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The French National Authority for Health (HAS) recently issued guidelines for patient blood management (PBM) in surgical procedures. These recommendations are based on three usual pillars of PBM: optimizing red cell mass, minimizing blood loss and optimizing anemia tolerance. In the preoperative period, these guidelines recommend detecting anemia and iron deficiency and taking corrective measures well in advance of surgery, when possible, in case of surgery with moderate to high bleeding risk or known preoperative anemia. In the intraoperative period, the use of tranexamic acid and some surgical techniques are recommended to limit bleeding in case of high bleeding risk or in case of hemorrhage, and the use of cell salvage is recommended in some surgeries with a major risk of transfusion. In the postoperative period, the limitation of blood samples is recommended but the monitoring of postoperative anemia must be carried out and may lead to corrective measures (intravenous iron in particular) or more precise diagnostic assessment of this anemia. A "restrictive" transfusion threshold considering comorbidities and, most importantly, the tolerance of the patient is recommended postoperatively. The implementation of a strategy and a program for patient blood management is recommended throughout the perioperative period in healthcare establishments in order to reduce blood transfusion and length of stay. This article presents an English translation of the HAS recommendations and a summary of the rationale underlying these recommendations.
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AIMS: Pulsed field ablation (PFA) has been proposed as a novel alternative to radiofrequency (RF) and cryoablation in the treatment of atrial fibrillation (AF). Following the occurrence of two cases of acute kidney injury (AKI) secondary to haemolysis after a PFA procedure, we evaluated haemolysis in a cohort of consecutive patients. METHODS AND RESULTS: Two cases of AKI occurred in last May and June 2023. AKI was secondary to acute and severe haemolysis after a PFA procedure. From June 2023, a total of 68 consecutive patients (64.3 ± 10.5 years) undergoing AF ablation with PFA were enrolled in the study. All patients had a blood sample the day after the procedure for the assessment of haemolysis indicators. The pentaspline PFA catheter was used with a total number of median applications of 64 (54; 76). Nineteen patients (28%) showed significantly depleted haptoglobin levels (<0.04â g/L). A significant inverse correlation was found between the plasma level of haptoglobin and the total number of applications. Two groups were compared: the haemolysis+ group (haptoglobin < 0.04â g/L) vs. the haemolysis- group. The total number of applications was significantly higher in the haemolysis+ group vs the haemolysis - group respectively 75 (62; 127) vs 62 (54; 71) P = 0.011. More than 70 applications seem to have better sensitivity and specificity to predict haemolysis. CONCLUSION: Intravascular haemolysis can occur after certain procedures of PFA. Acute kidney injury is a phenomenon that appears to be very rare after a PFA procedure. However, caution must be exercised in the number of applications to avoid severe haemolysis.
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Injúria Renal Aguda , Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Hemólise , Haptoglobinas , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Ablação por Cateter/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: Suspicion of myelodysplastic syndromes (MDS) is the most common reason for bone marrow aspirate in elderly patients. Peripheral blood neutrophil myeloperoxidase expression quantified by flow cytometric analysis might rule out MDS for up to 35% of patients referred for suspected disease, without requiring bone marrow aspiration. Yet laboratory-developed liquid antibody cocktails have practical limitations, because of lack of standardisation and poor stability. This research project aims to estimate the level of agreement and comparative accuracy between a single-use flow cytometry tube of lyophilised reagents (BD Lyotube Stain 468) and its laboratory-developed liquid reagent counterpart in quantifying peripheral blood neutrophil myeloperoxidase expression, among adult patients referred for suspected MDS. METHODS AND ANALYSIS: The MPO-MDS-Develop project is a cross-sectional diagnostic accuracy study of two index tests by comparison with a reference standard in consecutive unselected adult patients conducted at a single university hospital. Flow cytometry analysis of peripheral blood samples will be performed by independent operators blinded to the reference diagnosis, using either Lyotube Stain 468 or laboratory-developed liquid reagent cocktail. The reference diagnosis of MDS will be established by cytomorphological evaluation of bone marrow aspirate by two independent haematopathologists blinded to the index test results. Morphologic assessment will be complemented by bone marrow flow cytometric score, karyotype and targeted next-generation sequencing panel of 43 genes, where relevant. The target sample size is 103 patients. ETHICS AND DISSEMINATION: An institutional review board (Comité de Protection des Personnes Sud Est III, Lyon, France) approved the protocol prior to study initiation (reference number: 2020-028-B). Participants will be recruited using an opt-out approach. Efforts will be made to release the primary results within 6 months of study completion. TRIAL REGISTRATION NUMBER: NCT04399018.
