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Olivier Hequet,1,2 Valerie Mialou,2 Francoise Audat,3 Eric Wattel,4 Valerie Chapel,4 Damiela Revesz,1 Jean-Piere Jouet,3 Brigitte Fisseaux,5 Mohamed Saoud,6 Mauricette Michallet4 1Apheresis Unit, 2Cell Therapy Laboratory, Etablissement Français du Sang (EFS) Rhône Alpes, Centre Hospitalier Lyon Sud, Pierre Bénite, 3Biomedicine Agency, Saint-Denis, 4Hematological Unit, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, 5Psychiatric Unit, Hospices Civils de Lyon, Centre Hospitalier, Bourgoin Jallieu, 6Psychiatric Unit, Hospices Civils de Lyon, Centre Hospitalier P Wertheimer, Lyon, France Abstract: Allogeneic hematopoietic stem cell transplantation can efficiently treat patients with severe hematological diseases. A human leukocyte antigen-compatible donor is required for performing transplantation. The occurrence of unexpected acute severe diseases in a donor can compromise the feasibility of allogeneic hematopoietic stem cell transplantation. However, when a severe health problem occurs in a donor while the recipient has already received a conditioning regimen, hematologists have to find the best solutions for the recipient, while the team in charge of the donor has to find the best medical solutions for the donor. We describe here the occurrence of psychiatric acute complications in an unrelated donor while the myeloablative conditioning regimen had already been given to the recipient. We report the successive decisions that were made in an emergency based upon the expertise of physicians specialized in hematology, apheresis, cell therapy, and psychiatry to preserve the donor’s health and recipient’s life. Keywords: hematopoietic stem cells, mobilization, harvest, psychiatric complication, CD34+ cells, unrelated donor

Olivier Hequet1,2 1Etablissement Français du Sang Rhône Alpes, Apheresis Unit, Centre Hospitalier Lyon Sud France, 2Cell Therapy Unit, Etablissement Français du Sang (EFS) Rhône-Alpes, Hospital Edouard Herriot, Lyon, France Abstract: Hematopoietic stem and progenitor cell (HSPC) transplantations require prior harvesting of allogeneic or autologous HSPCs. HSPCs are usually present in bone marrow (BM) during the entire life, in cord blood (CB) at birth, or in peripheral blood (PB) under particular circumstances. HSPCs were first harvested in BM and later in CB and PB, as studies showed interesting features of such grafts. All harvesting methods were in use throughout the years, except BM harvesting for HSPC autologous transplantation, which was replaced by PB harvesting. BM, CB, and PB harvesting methods have been developed, and materials and devices technically improved to increase the number of HSPCs harvested. In parallel, knowing the features of the donors or patients associated with successful numbers of HSPCs allows the adaptation of appropriate harvesting methods. Moreover, it is important to ensure the safety of donors or patients while harvesting. This review describes the methods used for harvesting based on recent studies or developments around these methods, and more particularly, the means developed to increase the numbers of HSPCs harvested in each method. It also explains briefly the influence of technical improvements in HSPC harvesting on potential changes in HSPC graft composition. Keywords: hematopoietic stem cell, harvesting, cord blood, bone marrow, mobilization, peripheral blood, apheresis

Background: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device.Study Design and Methods: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed. The numbers of RBCPs saved using this protocol compared to the SO device without depletion and to the CSP device were determined.Results: The SO/DE protocol appeared to be safe, as only 5% and 17% of the sessions were characterized by a significant decrease in blood pressure and increase in heart rate (grade 2 adverse events), respectively. Postapheresis hematocrit and fraction of cells remaining reached expected values. The SO/DE protocol required 16% fewer RBCPs compared to SO without depletion, allowing a mean saving of 12 RBCPs per patient and per year and 13% fewer compared to CSP device. Interestingly, the saving was more important for patients with high total blood volume and/or high preapheresis hematocrit.Conclusion: The SO/DE protocol is an efficient, safe and cost-effective procedure for patients with sickle cell anemia under a chronic transfusion program. [ABSTRACT FROM AUTHOR]

