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1.
Transplant Proc ; 56(8): 1841-1846, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39232921

RESUMEN

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with TCR αß+/CD19+ cell depletion is a promising therapeutic alternative for children with nonmalignant hematologic disorders, especially in low-income countries where finding a compatible donor is challenging. The use of this transplantation approach for nonmalignant hematologic disorders has not been previously described in the Peruvian pediatric population. METHODS: We present the outcomes of children under 19 with nonmalignant hematologic disorders who underwent haplo-HSCT with TCR αß+/CD19+ cell depletion between 2018-2022 at a referral center in Lima, Peru. Survival probabilities and cumulative incidence functions were calculated using the Kaplan-Meier method. RESULTS: A total of 17 children aged between 1 to 18.6 years (median = 9.7 years) were included. The follow-up period ranged from 10 days to 66.20 months, with a median of 4.34 months. The probability of overall survival, event-free survival, and failure-free survival was 33.70%, 31.40%, and 68.8%, respectively. The incidence rate of graft failure was 49.80%, while the mortality rate not associated with graft failure was 18.8%. The incidence rate of acute graft-versus-host disease (GvHD) was 25.60%, and the incidence rate of viral infections was 59.40%. CONCLUSIONS: The high incidence rates of graft failure and viral infections suggest that these factors may negatively impact the survival of children with nonmalignant hematologic disorders who undergo haplo-HSCT with TCR αß+/CD19+ cell depletion. Therefore, optimizing the current conditioning regimens and ensuring timely access to first, second, and third-line antivirals is crucial to improve the survival of these patients.


Asunto(s)
Antígenos CD19 , Enfermedad Injerto contra Huésped , Enfermedades Hematológicas , Trasplante de Células Madre Hematopoyéticas , Trasplante Haploidéntico , Humanos , Niño , Adolescente , Preescolar , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Perú , Masculino , Femenino , Lactante , Enfermedades Hematológicas/terapia , Enfermedades Hematológicas/cirugía , Enfermedad Injerto contra Huésped/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta , Resultado del Tratamiento , Depleción Linfocítica , Estudios Retrospectivos
2.
Curr Opin Hematol ; 31(6): 261-269, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39046889

RESUMEN

PURPOSE OF REVIEW: Recent progress in human leukocyte antigen (HLA) characterization, increased accrual of unrelated donors and cord blood units, and a new platform for haploidentical transplantation have resulted in the widespread availability of donors for allogeneic hematopoietic stem cell transplantation. RECENT FINDINGS: Advances in HLA typing have identified an increasing number of loci and alleles that are crucial for successful transplantation. Newer HLA A, B, C, DRB1, and DQB1 alleles, DPB1 mismatches, and HLA B leader sequence matching are incorporated into donor selection algorithms. Donor selection is highly relevant because of recently published conflicting studies using different donor types. These studies are largely retrospective and compare patients with different diseases and stages, conditioning regimens, graft versus host disease (GVHD) prophylaxis, and time periods. A broad consensus indicates that the best donor is an available matched sibling, followed by a matched unrelated donor, and then alternative donors such as haploidentical, mismatched unrelated, and cord blood units. This consensus is being challenged by other factors, such as donor age, patient condition, urgency of transplantation, and costs involved. SUMMARY: In this review, we will analyze the unique characteristics of each donor type, the HLA and non HLA factors that affect donor choices, and the outstanding comparative outcome studies of different donor usage in hematologic malignancies.


Asunto(s)
Selección de Donante , Trasplante de Células Madre Hematopoyéticas , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Prueba de Histocompatibilidad , Antígenos HLA/inmunología , Antígenos HLA/genética , Donante no Emparentado , Neoplasias Hematológicas/terapia , Donantes de Tejidos , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/etiología
3.
Pediatr Transplant ; 28(5): e14820, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38977381

