Analysis of INF-gamma, TNF-alpha and dendritic cells to predict hepatitis C virus recurrence in liver transplant patients.

INTRODUCTION: Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease and the reason for more than 50% of liver transplantations (OLT). Recurrent HCV infection occurs in almost all transplant recipients and has an unfavorable course. Although immunosuppressive agents are necessary to avoid allograft rejection, these drugs may favor viral replication facilitating viral-mediated graft injury. METHODS: To predict the evolution of two HCV(+) patients who underwent OLT, we studied INF-gamma and TNF-alpha production and the maturation capacity of dendritic cells (DCs) at three time points: before transplantation (Pre-Tx) and at 2 (2M) and 6 (6M) months after transplantation. Cytometric bead assays were used to quantify INF-gamma and TNF-alpha production in the supernates of mixed leukocyte reactions (MLR) between spleen cells from the liver donor and CD4(+) cells from the recipients. Immature and mature DCs were generated in vitro from patient monocytes. RESULTS: The one patient who experienced recurrent HCV showed loss of CD4(+) responses to donor antigens and INF-gamma and TNF-alpha production after OLT. In contrast, the other patient maintained detectable levels of these cytokines after OLT. It was possible to generate mature DCs from monocytes with the aid of CD40L in both cases, but decreased expression of HLA-DR, CD80, and CD86 markers was observed upon posttransplantation analyses in the patient with recurrent HCV. CONCLUSION: Loss of the proliferative response as well as INF-gamma and TNF-alpha production, together with a decreased HLA-DR, CD80, and CD86 (markers of mature DCs), indicated an inadequate immune response to viral progression in the liver transplant recipient with relapsing HCV infection.

Allogeneic and autologous bone marrow transplantation in AML in first remission. The Spanish experience.

From 1983 to 1994 two types of trials were performed. Between 1983 and 1987 a modified VAPA protocol (post-remission therapy with intensive sequential blocks for 12-16 months) was given to 40 patients from two institutions. CR was attained in 75% and 5-year EFS was 35%. In 1988 a post-remission protocol based on intensification chemotherapy (two high-dose Ara C treatments combined with mitoxantrone in the first and amsacrine in the second) followed by BMT was initiated. Remission induction was DAE combination (1 or 2). Patients in CR or PR with HLA-compatible donor received an allogeneic transplant (al-BMT) and those without an autologous transplant (ABMT) with "purged" marrow. Pre-BMT therapy was fractionated TBI and CYCLO in patients over 3 years and Busulfan + CYCLO + VP-16 in those under 3. Between April '88 and December '94, 51 patients (aged 3 months to 15 years) were enrolled. 80% attained CR, 14% were failures or partial responses and 6% died before the 30th day. During the intensification phase, 5 patients attained CR and one relapsed and died. 47 patients (45 in CR and 2 in PR) proceeded to the BMT phase. 16 patients (14 in CR and 2 in PR) received al-BMT and 31 (all in CR) ABMT. Both group characteristics were comparable.

Umbilical cord blood as a good alternative to bone marrow for allogeneic cell transplantation in children with hemoblastosis.

Umbilical cord blood (UCB) is an alternative source of hematopoietic progenitors and has potential advantages over bone marrow. We present our experience with UCB transplants performed between July 1994 and June 1997 in seven children with hemoblastosis. Two patients underwent transplantation from an HLA-identical sibling donor and five from an unrelated donor. Engraftment was obtained in all but one patient. Acute GVHD was absent in patients with related donors and present in all patients with unrelated donors. No patient showed chronic GVHD. Two patients died from transplant-related complications and a further two relapsed. Four patients were alive with a follow-up of 14, 15, 21 and 39 months post-transplant, respectively. Overall survival was 57% (s.e. 0.19). We conclude that cord blood is a good alternative source of hematopoietic stem cells for children with malignant hematologic diseases.

[Economic study of the cost of peripheral blood hematopoietic precursor autotransplantation compared with bone marrow transplantation]. / Estudio económico del coste del autotrasplante de precursores hematopoyéticos de sangre periférica comparado con el de médula ósea.

BACKGROUND: Rescue with progenitor cells (blood or bone marrow) following intensive chemotherapy is used ever more frequently and the results are particularly satisfactory in leukemias and lymphomas. Nonetheless, the real cost of this procedure is not known in Spain, thus the aim of this study. METHODS: The costs of autologous bone marrow transplantation (ABMT) in 10 patients was compared with another group of 10 patients with the same type of tumoral pathology in which autologous transplantation of peripheral blood precursors (APBP) was used. The period studied included from the first intervention related with the transplantation to 30 days post transplantation. RESULTS: The mean total price of ABMT (1,998 +/- 372 thousand pesetas) is similar to that of APBP (1,736 +/- 383). The length of neutropenia was lower in the APBP requiring fewer platelet transfusions but these difference did not reflect in significantly fewer admissions or in a lesser use of antibiotics. The main expense in both procedures was that of pharmacy followed by blood bank expenses in the ABMT and the expenses of obtaining hematopoietic precursors in the APBP. The saving achieved with the APBP in relation with its faster recovery are countered by the greater cost in obtaining the progenitor cells. Some factors (platelet support and days in the Intensive Care Unit) are responsible for the excessive increases in the cost of these procedures. CONCLUSIONS: Although the transfusion requirements are lesser in autologous transplantation of hematopoietic precursors and the speed of hematologic recovery is greater than in autologous bone marrow transplantation, the cost of both procedures is identical.

