nearly all patients exhibited at least one feature consistent with inflammation including recurrent fever, headaches with meningeal enhancement and premature basal ganglia/brainstem mineralisation on MRI, deforming arthritis and AA amyloidosis. However, there was significant phenotypic variation, even within families and some adults lacked functional visual deficits. While anti-TNF and anti-IL-1 therapies suppressed systemic inflammation and improved quality of life, anti-IL-6 (tocilizumab) was the only anticytokine therapy that improved intraocular inflammation (two of two patients).Patients' primary samples and in vitro assays with mutated ALPK1 constructs showed immune activation with increased NF-κB signalling, STAT1 phosphorylation and interferon gene expression signature. Knock-in mice with the Alpk1 T237M mutation exhibited subclinical inflammation.Clinical features not conventionally attributed to inflammation were also common in the cohort and included short dental roots, enamel defects and decreased salivary flow. CONCLUSION: ROSAH syndrome is an autoinflammatory disease caused by gain-of-function mutations in ALPK1 and some features of disease are amenable to immunomodulatory therapy.
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Enfermedades Autoinflamatorias Hereditarias , FN-kappa B , Proteínas Quinasas/genética , Amiloidosis , Animales , Estudios de Cohortes , Mutación con Ganancia de Función , Enfermedades Autoinflamatorias Hereditarias/genética , Humanos , Inflamación/genética , Ratones , Mutación , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Quinasas/metabolismo , Calidad de Vida , Proteína Amiloide A Sérica , Síndrome , Inhibidores del Factor de Necrosis TumoralRESUMEN
BACKGROUND: Chronic graft-versus-host disease (GVHD) is a major cause of late morbidity and non-relapse mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Its biology, however, remains poorly understood, making the studies of its biology and immunomodulatory therapies a difficult task. Such research is often hampered by lymphopenia which is common in these patients and precludes studies of critical cellular subsets across the spectrum of severity of disease. This study explores the potential of leukapheresis to safely acquire and efficiently store immune cells for immunology research in chronic GVHD. METHODS: This is a cross-sectional study in which 132 consecutively accrued patients undergo optional research leukapheresis and a one-week comprehensive outpatient evaluation. Baseline clinical and laboratory data and efficiency of the procedure were reported. RESULTS: Ninety-four of 132 patients (71%) achieved the goal collection of 2 × 10^9 PBMNCs with a mean volume processed of 4.6 L. Only mild decreases in hemoglobin, platelet, lymphocyte and monocytes were observed. All adverse events were mild (grade 1) and had resolved by the time of discharge from the apheresis unit. CONCLUSION: This study demonstrates feasibility, safety, and efficiency of research leukapheresis in a frail patient population. Results presented promote leukapheresis as a standard research practice option in studies of chronic GVHD in humans which may expedite advances in our understanding of this complex multisystem disease.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Leucaféresis/métodos , Trasplante Homólogo/efectos adversos , Estudios Transversales , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Cases of new-onset pernio and recurrences in our cohort align tightly with trends in mean 7-day COVID-19 positivity in Wisconsin and mean temperature in Madison, Wisconsin by month.
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COVID-19 , Eritema Pernio , Antivirales , Eritema Pernio/diagnóstico , Eritema Pernio/epidemiología , Eritema Pernio/genética , Humanos , Interferones , Estudios Prospectivos , SARS-CoV-2/genéticaRESUMEN
A woman with ichthyosis, contractures, and progressive neuropathy represents the first case of phosphoserine aminotransferase deficiency diagnosed and treated in an adult. She has novel compound heterozygous mutations in the gene PSAT1. Treatment with high dose oral L-serine completely resolved the ichthyosis. Consideration of this diagnosis is important because early treatment with L-serine repletion can halt progression of neurodegeneration and potentially improve neurological disabilities. As exome sequencing becomes more widely implemented in the diagnostic evaluation of progressive neurodegenerative phenotypes, adult neurologists and geneticists will increasingly encounter later onset manifestations of inborn errors of metabolism classically considered in infancy and early childhood.
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Anomalías Congénitas/genética , Ictiosis/genética , Serina/biosíntesis , Transaminasas/genética , Adulto , Preescolar , Anomalías Congénitas/patología , Femenino , Retardo del Crecimiento Fetal/genética , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/patología , Humanos , Ictiosis/metabolismo , Ictiosis/patología , Deformidades Congénitas de las Extremidades/genética , Deformidades Congénitas de las Extremidades/patología , Microcefalia/genética , Microcefalia/patología , Trastornos Psicomotores/genética , Trastornos Psicomotores/patología , Convulsiones/genética , Convulsiones/patología , Serina/deficiencia , Serina/genética , Esfingolípidos/deficiencia , Esfingolípidos/genética , Transaminasas/deficiencia , Secuenciación del ExomaRESUMEN
BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.