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Síndromes Mielodisplásicas , Neutrófilos , Adulto , Idoso , Estudos Transversais , Citometria de Fluxo/métodos , Humanos , Indicadores e Reagentes , Síndromes Mielodisplásicas/diagnóstico , Neutrófilos/metabolismo , PeroxidaseRESUMO
OBJECTIVE: To evaluate the impact of pathogen-reduced (PR) platelet transfusions on blood products requirement for clinical practice. BACKGROUND: PR platelets are increasing in use as standard blood products. However, few randomised trials have evaluated their impact on bleeding control or prevention. Furthermore, PR platelets recirculate less than untreated platelets. METHODS: A subgroup study of the randomised clinical trial EFFIPAP compared three arms of platelet preparations (PR: P-PRP/PAS, additive solution: P-PAS and plasma P-P arms respectively). The subgroup of acute leukaemia patients, in their chemotherapy induction phase, included 392 patients (133 P-PRP/PAS arm, 132 P-PAS arm and 130 P-P arm). Blood requirements were analysed across over periods of 7 days. RESULTS: The number of platelet transfusions per week was significantly higher in the P-PRP/PAS group 2.3 [1.6-3.3] compared to the control groups 1.9 [1.3-2.8] and 2.0 [1.3-3.0] for P-P and P-PAS groups respectively (p < 0.0001). However, the total number of platelets transfused per week was not different. The number of red blood cell concentrates (RBC) transfusion per week did not differ either. CONCLUSION: In a homogeneous group of patients, platelet pathogen reduction resulted in an increased number of platelet units transfused per week while having no impact on the total number of platelets transfused or the number of RBC transfusion; resulting to an average requirement of 2 RBC and 2-3 platelets transfusions per week of marrow aplasia.
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Leucemia , Trombocitopenia , Plaquetas , Hemorragia , Humanos , Leucemia/terapia , Transfusão de Plaquetas/efeitos adversos , Trombocitopenia/terapiaAssuntos
Plaquetas/microbiologia , Desinfecção/métodos , Doenças Hematológicas , Neoplasias , Transfusão de Plaquetas , Furocumarinas/uso terapêutico , Doenças Hematológicas/sangue , Doenças Hematológicas/microbiologia , Doenças Hematológicas/terapia , Humanos , Neoplasias/sangue , Neoplasias/microbiologia , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Riboflavina/uso terapêutico , Raios UltravioletaRESUMO
Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for acute myeloid leukemia. In the absence of an HLA-matched related or unrelated donor (MRD or MUD), the best alternative donor source remains controversial. Umbilical cord blood and haploidentical donors offer a shorter delay from indication to transplantation. This retrospective multicentre study of a French registry compares overall survival in the 18 months following registration in the absence of a MRD between four types of donors. Between 2012 and 2016, 1302 patients were transplanted using MUD (control, n = 803), mismatched MUD (n = 219), umbilical cord blood (n = 153) and haploidentical (n = 127) donors. Multivariate analyses were conducted for overall survival after registration, after transplant, and transplant-related mortality. After adjustment for variables, the type of donor did not influence any of the three end points. Our results confirmed the significant negative impact of longer time between registration and transplant: HR = 1.04 [1.02-1.06] (p < 0.0001). This indicates a positive correlation between better survival and shorter registration-to-transplantation wait time. In the absence of a sibling donor, the alternative stem cell source does not impact early survival in acute myeloid leukemia patients. The minimization of registration-to-transplantation time should be considered when weighing the alternative donor options.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Irmãos , Transplante Homólogo , Doadores não RelacionadosRESUMO
The recommendations of the French Health and Drug Safety Authorities (HAS/ANSM-Haute Autorité de santé/Agence nationale de sécurité du médicament) are known, but there are always new developments underway. With regards to CMV suppression, there is the introduction of platelet glycoprotein Ia and the Intercept (Amotosalem+UVA) inactivation method which addresses bacterial risk. The irradiation of platelets is included in the recommendations to ensure HEV-negative plasma post allograft. In terms of blood transfusion safety, these measures as well as the broader spectrum of Ia, particularly for arboviruses, are a real breakthrough. The survey conducted in clinical services and the services providing blood products for transfusion along with a literature review have shown that several improvements need to be made. The first is a reduction of transfusions of concentrated red blood cells with introduction at a threshold of 7g/dL during hospitalization of patients without a fragile clinical status. The second improvement would address transfusion of refractory thrombocytopenia, encouraging an increase in discussion between clinicians and those conducting the transfusion in order to consider different etiologies and to identify appropriate care protocols. Third would be the need for the transmission of information between the transplantation doctors and blood transfusion specialists in order to define an approach to transfusion care adapted to the patient's situation. It is important to inform and educate patients about transfusion protocols post allotransplant or autotransplant. It must be clearly communicated to patients that they should always have on their person their blood group documentation. This is especially true when receiving care for a hemopathy or an autologous transplant. If undergoing an allogeneic transplant, patients should also carry transfusion guidelines post autotransplant or post allotransplant along with the phone numbers for the stem cell transplantation department and the blood transfusion center responsible for their care.