Infusion of platelets transiently reduces nucleoside overload in MNGIE.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by thymidine phosphorylase (TP) deficiency, which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). In this work, we report that infusion of platelets from healthy donors to patients with MNGIE restored transiently circulating TP and reduced plasma dThd and dUrd levels, suggesting that treatments to achieve permanent restoration of circulating TP such as allogeneic stem cell transplantation or gene transfer might be therapeutic.

Enhanced HPC recruitment in children using LVL and a new automated apheresis system.

BACKGROUND: A new automated apheresis system has recently been reported as useful in improving peripheral blood HPC collection in adults. The aim of this study has been to verify the utility of this system (AutoPBSC, COBE BCT) for standard leukapheresis and for LVL in the pediatric setting. STUDY DESIGN AND METHODS: A prospective study was set up in 29 leukapheresis procedures carried out in 26 children with malignant diseases and body weight under 40 kg who had undergone mobilization with G-CSF or with G-CSF and chemotherapy. Leukapheresis procedures were performed under two protocols, depending on the total blood volume processed: standard leukapheresis (< or=3) and LVL (>3). The need to prime the tubing set with blood was determined, and the inlet flow rate, collection time, recruitment of CD34+ cells, CD34+ cell collection efficiency, component volume, leukapheresis cell composition, and preapheresis and postapheresis peripheral blood counts were measured. Paired t test, Spearman's correlation coefficient, and the Mann-Whitney U test were employed for statistical analysis. RESULTS: Because of the low extracorporeal volume (167 mL) of the tubing set of the automated blood processor, priming was necessary in only 2 of 26 patients, both weighing under 10 kg. LVL showed better CD34+ cell yield (7.5 vs. 2.3 x 10(6)/kg; p = 0.047), higher recruitment (2.1 vs. 0.9; p = 0.002), and greater collection efficiency (50% vs. 33%; p = 0.005) than standard leukapheresis. No significant differences were found between groups in collection time. In LVL procedures, CD34+ cell collection efficiency and recruitment were not significantly influenced by the inlet flow rate. CONCLUSION: The AutoPBSC is a reliable system for peripheral blood HPC collection in children mainly when used in combination with LVL. The major advantage of this software is a reduced need for priming. LVL allows better CD34+ cell collection efficiency, enhanced recruitment, and improved CD34+ cell yield.

Disulphide bonds are a requirement for adsorption of cephalosporins on the red cell membrane.

The authors studied the behavior of red cells (RBCs), treated with 2-aminoethylisothiouronium bromide (AET), against 100 serums containing cephalothin antibodies and 27 serums with cephapirin antibodies. None of the serums reacted with cephalosporin-coated RBCs that had been exposed previously to AET. The possibility of the Kell system acting as a receptor for cephalosporins was excluded. The authors discuss the significance of cysteine disulphide bonds and the tertiary or quaternary structure of red cell membrane proteins in the binding of cephalosporins to RBCs.

Autoimmune thrombocytopenia: serological behavior of platelet antibodies.

The study of the specificity of platelet autoantibodies has made it possible to expand our knowledge about the immune characterization of idiopathic thrombocytopenic purpura. We report on a study of eluates obtained from 10 patients' platelets with autoimmune thrombocytopenia. They were tested with platelets obtained from healthy donors (Zw a + and Zw a-) and with type I Glanzmann platelets. Our results, as those reported by van Leeuwen et al. in 1982, suggest that the autoantibodies recognize one or more antigenic markers probably carried by glycoproteins IIb and IIIa.

Antibody elution from red blood cells by chloroform and trichloroethylene.

Antibody elution by chloroform and trichloroethylene was compared with the Rubin ether method modified by Hughes-Jones for IgG antibodies and the Landsteiner and Miller heat method for IgM antibodies. After washing the cells, the chloroform and trichloroethylene method was done at 37 degrees C for 10 minutes. With this technique the eluate remained on the upper layer above the red blood cell stroma layer, while with Rubin's method the eluate remained below the cell stroma. The reported technique was as effective as the Landsteiner and Miller heat method for IgM antibodies, and a double volume of eluate was obtained.