A clinical trial combining megakaryocytes and haematopoietic stem cells to promote engraftment after autologous transplantation

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Transfusion-associated or nosocomial hepatitis G virus infection in patients undergoing surgery

International audienceBACKGROUND: Despite blood donor screening, there are still cases of transfusion-associated hepatitis. From 1988 to 1992, a prospective study was conducted on the incidence of non-A, non-B posttransfusion hepatitis (PTH). STUDY DESIGN: The present investigation was designed to determine if transfusion recipients with PTH who are negative for hepatitis C virus (HCV) were positive for hepatitis G virus (HGV). Patients admitted for surgery who had normal liver tests and no transfusions during the previous 6 months were enrolled. Alanine amino transferase levels were determined monthly for 6 months after surgery and for 1 year in the case of PTH (defined as alanine aminotranferase twice the upper limit of normal in two consecutive assays). HGV RNA and E2 antibodies were tested for in samples from transfusion recipients with or without PTH and from nontransfused patients. RESULTS: Of the 308 blood recipients who were enrolled in the study, 21 (6.8%) had PTH. HGV RNA was detected at the onset of hepatitis in 3 patients with PTH (14%), 2 of whom were also anti-HCV and HCV RNA positive. One patient developed E2 antibodies without detectable HGV RNA. Three (10.7%) of 28 recipients of an allogeneic transfusion without PTH developed HGV infection. HGV RNA was also found in two nontransfused patients, which suggests nosocomial transmission of HGV. CONCLUSION: Some cases of PTH are associated with HGV; most cases of postoperative HGV infection are not associated with liver abnormalities; and most PTH cases are not associated with known hepatotropic viruses

Plerixafor in poor mobilizers with non-Hodgkin's lymphoma: a multi-center time-motion analysis

High-dose chemotherapy alongside peripheral blood stem cell (PBSC) infusion has become the standard of care in different hematologic malignancies. The goal of PBSC mobilization is to allow collection of sufficient CD34+ cells to proceed to transplantation. The current mobilization regimen with granulocyte colony-stimulating factor (G-CSF), alone or in combination with chemotherapy, still fails in 10-25% of patients. Plerixafor is able to rescue most of these patients from mobilization failure. In this study, we investigated the impact of plerixafor on the cost and time spent on apheresis in patients who were considered poor mobilizers, with < 20x10(6)/mu l peripheral CD34+ cells after mobilization but prior to apheresis. Patient hospital records from ten centers in three European countries were reviewed and compared during two time periods, namely prior and after plerixafor introduction to the market. During the plerixafor period, patients spent less time on apheresis (350 vs. 461 min). Poor mobilizers given plerixafor collected more CD34+ cells during the first apheresis session, leading to a decrease in the average number of apheresis sessions needed. The total apheresis yield was unaffected. This analysis shows that the use of plerixafor lessens the time-effort associated with the management of poor mobilizers and reduces apheresis costs

Plerixafor in poor mobilizers with non-Hodgkin's lymphoma: a multi-center time-motion analysis

High-dose chemotherapy alongside peripheral blood stem cell (PBSC) infusion has become the standard of care in different hematologic malignancies. The goal of PBSC mobilization is to allow collection of sufficient CD34+ cells to proceed to transplantation. The current mobilization regimen with granulocyte colony-stimulating factor (G-CSF), alone or in combination with chemotherapy, still fails in 10-25% of patients. Plerixafor is able to rescue most of these patients from mobilization failure. In this study, we investigated the impact of plerixafor on the cost and time spent on apheresis in patients who were considered poor mobilizers, with < 20x10(6)/mu l peripheral CD34+ cells after mobilization but prior to apheresis. Patient hospital records from ten centers in three European countries were reviewed and compared during two time periods, namely prior and after plerixafor introduction to the market. During the plerixafor period, patients spent less time on apheresis (350 vs. 461 min). Poor mobilizers given plerixafor collected more CD34+ cells during the first apheresis session, leading to a decrease in the average number of apheresis sessions needed. The total apheresis yield was unaffected. This analysis shows that the use of plerixafor lessens the time-effort associated with the management of poor mobilizers and reduces apheresis costs