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Autoenxertos , Transfusão de Eritrócitos/normas , Transplante de Células-Tronco Hematopoéticas/normas , Prontuários Médicos , Transfusão de Plaquetas/normas , Trombocitopenia/terapia , Adulto , Antígenos de Grupos Sanguíneos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Comunicação Interdisciplinar , Educação de Pacientes como Assunto , Trombocitopenia/etiologia , Transplante HomólogoRESUMO
INTRODUCTION: The use of autologous haematopoietic stem cell transplantation (AHSCT) in autoimmune disease (AD) patients has increased progressively worldwide. We retrospectively analysed the long-term outcome of AHSCT for AD reported to the French Society for Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). METHOD: All French AD patients (≥ 18 years at transplant) with a first AHSCT between 1997 and 2013 were included. Primary data were derived from the European Society for Blood and Marrow Transplantation (EBMT) registry, and additional data were obtained through a specific questionnaire designed for the study. Primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS) and non-relapse mortality (NRM). RESULTS: Ninety-four AD patients were included, of whom 71% suffered from rheumatologic diseases (n = 67, including 56 systemic sclerosis (SSc)), 16% from neurological disease (n = 15, including 14 multiple sclerosis (MS)) and 13% from various other AD (n = 12). After a median (interquartile range, IQR) follow-up of 83 months (38-130), OS at 5 and 10 years were 77% (95% CI 68.5-86.2) and 64% (95% CI 51.7-76.3), and for PFS 51% (95% CI 40.4-61.6) and 44% (95% CI 32.8-55.3), respectively. Overall, NRM was 8.7% (95% CI 4.0-15.5) at day 100, 9.8% (95% CI 4.8-16.9) at 5 years and 13.6% (95% CI 6.9-22.5) at 10 years. CONCLUSIONS: This first SFGM-TC retrospective report shows long-term benefit of AHSCT in AD patients with acceptable toxicity.
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Doenças Autoimunes/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Doenças Autoimunes/epidemiologia , Transplante de Medula Óssea , Terapia Baseada em Transplante de Células e Tecidos , Intervalo Livre de Doença , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Sociedades Médicas , Transplante AutólogoRESUMO
Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level <10 g/dL. Patients could be red blood cell transfusion-dependent or not and were given epoetin zeta 40 000 IU/week. Serum erythropoietin level, iron parameters, hepcidin, flow cytometry Ogata and RED scores, and growth-differentiation factor-15 levels were determined at baseline, and molecular analysis by next-generation sequencing was also conducted. Erythroid response (defined according to the International Working Group 2006 criteria) was assessed at week 12. Seventy patients, with a median age of 78 years, were included in the study. There were 22 patients with refractory cytopenia with multilineage dysplasia, 19 with refractory cytopenia with unilineage dysplasia, 14 with refractory anemia with ring sideroblasts, four with refractory anemia with excess blasts-1, six with chronic myelomonocytic leukemia, two with del5q-and three with unclassifiable myelodysplastic syndrome. According to the revised International Prognostic Scoring System, 13 had very low risk, 47 had low risk, nine intermediate risk and one had high-risk disease. Twenty patients were transfusion dependent. Forty-eight percent had an erythroid response and the median duration of the response was 26 months. At baseline, non-responders had significantly higher RED scores and lower hepcidin:ferritin ratios. In multivariate analysis, only a RED score >4 (P=0.05) and a hepcidin:ferritin ratio <9 (P=0.02) were statistically significantly associated with worse erythroid response. The median response duration was shorter in patients with growth-differentiation factor-15 >2000 pg/mL and a hepcidin:ferritin ratio <9 (P=0.0008 and P=0.01, respectively). In multivariate analysis, both variables were associated with shorter response duration. Erythroid response to epoetin zeta was similar to that obtained with other erythropoiesis-stimulating agents and was correlated with higher baseline hepcidin:ferritin ratio and lower RED score. ClinicalTrials.gov registration: NCT 03598582.