Automatic red blood cell exchange i.e. using devices (RBCX) has become a standard therapy to remove abnormal red blood cells (RBC) in adults and children affected by sickle cell disease (SCD). This treatment is performed both in emergency to treat acute complications and through a regular program of RBCX to prevent the recurrence of complications. However, small children, i.e. those with a low body weight, height and total blood volume, are at risk of relative hypovolemia and metabolic complications during the procedure. Moreover, the peripheral venous access is limited among young children, which requires alternative short- or long-term venous access. These two main limiting factors necessitate adaptations of the procedures and subsequent monitoring during and after the sessions. However, performing RBCX in children requires other adaptations and cautions that must be considered. Our review summarizes the limits, safety precautions and the adaptations of the techniques to ensure RBCX in children. [ABSTRACT FROM AUTHOR]

Red blood cell exchange (RBCX) has become a standard therapy to remove abnormal red blood cells (RBC) in patients with sickle cell disease (SCD). In the last few decades, RBCX techniques have gradually improved, allowing sickle RBCs to be removed with greater precision and enabling specific hematological targets to be set. Improved knowledge of the techniques as well as the clinical and biological targets has led to optimization of the procedures. The aim of this review is to summarize the current technique, methods, targets and schedules of RBCX and to consider the outstanding issues that require additional investigation. [ABSTRACT FROM AUTHOR]

Repeated therapeutic plasma exchange (TPE) procedures using centrifugation techniques became a standard therapy in some diseases. As the new device Spectra Optia (SPO; Terumo BCT) was available, we studied its performances in repeated procedures in 20 patients in three apheresis units. First we analysed the performance results obtained by SPO. Second we compared the performances of the SPO device to a standard device, COBE Spectra (CSP; Terumo BCT) in the same patients using statistical method of mixed effects linear regression that considers variability between patients, centres and apheresis procedures. The performances analysed were classified according to plasma removal performances and their consequences on patients whose blood disturbances were assessed. Primary outcome was plasma removal efficiency (PRE) and PRE-anticoagulant corrected which was a more accurate parameter. Secondary outcomes corresponded to the volume of ACD-A consumed, platelets content in waste bag, procedure duration and status of coagulation system observed after TPE sessions. Before comparing the performances of both devices we compared the plasma volumes (PVs) processed in both techniques which showed that the PVs processed in SPO procedures were lower than in CSP procedures. In these conditions the statistical analysis revealed similar performances in both apheresis devices in PRE (p = ns) but better performances with SPO when considering higher PRE corrected by anticoagulant volume used (p < 0.05). Comparison of secondary outcomes showed no difference after SPO and CSP. After verifying that pre-apheresis patients' coagulation blood levels were identical before SPO and CSP, we showed identical haemostasis disturbances after SPO and CSP but lower platelet losses and higher fibrinogen post-apheresis blood levels after SPO (p < 0.05). No side effects or technical complications occurred during and after SPO and CSP. This study demonstrated that the Spectra Optia device is an alternative device to today's standard, the COBE Spectra device. [ABSTRACT FROM AUTHOR]

Presents updates on bone marrow transplantation as of March 2002. Information on the potential pathogenicity of human parainfluenza virus type 4 in post-hematopoietic stem cell transplants; Details on the possible role of defibrotide in treating thrombotic thrombocytopenic purpura in patients undergoing bone marrow transplantation; Discussion on acute toxicities associated with autologous peripheral progenitor cell infusion in patients receiving high-dose chemotherapy.