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Dermatología/métodos , Hospitalización , Consulta Remota/métodos , Enfermedades de la Piel/diagnóstico , Adulto , Anciano , Estudios de Factibilidad , Femenino , Médicos Hospitalarios/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Fotograbar , Estudios Prospectivos , Piel/diagnóstico por imagen , Encuestas y Cuestionarios/estadística & datos numéricos , Centros de Atención TerciariaRESUMEN
Graft-versus-host disease (GVHD) is a multisystemic disorder that affects 30%-80% of patients who undergo allogeneic hematopoietic stem cell transplantation 10%-15% of GVHD patients develop sclerotic features affecting the skin or deeper tissues, leading to functional limitations and poor quality of life. There is limited literature regarding the indications and efficacy of specific rehabilitative interventions in sclerotic GVHD (sclGVHD). In this article, we summarize the current evidence supporting rehabilitation intervention in sclGVHD and offer our approach to the multidisciplinary management of this disease. In addition, we review techniques that have been employed in other sclerotic skin diseases (eg, iontophoresis, extracorporeal shock waves, botulinum toxin A, adipose derived stromal vascular fraction), but that require further validation in the sclGVHD setting. Ultimately, optimal care for this complex disease requires a multidisciplinary approach that includes a rehabilitation and adaptive program tailored to each patient's needs.
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Enfermedad Injerto contra Huésped/rehabilitación , Trasplante de Células Madre Hematopoyéticas , Terapia Ocupacional , Grupo de Atención al Paciente , Modalidades de Fisioterapia , Enfermedades de la Piel/rehabilitación , Fascia/patología , Humanos , Calidad de Vida , EsclerosisRESUMEN
Chronic graft-versus-host disease (cGVHD) is the leading late complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients receive multiple lines of systemic therapy until cGVHD resolves, but about 15% remain on systemic treatment for more than 7 years after cGVHD diagnosis. This study describes the clinical and biological factors of patients who present with cGVHD persisting for ≥7 years (persistent cGVHD). Patients with persistent cGVHD (n = 38) and those with cGVHD for <1 year (early cGVHD) (n = 83) were enrolled in a prospective cross-sectional natural history study. Patients in the persistent cGVHD group were a median of 10.2 years from cGVHD diagnosis (range 7-27 years). Fifty-eight percent of persistent cGVHD patients (22/38) were receiving systemic immunosuppression, compared to 88% (73/83) in the early cGVHD group. In multivariable analysis, bone marrow (BM) stem cell source, presence of ENA autoantibodies, higher NIH lung score, higher platelet counts, and higher IgA levels were significantly associated with persistent cGVHD. A high sensitivity panel of serum biomarkers including seven cytokines diagnostic for cGVHD was analyzed and showed significantly lower levels of BAFF and CXCL10 in patients with persistent cGVHD. In conclusion, standardly accepted clinical measures of disease severity may not accurately reflect disease activity in patients with persistent cGVHD. However, many patients with persistent cGVHD are still receiving systemic immunosuppression despite lacking evidence of disease activity. Development of reliable clinical biomarkers of cGVHD activity may help guide future systemic treatments.
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Citocinas/sangre , Enfermedad Injerto contra Huésped/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Anciano , Aloinjertos , Biomarcadores , Niño , Enfermedad Crónica , Estudios Transversales , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Acondicionamiento Pretrasplante , Adulto JovenRESUMEN
PURPOSE: To explore improvement in motor ability, function, health-related quality of life (HRQOL), and symptom severity in patients with sclerotic chronic graft-versus-host disease (ScGVHD) in response to treatment as well as the relationship among changes on such measures. METHODS: This study was a secondary analysis of data from 13 individuals with severe ScGVHD enrolled in a clinical trial evaluating the efficacy of imatinib mesylate (clinicaltrials.gov identifier: NCT00702689). Self-reported, clinician-reported, and performance-based indicators of motor ability, function, HRQOL, and symptom severity were assessed at baseline and 6 months following the administration of imatinib mesylate. RESULTS: Participants did not show statistically significant improvement on any measures over time. Approximately one-third of patients displayed clinically significant improvement on measures of motor ability (palmar pinch strength, dominant hand, 30.8%), functioning (Manual Ability Measure-36, 41.7%), HRQOL (Short Form 36 [SF-36] Mental Component Summary, 33.3%), and symptom severity (Lee Symptom Scale, 38.5%). Improvement in cGVHD symptom burden was correlated with improvement in function (Assessment of Motor and Process Skills [AMPS] and Disabilities of the Arm, Shoulder, and Hand [DASH] scores) and HRQOL (SF-36 Physical Component Summary scores). CONCLUSIONS: Findings suggest the potential utility of administering patient-reported and performance-based functional measures, such as the DASH and the AMPS, to patients with cGVHD. By understanding the functional consequences of ScGVHD, interdisciplinary teams of health care providers, including rehabilitation professionals, can work to improve long-term outcomes.
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Enfermedad Injerto contra Huésped/tratamiento farmacológico , Mesilato de Imatinib/uso terapéutico , Destreza Motora/efectos de los fármacos , Adolescente , Adulto , Niño , Enfermedad Crónica , Ensayos Clínicos Fase II como Asunto , Femenino , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Destreza Motora/fisiología , Calidad de Vida , Esclerosis , Adulto JovenRESUMEN
Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.
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Fístula Arteriovenosa , Arteria Pulmonar/anomalías , Venas Pulmonares/anomalías , Telangiectasia , Telómero , Animales , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/patología , Educación , Humanos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Venas Pulmonares/metabolismo , Venas Pulmonares/patología , Telangiectasia/genética , Telangiectasia/metabolismo , Telangiectasia/patología , Telómero/genética , Telómero/metabolismo , Telómero/patologíaRESUMEN
KEY TEACHING POINTS.