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1.
Pediatr Hematol Oncol ; 41(3): 224-228, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37898904

RESUMO

After primary infection, Varicella Zoster (VZV) persists in sensory dorsal root ganglia and may be reactivated in periods of diminished T-cell immunity. Varicella Zoster reactivation post allogenic stem cell transplantation (HSCT) can be challenging to diagnose as it does not always present with characteristic skin lesions. We describe a pediatric patient who presented with isolated severe abdominal pain with no other symptoms. Cutaneous lesions appeared only 10 days later resulting in delayed diagnosis and treatment. He was successfully treated with intravenous acyclovir and recovered after a prolonged hospital stay with post-herpetic neuralgia. Abdominal pain in children post HSCT has a broad differential and VZV reactivation should be considered even in absence of cutaneous lesions. Early diagnosis and treatment are essential to reduce VZV-related morbidity and mortality. In this article we present a case report and review clinical presentation and outcome of similar cases in the literature.


Assuntos
Varicela , Transplante de Células-Tronco Hematopoéticas , Herpes Zoster , Humanos , Criança , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/etiologia , Herpesvirus Humano 3/fisiologia , Ativação Viral , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Dor Abdominal/complicações , Transplante de Células-Tronco/efeitos adversos
2.
Crit Rev Clin Lab Sci ; 58(3): 153-166, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33161794

RESUMO

Mixed phenotype acute leukemia (MPAL) is a heterogeneous group of leukemias that are defined immunophenotypically by antigen expression on blasts of both myeloid and lymphoid lineage. With the exception of BCR-ABL positive and KMT2A rearranged MPAL, the biology of the majority of MPAL remains uncertain. Several recent studies have explored the genomic and epigenetic landscape of MPAL and have suggested a further refinement of the WHO classification to emphasize the genomic heterogeneity of MPAL. Further studies including single cell analysis, whole exome sequencing and time of flight cytometry will provide for further biological characterization. Treatment decisions are complicated due to this lack of classification and the dearth of prospective randomized studies. Acute lymphoblastic leukemia-type therapy appears to achieve higher remission rates, and allogenic stem cell transplantation may be beneficial in a select group of patients in first complete remission. Multi-center collaborations may answer these questions more conclusively. Our review aims to discuss the diagnostic challenges, recent genomic studies and therapeutic strategies in this poorly understood disease.


Assuntos
Genômica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas de Fusão bcr-abl/genética , Humanos , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Prospectivos
3.
Transfus Apher Sci ; 60(5): 103243, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34420879

RESUMO

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) is a treatment strategy in steroid-refractory chronic graft-versus-host disease (cGvHD). In this study, we aimed to share our multicenter experience using ECP in our steroid-refractory cGvHD patients. MATERIALS AND METHODS: In this multicenter observational retrospective study with the participation of four Turkish transplant centers, 100 patients with the diagnosis of steroid-refractory cGvHD who underwent ECP were analyzed. All ECP procedures were performed with the off-line system. RESULTS: Severe cGvHD was observed in 77 % of the patients. 50 % of the patients had more than 1 organ involvement. The overall response rate in cGvHD was 58 %, and the complete response (CR) rate was 35 %. The skin was the most involved organ, with a response rate of 61.2 % (CR rate 30.6 %) in cGvHD. At a median 13 months (1-261) follow-up, overall survival (OS) was 41 % (n = 41) and the mortality rate was 59 % (n = 59). Median overall survival (OS) was 2 months for non-responders and 91 months for responders (p < 0.001). Significant OS differences were observed for patients responding to ECP in cGvHD (HR = 4.1, p = 0.001) patients. CONCLUSIONS: ECP is a good therapeutic alternative and could be used earlier in patients with steroid-resistant cGvHD.


