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1.
Rinsho Ketsueki ; 62(8): 1275-1280, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497216

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) plays an important role as the most potent therapeutic option for refractory acute lymphoblastic leukemia (ALL). However, advances of supporting therapy have enabled more intensive chemotherapy, and severe late complication of allo-HCT has been recognized, thus, indication of allo-HCT is now limited to carefully selected population with highest risk for relapse, based on assessment by minimal residual disease status. Furthermore, especially for B-cell precursor ALL, we should re-establish a role of allo-HCT in the entire of therapeutic strategy, including novel options, such as small molecular agents and immunotherapy. We are now required to maximize safety and efficacy of allo-HCT for selected high-risk ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Transplante Homólogo
2.
Rinsho Ketsueki ; 62(8): 1281-1287, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497217

RESUMO

Graft-versus-host disease (GVHD) is a major complication that occurs after allogeneic hematopoietic stem cell transplantation (HSCT). While the allogeneic immune response may cause GVHD, it also plays essential roles in the resultant antitumor effects and in engraftment facilitation. Therefore, the application of necessary and sufficient immune control at an appropriate time according to the condition of each individual patient is the key to successful HSCT. Recently, the landscape of HSCT has changed drastically due to the diversification of transplanted grafts and the emergence of novel immunosuppressive methods and immune-modulatory agents. In this review, we first describe the current understanding of the immune pathogenesis of acute and chronic GVHD, and then, we discuss the characterization and therapeutic intervention for GVHD after diversified HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunossupressores , Transplante Homólogo
3.
Rinsho Ketsueki ; 62(8): 1334-1342, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497224

RESUMO

Viral infections are one of the leading causes of death in hematopoietic cell transplantation (HCT) and are a problem that should be resolved. For post-HCT viral infections, reduction of antiviral treatment or immunosuppressive drug dose is generally performed; however, the effect of antiviral drug is sometimes limited, and reduction of immunosuppressive treatment might worsen the graft-versus-host disease. Therefore, appropriate infection preventive measures and early diagnosis and therapeutic intervention for viral infections are important. In addition, virus-specific T-cell (VST) therapy is attracting attention as a new treatment method for intractable and refractory post-HCT viral infections. Various methods have been developed to establish VSTs, from a single- to multiple-virus targeting and from related- to third-party-derived donors. Its safety and efficacy have already been reported in clinical trials, and thereby, it is expected to be established as one of the important treatments for post-HCT viral infections.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Viroses , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfócitos T , Transplante Homólogo , Viroses/terapia
4.
Blood Adv ; 5(17): 3418-3426, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34495311

RESUMO

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Transplante Homólogo
5.
N Engl J Med ; 385(10): 921-929, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34469647

RESUMO

Human papillomavirus (HPV) infections underlie a wide spectrum of both benign and malignant epithelial diseases. In this report, we describe the case of a young man who had encephalitis caused by herpes simplex virus during adolescence and currently presented with multiple recurrent skin and mucosal lesions caused by HPV. The patient was found to have a pathogenic germline mutation in the X-linked interleukin-2 receptor subunit gamma gene (IL2RG), which was somatically reverted in T cells but not in natural killer (NK) cells. Allogeneic hematopoietic-cell transplantation led to restoration of NK cytotoxicity, with normalization of the skin microbiome and persistent remission of all HPV-related diseases. NK cytotoxicity appears to play a role in containing HPV colonization and the ensuing HPV-related hyperplastic or dysplastic lesions. (Funded by the National Institutes of Health and the Herbert Irving Comprehensive Cancer Center Flow Cytometry Shared Resources.).


