A dose of 100 IU intravenous anti-D gammaglobulin is effective for the prevention of RhD immunisation after RhD-incompatible single donor platelet transfusion.
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Biomedical subjects
Publications and source records attributed to J Zingsem.
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We have determined the incidence and clinical significance of positive microbiologic cultures in a series of 290 peripheral blood stem cell concentrates in 95 patients undergoing multiple apheresis procedures for autologous stem cell rescue. Specimens for bacterial cultures were obtained after processing of the autografts just prior to freezing. The incidence of microbial contamination was 4.5% (n = 13). The predominant pathogenic microorganism cultured was coagulase-negative Staphylococcus (n = 11). From 8 patients with contaminated leukapheresis products 6 underwent autologous stem cell transplantation. Five patients received 1-5 culture-positive stem cell concentrates without serious sequelae, whereas the sixth patient was autografted with noncontaminated leukapheresis products, 1 concentrate contaminated with Aspergillus fumigatus being not reinfused. No microorganism present in the stem cell autograft was recovered in vivo in the posttransplantation period, although fever as a sign of infection occurred in all but 1 patient. Peripheral blood stem cell collection and ex vivo processing for cryopreservation may result in microbiologic contamination. However, our data show that infusion of contaminated stem cell autografts does not play a significant role as a source for infections in the clinical setting of autologous stem cell rescue.
BACKGROUND: Antibodies to HLA determinants may decrease the increment after platelet transfusion and are correlated with increased rates of rejection in renal transplantation. Cross-match tests and HLA antibody specification are used to identify compatible donors for sensitized patients. However, search for cross-match negative donors may be ineffective, and many sera containing antibodies toward public HLA epitopes give no clear results in conventional specificity analysis. MATERIALS AND METHODS: We tested a series of 4,625 sera from 1,073 patients with hematological, malignant or other diseases using a fluorescence lymphocytotoxicity test (LCT). We applied an evaluation program incorporating a list of public antigens belonging to known cross-reacting groups (CREGs) to detect antibodies toward private and just as well public epitopes. RESULTS: In 694 sera (15.0%) from 240 patients the panel reactivity (PRA) in LCT assay was higher than 5%. PRA was > or = 50% in 258 (37.2%) and < 50% in 436 sera (62.8%). In both groups we identified specific antibodies toward public HLA class I epitopes. Overall antibody specification was successful in 429 of 694 sera (61.8%) and in 175 of 240 patients (72.9%), respectively. The rate of antibodies against public epitopes shared by more than one HLA class I gene product was 203/694 (29.3%) with respect to tested sera and 83/240 (34.5%) with respect to patients. The rate of public epitope antibodies was highest in sera with PRA values from 30 to 90% showing public epitope specificity in 159 of 353 sera (45.0%). CONCLUSIONS: We conclude that antibodies toward public HLA class I determinants are detectable not only in highly sensitized patients. The described program may increase the rate of antibody specification and facilitate the platelet supply in platelet refractory patients.
PURPOSE: This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS: Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS: The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION: High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.
BACKGROUND: Since October 1991 the third-generation cell separator Fresenius AS 104 offers a single-needle (SN) option for thrombocytapheresis. Here we present our first 18-month experience with this new single-needle system. MATERIALS AND METHODS: We performed 395 thrombocytaphereses in 225 donors. The influence of blood flow, cycle volume, and interface position on efficacy and leukocyte contamination was evaluated. RESULTS: 395 thrombocytaphereses were performed with an average thrombocyte yield of 3.00 +/- 0.69 x 10(11) platelets and a leukocyte contamination of 1.66 +/- 3.1 x 10(8) per concentrate. Blood flow rates of 50 ml/min (vs. 60 ml/min) and an interface position of 6:2 (vs. 7:1) resulted in a lower leukocyte contamination, but without statistical significance. CONCLUSION: The SN program of the AS 104 provides high thrombocyte yields and less leukocyte contamination than other SN systems, but 77% of the concentrates still contain more than 0.5 x 10(8) leukocytes.
We intended to answer two questions: (1) Does storage time of platelet concentrates (PCs) influence the efficacy of leucocyte depletion by filtration? (2) Does pre-storage leucocyte depletion by filtration of PCs improve the post-storage quality? To this end we tested in parallel the halves of 10 double-sized PCs, one half stored after filtration through a polyester filter (PL 50, Pall), the other half filtered after a 5-day storage period. Efficacy of leucocyte depletion showed to be independent of the age of PCs, and pre-storage leucocyte depletion of PCs was not able to improve the quality of PCs stored for 5 days, as long as the leucocyte contamination of unfiltered PCs was lower than 0.5 x 10(8)/unit.
In light of the increasing demands being placed on cytapheresis donors and their occasional venous problems, it has become necessary to use 1-needle in addition to 2-needle separation techniques in thrombocytapheresis. We therefore compared five 1-needle and three 2-needle programs on four different cell separators and found that meanwhile both the platelet yields and the leukopenia (controlled by Nageotte chamber counting) of the products obtained with the 1-needle technique are equivalent to those obtained using the 2-needle technique, as long as the program is suitably adjusted.