Assuntos
Doença Enxerto-Hospedeiro/terapia , Fotoferese/métodos , Esteroides/farmacologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Turquia
4.
J Artif Organs ; 24(3): 402-406, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33459910

RESUMO

Lymphoma-associated Hemophagocytic lymphohistiocytosis (HLH) represents a severe complication of disease progression, mediated through cytokine release from the lymphoma cells. Cytokine adsorption may contribute as a supportive treatment to stabilize organ function by reduction of cytokine levels. So far, no experiences of cytokine adsorption and simultaneous stem cell transplantation were published. We report the case of a patient with aggressive lymphoma secondary to chronic lymphocytic leukemia with rapidly progressive HLH (Richter's transformation) upon conditioning chemotherapy prior to allogeneic stem cell transplantation (ASCT). Continuous hemodiafiltration was initiated in the treatment of shock with acute renal failure, lactacidosis and need for high-dose catecholamine therapy, integrating an additional cytokine-adsorbing filter (CytoSorb®) to reduce cytokine levels. This was followed by scheduled allogenic stem cell transplantation. We observed a marked decrease in interleukin-6 plasma levels, associated with a reduced need for vasopressor therapy and organ function stabilization. Hematopoietic engraftment was present at day 14 post-ASCT, leading to disease-free discharge at day 100 post-transplantation. Cytokine adsorption may serve as a safe adjunct to HLH/sepsis treatment during allogeneic stem cell transplantation. Clinical studies are required to make future treatment recommendations.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica , Linfoma , Adsorção , Citocinas , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Transplante de Células-Tronco , Condicionamento Pré-Transplante
5.
Clin Infect Dis ; 70(7): 1429-1437, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-31067570

RESUMO

BACKGROUND: Human cytomegalovirus (HCMV) infection, especially persistent HCMV infection, is an important cause of morbidity and mortality after allogenic stem cell transplantation (allo-SCT). Antiviral agents remain the first-line therapy but are limited by side effects and acquired resistance. METHODS: We evaluated the safety and efficacy of donor-derived HCMV-specific cytotoxic T cells (CTLs) as a first-line therapy for HCMV infection after allo-SCT and investigated the underlying mechanisms. RESULTS: In humanized HCMV-infected mice, first-line therapy with CTLs effectively combated systemic HCMV infection by promoting the restoration of graft-derived endogenous HCMV-specific immunity in vivo. In a clinical trial, compared with the pair-matched, high-risk control cohort, first-line therapy with CTLs significantly reduced the rate of persistent (2.9% vs 20.0%, P = .018) and late (5.7% vs 20.0%, P = .01) HCMV infection and cumulative incidence of persistent HCMV infection (hazard ratio [HR], 0.13; 95% confidence interval [CI], 0.10-0.82; P = .02), lowered 1-year treatment-related mortality (HR, 0.15. 95% CI, 0.11-0.90. P = .03), and improved 1-year overall survival (HR, 6.35; 95% CI, 1.05-9.00; P = .04). Moreover, first-line therapy with CTLs promoted the quantitative and functional recovery of CTLs in patients, which was associated with HCMV clearance. CONCLUSIONS: We provide robust support for the benefits of CTLs combined with antiviral drugs as a first-line therapy for treating HCMV infection and suggest that adoptively infused CTLs may stimulate the recovery of endogenous HCMV-specific immunity. CLINICAL TRIALS REGISTRATION: NCT02985775.


Assuntos
Antivirais , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Animais , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Humanos , Camundongos , Transplante de Células-Tronco , Transplante Homólogo
6.
Biol Blood Marrow Transplant ; 26(4): 651-658, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31917270

RESUMO

Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory graft-versus-host disease (GVHD). This study's main objective was to analyze the clinical response and impact of ECP therapy in steroid dose reduction. A retrospective observational series of 113 patients from 7 transplantation centers was analyzed. Sixty-five patients (58%) had acute GVHD (aGVHD), and 48 (42%) had chronic GVHD (cGVHD). All ECP procedures were performed with the off-line system. The median number of procedures until achievement of initial response was 3 for both patients with aGVHD and those with cGVHD. ECP was the second-line therapy in 48% of the aGVHD cases and in 50% of the cGVHD cases. 71% of the cases of aGVHD were grade III-IV, and 69% of the cases of cGVHD were severe. The overall response rate on day 28 was 53% (complete response [CR] rate, 45%) in the patients with aGVHD and 67% (CR, 23%) in those with cGVHD. Skin was the most frequently involved organ, with a response rate of 58% (CR, 49%) in the patients with aGVHD and 69% (CR 29%) in those with cGVHD. At the end of ECP treatment, 60% of patients treated for aGVHD who responded were able to stop steroid therapy, with a median dose reduction of 100%. Significant differences in overall survival were observed for patients responding to ECP with aGVHD (hazard ratio [HR], 4.3; P < .001) and with cGVHD (HR, 4.8; P = .003). Our data indicate that ECP is a valid therapeutic alternative in patients with steroid-refractory aGVHD and cGVHD, permitting significant steroid dosage reductions.