Background & Objectives: The primary objective of this observational study was to perform an exhaustive description concerning patients receiving extracorporeal photopheresis (ECP) as second line treatment after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes., Study Design: A total of 106 patients were included, 65 (61%) males and 41 (39%) females with a median age at transplantation of 52 years (range: 20-67). ECP was initiated after transplantation either for acute GVHD [N = 25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N = 5), gut alone (N = 12), gut and liver (N = 8), or chronic GVHD [N = 81 (76%), 15 (14%) limited and 66 (62%) extensive]., Results: Among the 25 patients treated for acute GHVD, 67% were responders and among the 81 patients with chronic GVHD, 78% were responders. Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 35% [95%CI: 14-56]. Patients with chronic GVHD had a median OS of 72 months with a survival probability at 2 years of 68% [95%CI: 56-78]. There was a significant difference in terms of survival for patients responding to ECP compared to non-responders in both acute and chronic GVHD forms. Acute GVHD grade III-IV, negatively impacted on OS (HR=7.77, 95%CI: 1.7-34), p = 0.007 and on disease relapse HR= 5.88, 95%CI: 1.7-20, p = 0.005., Conclusion: We demonstrated that ECP is an effective treatment for GVHD in a good proportion of patients with high overall response rate., Competing Interests: Declaration of Competing Interest None for this study., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: The aim of this study was to determine, in critically ill patients treated with therapeutic plasma exchange (TPE), the incidence of adverse events as well as the incidence of secondary infections and its predictive factors., Design: A multicenter retrospective cohort study of an intensive care population treated with TPE to collect adverse events and infectious complications. The characteristics of patients who developed an infection after plasma exchange were compared with those of patients who did not., Setting: Four ICUs of French university hospitals., Patients: All adults admitted between January 1, 2015, and December 31, 2019, who received at least one plasma exchange session were included., Interventions: None., Measurements and Main Results: A total of 711 TPE sessions were performed on 124 patients. The most frequent TPE indications were thrombotic microangiopathies ( n = 32, 26%), myasthenia gravis ( n = 25, 20%), and acute polyradiculoneuropathy ( n = 12, 10%). Among the 124 patients, 22 (21%) developed arterial hypotension, 12 (12%) fever, and 9 (9%) electrolyte disturbance during TPE. Moreover, 60 (48%) presented at least one infectious complication: ventilator-associated pneumonia 42, pneumonia 13, bacteremia 18 (of which 6 catheter-related infections) viral reactivation 14. Independent risk factors for ICU-acquired infection were the ICU length of stay (24 vs. 7 d; hazard ratio [HR]: 1.09 [1.04-1.15], p < 0.001) and invasive mechanical ventilation (92% vs. 35%; HR: 16.2 [5.0-53.0], p < 0.001)., Conclusions: In critically ill patients treated with TPE, adverse events occurring during the procedure remain moderately frequent and are mostly not life-threatening. Infectious complications, mainly ventilation-associated pneumonia, are frequent in this population. The need of mechanical ventilation and longer ICU stay is associated with an increased risk of infection., Competing Interests: The authors disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Coronavirus disease (COVID)-19 is characterised in particular by vascular inflammation with platelet activation and endothelial dysfunction. During the pandemic, therapeutic plasma exchange (TPE) was used to reduce the cytokine storm in the circulation and delay or prevent ICU admissions. This procedure consists in replacing the inflammatory plasma by fresh frozen plasma from healthy donors and is often used to remove pathogenic molecules from plasma (autoantibodies, immune complexes, toxins, etc.). This study uses an in vitro model of platelet-endothelial cell interactions to assess changes in these interactions by plasma from COVID-19 patients and to determine the extent to which TPE reduces such changes. We noted that exposure of an endothelial monolayer to plasmas from COVID-19 patients post-TPE induced less endothelial permeability compared to COVID-19 control plasmas. Yet, when endothelial cells were co-cultured with healthy platelets and exposed to the plasma, the beneficial effect of TPE on endothelial permeability was somewhat reduced. This was linked to platelet and endothelial phenotypical activation but not with inflammatory molecule secretion. Our work shows that, in parallel to the beneficial removal of inflammatory factors from the circulation, TPE triggers cellular activation which may partly explain the reduction in efficacy in terms of endothelial dysfunction. These findings provide new insights for improving the efficacy of TPE using supporting treatments targeting platelet activation, for instance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ebermeyer, Hequet, Berard, Prier, Eyraud, Arthaud, Heestermans, Duchez, Guironnet- Paquet, Berthelot, Cognasse and Hamzeh-Cognasse.)