RESUMEN

BACKGROUND: There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). METHODS: Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). RESULTS: OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. CONCLUSIONS: OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estado Nutricional , Estomatitis , Acondicionamiento Pretrasplante , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Femenino , Masculino , Niño , Preescolar , Estomatitis/etiología , Estudios Retrospectivos , Adolescente , Lactante , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/efectos adversos , Factores de Riesgo , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias/complicaciones
4.
Lima; INS-CETS; jun. 2024.
No convencional en Español | BRISA/RedTESA | ID: biblio-1568037

RESUMEN

INTRODUCCIÓN: Cuadro clínico: La Enfermedad de Injerto Contra Huésped (EICH) es una complicación multisistémica frecuente y potencialmente mortal del Trasplante Alogénico de Células Progenitoras Hematopoyéticas (TACPH). Las complicaciones están influenciadas por factores relacionados con el paciente como la edad, el estado funcional, comorbilidades, y pueden afectar la piel, boca, ojos, pulmón, hígado e intestinos. La EICH crónica se presenta entre el 30% - 70% de pacientes post TACPH. Entre los factores de riesgo se ha descrito el aumento de la edad del huésped, el estado del citomegalovirus (CMV) del donante y del huésped, la seropositividad del virus de Epstein-Barr (VEB) del donante, el trasplante de células madre de sangre periférica versus trasplante de médula ósea, EICH aguda previa, la presencia de un ambiente estéril (incluida la descontaminación intestinal), y el desajuste inmunitario. Según la gravedad, la EICH crónica puede ser leve, moderada o severa. La clasificación orientará el tratamiento y el pronóstico de la enfermedad. La clasificación se basa en el sistema de puntuación del Instituto Nacional de Salud de los Estados Unidos (NIH por sus siglas en inglés) modificado el cual incluye evaluación de la piel, la boca, los ojos, el tracto gastrointestinal, el hígado, los pulmones, las articulaciones/fascia y el tracto genital. En casos de EICH crónica leve, generalmente se puede manejar con tratamiento localizado o tópico, a menos que la manifestación clínica sea extensa. En pacientes en las que la EICH crónica leve, mo


Asunto(s)
Humanos , Corticoesteroides/efectos adversos , Trasplante de Células Madre Hematopoyéticas/instrumentación , Janus Quinasa 1/uso terapéutico , Janus Quinasa 2/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Evaluación en Salud/economía , Eficacia , Análisis Costo-Beneficio/economía
5.
Eye Contact Lens ; 50(5): 212-221, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38518064

RESUMEN

ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.


Asunto(s)
Síndromes de Ojo Seco , Enfermedad Injerto contra Huésped , Humanos , Síndromes de Ojo Seco/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos
6.
Eye Contact Lens ; 50(4): 189-193, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38350098

RESUMEN

PURPOSE: To report the outcomes of cataract surgery in patients with ocular graft-versus-host disease (oGVHD) using a novel preoperative immunomodulatory regimen in a collaborative subspecialty care setting. METHODS: Retrospective case series of patients with oGVHD who underwent cataract surgery using a novel preoperative immunomodulatory regimen in a collaborative care setting. A preoperative regimen consisting of pooled human immune globulin 1%, autologous serum 50%, and methylprednisolone 1% eye drops was prescribed. Outcome measures included visual acuity (VA), ocular surface disease index (OSDI) score, lissamine green staining, and complications with a minimum of 2 years of follow-up. RESULTS: Thirty-five eyes from 20 patients with oGVHD were studied. The mean age was 59 years (range 30-70 years). A healthy comparison group included 35 eyes from 24 patients with a mean age of 63 years (range 44-74 years). At the 2-year follow-up, the mean corneal staining score was 2.3/15, the mean OSDI score was 37.5, and the mean VA was 20/30 (logarithm of the minimal angle of resolution 0.17). The global complication rate was 2.8% at the last follow-up with no difference versus a healthy comparison group. CONCLUSIONS: A collaborative care model improving ocular surface health before cataract surgery with dry eye and cataract subspecialists can optimize outcomes in patients with oGVHD.