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement

We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous hematopoietic stem cell transplantation might help to control refractory central nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS involvement were treated in this way. Two patients achieved non-active disease status, although one relapsed at 84 months. Two patients had regressive disease, one of whom progressed at 21 months. One patient had progressive disease at 14 months. One patient had extra-CNS progression but CNS regression. After a median follow-up of 22.4 months, only one of the six patients still has non-active disease. Treatment was effective on craniofacial and space-occupying brainstem lesions, and was ineffective on neurodegenerative lesions

Finely-tuned regulation of AMP-activated protein kinase is crucial for human adult erythropoiesis

International audienceAMP-activated protein kinase (AMPK) is a heterotrimeric complex containing α, β, and γ subunits involved in maintaining integrity and survival of murine red blood cells. Indeed, Ampk α1-/- , Ampk β1-/- and Ampk γ1-/- mice develop hemolytic anemia and the plasma membrane of their red blood cells shows elasticity defects. The membrane composition evolves continuously along erythropoiesis and during red blood cell maturation; defects due to the absence of Ampk could be initiated during erythropoiesis. We, therefore, studied the role of AMPK during human erythropoiesis. Our data show that AMPK activation had two distinct phases in primary erythroblasts. The phosphorylation of AMPK (Thr172) and its target acetyl CoA carboxylase (Ser79) was elevated in immature erythroblasts (glycophorin Alow), then decreased conjointly with erythroid differentiation. In erythroblasts, knockdown of the α1 catalytic subunit by short hairpin RNA led to a decrease in cell proliferation and alterations in the expression of membrane proteins (band 3 and glycophorin A) associated with an increase in phosphorylation of adducin (Ser726). AMPK activation in mature erythroblasts (glycophorin Ahigh), achieved through the use of direct activators (GSK621 and compound 991), induced cell cycle arrest in the S phase, the induction of autophagy and caspase-dependent apoptosis, whereas no such effects were observed in similarly treated immature erythroblasts. Thus, our work suggests that AMPK activation during the final stages of erythropoiesis is deleterious. As the use of direct AMPK activators is being considered as a treatment in several pathologies (diabetes, acute myeloid leukemia), this observation is pivotal. Our data highlighted the importance of the finely-tuned regulation of AMPK during human erythropoiesis

Massive expansion of regulatory T-cells following interleukin 2 treatment during a phase I-II dendritic cell-based immunotherapy of metastatic renal cancer.

International audienceCytotoxic chemotherapy is ineffective in metastatic renal cancer. However, systemic administration of interleukin 2 (IL-2) or infusion of dendritic cells (DCs) loaded with tumor extracts can lead to some response rates with concomitant survival improvements. We report the results of a phase I-II pilot study combining DCs and IL-2 where six patients were included. DCs were derived from bone marrow CD34+ cells and loaded with autologous tumor extracts. CD34-DC vaccines were infused subcutaneously at day 45, 52, 59, 90 and 120 following surgery in combination with IL-2, that was subsequently administrated after the 3rd and 4th DC vaccinations. Preparation of tumor extracts and CD34-DCs were satisfactory in all patients but one. Due to rapid tumor progression, one patient was excluded before vaccination. In the 4 remaining patients, two received 3 vaccinations, while the 2 others received 5 vaccinations and the full IL-2 treatment. No adverse effect due to the vaccinations was observed. A specific immune response against autologous tumor cells was observed in the 2 patients who completed the treatment. Interestingly, these 2 patients had a more prolonged survival than the patients receiving 3 vaccinations. Importantly, a transient and massive increase of circulating natural regulatory T-cells (nTregs) was evidenced in 3 patients following IL-2 administration. Overall, the use of CD34-DC vaccines is feasible, safe and non-toxic. A specific anti-tumor immune response can be detected. However, our data highlights that IL-2 is a potent inducer of nTregs in vivo and as such may have a negative impact on cancer immunotherapy