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Eritropoese/efeitos dos fármacos , Eritropoetina/uso terapêutico , Ferritinas/sangue , Hepcidinas/sangue , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Feminino , Citometria de Fluxo , Humanos , Ferro/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/etiologia , Prognóstico , Curva ROC , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
IMPORTANCE: Pathogen reduction of platelet concentrates may reduce transfusion-transmitted infections but is associated with qualitative impairment, which could have clinical significance with regard to platelet hemostatic capacity. OBJECTIVE: To compare the effectiveness of platelets in additive solution treated with amotosalen-UV-A vs untreated platelets in plasma or in additive solution in patients with thrombocytopenia and hematologic malignancies. DESIGN, SETTING, AND PARTICIPANTS: The Evaluation of the Efficacy of Platelets Treated With Pathogen Reduction Process (EFFIPAP) study was a randomized, noninferiority, 3-arm clinical trial performed from May 16, 2013, through January 21, 2016, at 13 French tertiary university hospitals. Clinical signs of bleeding were assessed daily until the end of aplasia, transfer to another department, need for a specific platelet product, or 30 days after enrollment. Consecutive adult patients with bone marrow aplasia, expected hospital stay of more than 10 days, and expected need of platelet transfusions were included. INTERVENTIONS: At least 1 transfusion of platelets in additive solution with amotosalen-UV-A treatment, in plasma, or in additive solution. MAIN OUTCOMES AND MEASURES: The proportion of patients with grade 2 or higher bleeding as defined by World Health Organization criteria. RESULTS: Among 790 evaluable patients (mean [SD] age, 55 [13.4] years; 458 men [58.0%]), the primary end point was observed in 126 receiving pathogen-reduced platelets in additive solution (47.9%; 95% CI, 41.9%-54.0%), 114 receiving platelets in plasma (43.5%; 95% CI, 37.5%-49.5%), and 120 receiving platelets in additive solution (45.3%; 95% CI, 39.3%-51.3%). With a per-protocol population with a prespecified margin of 12.5%, noninferiority was not achieved when pathogen-reduced platelets in additive solution were compared with platelets in plasma (4.4%; 95% CI, -4.1% to 12.9%) but was achieved when the pathogen-reduced platelets were compared with platelets in additive solution (2.6%; 95% CI, -5.9% to 11.1%). The proportion of patients with grade 3 or 4 bleeding was not different among treatment arms. CONCLUSIONS AND RELEVANCE: Although the hemostatic efficacy of pathogen-reduced platelets in thrombopenic patients with hematologic malignancies was noninferior to platelets in additive solution, such noninferiority was not achieved when comparing pathogen-reduced platelets with platelets in plasma. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01789762.
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Plaquetas/citologia , Transmissão de Doença Infecciosa/prevenção & controle , Doenças Hematológicas/terapia , Transfusão de Plaquetas/métodos , Trombocitopenia/terapia , Adulto , Idoso , Segurança do Sangue/métodos , Desinfecção/métodos , Estudos de Equivalência como Asunto , Feminino , França , Hemostasia/fisiologia , Hemostáticos/uso terapêutico , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We performed a prospective multicenter phase 2 study to evaluate the safety and efficacy of prophylactic Extracorporeal Photopheresis (ECP) in adult patients with hematological malignancies early after RIC allo-HSCT on day 21 twice per week during the first two weeks and then once per week for the next four weeks for a total of eight ECP courses. A total of 20 patients were included; 10 were males, median age was 60 years. All patients engrafted, 17 (85%) received the total eight ECP courses. There were no adverse effects related to ECP. Seven patients developed acute graft-versus-host disease (GVHD), with 15% grade ≥ II cumulative incidence at day 100. The cumulative incidence of chronic GVHD at 2 years was 22%. The 2 years probability of overall survival (OS) and progression-free survival (PFS) were 84 and 74%, respectively. This study shows encouraging results with low acute and chronic GVHD incidence and no interference with graft-versus-leukemia (GVL) effect.