Assuntos
Doença Enxerto-Hospedeiro , Fotoferese , Doença Aguda , Doença Crônica , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Estudos Retrospectivos , Esteroides/uso terapêutico
7.
Ann Hematol ; 99(2): 343-349, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879790

RESUMO

Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Pirazóis/administração & dosagem , Dermatopatias , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Resistência a Medicamentos/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Nitrilas , Pirimidinas , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/mortalidade , Esteroides/administração & dosagem , Taxa de Sobrevida
8.
Biol Blood Marrow Transplant ; 25(1): 129-136, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30064013

RESUMO

Despite clinical advances, late onset pulmonary complications in adult recipients of allogenic stem cell transplantation are a major cause of morbidity and mortality. Reported incidence and risk factors in the literature vary broadly and are partly contradictory. Identification of pretransplant factors associated with major complications would be helpful to define individual treatment strategies and early initiation of preventive measures. To evaluate incidence and risk factors of late onset noninfectious pulmonary complications, with special regard to small airways disease (SAD) and bronchiolitis obliterans syndrome (BOS), indicating graft-versus-host disease, following myeloablative versus nonmyeloablative allogenic stem cell transplantation. We reviewed the clinical records and assessed the course of lung function and pulmonary complications in adults who underwent allogenic stem cell transplantation for hematological malignancies between 1999 and 2015 using nonmyeloablative (n = 179) or myeloablative (n = 130) conditioning at the Division of Hematology of the Medical University of Graz. All patients underwent body plethysmography pulmonary function test (PFT), diffusion capacity for carbon monoxide, and arterial blood gas analysis before and repeatedly after transplant. SAD was defined as maximal expiratory flow at 50% and 25% of forced vital capacity <70% predicted. Ventilatory disorders and gas transfer abnormalities were common before and after allogenic stem cell transplantation, independent of conditioning regimen. SAD was common in the nonmyeloablative (34%) and myeloablative (29%) groups. The 100-day post-transplant mortality was significantly associated with reduced pretransplant total lung capacity <80%. Mortality 100 days post-transplant was significantly associated with pretransplant SAD and a pretransplant smoking history. In this subset, a smoking history was independently associated with increased mortality, with a 5-year mortality of 45% compared with 26% in never-smokers. Pretransplant SAD was not predictive for the later development of BOS. Smoking history, pretransplant restrictive PFT, and pre-existing SAD are important risk factors for death following allogenic stem cell transplantation. However, pretransplant SAD is not a predictor of long-term complications, including BOS.


Assuntos
Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Pulmão/fisiopatologia , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/mortalidade , Bronquiolite Obliterante/fisiopatologia , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/fisiopatologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/fisiopatologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos
9.
Biol Blood Marrow Transplant ; 25(10): 1970-1974, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31173901

RESUMO

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged ≥40 years had a higher transplant-related mortality (29.4% versus 7.8%; P = .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (P = .022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged ≥40 years is problematic, and clinical trials addressing this issue are warranted.


Assuntos
Anemia Aplástica/terapia , Adolescente , Adulto , Idoso , Anemia Aplástica/patologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Suécia , Doadores de Tecidos , Doadores não Relacionados , Adulto Jovem
10.
Ann Hematol ; 98(2): 465-471, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30264165

RESUMO

Accurate risk assessment to determine the eligibility for allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with adult T cell leukemia (ATL) is necessary to improve survival outcomes. The controlling nutritional status (CONUT) score predicts prognosis in several tumors; however, the prognostic significance of the CONUT score in ATL remains unclear. The present study investigated the correlation between the CONUT score and the survival outcomes of transplant-eligible ATL patients. Mogamulizumab, a humanized monoclonal antibody against C-C chemokine receptor 4, was recently identified as a promising salvage chemotherapy agent for transplant-ineligible ATL patients. We therefore evaluated the efficacy of mogamulizumab in transplant-ineligible ATL patients. Patients diagnosed with aggressive ATL (acute lymphoma of unfavorable chronic type) between January 2008 and March 2017 at Saga University Hospital, Japan, were retrospectively enrolled. Of 54 patients, 25 were < 70 years of age and 14 received allo-HCT. The median overall survival (OS) and non-relapse mortality (NRM) rate at 1 year among patients receiving allo-HCT were 1685.5 days and 30% in those with a CONUT score 0-3 (n = 10) and 184.5 days and 100% in those with a score ≥ 4 (n = 4) (p = 0.017, OS; p = 0.064, NRM). Older patients who received mogamulizumab had a significantly longer OS (n = 12, median 432 days) than those who did not receive mogamulizumab (n = 17, median 199 days) (p = 0.018). The CONUT score was identified as a prognostic tool for transplant-eligible ATL patients, and mogamulizumab improved OS in transplant-ineligible ATL patients.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Anticorpos Monoclonais Humanizados/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Taxa de Sobrevida
11.
Rinsho Ketsueki ; 60(12): 1635-1640, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31902813

