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1.
Ann Hematol ; 100(4): 865-878, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33547921

RESUMO

Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication of haematopoietic stem cell transplantation (HSCT), occurring in a setting of immune suppression and dysregulation. The disease is in most cases driven by the reactivation of the Epstein-Barr virus (EBV), which induces B cell proliferation through different pathomechanisms. Beyond EBV, many factors, variably dependent on HSCT-related immunosuppression, contribute to the disease development. PTLDs share several features with primary lymphomas, though clinical manifestations may be different, frequently depending on extranodal involvement. According to the WHO classification, histologic examination is required for diagnosis, allowing also to distinguish among PTLD subtypes. However, in cases of severe and abrupt presentation, a diagnosis based on a combination of imaging studies and EBV-load determination is accepted. Therapies include prophylactic and pre-emptive interventions, aimed at eradicating EBV proliferation before symptoms onset, and targeted treatments. Among them, rituximab has emerged as first-line option, possibly combined with a reduction of immunosuppression, while EBV-specific cytotoxic T lymphocytes are effective and safe alternatives. Though prognosis remains poor, survival has markedly improved following the adoption of the aforementioned treatments. The validation of innovative, combined approaches is the future challenge.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Adulto , Idoso , Linfócitos B/patologia , Linfócitos B/virologia , Criança , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 4/fisiologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , MicroRNAs/genética , Pessoa de Meia-Idade , Mutação , Prognóstico , Fatores de Risco , Rituximab/uso terapêutico , Linfócitos T Citotóxicos/transplante , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Ativação Viral
2.
Lancet Haematol ; 8(3): e229-e239, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33636143

RESUMO

Immune-mediated cytopenia after allogeneic haematopoietic stem-cell transplantation is rare. The pathophysiology of immune-mediated anaemia, thrombocytopenia, and neutropenia, which occur alone or in combination with other cytopenias, is unclear and most probably a consequence of immune dysregulation. Risk factors for this complication have been identified in retrospective studies but these should be interpreted with caution and should not be generalised to this heterogeneous patient population. Diagnosis is challenging, requires awareness of such complications, and has to be differentiated from a multitude of other, and sometimes overlapping, possible complications. The clinical course of immune-mediated cytopenia is highly variable. Treatment requires an interdisciplinary approach and ranges from observation to symptomatic measures and directed therapies. Intensive immunosuppression is associated with an increased risk of infections and relapse, and current treatments are based on approaches in patients who have not undergone transplantation. Plasma cell-directed therapies, immunomodulation, and receptor-stimulating agents can be used to treat immune-mediated cytopenia.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neutropenia/etiologia , Trombocitopenia/etiologia , Transplante Homólogo/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Neutropenia/tratamento farmacológico , Fatores de Risco , Trombocitopenia/tratamento farmacológico
3.
Medicine (Baltimore) ; 100(7): e24498, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607779

RESUMO

INTRODUCTION: No standard guideline has been established for the treatment of plasmablastic lymphoma (PBL) and prognosis remains extremely poor, given that patients relapse early after chemotherapy and show resistance to commonly used cytostatic drugs. PATIENT CONCERNS: We present the case of a 52-year-old HIV-negative man who presented with a mass at the left sternoclavicular joint. He had no significant comorbidities and no latent immunosuppression. DIAGNOSIS: The largest lymph node measured was 36 × 19 mm. An excisional biopsy showed diffuse proliferation of large lymphoid cells which were positive for CD38 and CD138, but negative for CD20. He was diagnosed with stage IV PBL with a low IPI. INTERVENTIONS: The patient was treated with four cycles of induction therapy with bortezomib, epirubicin and dexamethasone. He achieved complete remission. But 3 months after receiving consolidated autologous hematopoietic stem cell transplantation, he relapsed. Allogeneic hematopoietic stem cell transplantation was performed on the patient. OUTCOMES: The patient achieved remission again and there were no serious complications after allogeneic hematopoietic stem cell transplantation. This patient was followed up once every three months, and to date, he has been disease-free for more than 4 years. CONCLUSION: The survival of recurrent PBL after autologous hematopoietic stem cell transplantation is very poor. Salvage allogeneic hematopoietic stem cell transplantation may bring long-term survival opportunities for those patients. Further clinical studies are needed to explore the role of allogeneic hematopoietic stem cell transplantation in refractory and recurrent PBL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Plasmablástico/terapia , Transplante Homólogo/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Soronegatividade para HIV , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patologia , Indução de Remissão/métodos , Transplante Homólogo/efeitos adversos
4.
Ann Hematol ; 100(3): 763-777, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33491135

