Impact of transfusion on survival in patients with myelodysplastic syndromes: Current knowledge, new insights and transfusion clinical practice.

Red Blood Cell (RBC) transfusion dependence is a prevalent consequence of anaemia in patients with lower risk Myelodysplastic Syndromes (MDS). These patients have shorter survival compared to patients responding to Erythropoiesis-stimulating agents (ESA), raising the question of potential negative effects of chronic RBC transfusions on MDS prognosis, independently of IPSS-R. Besides commonly identified complications of transfusions like iron toxicity or cardiac events, oxidative stress could be a risk factor for ineffective haematopoiesis. Recently, physicochemical changes of RBC during storage have been described. These changes called storage lesions could play a role in immunomodulation in vivo. We review the currently identified sources of potential impact on transfusion-associated effects in MDS patients and we discuss the unexplored potential role of erythrocyte-derived-extracellular vesicles. They could amplify impairment of haematopoiesis in addition to the negative intrinsic effects underlying the pathology in MDS. Thus, chronic RBC transfusions appear to potentially impact the outcome of MDS.

Choroidal blood flow after isovolemic hemodilution in an eye with retinal vein occlusion and the contralateral healthy eye.

PURPOSE: To evaluate the effect of hemodilution on subfoveal choroidal blood flow in the human eye with or without retinal vein occlusion. METHODS: Choroidal blood flow was measured using laser Doppler flowmetry in 28 patients with retinal vein occlusion in 1 eye. Isovolemic hemodilution was performed when hematocrit was >35%. Laser Doppler flowmetry parameters, velocity, volume, and flow were measured in both eyes in 4 sessions: 1 hour before and 1 hour after the first hemodilution on Day 1 and Day 7. RESULTS: Hematocrit decreased significantly by 23.7%, 19.8%, and 16.1% in the first hour, on the first day, and the seventh day after hemodilution, respectively (P < 0.001). The ocular perfusion pressure of the healthy eye and the eye with retinal vein occlusion decreased by 7.7% and 7.2% after 1 hour and by 5.3% and 4.7% 1 day after hemodilution, respectively (P < 0.01). After hemodilution, subfoveal choroidal blood velocity, volume, flow, and vascular resistance did not significantly change in either eye. CONCLUSION: Laser Doppler flowmetry measurement in the subfoveal choroid is a feasible technique for blood flow assessment in patients with retinal vein occlusion. A substantial change of hematocrit after isovolemic hemodilution does not lead to a significant change in choroidal blood flow. Vascular regulation is expected to keep blood flow constant and needs to be further explored.

Autologous platelet concentrates for bone graft enhancement in sinus lift procedure.

BACKGROUND: Autologous platelet (PLT)-rich plasma has been reported in some studies to promote osteogenesis. The goal of this study was to demonstrate that osteogenesis gained by mixing autologous PLT concentrates (APCs) with a small quantity of autologous bone graft could give a sufficient quality to lead to dental implant placement. The second goal was to compare this osteogenesis with that obtained by a traditional method (iliac bone graft), through clinical, radiologic, and histologic methods. STUDY DESIGN AND METHODS: Eighteen patients needing bilateral sinus floor augmentation were enrolled. One sinus was grafted with iliac crest bone alone, and the other sinus with a small quantity of bone and APC. Panoramic view, computed tomography scan, and biopsies were performed 6 months after the initial surgery to compare ossification. RESULTS: The adjunction of APCs permitted a 60 percent reduction of bone graft required for sinus floor elevation. The bone obtained with APCs had the same histologic and mechanical characteristics as the bone obtained by traditional graft. CONCLUSION: Topical use of APCs might be helpful in bone reconstruction. No clinical, radiologic, or histologic osteogenesis inhibition of high PLT concentration was observed. The resulting osteogenesis was adapted to dental implant placements.

Extracorporeal photophoresis increases sensitivity of monocytes from patients with graft-versus-host disease to HLA-DR-mediated cell death.