Background: COVID-19 convalescent plasma (CCP) contains neutralising anti-SARS-CoV-2 antibodies that may be useful as COVID-19 passive immunotherapy in patients at risk of developing severe disease. Such plasma from convalescent patients may also have additional immune-modulatory properties when transfused to COVID-19 patients., Methods: CCP (n = 766) was compared to non-convalescent control plasma (n = 166) for soluble inflammatory markers, ex-vivo inflammatory bioactivity on endothelial cells, neutralising auto-Abs to type I IFNs and reported adverse events in the recipients., Findings: CCP exhibited a statistically significant increase in IL-6 and TNF-alpha levels (0.531 ± 0.04 vs 0.271 ± 0.04; (95% confidence interval [CI], 0.07371-0.4446; p = 0.0061) and 0.900 ± 0.07 vs 0.283 ± 0.07 pg/mL; (95% [CI], 0.3097-0.9202; p = 0.0000829) and lower IL-10 (0.731 ± 0.07 vs 1.22 ± 0.19 pg/mL; (95% [CI], -0.8180 to -0.1633; p = 0.0034) levels than control plasma. Neutralising auto-Abs against type I IFNs were detected in 14/766 (1.8%) CCPs and were not associated with reported adverse events when transfused. Inflammatory markers and bioactivity in CCP with or without auto-Abs, or in CCP whether or not linked to adverse events in transfused patients, did not differ to a statistically significant extent., Interpretation: Overall, CCP exhibited moderately increased inflammatory markers compared to the control plasma with no discernible differences in ex-vivo bioactivity. Auto-Abs to type I IFNs detected in a small fraction of CCP were not associated with reported adverse events or differences in inflammatory markers. Additional studies, including careful clinical evaluation of patients treated with CCP, are required in order to further define the clinical relevance of these findings., Funding: French National Blood Service-EFS, the Association "Les Amis de Rémi" Savigneux, France, the "Fondation pour la Recherche Médicale (Medical Research Foundation)-REACTing 2020"., Competing Interests: Declaration of interests The authors have no competing financial interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Blood products in therapeutic transfusion are now commonly acknowledged to contain biologically active constituents during the processes of preparation. In the midst of a worldwide COVID-19 pandemic, preliminary evidence suggests that convalescent plasma may lessen the severity of COVID-19 if administered early in the disease, particularly in patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms. This study examined the influence of photochemical Pathogen Reduction Treatment (PRT) using amotosalen-HCl and UVA light in comparison with untreated control convalescent plasma (n= 72 - paired samples) - cFFP, regarding soluble inflammatory factors: sCD40L, IFN-alpha, IFN-beta, IFN-gamma, IL-1 beta, IL-6, IL-8, IL-10, IL-18, TNF-alpha and ex-vivo inflammatory bioactivity on endothelial cells. We didn't observe significant modulation of the majority of inflammatory soluble factors (8 of 10 molecules tested) pre- or post-PRT. We noted that IL-8 concentrations were significantly decreased in cFFP with PRT, whereas the IL-18 concentration was increased by PRT. In contrast, endothelial cell release of IL-6 was similar whether cFFP was pre-treated with or without PRT. Expression of CD54 and CD31 in the presence of cFFP were similar to control levels, and both were significant decreased in when cFFP had been pre-treated by PRT. It will be interesting to continue investigations of IL-18 and IL-8, and the physiopathological effect of PRT- treated convalescent plasma and in clinical trials. But overall, it appears that cFFP post-PRT were not excessively pro-inflammatory. Further research, including a careful clinical evaluation of CCP-treated patients, will be required to thoroughly define the clinical relevance of these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cognasse, Hamzeh-Cognasse, Duchez, Shurko, Eyraud, Arthaud, Prier, Heestermans, Hequet, Bonneaudeau, Rochette-Eribon, Teyssier, Barlet-Excoffier, Chavarin, Legrand, Richard, Morel, Mooney and Tiberghien.)