RESUMO

Allogeneic hematopoietic cell transplant (allo-HCT) is a potentially curative therapeutic strategy that showed encouraging long-term outcomes in hematological diseases. A number of factors can influence post-transplant clinical outcomes. While Epstein-Barr virus (EBV) constitutes a trigger for development of various adverse conditions, no clinical study yet has been powered to assess the effect of EBV serostatus on the clinical outcomes in allo-HCT population. To systematically summarize and analyze the impact of donor and recipient EBV serostatus on transplant outcomes in allo-HCT recipients, meta-analyses were conducted. Selected endpoints were overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and de novo cGVHD. Three studies with 26,650 patients, transplanted for acute leukemias, lymphomas, chronic hematological malignancies, or non-malignant hematological diseases were included in the meta-analysis. In the whole population, with a total of 53,300 donors and recipients, the rate of EBV seropositivity was 85.1%, including 86.6% and 83.6% among transplant recipients and healthy donors, respectively. Donor EBV seropositivity increased the risk of cGVHD by 17%, de novo cGVHD by 14%, and aGHVD by 5%. Recipient EBV seropositivity increased the risk of cGVHD by 12%, de novo cGVHD by 17%; increased NRM by 11%, increased RI by 11%, decreased OS by 14%, and decreased RFS by 11%. In performed meta-analyses, donor and recipient EBV seropositivity was found to have a significant impact on transplant outcomes in patients after allo-HCT.


Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Herpesvirus Humano 4/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Soroepidemiológicos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade , Resultado do Tratamento , Adulto Jovem
5.
Ann Hematol ; 100(3): 779-787, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33515310

RESUMO

The immunomodulatory fusion protein abatacept has recently been investigated for the treatment of steroid-refractory chronic graft-versus-host disease (cGvHD) in a phase 1 clinical trial. We analyzed the safety and efficacy of abatacept for cGvHD therapy in a retrospective study with 15 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and received abatacept for cGvHD with a median age of 49 years. Grading was performed as part of the clinical routine according to the National Institute of Health's (NIH) consensus criteria at initiation of abatacept and 1, 3, 6, 9 and 12 months thereafter. The median time of follow-up was 191 days (range 55-393 days). Best overall response rate (ORR) was 40%. In particular, patients with bronchiolitis obliterans syndrome showed significant clinical improvement and durable responses following abatacept treatment with a response rate of 89% based on improvement in lung severity score (n = 6) or stabilized lung function (n = 4) or both (n = 3). Infectious complications CTCAE °III or higher were observed in 3/15 patients. None of the patients relapsed from the underlying malignancy. Thus, abatacept appears to be a promising treatment option for cGvHD, in particular for patients with lung involvement. However, further evaluation within a phase 2 clinical trial is required.


Assuntos
Abatacepte/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia de Salvação/métodos , Abatacepte/efeitos adversos , Adolescente , Adulto , Idoso , Bronquiolite Obliterante/tratamento farmacológico , Bronquiolite Obliterante/etiologia , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Seguimentos , Alemanha/epidemiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Suécia/epidemiologia , Transplante Homólogo/efeitos adversos , Adulto Jovem
6.
Ann Hematol ; 100(3): 789-798, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33415423

RESUMO

Allogeneic hematopoietic stem cell transplantation (HCT) is associated with significant morbidity and mortality. Elevated pre-transplant ferritin level (ferritinPre-HCT) is reported to be associated with increased mortality following HCT. The present study attempted to determine whether post-transplant ferritin level (ferritinPost-HCT) is associated with outcomes post-HCT, especially in the subgroups which developed acute or chronic graft-versus-host disease (GVHD). Out of 229 patients with serum ferritin level measured post-HCT, median ferritinPost-HCT was 2178 ng/mL. Patients were stratified into low- or high-risk groups using recursive partitioning, based on ferritinPost-HCT (≤ 3169 vs > 3169 ng/mL) and ferritinPre-HCT (≤ 669 vs > 669 ng/mL). Compared to the low ferritinPost-HCT group, the high ferritinPost-HCT group had lower 3-year overall survival (OS) (40.0% vs 66.7%, p < 0.001) and higher non-relapse mortality (NRM) (48.6% vs 17.8%, p < 0.001), but no difference in relapse (10.5% vs 19.7%, p = 0.079). Multivariate analysis confirmed ferritinPost-HCT as an independent prognostic factor for OS (p = 0.001, HR = 2.323) and NRM (p < 0.001, HR = 3.905). However, ferritinPre-HCT did not stratify well for OS or NRM. FerritinPost-HCT was also found to be an independent prognostic marker for OS and NRM in the subgroups which developed GVHD. In our cohort, high ferritinPost-HCT levels were significantly associated with decreased OS and increased NRM independent of ferritinPre-HCT or GVHD. Additional studies including larger sample sizes and prospective investigation are warranted to clarify the prognostic significance and pathophysiology of pre- and post-transplant hyperferritinemia.