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Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fotoferese , Condicionamento Pré-Transplante , Doença Aguda , Idoso , Biomarcadores , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Fotoferese/métodos , Análise de Sobrevida , Quimeras de Transplante , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do TratamentoRESUMO
The evolution of HLA typing and transplantation techniques makes it easier to identify a donor for hematopoietic stem cell (HSC) transplantation. This activity, strongly regulated by regulatory or normative texts, implies in addition biological, medical, para-medical and sometimes psychological evaluations. The benefit/risk discussion is complicated because it must take into account the benefit/risk ratio for the recipient, and the donor risk. No Evidence-Based Medicine data is available and serious events are very rare situations. Biovigilance declarations and their analysis are of fundamental importance. Certain obvious and definite contraindications could be detected very early in the process. It is important to assess whether a risk factor or pathology contributes to increasing the risk associated with collection. In case of recipient risk, the situation should be discussed with the patient team. These recommendations focus on adult peripheral blood HSC donors. They refer to donor information, confidentiality of exchanges, the impact of moral or material pressures, declarations of biovigilance, collegiality and traceability of difficult decisions, desirable experience and training for doctors in charge, use of expert advice informed by an explicit exchange on the possible risks, parsimony of therapeutic interventions and minimization of risks for the donor. We also recommend creation, availability and use by the community of tools and documents (registries, questionnaires, synthetic recommendations, feedback, and collegial qualification meetings) useful for practice.
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Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/normas , Doadores Vivos , Adulto , Confidencialidade , Tomada de Decisões , França , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade/efeitos adversos , Teste de Histocompatibilidade/ética , Humanos , Princípios Morais , Risco Ajustado , Medição de Risco , Sociedades MédicasRESUMO
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements. Herein, we set-up an efficient cellular penetration of recombinant TFs fused to the minimal transduction domain (MD) from the ZEBRA protein. We show that ZEBRA MD-fused TFs applied on primary human fibroblasts and cord blood CD34+ hematopoietic stem cells route through the cytoplasm to the nucleus. The delivery of Oct4, Sox2 and Nanog by MD leads to the activation of mRNA transcripts from genes regulated by these TFs. Moreover, the expression of genes involved in the pluripotency network but not directly bound by these TFs, is also induced. Overall, the repeated application of MD-Oct4, MD-Sox2, MD-Nanog TFs and the post-transcriptional regulator RNA-binding protein MD-Lin28a, triggers the rejuvenation of human fibroblasts and CD34+ cells. This study provides powerful tools for cell fate reprogramming without genetic interferences.
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Peptídeos Penetradores de Células/farmacologia , Reprogramação Celular , Sistemas de Liberação de Medicamentos , Fatores de Transcrição/metabolismo , Animais , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Proteína Homeobox Nanog/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Fatores de Transcrição SOXB1/metabolismoAssuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Doadores não Relacionados , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Recidiva Local de Neoplasia , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Ectopic expression of defined transcription factors (TFs) for cell fate handling has proven high potential interest in reprogramming differentiated cells, in particular for regenerative medicine, ontogenesis study and cell based modelling. Pluripotency or transdifferentiation induction as TF mediated differentiation is commonly produced by transfer of genetic information with safety concerns. The direct delivery of proteins could represent a safer alternative but still needs significant advances to be efficient. We have successfully developed the direct delivery of proteins by an attenuated bacterium with a type 3 secretion system that does not require challenging and laborious steps for production and purification of recombinant molecules. Here we show that this natural micro-syringe is able to inject TFs to primary human fibroblasts and cord blood CD34+ hematopoietic stem cells. The signal sequence for vectorization of the TF Oct4 has no effect on DNA binding to its nucleic target. As soon as one hour after injection, vectorized TFs are detectable in the nucleus. The injection process is not associated with toxicity and the bacteria can be completely removed from cell cultures. A three days targeted release of Oct4 or Sox2 embryonic TFs results in the induction of the core pluripotency genes expression in fibroblasts and CD34+ hematopoietic stem cells. This micro-syringe vectorization represents a new strategy for TF delivery and has potential applications for cell fate reprogramming.