Assuntos
Mutação em Linhagem Germinativa , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/fisiologia , Infecções por Papillomavirus/terapia , Citotoxicidade Imunológica , Encefalite/virologia , Feminino , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Masculino , Microbiota/efeitos dos fármacos , Células T Matadoras Naturais/fisiologia , Papillomaviridae , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Linhagem , Pele/microbiologia , Transplante Homólogo , Adulto Jovem
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 854-859, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511177

RESUMO

Haploidentical hematopoietic stem cell transplantation is a recommended alternative therapy for children with severe aplastic anemia who lack a human leukocyte antigen (HLA)-identical sibling donor and do not respond well to immunosuppressive therapy; however, due to non-identical HLA, the patients may have donor-specific anti-HLA antibody, which may lead to a relatively high incidence rate of poor graft function. Compared with HLA-identical transplantation, conditioning regimen for haploidentical transplantation still needs to be explored. This article reviews the detection and treatment of donor-specific anti-HLA antibody, the selection of conditioning regimen, and the mechanism and treatment of poor graft function in haploidentical hematopoietic stem cell transplantation.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Criança , Humanos , Condicionamento Pré-Transplante , Transplante Homólogo
7.
Zhonghua Yan Ke Za Zhi ; 57(8): 608-613, 2021 Aug 11.
Artigo em Chinês | MEDLINE | ID: mdl-34344122

RESUMO

Objective: To study the ultrastructural features of the corneal epithelium in the corneal allograft of rats with micromolecular compound J2. Methods: An experimental study. Primarily cultured corneal epithelial cells of rats were used. Mononuclear cells (MNCs) by density gradient centrifugation were assigned into the experimental group [MNCs (2 ml)+corneal epithelial cells+J2], control group [MNCs (2 ml)+corneal epithelial cells] and blank group (corneal epithelial cells). Quantity of CD80 expression was obtained by flow cytometry after coculture. Amplitude and height images were obtained by tapping mode atomic force microscopy (AFM) with a scan rate of 2 Hz and an integral gain of 0.3 to 0.5. Statistical analysis of Ra, Rq, Rvm and Rt was performed using the single-factor analysis of variance, and P value was calculated. Results: There were obvious differences in the ultrastructure measured by AFM among groups. Ra was 86.75±12.60 in the experimental group, 120.23±12.11 in the control group, and 61.94±10.62 in the blank group (F=306.92, P<0.01). Rq was 102.53±9.45, 138.30±10.13, and 91.96±7.25, respectively, in the three groups (F=361.85, P<0.01). Rvm was -42.21±14.22, -67.36±10.89, and -32.18±19.01, respectively (F=72.22, P<0.01). Rt was 437.32±15.66, 495.32±13.96, and 339.92±11.22, respectively (F=1634.26, P<0.01). The one way analysis of variance showed significant differences in these parameters among groups. Conclusions: Corneal epithelial cells of rats activated by MNCs had higher CD80 expression, but the expression became decreased with micromolecular compound J2. The ultrastructure of the corneal epithelium became coarser after MNCs activation, and the number of protrusions increased significantly. The ultrastructural changes were alleviated by J2.(Chin J Ophthalmol, 2021, 57: 608-613).


Assuntos
Transplante de Córnea , Epitélio Corneano , Animais , Córnea , Microscopia de Força Atômica , Ratos , Transplante Homólogo
8.
Int J Mol Sci ; 22(15)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34361109

RESUMO

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for blood cancers and other haematological disorders. However, allo-HSCT leads to graft-versus-host disease (GVHD), a severe and often lethal immunological response, in the majority of transplant recipients. Current therapies for GVHD are limited and often reduce the effectiveness of allo-HSCT. Therefore, pro- and anti-inflammatory factors contributing to disease need to be explored in order to identify new treatment targets. Purinergic signalling plays important roles in haematopoiesis, inflammation and immunity, and recent evidence suggests that it can also affect haematopoietic stem cell transplantation and GVHD development. This review provides a detailed assessment of the emerging roles of purinergic receptors, most notably P2X7, P2Y2 and A2A receptors, and ectoenzymes, CD39 and CD73, in GVHD.