Red blood cell exchanges are frequently used to treat and prevent cerebrovascular complications in patients with sickle cell anemia (SCA). However, the low weight of young children represents serious concerns for this procedure. The Spectra Optia device can perform automatic priming using red blood cells (RBCs) (RCE/RBC-primed) which could allow RBC exchanges (RCE) to be performed in young children without hypovolemic complications, but this method requires evaluation. We prospectively analyzed the clinical safety of the RCE/RBC-primed procedure in 12 SCA low-weight children under either a chronic RCE program or emergency treatment over 65 sessions. We monitored grade 2 adverse events (AEs) such as a decrease in blood pressure, increase in heart rate, fainting sensation, or transfusion reactions and identified the critical times during the sessions in which AEs could occur. Post-apheresis hematocrit (Hct) and a fraction of cell remaining (FCR) values were compared to the expected values. We also compared the impact of automatic RCE ( n = 7) vs. RCE/RBC-primed ( n = 8) on blood viscosity and RBC rheology. A low incidence of complications was observed in the 65 RCE sessions with only seven episodes of transient grade 2 AEs. Post-apheresis Hct and FCR reached expected values with the RCE/RBC-primed method. Both the automatic and priming procedures improved RBC deformability and decreased the sickling tendency during deoxygenation. Blood rheological features improved in both RCE/RBC-primed and automatic RCE without priming conditions. The RCE/RBC-primed procedure provides blood rheological benefits, and is safe and efficient to treat, notably in young children with SCA in prophylactic programs or curatively when a SCA complication occurs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hequet, Boisson, Joly, Revesz, Kebaili, Gauthier, Renoux, Creppy, Nader, Nicolas, Berard, Cognasse, Vocanson, Bertrand and Connes.)

Purpose of the Report: We aimed to evaluate the role of 18F-FDG PET/CT in predicting patient outcome following chimeric antigen receptor T (CAR T) cells infusion in aggressive B-cell lymphoma., Methods: 18F-FDG PET/CT data before leukapheresis, before CAR T-cell infusion and 1 month (M1) after CAR T-cell infusion, from 72 patients were retrospectively analyzed. SUVmax, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and parameters describing tumor kinetics were calculated for each 18F-FDG PET/CT performed. The aim was to evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters for predicting progression-free survival (PFS) and overall survival (OS) following CAR T-cell therapy., Results: Regarding PFS, ∆MTVpre-CAR and ∆TLGpre-CAR were found to be more discriminating compared with metabolic parameters at preinfusion. Median PFS in patients with a ∆MTVpre-CAR of less than 300% was 6.8 months (95% confidence interval [CI], 2.8 months to not reached) compared with 2.8 months (95% CI, 0.9-3.0 months) for those with a value of 300% or greater (P = 0.004). Likewise, median PFS in patients with ∆TLGpre-CAR of less than 420% was 6.8 months (95% CI, 2.8 months to not reached) compared with 2.7 months (95% CI, 1.3-3.0 months) for those with a value of 420% or greater (P = 0.0148). Regarding OS, metabolic parameters at M1 were strongly associated with subsequent outcome. SUVmax at M1 with a cutoff value of 14 was the most predictive parameter in multivariate analysis, outweighing other clinicobiological variables (P < 0.0001)., Conclusions: Disease metabolic volume kinetics before infusion of CAR T cells seems to be superior to initial tumor bulk itself for predicting PFS. For OS, SUVmax at M1 might adequately segregate patients with different prognosis., Competing Interests: Conflicts of interest and sources of funding: P. Sesques: honoraria, advisory/consultancy from Novartis and Kite/Gilead; F.W.: honoraria, advisory/consultancy from Novartis and Kite/Gilead; V. Schwiertz: honoraria, advisory/consultancy from Kite/Gilead and Novartis; G.S.: advisory board/consulting for Gilead, Kite, Novartis; E.B.: honoraria, consultancy from Gilead, Novartis. The other authors have none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β + ) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment.