Asunto(s)
Extracción de Catarata , Catarata , Síndromes de Ojo Seco , Enfermedad Injerto contra Huésped , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Enfermedad Injerto contra Huésped/complicaciones , Extracción de Catarata/efectos adversos , Síndromes de Ojo Seco/complicaciones , Catarata/complicaciones , Inflamación
7.
Arch. argent. pediatr ; 122(1): e202310061, feb. 2024. tab, ilus
Artículo en Inglés, Español | BINACIS, LILACS | ID: biblio-1525854

RESUMEN

El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.


Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.


Asunto(s)
Humanos , Masculino , Lactante , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Trasplante de Médula Ósea/efectos adversos , Ciclofosfamida
8.
Bone Marrow Transplant ; 59(4): 473-478, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38253868

RESUMEN

Anti-thymocyte globulin (ATG) has become a standard in preventing GVHD in related and unrelated donor transplantation, but there is no consensus on the best administration schedule. The PARACHUTE trial reported excellent CD4 immune reconstitution (CD4 IR) using a dosing schedule based on the patient's weight and pre-conditioning absolute lymphocyte count (ALC). In 2015 we introduced the PARACHUTE dosing schedule for pediatric patients at our center. One hundred one patients were transplanted for malignant and non-malignant diseases. In this non-concurrent cohort CD4 IR+, defined by a single CD4 count >50/µL on day 90, was seen in 81% of patients. The incidence of grade II-IV and III to IV aGvHD was 26.6% and 15.3% and 5% for cGvHD with no severe cases. We found no difference in aGvHD between donor type and stem cell sources. Five-year EFS and OS were 77.5% and 83.5%. Grade III-IV GFRS was 75.2%. CD4 IR+ patients had better EFS (93.1% vs. 77.7%, p = 0.04) and lower non-relapse mortality (2.7% vs. 22.2%, p = 0.002). The PARACHUTE ATG dosing schedule individualized by weight and ALC results in good early immune reconstitution, low incidence of cGvHD, and favorable survival for patients with different disease groups, donor types, and stem cell sources.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Niño , Suero Antilinfocítico/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad Injerto contra Huésped/etiología , Recuento de Linfocitos , Acondicionamiento Pretrasplante/métodos , Donante no Emparentado , Estudios Retrospectivos
9.
Transpl Immunol ; 83: 102002, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38286299

RESUMEN

INTRODUCTION: Hematopoietic Stem Cell Transplant (HSCT) is currently an important curative treatment for many patients with malignant and non-malignant diseases. Graft versus host disease (GVHD) represents a major complication in allogeneic HSCT recipients. Several polymorphisms in cytokine genes have recently been investigated as candidates for risk factors for acute-GVHD (aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). OBJECTIVE: In this study, we analyzed specific interleukin (IL)-10 haplotypes polymorphisms, in a cohort of 99 patients and their respective allo-HSCT donors for aGVHD and risk. RESULTS: An association was found between IL-10 promoter haplotype polymorphisms at positions -1082, -819 and - 592 with the occurrence of aGVHD. Patients who have the GCC/GCC haplotype are at increased risk of aGVHD (P = 0.017, HR: 5.42 (95% CI: 1.34-21.84). In the donors group and severity of aGVHD as not found statistical significancy. CONCLUSION: The results obtained show the IL-10 GCC/GCC haplotype can be an important biomarker to identify the greatest risk of aGVHD in the patient undergoing HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Interleucina-10 , Haplotipos , Brasil , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Estudios Retrospectivos
11.
Transpl Immunol ; 82: 101989, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38199270