Assuntos
Ferritinas/sangue , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Ferritinas/análise , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
7.
Ann Hematol ; 100(3): 753-761, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33439306

RESUMO

Adenovirus (ADV)- or BK virus (BKV)-associated hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several risk factors have been previously reported; however, it is unclear whether virus-associated HC can be transmitted. To clarify this point, we performed a retrospective cohort study on 207 consecutive patients who underwent allo-HSCT at Kyoto University Hospital between 2012 and 2018. We evaluated the incidence and risk factors of virus-associated HC and performed a phylogenetic analysis of the ADV partial sequence. The median age at transplantation was 50 (range, 17-68) years. Fifty-eight patients (28%) developed HC. ADVs were detected in 18 cases, BKVs were detected in 51, both were detected in 12, and only John Cunningham virus (JCV) was detected in 1 case. No factor was significantly associated with HC. However, both ADV- and BKV-HC occurred intensively between April 2016 and September 2017, which suggested possible nosocomial transmission of ADV and BKV. Genome sequencing of the hexon, E3, and penton regions of detected ADVs identified 7 cases of ADV type 11, 2 cases of type 35, and 3 cases of a type 79-related strain. A sequence analysis revealed that these strains in each type were almost identical, except for one case of a type 79-related strain. In conclusion, ADV-HCs with possible nosocomial transmission were described based on genotyping of the virus and partial sequencing of the viral genome. Although viral HC after allo-HSCT is thought to mainly be due to reactivation of a latent virus, nosocomial transmission of ADV or BKV should also be considered.


Assuntos
Infecção Hospitalar/etiologia , Cistite/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/virologia , Viroses/etiologia , Adenoviridae/isolamento & purificação , Adenoviridae/fisiologia , Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/etiologia , Adolescente , Adulto , Idoso , Vírus BK/isolamento & purificação , Vírus BK/fisiologia , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Cistite/epidemiologia , Cistite/etiologia , Feminino , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Vírus JC/isolamento & purificação , Vírus JC/fisiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/etiologia , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/efeitos adversos , Transplante Homólogo/estatística & dados numéricos , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/etiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Viroses/epidemiologia , Adulto Jovem
8.
Ann Hematol ; 100(3): 817-824, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33442793

RESUMO

Prognosis in patients with post allogeneic HCT-early relapse of acute myeloid leukemia (<6 months post HCT) is dismal and response to salvage treatment is < 20%. In addition, majority of patients at this early point are unable to withstand intensive salvage chemotherapy. We hypothesized that the combination of donor lymphocyte infusion (DLI) and venetoclax may result in increased response in this difficult to treat patient group. We retrospectively analyzed 22 patients from February 2017-December 2019, who were given the Venetoclax/DLI combination. Median age was 65 (43-75) years. There were no cases of tumor lysis syndrome. Microbiology documented infections occurred in 8 patients (36%). Majority were able to tolerate the protocol without admissions. Acute GVHD was observed in 4 (18%) patients and cGVHD was observed in 6 (27%) patients. Overall response was observed in 11 (50%) patients (CR, n = 4; CRi, n = 1; CRp, n = 4; MLFS n = 2). Median time to response was 28 (18-67) days and median cycles of venetoclax 2 [1-8] and duration of response were 135 (31-564) days. Median survival was 6.1 months (95% CI .73-11.4). Cox regression model for survival showed decreased WBC at relapse, GVHD and better performance status were associated with better survival. These results may endorse the hypothesis that enhancing alloreactivity combined with venetoclax is safe and efficacious and should be further investigated in prospective trials.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Transfusão de Linfócitos , Sulfonamidas/uso terapêutico , Adulto , Idoso , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Terapia de Salvação/métodos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo/efeitos adversos
9.
Trials ; 22(1): 9, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407777