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe., (© 2020 Wiley Periodicals LLC.)

Extracorporeal photochemotherapy (ECP) that takes advantage of the immunomodulatory effects of UV light has been extensively used for many years for the treatment of several T cell-mediated diseases, including graft-versus-host disease (GvHD) and systemic scleroderma. Immune mechanisms that lead to the establishment of T cell tolerance in ECP-treated patients remain poorly known. In this study, we have tested the effect of UV/psoralen-treated BM-derived dendritic cells, referred to as ECP-BMDCs on the outcome of an antigen-specific T cell-mediated reaction, that is, contact hypersensitivity (CHS), which is mediated by CD8 + effector T cells (CD8 + T eff ). The intravenous (i.v.) injection of antigen-pulsed ECP-BMDCs in recipient C57BL/6 mice induced specific CD8 + T cells endowed with immunomodulatory properties (referred to as CD8 + T ECP ), which prevented the priming of CD8 + T eff and the development of CHS, independently of conventional CD4 + regulatory T cells. CD8 + T ECP mediated tolerance by inhibiting the migration and functions of skin DC and subsequently the priming of CD8 + T eff . CD8 + T ECP displayed none of the phenotypes of the usual CD8 + T regulatory cells described so far. Our results reveal an underestimated participation of CD8 + T cells to ECP-induced immunomodulation that could explain the therapeutic effects of ECP in T cell-mediated diseases., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

Decompressive craniotomy (DC) in children is a life-saving procedure for the treatment of refractory intracranial hypertension related to traumatic, ischemic and infectious lesions. Different surgical procedures have been proposed including uni or bilateral hemicraniectomy, bi-frontal, bi-temporal, or bi-parietal craniotomies. DC can avoid the cascade of events related to tissue hypoxia, brain perfusion reduction, hypotension and the evolution of brain edema that can be responsible for brain herniation. The monitoring of intracranial pressure (ICP) is very important to take a decision as well as the value of Trans cranial Doppler (TCD). Repeated TCD in the intensive care unit give important information about the decrease of the cerebral perfusion pressure (CPP) and facilitates the decision making. The important question is about how long time we have to wait before to perform the DC. Three conditions can be distinguished: 1) ICP stable and TCD with good parameters: the decision can be postponed; 2) ICP>20 mmHg with good TCD and without clinical signs of deterioration: the decision can be postponed; 3) ICP>20 mmHg with altered CPP and degraded TCD value and clinical signs of brain herniation: the surgical procedure is indicated. The decision of a ventricular drainage can also be discussed but in cases of slit ventricles it is preferable to realize a DC to avoid the problems of multiple taps without finding the ventricular system. In some very specific situations, DC has to be contraindicated. The first one is a prolonged cardiopulmonary arrest with a no-flow longer than 15 minutes and irreversible lesions on the TCD or on the CT-scan. The second most common situation is a patient with GCS of 3 on admission associated with bilaterally fixed dilated pupils. In this case TCD is very useful to document the decrease or the absence of diastolic flux that indicates a very poor cerebral perfusion. In case of severe polytraumatism with multiorgan failure, especially in very severe hemorrhagic shock with incontrollable coagulopathy, the realization of DC is definitely hazardous with y a high risk of cardiac arrest during the surgical procedure. The decision to realize a hemicraniectomy or a bi-frontal craniotomy is related to the presence or not of associated traumatic lesions as hemorrhagic contusions or a sub-dural or extradural hematoma. In cases of diffuse cerebral edema the bi-frontal bone flap is indicated. In all cases a closure of the dura mater with a large dural patch has to be performed avoiding compression of the nervous system. Our results showed a mortality rate of 18%. Eighty percent of the survivors have a good quality of life but only 43% in a scholar age could attend a normal program. Patients treated with DC need a long follow-up and an important rehabilitation program to improve their quality of life. Our report shows that DC in children is effective to control the post-traumatic intracranial hypertension but a long follow-up is recommended to access the sequels and quality of life of these patients.