RESUMEN

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) remains a critical treatment for advanced or high-risk hematological malignancies, posing challenges such as finding suitable donors and managing of graft-versus-host disease (GvHD). This study estimates 3-year overall survival in patients who underwent HSCT at our referral service in the state of Minas Gerais, Brazil. MATERIAL AND METHODS: This retrospective observational cohort study involved 41 patients who received HSCT between 2017 and 2021 at the Felício Rocho Hospital. Recipients received HSCT from either haploidentical donor (Haplo), matched unrelated donor (MUD), or HLA-matched sibling donor (MSD). The study evaluated parameters that included 3-year overall survival (OS), treatment-related mortality (TRM), GvHD incidence, post-transplant relapse rate, and engraftment. ANOVA, Kruskal-Wallis, and chi-square tests were used for statistical analysis. Survival curves were calculated using the Kaplan-Meier method and the Log-rank test compared the curves. RESULTS: Our study found that the engraftment time differed among groups: Haplo recipients engrafted earlier within a median of 16 days (ranging between 10 and 20 days) than MSD recipients with 18 days (ranging between 11 and 28 days), and MUD recipients with 19 days (ranging between 11 and 24 days; p = 0.019). Mild acute GvHD (grade I-II) was observed in 13 patients, progressing to chronic GvHD in 5 patients. Three-year OS rates were as follows: MSD group - 67.7%, Haplo group - 42.2%, and MUD group - 44.4% (MSD vs Haplo, p = 0.039). Three-year cumulative treatment-related mortality (TRM) rates were 17.8% for MSD group, 22.9% for Haplo group, and 22.1% for MUD group (pairwise comparisons p > 0.05). Infection-related mortality was reported in eight patients, while relapse rates at 3 years were similar across MSD, Haplo, and MUD groups (p = 0.891). Donor age influenced OS rates, showing better outcomes with donors under 45 years old, and significant differences were found in pairwise comparisons (p = 0.015). CONCLUSION: Donor type and donor age significantly impacted HSCT outcomes in our analysis, thus emphasizing the importance of rigorous donor selection in risk stratification and suggesting potential benefits for younger donors.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Recurrencia Local de Neoplasia/complicaciones , Recurrencia , Estudios Retrospectivos , Hermanos , Donante no Emparentado , Adulto
12.
Arch Argent Pediatr ; 122(1): e202310061, 2024 02 01.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37471507

RESUMEN

Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available.


El síndrome de Wiskott-Aldrich es un error innato de la inmunidad de herencia ligada al cromosoma X, producido por variantes en el gen que codifica la proteína del síndrome de Wiskott-Aldrich (WASp). Reportamos el caso clínico de un paciente de 18 meses con diagnóstico de Wiskott-Aldrich que no presentaba donante antígeno leucocitario humano (HLA) idéntico y recibió un trasplante de células progenitoras hematopoyéticas (TCPH) con donante familiar haploidéntico. La profilaxis para enfermedad de injerto contra huésped incluyó ciclofosfamida (PT-Cy). El quimerismo del día +30 fue 100 % del donante y la evaluación postrasplante de la expresión de la proteína WAS fue normal. Actualmente, a 32 meses del trasplante, presenta reconstitución hematológica e inmunológica y quimerismo completo sin evidencia de enfermedad injerto contra huésped. El TCPH haploidéntico con PT-Cy se mostró factible y seguro en este caso de síndrome de WiskottAldrich en el que no se disponía de un donante HLA idéntico.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Síndrome de Wiskott-Aldrich , Masculino , Niño , Humanos , Lactante , Trasplante de Médula Ósea/efectos adversos , Síndrome de Wiskott-Aldrich/terapia , Síndrome de Wiskott-Aldrich/diagnóstico , Síndrome de Wiskott-Aldrich/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Ciclofosfamida , Enfermedad Injerto contra Huésped/etiología
13.
Med Oral Patol Oral Cir Bucal ; 29(1): e135-e144, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37992141

RESUMEN

BACKGROUND: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with a history of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of the host. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) that developed from GVHD areas in patients undergoing HSCT. MATERIAL AND METHODS: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE, SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines. RESULTS: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying disease for performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection for males (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%). The average time between transplantation and the development of GVHD was of approximately of 8 months, while the average period of development between transplantation and the development of OSCC was of approximately of 111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids. CONCLUSIONS: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas, since they affect younger patients, smoking and alcohol are not important etiological factors and finally because they present good prognosis, but further studies with larger number cases followed are needed to confirm our findings.