RESUMO

Although elotuzumab (ELO) is associated with improved outcomes in patients with relapsed/refractory multiple myeloma (MM), no data are available for the usage of ELO following allogeneic stem cell transplantation (allo-SCT). Here, we report two cases of relapsed MM treated with ELO in combination with lenalidomide (LEN) and dexamethasone (ELd) following allo-SCT. Case 1 had been treated with 11 lines of therapy followed by cord blood transplantation resulting in partial response. ELd was introduced 140 days post-transplantation and continued for eight cycles until disease progression. No worsening in graft-versus-host disease (GvHD) was observed under ELd treatment. Case 2 had received unrelated bone marrow transplantation due to primary refractory disease after undergoing six regimens. Carfilzomib-based maintenance therapy had to be discontinued owing to severe myelosuppression. Subsequently, ELd treatment was initiated 544 days following the allo-SCT, which led to an improvement in serum paraprotein level and amelioration in GvHD. In both cases, immunosuppressants were tapered off. Several studies have shown exacerbation of GvHD under LEN monotherapy following allo-SCT. However, an ELd regimen may be one of the safer options for treating post-allo-SCT relapse.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Transplante de Células-Tronco , Transplante Homólogo
12.
J Oncol Pharm Pract ; : 1078155217743069, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29207936

RESUMO

Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based salvage therapies for Hodgkin's lymphoma; however, the use of programmed death 1 blocking agents in the allogeneic stem cell transplantation setting could augment the incidence of steroid refractory graft-versus-host disease. Few studies suggest that that nivolumab is safe in patients previously treated with an allogeneic stem cell transplantation. Likewise, there are very limited data on the use of nivolumab before allogeneic stem cell transplantation. Here, we report a case of fatal graft-versus-host disease in a patient who underwent allogeneic stem cell transplantation 26 days after the last administration of nivolumab. Careful monitoring and close clinical assessment of atypical presentation for graft-versus-host disease in these patients, interval of time from nivolumab administration to allogeneic stem cell transplantation, drug dosage adjustments or more effective allo prophilaxys should been evaluated in prospective clinical trial.

13.
Front Immunol ; 15: 1327035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38433830

RESUMO

Despite the numerous advantages of allogeneic hematopoietic stem cell transplants (allo-HSCT), there exists a notable association with risks, particularly during the preconditioning period and predominantly post-intervention, exemplified by the occurrence of graft-versus-host disease (GVHD). Risk stratification prior to symptom manifestation, along with precise diagnosis and prognosis, relies heavily on clinical features. A critical imperative is the development of tools capable of early identification and effective management of patients undergoing allo-HSCT. A promising avenue in this pursuit is the utilization of proteomics-based biomarkers obtained from non-invasive biospecimens. This review comprehensively outlines the application of proteomics and proteomics-based biomarkers in GVHD patients. It delves into both single protein markers and protein panels, offering insights into their relevance in acute and chronic GVHD. Furthermore, the review provides a detailed examination of the site-specific involvement of GVHD. In summary, this article explores the potential of proteomics as a tool for timely and accurate intervention in the context of GVHD following allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Biomarcadores , Condicionamento Psicológico , Proteômica
14.
Clin Case Rep ; 12(7): e9159, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38979088

RESUMO

Key Clinical Message: Belinostat therapy followed by hematopoietic stem cell transplantation is a promising salvage strategy for heavily pretreated patients with peripheral T-cell lymphoma. Abstract: Effective treatments for peripheral T-cell lymphoma in the relapsed and refractory (r/r) setting are limited. However, with the development and approval of innovative therapies, effective therapeutic options are becoming available for this patient population. This case report describes the treatment course of a patient with multiple r/r nodal follicular T-helper cell lymphoma of angioimmunoblastic type. Treatment with the histone deacetylase inhibitor belinostat as bridging, enabled allogeneic stem cell transplantation and resulted in a durable complete hematologic response for at least 21 months post-transplantation.