Background: Homozygous familial hypercholesterolemia (HFH) is a rare genetic disease leading to early onset atherosclerosis, due to high concentrations of LDL-C in the blood. Aortic root atheromas may be complicated by obstruction to left ventricle outflow or coronary stenosis. The aim of this study was to describe the progression of aortic root atheroma in patients requiring lipoprotein apheresis before 16 years of age and to examine the requirement of these patients for aortic surgery., Method: Clinical reports, lipid profiles and echocardiogram results were obtained retrospectively for patients with HFH from three French hemapheresis centers. Data are presented as group medians., Results: Twenty patients were included, of which 53% had aortic root atheroma (as assessed by echocardiogram) before starting lipoprotein apheresis. These patients began lipoprotein apheresis later than children without aortic root atheroma (10.3 years old [range 5.6-15.9 years] vs. 5.0 years old [range 4.5-11.6 years], respectively, p < 0.05). After 16.4 years (range 2.2-22.8 years) of lipoprotein apheresis treatment, aortic root atheroma had progressed in 64% of patients. Five patients needed surgery for aortic stenosis, which was associated with a coronary artery by-pass for two of them. There were significantly more operations among patients with an aortic root atheroma at the beginning of lipoprotein apheresis than among patients without preexisting lesions (p < 0.01). One patient died after aorta replacement surgery during this period., Conclusion: Our results suggest that the initiation of lipoprotein apheresis before the onset of aortic root atheroma should reduce the requirement for aortic surgery., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Relapse in acute myeloid leukemia (AML) after chemotherapy reflects the persistence of resistant leukemia stem cells (LSCs). These cells have been described in the CD34 + CD38- cell fraction. Leukapheresis products were harvested in 123 patients in morphological complete remission and analyzed by multiparameter flow cytometry. The CD34 + CD38- cell population showed a prognostic impact on survival. Median event-free survival (EFS) was 8.2 months (3-year EFS: 29%) for those with a higher percentage of CD34 + CD38- versus 91.9 months (3-year EFS: 62%) for those with a lower percentage for the entire cohort. These differences were confirmed in patients undergoing autologous stem cell transplant, with median EFS of 7.3 months versus 91.1 months (3-year EFS: 31% vs. 70%). Higher proportions of CD34 + CD38- cells were associated with adverse cytogenetics and with earlier relapses. Higher percentages of CD34 + CD38- cells in apheresis products reflect inadequate in vivo purging and reliably distinguish samples enriched in LSCs from those involving mainly normal cells.

Erythrocytapheresis procedures, increasingly used in the management of patients with severe complications of sickle cell disease, are limited by adequate venous access. We have successfully used short-term femoral catheter insertion, during a 6.5-year period for a total of 443 procedures, to perform long-term erythrocytapheresis in 18 consecutive children with sickle cell disease., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: The ACVBP regimen is an efficient induction regimen for poor-risk patients with diffuse large B-cell lymphoma (DLBCL) before consolidative autologous stem cell transplantation. Adjunction of the monoclonal anti-CD20 antibody rituximab (R-ACVBP) was recently found to be superior to ACVBP alone. This study assessed the impact of rituximab on stem cell mobilization in two similar consecutive groups of patients treated with ACVBP in two prospective, controlled trials., Study Design and Methods: The first trial (LNH-98B-3) involved 137 patients treated with ACVBP alone. In the second trial (LNH-03-3B), 91 patients received an R-ACVBP regimen. Stem cell mobilization was performed after a course of (R)-ACVBP., Results: The median peak numbers of blood CD34+ cell counts recorded before the first apheresis procedure in the ACVBP and R-ACVBP groups were 69×10(6) and 63×10(6) /L, respectively (p=0.55). The median numbers of CD34+ cells collected were 7.1×10(6) and 6.0×10(6) CD34+ cells/kg for the ACVBP and R-ACVBP groups, respectively (p=0.13). The median number of apheresis procedures required for gathering the minimum amount of CD34+ cells (2×10(6) /kg) was the same in the two groups., Conclusion: When compared with ACVBP alone, adjunction of rituximab does not impair stem cell mobilization., (© 2012 American Association of Blood Banks.)