Assuntos
Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Receptores Purinérgicos/metabolismo , Transdução de Sinais , Animais , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Humanos , Transplante Homólogo
9.
Ann Palliat Med ; 10(7): 7736-7746, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353061

RESUMO

BACKGROUND: There has been long-standing controversy regarding the effectiveness and safety of lenalidomide as a maintenance treatment for patients with multiple myeloma (MM) after allogeneic cell transplantation. This meta-analysis aimed to explore the effectiveness and safety of lenalidomide in the maintenance treatment of MM patients after allogeneic cell transplantation based on published data. METHODS: A systematic review and meta-analysis was conducted in English and Chinese databases, covering all available publications until 1 December 2020. Statistical analysis was performed using the software STATA 14.0, and odds ratios (ORs) combined with 95% confidence intervals (CIs) were calculated to explore the efficacy and safety of lenalidomide in the treatment of MM patients after allogeneic cell transplantation. RESULTS: A total of 173 MM cases in 8 independent studies from 2007 to 2014 were included. Through a single-arm meta-analysis of the disease status of MM patients after lenalidomide treatment, 3.6% of patients were in minimal response (MR, P=0.006), 39.0% were in complete remission (CR, P=0.169), 20.2% in partial remission (PR, P<0.001), 12.8% in very good partial remission (VGPR, P=0.049), and 9.7% in SD (P=0.023); the PD was 5.6% (P=0.010). Through meta-analysis of adverse reactions after taking lenalidomide, 35.3% (P=0.628) of participants developed acute graft-versus-host disease (GVHD); 22.6% (P=0.049) developed chronic GVHD; 20.3% (P=0.001) developed infection; 22.5% (P=0.352) had thrombocytopenia; 32.5% (P<0.000) had neutropenia; pain occurred in 17.8% (P=0.350) of patients, and peripheral neuropathy occurred in 17.8% (P=0.995) of participants. The overall survival (OS) of ≥2 years and progression-free survival (PFS) of ≥2 years of MM patients after allo-hematopoietic-stem-cell transplantation (HSCT) taking lenalidomide were analyzed, and the results were 64.9% (P=0.049) and 58.4% (P=0.890), respectively. DISCUSSION: Lenalidomide is effective in the treatment of MM patients after allo-HSCT, and reducing the incidence of infection and peripheral neuropathy, but it is not effective in reducing GVHD and blood system adverse reactions.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Intervalo Livre de Doença , Humanos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Transplante Homólogo , Resultado do Tratamento
10.
Transplantation ; 105(8): 1643-1652, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34291765

RESUMO

Livers for transplantation from donation after circulatory death donors are relatively more prone to early and ongoing alterations in graft function that might ultimately lead to graft loss and even patient death. In consideration of this fact, this working group of the International Liver Transplantation Society has performed a critical evaluation of the medical literature to create a set of statements regarding the assessment of early allograft function/dysfunction and complications arising in the setting of donation after circulatory death liver transplantation.


Assuntos
Transplante de Fígado/efeitos adversos , Consenso , Humanos , Complicações Pós-Operatórias/etiologia , Guias de Prática Clínica como Assunto , Fatores de Risco , Sociedades Médicas , Transplante Homólogo
11.
Transplantation ; 105(8): 1747-1759, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34291766

RESUMO

BACKGROUND: The lymphatic system plays an active role in modulating inflammation in autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis and influence rejection in vascularized composite allotransplantation (VCA). METHODS: Hindlimb transplantations were performed in which (1) recipient rats received VCA containing donor LN (D:LN+), (2) recipient rats received VCA depleted of all donor LN (D:LN-), and (3) D:LN+ transplantations were followed by lymphangiogenesis inhibition using a vascular endothelial growth factor receptor-3 (VEGFR3) blocker. RESULTS: Our data show that graft rejection started significantly later in D:LN+ transplanted rats as compared to the D:LN- group. Moreover, we observed a higher level of VEGF-C and a quicker and more efficient lymphangiogenesis in the D:LN+ group as compared to the D:LN- group. The presence of donor LN within the graft was associated with reduced immunoactivation in the draining LN and increased frequency of circulating and skin-resident donor T regulatory cells. Blocking of the VEGF-C pathway using a VEGFR3 blocker disrupts the lymphangiogenesis process, accelerates rejection onset, and interferes with donor T-cell migration. CONCLUSIONS: This study demonstrates that VCA LNs play a pivotal role in the regulation of graft rejection and underlines the potential of specifically targeting the LN component of a VCA to control graft rejection.