15.
Clin Rheumatol ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39347920

RESUMO

Vacuolation, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a multisystem disease due to a genetic mutation in the ubiquitin-activating enzyme (UBA1). Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers both therapeutic and cure but also carries significant risks. A review of VEXAS and HSCT cases was undertaken. Thirty-three patients were identified; majority males (n = 32, 97.0%), median time from symptoms to HSCT: 3 years (IQR 2.0-4.8) and median age of 59 years (IQR 52.5-65.5). UBA1 mutation Met41Thr was most common (11/32, 34.4%). The median variant allele frequency was 56.5% (IQR 43.0-73.5) with no correlation with increasing age. Prior to HSCT, 4.5 (IQR 2.8-6) treatments were trialled. Peripheral blood HSCT (30/31, 96.8%) and HLA-matched, unrelated donor (18/32, 56.3%) were most common. Conditioning regimens varied, with reduced intensity treatment with fludarabine as a co-agent most frequently administered (12/31, 38.7%). Both acute and/or chronic GVHD (18/32, 56.3%) and infections were common (12/32, 37.5%). Overall, 27 individuals (81.8%) were alive, and those undergoing HSCT prospectively had median follow up of 9 months (IQR 3.8-14.4). Of the six deceased, infection was implicated in four. In 11 cases with post-HSCT molecular data, a complete eradication of UBA1 mutation was reported. In summary, while consensus treatment strategy regarding VEXAS is lacking, this review highlights HSCT may remain not only a therapeutic option but also enable cure. However, considerations regarding comorbidities, concurrent haematological disorders as well as overall risks of GVHD and infections need to be made. Key points • Very few reported prospective cases of VEXAS and allogeneic haematopoietic stem cell transplantation (allo-HSCT) have been reported. • While risks of graft versus host disease and infection remain barriers, this treatment modality remains an option for selected patients. • Allo-HSCT is the only treatment strategy which can remove the UBA1 mutation.

16.
Oncol Res Treat ; 47(4): 136-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38266509

RESUMO

INTRODUCTION: This study explored qualitatively, in a sample of German hematologists working in clinical allogeneic hematopoietic stem cell transplantation (alloHSCT), perceptions of barriers and facilitators to participate in continuous medical education (CME), to provide detailed information on how to improve participation in CME activities related to alloHSCT, which may also be applicable to other areas of medicine. METHODS: Based on a recruitment campaign of the German Association for Hematopoietic Stem Cell Transplantation (DAG-HSZT), 21 semi-structured telephone interviews were conducted, transcribed, and analyzed using framework analysis. RESULTS: Three clusters of barriers were identified that explain why alloHSCT physicians may or may not participate in CME: individual constraints (e.g., better networking, young physicians being overwhelmed by the complexity of alloHSCT), structural constraints (e.g., time and financial issues, tailoring CME courses according to the targeted audience), and content-related constraints (e.g., requirement of CME sessions, provision of an overview of CME courses, more flexible offers). We discuss the ten most frequently raised issues, including the use of incentives and the need for support at the start of residency, staff shortages, and requirements for learning sessions. CONCLUSION: There is a need for a paradigm shift in CME related to alloHSCT toward a more individualized and needs-based approach. Close monitoring of residents' needs and learning progress, as well as feedback systems, could help identify appropriate CME courses that should be integrated into a tiered learning system. CME should be more targeted to specific audiences (i.e., residents, fellows, and attendees) to provide training that is tailored to individual CME needs. On-demand courses can help balance work and family obligations. Finally, peer-reviewed, up-to-date information platforms should be expanded.