Background: The short-term effects of granulocyte-colony-stimulating factor (G-CSF) have been extensively studied, but recent reports of G-CSF-induced genetic perturbations raised concerns regarding its long-term safety. In this respect, duration of G-CSF-induced perturbations has been less studied than short-term effects and needs to be evaluated., Study Design and Methods: G-CSF mobilization-induced immunologic alterations were prospectively analyzed in a cohort of 24 healthy donors. Blood samples were taken before G-CSF administration; at the time of administration; and at 1, 3, 6, and 12 months and analyzed for blood cell counts and in vitro cytokines (interleukin [IL]-2, -8, and -10) and immunoglobulin production, quantified in the culture supernatant of peripheral blood mononuclear cells (PBMNCs) after, respectively, phytohemagglutinin and pokeweed mitogen stimulation., Results: Platelet, granulocyte, monocyte, B, and dendritic blood cell counts as well as the IL-2, -8, and -10 secretion by PBMNCs, perturbed at the time of G-CSF mobilization, returned to baseline values at 1 month, with T-cell and natural killer cell counts recovering at 3 months. In vitro immunoglobulin production was increased up to 6 months after mobilization., Conclusion: Although assessment of the potential long-term risk of G-CSF administration will require prolonged observation of larger cohorts, our data show that the duration of immunologic perturbations may be more persistent than previously anticipated, especially for B-cell functional alterations. Most perturbations remain, however, transient with a return to baseline values within 1 year., (© 2010 American Association of Blood Banks.)

Background: Hypoxia is a major cause of painful vaso-occlusive crisis in sickle cell disease (SCD). Simple transfusion and red blood cell (RBC) exchange are commonly used as preventive therapies whose aim is to dilute hemoglobin (Hb)S-containing RBCs (SS-RBCs) with normal RBCs (AA-RBCs) to prevent sickling. We hypothesized that the effectiveness of transfusion could be improved by the encapsulation of inositol hexaphosphate (IHP), an allosteric Hb effector, in transfused AA-RBCs. Indeed, apart from their diluting effect on SS-RBCs, IHP-loaded RBCs (IHP-RBCs) with increased oxygen release capacity could palliate in vivo oxygen deprivation and reduce sickling., Study Design and Methods: The study was designed to investigate the therapeutic effect of IHP-RBCs transfusion on in vitro sickling of SS-RBCs collected from 20 SCD patients. Patients' RBCs were diluted with various proportions of IHP-RBCs or AA-RBCs (processed or stored RBCs as controls). Resulting suspensions were subjected to deoxygenation followed by partial reoxygenation at 5% oxygen. Sickling was evaluated by microscopy., Results: Stored RBCs (50% dose) used to mimic simple transfusion exhibited a poor antisickling effect (5.6%) and a low response rate (65%). In contrast, IHP-RBCs treatment was seven times more effective resulting in 35% of sickling reduction and a 94% response rate. Sickling was inhibited in a dose-dependent manner: 9.9, 25.1, and 35.0% for IHP-RBCs in percentages of 10, 30, and 50%, respectively., Conclusion: Our results indicate that IHP-RBCs prevent in vitro sickling and suggest that it could improve conventional transfusion therapy in terms of transfused volume, frequency, and efficacy., (© 2010 American Association of Blood Banks.)