Asunto(s)
Carcinoma de Células Escamosas , Enfermedad Injerto contra Huésped , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Masculino , Humanos , Adulto , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Neoplasias de la Boca/etiología , Enfermedad Injerto contra Huésped/complicaciones , Neoplasias de Cabeza y Cuello/complicaciones
14.
Haematologica ; 109(1): 143-150, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37226713

RESUMEN

Chronic graft-versus-host disease (GvHD) treatment response is assessed using National Institutes of Health (NIH) Consensus Criteria in clinical trials, and by clinician assessment in routine practice. Patient-reported treatment response is central to the experience of chronic GvHD manifestations as well as treatment benefit and toxicity, but how they correlate with clinician- or NIH-responses has not been well-studied. We aimed to characterize 6-month patientreported response, determine associated chronic GvHD baseline organ features and changes, and evaluate which patientreported quality of life and chronic GvHD symptom burden measures correlated with patient-reported response. From two nationally representative Chronic GVHD Consortium prospective observational studies, 382 subjects were included in this analysis. Patient and clinician responses were categorized as improved (completely gone, very much better, moderately better, a little better) versus not improved (about the same, a little worse, moderately worse, very much worse). At six months, 270 (71%) patients perceived chronic GvHD improvement, while 112 (29%) perceived no improvement. Patient-reported response had limited correlation with either clinician-reported (kappa 0.37) or NIH chronic GvHD response criteria (kappa 0.18). Notably, patient-reported response at six months was significantly associated with subsequent failure-free survival. In multivariate analysis, NIH responses in eye, mouth, and lung had significant association with 6-month patient-reported response, as well as a change in Short Form 36 general health and role physical domains and Lee Symptom Score skin and eye changes. Based on these findings, patient-reported responses should be considered as an important complementary endpoint in chronic GvHD clinical trials and drug development.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Calidad de Vida , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Enfermedad Crónica , Medición de Resultados Informados por el Paciente
15.
Ann Hematol ; 103(5): 1483-1491, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37261557

RESUMEN

Posttransplant cyclophosphamide (PTCy) has practically revolutionized haploidentical (Haplo) hematopoietic cell transplantation (HCT). Comparisons between Haplo with PTCy and unrelated donor (URD) with conventional graft-versus-host disease (GVHD) prophylaxis have shown comparable overall survival with lower incidences of GVHD with Haplo/PTCy and led to the following question: is it PTCy so good that can be successfully incorporated into matched related donor (MRD) and URD HCT? In this review, we discuss other ways of doing PTCy, PTCy in peripheral blood haploidentical transplants, PTCy in the context of matched related and matched unrelated donors, PTCy with mismatched unrelated donors, and PTCy following checkpoint inhibitor treatment. PTCy is emerging as a new standard GVHD prophylaxis in haploidentical, HLA-matched, and -mismatched HCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante Haploidéntico , Ciclofosfamida/uso terapéutico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Donante no Emparentado , Estudios Retrospectivos
16.
Aliment Pharmacol Ther ; 59(1): 71-79, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37833826

RESUMEN

BACKGROUND: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis. AIMS: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre. METHODS: This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria. RESULTS: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001). CONCLUSIONS: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death.


Asunto(s)
Enfermedad Injerto contra Huésped , Hepatitis , Humanos , Femenino , Trasplante de Médula Ósea/efectos adversos , Estudios Transversales , Médula Ósea , Trasplante Homólogo/efectos adversos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Hepatitis/complicaciones
17.
Rio de Janeiro; s.n; 2024.
Tesis en Portugués | Coleciona SUS | ID: biblio-1553877

RESUMEN

A doença enxerto contra hospedeiro crônica é a principal complicação pós transplante alogênico não relacionada à recaída, impactando na morbimortalidade dos pacientes. Nesse contexto, o acometimento pulmonar leva a um dos piores prognósticos não só em relação a alta mortalidade como em piora da qualidade de vida. Sendo assim, o estudo da doença pulmonar pós-transplante é de suma importância, visto que o diagnóstico atual parece não englobar todo espectro da doença e o manejo depende do reconhecimento precoce e carece de melhores opções que ainda estão em estudo. O objetivo do trabalho é revisar os pontos principais do tema, elucidar questões relativas ao diagnóstico e proporcionar aos profissionais da área maior entendimento sobre o tema