BACKGROUND: Graft-versus-host disease (GVHD) remains a cause of long-term morbidity after allogeneic hematopoietic stem cell transplantation, and recent studies indicate that extracorporeal photophoresis (ECP) is useful for treatment of steroid-refractory GVHD although the mechanisms are unclear. Antigen-presenting cells (APCs) such as dendritic cells have a central role in GVHD, and apoptosis of APCs by HLA-DR monoclonal antibody (MoAb) has been documented in vitro and in vivo. Monocytes have been identified as precursors of dendritic cells in vivo and particularly under conditions of inflammation. STUDY DESIGN AND METHODS: This study examined whether ECP altered the survival of peripheral blood monocytes from patients with GVHD, monocyte apoptosis after engagement of HLA-DR antigens with MoAb, and monocyte apoptosis after allointeraction with primary CD4+ T lymphocytes. Samples from patients from two centers were studied. RESULTS: It is reported here that ECP induced apoptosis of monocytes over a period of at least 48 hours. ECP also clearly increased cell death of monocytes after engagement of HLA-DR antigens with MoAb. In contrast, engagement of HLA-DR by allointeraction failed to induce significant cell death of monocytes, and this was unaltered by ECP treatment. CONCLUSION: These data reveal that monocytes from patients with GVHD are sensitive to HLA-DR-mediated apoptosis and that ECP treatment increases sensitivity to both spontaneous and HLA-DR-mediated apoptosis. Therefore, ECP treatment in combination with HLA-DR MoAbs could rapidly deplete monocytes and thereby reduce the contribution of monocyte-derived dendritic cells to GVHD.

Extracorporeal chemophototherapy for the treatment of graft-versus-host disease: hematologic consequences of short-term, intensive courses.

BACKGROUND AND OBJECTIVES: Extracorporeal chemophototherapy (ECP) is considered an immunomodulatory agent useful in both acute and chronic graft-versus-host disease (GVHD). Little is known about the best treatment schedule, and there are no data concerning hematologic parameters and cellular compositions of products during the treatment. DESIGN AND METHODS: This was a single-center study of 27 patients treated with ECP for corticoresistant GVHD. Treatment was given in a short-term series of six courses over 3 weeks, and in case of response, consolidation treatment was given until complete response or stabilization of lesions. RESULTS: Nine out of 12 patients with acute GVHD responded to treatment. In patients with chronic GVHD, 13 out of 15 patients responded (11 complete and 2 partial responses). Responses were obtained essentially in skin or gut lesions; ECP was of particular effect in three cases of bronchiolitis obliterans associated with transplantation, with all three patients responding. Hematologic consequences were studied in patients with chronic GVHD: hemoglobin levels increased significantly after treatment and a reduction in red blood cell transfusion requirements was also observed. INTERPRETATION AND CONCLUSIONS: ECP is effective in both chronic and acute GVHD, particularly in lung forms. ECP can reduce the duration of immunosuppressive therapy and improve erythroid recovery. ECP product quality, including standardization for the number of mononuclear cells for each patient, needs further investigation.

[Extracorporeal photochemotherapy for treatment of clonal T cell proliferations]. / La photochimiothérapie extracorporelle dans le traitement de pathologies du système lymphocytaire T.

Extracorporeal photochimiotherapy (ECP) is based on the exposure of peripheral blood mononuclear cells to the photosensitizing agent (psoralen or 8MOP) and UVA radiation. Mononuclear cells are harvested by cytapheresis and reinfused to the patient after irradiation. This cell therapy has been shown to be effective in the treatment of selected diseases mediated by clonal T cells proliferation such as Sezary T cells lymphoma, rejection after solid organ transplantation and graft-versus-host disease but results obtained in autoimmune diseases are less convincing. ECP is well tolerated with very few side effects and can be combined with immunosuppressive drugs. Two methods of ECP are currently used: in the first one, the whole procedure is performed with the same equipment whereas in the second one, the cytapheresis is performed on a conventional cell separator and treated with an independent UVA irradiation: Experimental data and clinical results suggest that PCE might induced an immune response against pathological T cells clones. However, technical differences in the methods of PCE and weak knowledge on its mechanism of action impair the standardization and evaluation of this cell therapy process as well as its clinical development.

Quality control for the validation of extracorporeal photopheresis process using the Vilbert-Lourmat UV-A irradiation's system.

In agreement with good practices for therapeutic use of human cells, quality control has to be performed to valid the process of extracorporeal photopheresis (ECP) with the Vilbert-Lourmat system. Since no protocol exists, we evaluated a technique based on the measurement of the inhibition of mitogen (PHA, Con-A, OKT3)-induced proliferation, in 164 procedures from 16 patients. Whatever the pathology, we observed a high proliferation rate in most samples, and we obtained over 90% ECP-induced inhibition in as many as 94% of the cases. Since this approach proved to be relevant regarding our objective, a protocol for the ECP process validation is proposed.