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Reprogramação Celular , Pseudomonas aeruginosa , Fatores de Transcrição/genética , Sistemas de Secreção Tipo III/administração & dosagem , DNA/genética , Fibroblastos/metabolismo , Expressão Gênica , Técnicas de Transferência de Genes , Células-Tronco Hematopoéticas/metabolismo , Humanos , Plasmídeos , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
Inconsistent results have been reported regarding the influence of graft composition on the incidence of graft versus host disease (GVHD), disease control and survival after reduced-intensity conditioning (RIC) allogeneic peripheral blood stem cell transplantation (allo-PBSCT). These discrepancies may be at least in part explained by the differences in disease categories, disease status at transplant, donor type and conditioning. The current retrospective EBMT registry study aimed to analyze the impact of CD3+ and CD34+ cells dose on the outcome of RIC allo-PBSCT in patients with acute myelogenous leukemia (AML) in first complete remission, allografted from HLA-matched unrelated donors (10 of 10 match). We included 203 adults. In univariate analysis, patients transplanted with the highest CD3+ and CD34+ doses (above the third quartile cut-off point values, >347 x 10^6/kg and >8.25 x 10^6 /kg, respectively) had an increased incidence of grade III-IV acute (a) GVHD (20% vs. 6%, P = .003 and 18% vs. 7%, P = .02, respectively). There was no association between cellular composition of grafts and transplant-related mortality, AML relapse, incidence of chronic GVHD and survival. Neither engraftment itself nor the kinetics of engraftment were affected by the cell dose. In multivariate analysis, CD3+ and CD34+ doses were the only adverse predicting factors for grade III-IV aGVHD (HR = 3.6; 95%CI: 1.45-9.96, P = .006 and 2.65 (1.07-6.57), P = .04, respectively). These results suggest that careful assessing the CD3+ and CD34+ graft content and tailoring the cell dose infused may help in reducing severe acute GVHD risk without negative impact on the other transplantation outcomes.
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Doença Enxerto-Hospedeiro/diagnóstico , Leucemia Mieloide/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados , Doença Aguda , Adulto , Idoso , Antígenos CD34/sangue , Complexo CD3/sangue , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Adulto JovemRESUMO
Acute graft-versus-host disease (aGVHD) still remains the main cause of morbidity and mortality after allogeneic stem cell transplantation. Moreover, patients who did not respond to first-line treatment with glucocorticosteroids have a very poor outcome. Some studies suggested that alemtuzumab (a humanized monoclonal antibody against the CD52 antigen) might be effective for treatment of refractory aGVHD. Here we report a single-center experience with alemtuzumab in refractory gastrointestinal aGVHD. From September 2009 to April 2012 at the Grenoble medical university center, 24 patients who had presented a refractory gastrointestinal aGVHD to corticosteroid, or after another immunosuppressive drug, were retrospectively analyzed. Most patients (n = 19) presented stage 4 gastrointestinal aGVHD. Response to treatment (either complete or partial) was observed in 15 patients (62.4%). The overall survival rate at 1 year for all patients was 33.3% (95% confidence interval [CI], 15.9% to 51.9%) and for responders, 53.3% (95% CI, 26.3% to 74.4%). Two patients died from infection, 5 patients from recurrent GVHD, and 1 from an uncontrolled post-transplant lymphoproliferative disorder.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The role of reduced intensity allogeneic stem cell transplantation for the treatment of relapsed/refractory Hodgkin's lymphoma remains controversial. We retrospectively analyzed 191 patients who underwent reduced intensity allogeneic stem cell transplantation between 1998 and 2008 for relapsed or refractory Hodgkin's lymphoma and whose data were reported to the French registry. The median follow-up was 36 months. The estimated 3-year overall survival rate, progression-free survival rate, cumulative incidence of relapse and cumulative incidence of non-relapse mortality were 63%, 39%, 46%, and 16%, respectively. There was no difference in outcome between patients in complete response and in partial response at the time of transplantation with regards to overall survival (70% versus 74%, no significant difference) and progression-free survival (51% versus 42%, no significant difference). Patients with chemoresistant disease had a shorter overall survival (39% at 3 years; P=0.0003) and progression-free survival (18% at 3 years; P=0.001) than patients in complete remission. The use of umbilical cord blood as the source of stem cells was associated with a poor outcome with an increased risk of death with a hazard ratio of 3.49 (95% confidence interval: 1.26 to 9.63; P=0.016). The use of peripheral blood was associated with a better outcome for patients who where alive 1 year after transplantation with a hazard ratio of 0.38 (95% confidence interval: 0.17 to 0.83; P=0.016). Disease status at transplantation remains the most important risk factor for outcome. Our data suggest that the use of peripheral blood should be preferred whereas umbilical cord blood should be used with caution.