RESUMO

OBJECTIVES: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 106 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION: EudraCT Number: 2020-002193-27 , registered on July 14th, 2020. NCT number: NCT04615429 , registered on November 4th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Antivirais/administração & dosagem , Transplante de Células-Tronco Mesenquimais/métodos , /terapia , Administração Intravenosa , Adulto , Biomarcadores/sangue , /diagnóstico , Ensaios Clínicos Fase II como Assunto , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Método Duplo-Cego , Feminino , Humanos , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , /diagnóstico , /isolamento & purificação , Índice de Gravidade de Doença , Espanha , Padrão de Cuidado , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
10.
Anticancer Res ; 40(11): 6531-6537, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109594

RESUMO

BACKGROUND: Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. PATIENTS AND METHODS: A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. RESULTS: In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. CONCLUSION: Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.


Assuntos
Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Estomatite/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Intervalo Livre de Progressão , Estomatite/complicações , Estomatite/patologia , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
12.
Anticancer Res ; 40(10): 5707-5713, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988896

RESUMO

BACKGROUND/AIM: Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays. RESULTS: rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort. CONCLUSION: rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , RNA Longo não Codificante/genética , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Idoso , Feminino , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , Tacrolimo/farmacocinética , Transplante Homólogo/efeitos adversos
13.
Anticancer Res ; 40(10): 5909-5917, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988922

RESUMO

BACKGROUND/AIM: Cytomegalovirus (CMV) replication may cause life-threatening complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to characterize CMV events, and the outcome of letermovir (LTV) CMV prophylaxis. PATIENTS AND METHODS: In this retrospective analysis of patients treated with an allo-HSCT between 2010 and 2020, we determined plasma CMV events, as well as associated risk factors. RESULTS: We identified 423 patients who had undergone allo-HSCT between 2010 and 2020. CMV DNAemia was found in 130/423 (30.7%) of patients. CMV reactivation rate was significantly higher in patients with acute graft-versus-host disease, HLA mismatch, and CMV IgG seropositivity of donors and recipients. Among 42 patients receiving LTV prophylaxis those, 5 (11.9%) showed CMV DNAemia under LTV versus 87/353 (24.6%) in a control group. CONCLUSION: Despite the development of better approaches with weekly monitoring and early treatment initiation, CMV reactivations play an important role after allo-HSCT.


Assuntos
Acetatos/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quinazolinas/administração & dosagem , Adulto , Idoso , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Replicação Viral/efeitos dos fármacos
14.
PLoS One ; 15(9): e0238824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915853

RESUMO

Allogeneic-HCT (allo-HCT), while potentially curative, can result in significant complications including graft versus host disease (GVHD). Prior studies suggest that metabolic syndrome may be one risk factor for GVHD. We hypothesized that hepatic steatosis on pre-HCT computed tomography (CT) scans may be a marker for development of GVHD and poor outcomes in allo-HCT. In this retrospective study, we reviewed the pre-HCT CT scans and transplant outcome data of patients who underwent allo-HCT at Duke University Medical Center from 2009 to 2017. The presence of steatosis was confirmed using CT attenuation measurements. We then assessed the association between pre-HCT hepatic steatosis and HCT-related outcomes including GVHD. 80 patients who had pre-HCT CT scans were included in the study. Pre-transplant hepatic steatosis was associated with the development of chronic GVHD (OR 4.2, p = 0.02), but was not associated with acute GVHD (OR 1.3, p = 0.7), non-relapse mortality (p = 0.81) or overall survival (p = 0.74). Based on this single center retrospective study, pre-transplant hepatic steatosis is associated with development of chronic GVHD. Further, prospective study with other imaging modalities including non-contrasted CT scans is needed to determine if this association is reproducible.


Assuntos
Fígado Gorduroso/terapia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Transplante Homólogo/efeitos adversos
15.
Lancet Oncol ; 21(9): 1201-1212, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32791048