Chronic graft-versus-host disease is the leading non-relapse-related complication after allogeneic transplantation, impacting patient morbidity and mortality. In this context, pulmonary involvement leads to one of the worst prognoses, not only in terms of high mortality but also in terms of reduced quality of life. Therefore, the study of posttransplant pulmonary disease is of utmost importance, given that the current diagnostic approach does not seem to cover the entire spectrum of the disease, and its management relies on early recognition, lacking better options that are still under study. The objective of this work is to review the key points of the topic, elucidate issues related to diagnosis, and provide healthcare professionals with a better understanding of the subject


Asunto(s)
Humanos , Masculino , Femenino , Trasplante Homólogo , Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Enfermedades Pulmonares
18.
Braz J Med Biol Res ; 56: e12997, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38126537

RESUMEN

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Granzimas , Receptor 2 Celular del Virus de la Hepatitis A , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfocitos T CD8-positivos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Galectinas , Enfermedad Aguda
19.
Rev Invest Clin ; 75(5): 249-258, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37918011

RESUMEN

Background: Recipients of a related haploidentical stem cell transplant (haplo-SCT) can have preformed antibodies to HLA donor's antigens. Objective: The aim of the study was to evaluate the engraftment rate and major clinical associations of anti-HLA donor-specific antibodies (DSA) at two mean fluorescence intensity (MFI) thresholds in recipients of an outpatient haplo-SCT. Methods: Seventy haplo-HCT recipients were analyzed. A virtual crossmatch was performed using the donor HLA typing and the recipient's anti-HLA DSA test results. Data for anti-HLA-A, -B, -C, and -DR were analyzed. Recipients with DSA ≥ 500 MFI were considered positive, and those with < 500 were considered negative; the same was adopted for MFI ≥ 1000. Results: Post-transplant infection was higher in recipients with DSA ≥ 500 MFI (84.6%, p = 0.041). First-year mortality was higher in DSA-positive patients ≥ 500 MFI, p = 0.004, and DSA ≥ 1000 MFI, p = 0.022, than in DSA-negative recipients. Graft failure in the first 100 days was not associated with DSA ≥ 500 or ≥ 1000 MFI. There was no difference in acute (a-GVHD) or chronic (c-GVHD) graft versus host disease between DSA-positive and negative patients. Conclusions: There was no association of anti-HLA DSA at MFI ≥ 500 and ≥ 1000 with graft failure, however, increased infection and 1st-year mortality were documented in related haplo-HCT at the MFI cutoffs studied.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Isoanticuerpos , Pacientes Ambulatorios , Rechazo de Injerto , Donantes de Tejidos , Estudios Retrospectivos
20.
Transpl Immunol ; 81: 101951, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37939887

RESUMEN

BACKGROUND: During allogeneic Hematopoietic stem cell transplantation (HSCT), frequent pathological scenarios include graft versus host disease (GVHD) and viral infections. We hypothesized if exogenous stimulus as alloantigen and viral antigens might impact on central and effector memory T cells in pediatric recipients. PATIENTS AND METHODS: Subjects included 21 pediatric recipients and 20 healthy children (control group). Peripheral blood samples of patients were collected along the first 712 days post-HSCT. T cell phenotyping of naïve, central, and effector memory T cells (TCMs and TEMs, respectively) was conducted using flow cytometry. Viral nucleic acids were detected using real-time PCR. RESULTS: T cell reconstitution was not reached after 1 year post-HSCT. Chronic GVHD was associated with increased numbers of naïve CD4 T cells (p < 0.05) as well as an increase in TEM and TCM cells of the CD4 (p < 0.0001 and p < 0.05, respectively) and CD8 T cell TEM (p < 0.0001). and TCM (p < 0.001) populations too. Moreover, BK and Epstein-Barr viruses were the main viral pathogens detected (<104 copies), which were associated with a decrease in all T cell compartments. CONCLUSION: During chronic GVHD, alloantigen persistence generates TEM cell enrichment among CD4 and CD8 T cells, and viral infections are associated with deficient recovery of T cells after HSCT.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Virosis , Humanos , Niño , Células T de Memoria , Linfocitos T CD8-positivos , Isoantígenos
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