Assuntos
Rejeição de Enxerto/etiologia , Linfonodos/fisiologia , Linfangiogênese/fisiologia , Fator C de Crescimento do Endotélio Vascular/fisiologia , Animais , Linfonodos/transplante , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Doadores de Tecidos , Transplante Homólogo , Fator C de Crescimento do Endotélio Vascular/análise , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
12.
Br J Anaesth ; 127(3): 405-414, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34229832

RESUMO

BACKGROUND: Allogeneic red blood cell (RBC) transfusion can induce immunosuppression, which can then increase the susceptibility to postoperative infection. However, studies in different types of surgery show conflicting results regarding this effect. METHODS: In this retrospective cohort study conducted in a tertiary referral centre, we included adult patients undergoing clean-contaminated surgery from 2014 to 2018. Patients who received allogeneic RBC transfusion from preoperative Day 30 to postoperative Day 30 were included into the transfusion group. The control group was matched for the type of surgery in a 1:1 ratio. The primary outcome was infection within 30 days after surgery, which was defined by healthcare-associated infection, and identified mainly based on antibiotic regimens, microbiology tests, and medical notes. RESULTS: Among the 8098 included patients, 1525 (18.8%) developed 1904 episodes of postoperative infection. Perioperative RBC transfusion was associated with an increased risk of postoperative infection after controlling for 27 confounders by multivariable regression analysis (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.39-1.84; P<0.001) and propensity score weighing (OR: 1.64; 95% CI: 1.45-1.85; P<0.001) and matching (OR: 1.70; 95% CI: 1.43-2.01; P<0.001), and a dose-response relationship was observed. The transfusion group also showed higher risks of surgical site infection, pneumonia, bloodstream infection, multiple infections, intensive care admission, unplanned reoperation, prolonged postoperative length of hospital stay, and all-cause death. CONCLUSIONS: Perioperative allogeneic RBC transfusion is associated with an increased risk of infection after clean-contaminated surgery in a dose-response manner. Close monitoring of infections and enhanced prophylactic strategies should be considered after transfusion.


Assuntos
Infecções Bacterianas/microbiologia , Transfusão de Eritrócitos/efeitos adversos , Hospedeiro Imunocomprometido , Assistência Perioperatória/efeitos adversos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriemia/imunologia , Bacteriemia/microbiologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/mortalidade , Cuidados Críticos , Transfusão de Eritrócitos/mortalidade , Humanos , Tempo de Internação , Readmissão do Paciente , Assistência Perioperatória/mortalidade , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/mortalidade , Infecção da Ferida Cirúrgica/imunologia , Infecção da Ferida Cirúrgica/microbiologia , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Resultado do Tratamento
13.
Nat Commun ; 12(1): 4372, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272370

RESUMO

Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction.


Assuntos
Aloenxertos/imunologia , Linfócitos B/metabolismo , Rejeição de Enxerto/imunologia , Inflamação/metabolismo , Transplante de Rim/efeitos adversos , Animais , Autoanticorpos/imunologia , Linfócitos B/imunologia , Linfócitos B/patologia , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Ontologia Genética , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Imunoglobulina G/imunologia , Rim/imunologia , Rim/metabolismo , Camundongos , Tonsila Palatina/imunologia , Tonsila Palatina/metabolismo , RNA-Seq , Análise de Célula Única , Transplante Homólogo
14.
Rev Med Suisse ; 17(745): 1310-1313, 2021 Jul 14.
Artigo em Francês | MEDLINE | ID: mdl-34264033

RESUMO

Allografts in reconstructive knee surgery are an interesting option, due to the absence of donor site morbidity, its rather easy intraoperative handling, the different sizes, shorter surgical time, and therefore less peroperative risks. The risk of infection is very low. Their results are similar when non-irradiated and non-sterilized allografts are used in terms of postoperative strength, return to sport, and comparable stability testing. Nevertheless, allografts have not yet become current practice, due to the costs, the availability, its structural integration and ligamentisation process that might be prolonged and its increased re-rupture rate in the young and active population. Its undeniable value for multiligamentous or complexe knee reconstruction is however undeniable, which should however be reserved for specialized centers.