RESUMO

BACKGROUND: Findings of retrospective studies suggest that sorafenib maintenance post-transplantation might reduce relapse in patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. We investigated the efficacy and tolerability of sorafenib maintenance post-transplantation in this population. METHODS: We did an open-label, randomised phase 3 trial at seven hospitals in China. Eligible patients (aged 18-60 years) had FLT3-ITD acute myeloid leukaemia, were undergoing allogeneic haematopoietic stem-cell transplantation, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days post-transplantation. Patients were randomly assigned (1:1) to sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days post-transplantation. Randomisation was done with permuted blocks (block size four) and implemented through an interactive web-based randomisation system. The primary endpoint was the 1-year cumulative incidence of relapse in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02474290; the trial is complete. FINDINGS: Between June 20, 2015, and July 21, 2018, 202 patients were enrolled and randomly assigned to sorafenib maintenance (n=100) or control (n=102). Median follow-up post-transplantation was 21·3 months (IQR 15·0-37·0). The 1-year cumulative incidence of relapse was 7·0% (95% CI 3·1-13·1) in the sorafenib group and 24·5% (16·6-33·2) in the control group (hazard ratio 0·25, 95% CI 0·11-0·57; p=0·0010). Within 210 days post-transplantation, the most common grade 3 and 4 adverse events were infections (25 [25%] of 100 patients in the sorafenib group vs 24 [24%] of 102 in the control group), acute graft-versus-host-disease (GVHD; 23 [23%] of 100 vs 21 [21%] of 102), chronic GVHD (18 [18%] of 99 vs 17 [17%] of 99), and haematological toxicity (15 [15%] of 100 vs seven [7%] of 102). There were no treatment-related deaths. INTERPRETATION: Sorafenib maintenance post-transplantation can reduce relapse and is well tolerated in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation. This strategy could be a suitable therapeutic option for patients with FLT3-ITD acute myeloid leukaemia. FUNDING: None.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Sorafenibe/administração & dosagem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , China/epidemiologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Indução de Remissão , Sorafenibe/efeitos adversos , Sequências de Repetição em Tandem/genética , Transplante Homólogo/efeitos adversos , Adulto Jovem
16.
Transplantation ; 104(8): 1574-1579, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732834

RESUMO

BACKGROUND: Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important pathway responsible for antibody-mediated rejection (AMR). Imlifidase (IdeS) cleaves human IgG into F(ab')2 and Fc fragments, potentially inhibiting ADCC. Here we examined the effect of IdeS on allo-antibody-mediated NK cell activation (Allo-CFC) and ADCC in vitro. METHODS: For Allo-CFC, normal whole blood was incubated with third-party peripheral blood mononuclear cells (PBMCs) pretreated with anti-HLA antibody positive (HS) or negative (NC) sera to measure IFNγ+ NK cell%. For ADCC, normal PBMCs were incubated with Farage B (FB) cells with HS or NC sera to measure 7-AAD+ lysed FB cell%. To assess the effect of IdeS on these assays, serum-treated PBMCs (Allo-CFC-1) and serum used for PBMC pretreatment (Allo-CFC-2) in Allo-CFC, and serum used for ADCC were preincubated with IdeS. Sera from IdeS-treated patients were also tested for Allo-CFC (Allo-CFC-3). RESULTS: IFNγ+ NK cell% were significantly elevated in HS versus NC sera in Allo-CFC-1 (10 ± 3% versus 2 ± 1%, P = 0.001), Allo-CFC-2 (20 ± 10% versus 4 ± 2%, P = 0.01) and 7AAD+ FB cell% (11 ± 3% versus 4 ± 2%, P = 0.02) in ADCC. These were significantly reduced by IdeS treatment. Patient sera with significantly reduced anti-HLA antibody levels at 1 day postimlifidase lost the capacity to activate NK cells in Allo-CFC-3, but those at 1-3 months postimlifidase regained the capacity. CONCLUSIONS: IdeS inhibited NK cell activation and ADCC in vitro and in treated patients. These results and reported inhibition of complement activating anti-HLA antibodies by IdeS suggest its possible role in treatment of AMR.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Proteínas de Bactérias/uso terapêutico , Imunossupressores/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Transplante de Órgãos/efeitos adversos , Adulto , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Proteínas de Bactérias/farmacologia , Bioensaio , Células Cultivadas , Ativação do Complemento/efeitos dos fármacos , Dessensibilização Imunológica/métodos , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Interferon gama/imunologia , Interferon gama/metabolismo , Isoanticorpos/imunologia , Isoanticorpos/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares , Cultura Primária de Células , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Transplante Homólogo/efeitos adversos
17.
Transplantation ; 104(8): 1580-1590, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732835