Assuntos
Medicina , Médicos , Humanos , Educação Médica Continuada , Pesquisa Qualitativa , Transplante de Células-Tronco
18.
Pediatr Transplant ; 17(6): E146-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23773507

RESUMO

WAS is a severe X-linked recessive disorder characterized by microthrombocytopenia, eczema, and immunodeficiency. A six-yr-old boy with WAS diagnosed as B-cell NHL (Stage III) localized in the liver who underwent successful HSCT from HLA-one antigen mismatch sibling donor has been presented here. His conditioning regimen included ATG, busulfan, and fludarabine. He received 2.3 × 10(6) /kg CD 34+ stem cells and 11 × 10(8) /kg nucleated cells at day 0. Neutrophil engraftment was achieved at day +14 and platelet engraftment at day +20. He has been in CR for more than two yr after transplantation. Thus, HSCT is an effective treatment for children with WAS even after development of lymphoma.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Síndrome de Wiskott-Aldrich/terapia , Soro Antilinfocitário/administração & dosagem , Plaquetas/metabolismo , Bussulfano/administração & dosagem , Criança , Antígenos HLA/química , Teste de Histocompatibilidade , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/terapia , Linfoma não Hodgkin/complicações , Masculino , Neutrófilos/metabolismo , Indução de Remissão , Irmãos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Síndrome de Wiskott-Aldrich/complicações
19.
Pathol Biol (Paris) ; 61(4): 139-43, 2013 Aug.
Artigo em Francês | MEDLINE | ID: mdl-24011964

RESUMO

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding vaccination post Hematopoietic Stem Cell Transplantation with practical focus on which vaccines to use and when and how to vaccinate?


Assuntos
Transplante de Células-Tronco Hematopoéticas/normas , Esquemas de Imunização , Vacinação/estatística & dados numéricos , Vacinas/administração & dosagem , Adulto , Criança , Conferências de Consenso como Assunto , Contraindicações , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Prática Profissional/normas , Vacinação/normas
20.
Front Immunol ; 14: 1129687, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256146

RESUMO

Background: Low aerobic capacity is associated with an increased mortality risk in allogenic stem-cell transplantation (alloSCT) patients, but currently used risk scores in the pre-transplantation workup are still underestimating physical activity as a prognostic factor. Aim: To examine the physical condition, muscle function, blood inflammation and training adherence of alloSCT patients during inpatient time to identify potential biomarkers associated with development of myopathy and sarcopenia. Methods: Patients undergoing alloSCT were examined at four time points (T0: before alloSCT; Tha: hospital admission; T1: engraftment; T2: inpatient discharge). T0 included cardiopulmonary performance, body composition, grip and knee strength, motor skill tests (One-leg stand/Tinetti/Chair-rising), blood sampling (blood cell profiling and inflammation targets (Kynurenin/high sensitivity C-reactive Protein (hsCRP)/Tumor necrosis factor alpha (TNF-alpha)/Musclin/Galectin-3) and quality of life, state of health, fatigue, muscle weakness and physical activity by questionnaires (IPAQ/BSA/SARC-F/Fatigue). At T1 and T2, blood samples, grip strength and motor skill tests were repeated. Glucocorticoid dose and daily physical activity were documented during inpatient stay. Results: 26 of 35 included patients (4 females; age 55.58 ± 12.32 years; BMI 24.70 ± 3.27 kg/m2; VO2peak 16.55 ± 4.06 ml/min/kg) could proceed to alloSCT. Grip strength and Tinetti decreased from T0 until T2, no difference in Chair-rising test, One-leg and Tandem stand. All patients engrafted after 24.9 days ± 3.9 days. HsCRP and Kynurenine increased from T0 to T1, decreased at T2. TNF-alpha (T0vsT2/T1vsT2) and Musclin (T0vsT1) decreased. At T2, Galectin-3 was higher compared to T0/T1. Correlation analysis of grip strength and inflammatory markers revealed a positive correlation with TNF-alpha at T2. 50% of patients documented physical activity and questionnaire and reported a 50%-reduction of daily endurance and strength training between T1 to T2. Conclusion: Allogeneic stem-cell transplantation is associated with immune system vulnerability due to conditioning, increased inflammation and fatigue, and loss of muscle strength and function. In addition to hsCRP, Kynurenine seems to be a reliable biomarker to monitor acute and regenerative inflammation status of alloSCT patients, while Musclin and Galectin-3 may be added to physiological assessment regarding myopathy and sarcopenia. Grip strength and daily activity level should be documented by professionals to identify risk patients early and support them with optimal (exercise) therapy.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doenças Musculares , Sarcopenia , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Projetos Piloto , Proteína C-Reativa , Fator de Necrose Tumoral alfa , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Cinurenina , Qualidade de Vida , Galectina 3 , Inflamação , Biomarcadores , Fatores de Risco , Medição de Risco , Fadiga , Músculos
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