Assuntos
Articulação do Joelho , Procedimentos Cirúrgicos Reconstrutivos , Aloenxertos , Humanos , Articulação do Joelho/cirurgia , Ruptura , Transplante Homólogo
15.
Rinsho Ketsueki ; 62(6): 602-609, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34219087

RESUMO

Acute graft-versus-host disease (GVHD) is a systemic immune reaction in which mature T cells in the donor inoculum are abnormally activated by the host and donor antigen-presenting cells. These activated cells then attack normal host tissue after allogeneic hematopoietic stem cell transplantation (HSCT). Clinical GVHD develops when the damage exceeds the threshold for tissue tolerance. Furthermore, functional damage of hematopoietic and non-hematopoietic organs due to this acute immune response triggers the subsequent development of chronic GVHD. The endpoint of HSCT is shifting from just surviving the acute phase to having an enriched life until later years; therefore, seamless and detailed immune management is required from the acute to chronic phase after HSCT. Acute GVHD prophylaxis consisted of calcineurin inhibitors and short-term methotrexate for a long time. However, various novel immune-modulating strategies have been developed against the background of recent diversification in donor sources and changes in treatment goals. In this review, we discuss recent clinical developments in basic and clinical research regarding acute or chronic GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Metotrexato , Linfócitos T , Transplante Homólogo
16.
Ann Hematol ; 100(9): 2387-2398, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34232360

RESUMO

Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Of the non-refractory patients, 48.4% with a median age of 63 (range 17-85) years relapsed. Relapses occurred within 6 months after CR in 46.5%, between 7 and 18 months in 38.7%, and after 18 months in 14.8% of patients. Relapse treatment resulted in CR2 in 39% of patients depending upon age (54.5% of ≤ 60 and 28.6% of > 60 years), duration of CR1, and treatment of relapse. Overall survival (OS) was 10.9 (7.4-16.2) %, but OS after HCT ± intensive chemotherapy (ICT) was 39.3% (31.8-48.6) at 5 years and not different in younger and older patients. Donor lymphocyte infusion ± chemotherapy and ICT alone resulted only in OS of 15.4% and of 5%, respectively. Independent favorable factors for OS were long CR1 duration, and HCT, while non-monosomal disease was beneficial for OS in elderly patients. Leukemia-free survival [LFS; 24.9 (19.5-31.7) % at 10 years] was affected by similar risk factors. In a competing risk model, the relapse incidence at 5 years was 53.5 ± 3.5% and the non-relapse mortality rate 21.7 ± 2.9%. Lower relapse incidence was observed in patents with HCT, long CR1 duration, and female gender. Risk factors for non-relapse mortality were HCT in younger and type of AML in elderly patients. In conclusion, allogeneic HCT ± IC improved the results in relapsed AML in younger and elderly patients. Increasing CR2 rates and HCT frequency will be the challenge for the next years. Relapse of the disease remains the major problem.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
18.
Front Immunol ; 12: 634416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248931

RESUMO

Background: The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19. Methods: SARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions. Results: EASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha. Conclusion: EASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.


Assuntos
COVID-19/diagnóstico , Células Endoteliais/fisiologia , Transplante de Células-Tronco Hematopoéticas , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , COVID-19/mortalidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Respiração Artificial , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
19.
Transplant Cell Ther ; 27(8): 642-649, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34304802

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.


Assuntos
Quimerismo , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Rejeição de Enxerto/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Condicionamento Pré-Transplante , Transplante Homólogo , Estados Unidos
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