RESUMO

BACKGROUND: Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance. METHODS: Seven cynomolgus macaques received immune conditioning followed by simultaneous donor bone marrow and liver transplantation. The more extensive liver surgery required minor adaptations of the kidney protocol to decrease complications. All immunosuppression was discontinued on postoperative day (POD) 28. Peripheral blood chimerism, recipient immune reconstitution, liver function tests, and graft survival were determined. RESULTS: The level and duration of chimerism in liver recipients were comparable to those previously reported in renal transplant recipients. However, unlike in the kidney model, the liver was rejected soon after immunosuppression withdrawal. Rejection was associated with proliferation of recipient CD8 T effector cells in the periphery and liver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers did not increase. Antidonor antibody was also detected. CONCLUSIONS: These data show the transient chimerism protocol does not induce tolerance to livers, likely due to greater CD8 T cell responses than in the kidney model. Successful tolerance induction may depend on greater control or deletion of CD8 T cells in this model.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/efeitos adversos , Quimeras de Transplante/imunologia , Condicionamento Pré-Transplante/métodos , Aloenxertos/imunologia , Animais , Medula Óssea/imunologia , Transplante de Medula Óssea/métodos , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Fígado/imunologia , Transplante de Fígado/métodos , Macaca fascicularis , Linfócitos T Citotóxicos/imunologia , Tolerância ao Transplante , Transplante Homólogo/efeitos adversos
18.
Transplantation ; 104(8): 1591-1603, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732836

RESUMO

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Preservação de Órgãos/métodos , Idoso , Aloenxertos/imunologia , Aloenxertos/provisão & distribução , Isquemia Fria/instrumentação , Isquemia Fria/métodos , Isquemia Fria/estatística & dados numéricos , Doença Hepática Terminal/complicações , Estudos de Viabilidade , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Rim/imunologia , Transplante de Rim/ética , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/ética , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Futilidade Médica/ética , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Preservação de Órgãos/estatística & dados numéricos , Perfusão/instrumentação , Perfusão/métodos , Perfusão/estatística & dados numéricos , Insuficiência Renal/etiologia , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/ética , Transplante Homólogo/métodos , Resultado do Tratamento
19.
Transplantation ; 104(8): 1633-1643, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732841

RESUMO

BACKGROUND: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype. METHODS: PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3. RESULTS: Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes. CONCLUSIONS: T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Sistema Porta/imunologia , Adolescente , Adulto , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Biópsia , Criança , Pré-Escolar , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Feminino , Fibrose , Seguimentos , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Imunidade Celular , Lactente , Isoanticorpos/análise , Fígado/irrigação sanguínea , Fígado/imunologia , Fígado/patologia , Doadores Vivos/estatística & dados numéricos , Macrófagos/imunologia , Masculino , Sistema Porta/citologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Transplantados/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Adulto Jovem
20.
Transplantation ; 104(8): 1726-1737, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732853

RESUMO

BACKGROUND: De novo donor-specific antibodies (DSAs) are associated with antibody-mediated rejection (AMR) and allograft loss. Whether monitoring of de novo DSA (dnDSA) paired with systematic kidney biopsy should become routine remains to be established. METHODS: A retrospective multicentric study (9 French kidney transplant units of the Spiesser group) included patients without graft dysfunction biopsied because of the presence of dnDSA (One Lambda, mean fluorescence intensity [MFI], >1000). RESULTS: One hundred twenty-three patients (85 male/38 female; mean age, 49.5 ± 13.1 y old) were biopsied after the detection of a dnDSA, 65.3 months (median) after kidney transplantation. Graft function was stable within 3 months before biopsy (estimated glomerular filtration rate, 55.3 ± 18.9 mL/min/1.73 m). Fifty-one subclinical AMRs (sAMRs) (41.4%) were diagnosed, of which 32 (26%) active and 19 (15.5%) chronic active sAMR. Seventy-two biopsies revealed no AMR (58.5%). Predictive factors associated with the diagnosis of active sAMR were MFI of immunodominant DSA >4000, MFI of the sum of DSA >6300, age of the recipient <45 years old, and the absence of steroids at biopsy. The presence of proteinuria >200 mg/g was predictive of chronic active sAMR. The decrease of estimated glomerular filtration rate at 5 years post-biopsy was significantly higher in patients with acute sAMR (-25.2 ± 28.3 mL/min/1.73 m) and graft survival significantly lower. CONCLUSIONS: Performing a kidney graft biopsy for the occurrence of dnDSA without renal dysfunction leads to the diagnosis of a sAMR in over 40% of cases. Nevertheless, we did not observe any effect of standard treatment in acute sAMR.


Assuntos
Protocolos Clínicos , Rejeição de Enxerto/diagnóstico , Isoanticorpos/sangue , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Aloenxertos , Biópsia , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/normas , Humanos , Imunossupressores/uso terapêutico , Isoanticorpos/imunologia , Rim , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Resultado do Tratamento
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