We concentrated freshly taken bone marrow (BM) pooled from 21 patients from an original 1.265 ml (+/- 537 ml) down to 128 ml (+/- 36 ml) within 40-70 min with a modified version of the 'grancollect protocol' on the Fresenius AS 104 blood-cell separator using the P1-Y set. An average of 47% (+/- 21%) fo the initially present mononuclear cells and 68% (+/- 47%) of the colony-forming cells could be obtained in the concentrate. The erythrocyte concentration was reduced to 7% (+/- 4%) of the original amount. The technique described is very effective and makes is possible to obtain a BM cell population that is suitable for both immunomagnetic purging and cryopreservation or transplantation, e.g. in the case of blood group incompatibility.
In blood samples of members of the Berliner Altersstudie (BASE) (n = 427, 204 males, 223 females; mean = 85.2 years, range = 76-96 years, SD = 3.3 years), red cell, HLA-A, -B, -Cw and -Dr antigens were determined by standard methods. Lymphocyte reactivity was measured by 3H-thymidine uptake into DNA of lymphoblastic cells stimulated by 12 different mitogens and antigens. Cluster analysis, confirmed by t and F tests, defined 3 distinct clusters of lymphocyte reactivity. Clusters showed significantly different cumulations of 3 or more increased characteristic red cell and HLA antigens, and trends toward a decreased overall immunoresponsiveness in elder people. Like in middle-aged individuals, immunoresponsiveness in elder individuals can be dissected into at least 3 functionally different clusters which are not influenced by lymphocyte subsets or in vivo cell activation but by the patterns of both red cell and HLA antigens.
The improved graft survival in preoperatively transfused renal transplant recipients led to the hypothesis that blood transfusions have an immunosuppressive effect. We examined 12 patients undergoing cardiac surgery, who received autologous red cells and one homologous HLA class-I-matched platelet concentrate. None of these patients produced red cell or lymphocytotoxic antibodies. Using the mixed lymphocyte culture (MLC) we observed a reduced lymphocyte responce to cells of the platelet donor during the first 4 days after transfusion. The MLC reactivity recovered on days 4-5 to the initial strength and reached over 200% of the initial strength from day 6 on. It must be assumed that these changes in MLC reactivity represent the early signs of the transfusion-induced immunosuppression. As intraoperative transfusions might correlate with cancer relapse, further studies must show whether this immunosuppressive effect can be avoided by the application of filtered leucocyte-depleted red cell transfusions.
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HLA class I lymphocytotoxicity testing is strongly complement-dependent. We tested 13 commercially available rabbit complement batches (7 distributors) using a panel of 14 donors with decisive patterns of HLA antigens. We defined a scoring system that weights the different possible faulty reactions. The rating score ranged from 12.45 to 46.55 (median 16.09). Comparing the reactions in batches with low and high rating scores gave statistically significant differences (chi 2 test, p < 0.05). Our complement reaction score may be helpful to find the optimal complement batch for HLA class I lymphocytotoxicity testing.
Peripheral blood-derived haematopoietic stem cells (PBSC) are used as an alternative to bone marrow stem cells for autologous transplantation. One of the most important prerequisites for successful PBSC separation is the precise determination of the optimal separation days. As we previously demonstrated that neither PLT counts nor WBC counts in the peripheral blood (PB) are of predictive value for the amount of colony-forming cells (CFC) in the patients' PB, we started a daily monitoring of CD-34-positive cells to determine the beginning of the separation series. In addition to routine cell counts and CFU testing we assessed the number of CD 34+ in the PBSC concentrates to ascertain the number of separations needed for each patient. Due to the strong correlation of CD 34+ cells to CFC it is possible to predict the number of CFC collected within 2 h after finishing the PBSC separation and to calculate the efficiency of the separation for quality control.
Prior to purging or cryopreservation, we concentrated 21 bone marrow (BM) harvests using a modification of the 'grancollect-protocol' of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 min, the initial marrow volume of 1,265 ml (+/- 537 ml) was processed two to three times. A mean of 47% (+/- 21%) of the initial mononuclear cells was recovered in a mean volume of 128 ml (+36 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 68% (+/- 47%). Red blood cells in the BM concentrates were reduced to 7% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation and transplantation. At this time, 10 of the 21 patients whose BM was processed using this technique have been transplanted. Seven of these 10 patients have been grafted using the BM alone. Three of the 10 patients showed reduced cell viability and colony growth in the thawed BM samples, and therefore obtained BM and peripheral blood-derived stem cells. All transplanted patients showed an evaluable engraftment, achieving 1,000 granulocytes per microliter of peripheral blood in a mean of 18 days.
BACKGROUND: The antigen Dia is common among Mongols (5-12%), but rare in Caucasians (< 1%). OBJECTIVE: The accidental discovery of Diego A (Dia) antibodies in a South American tourist and in an elderly German patient prompted us to investigate the frequency of Dia antigens in the German population. DESIGN: 1,352 German random blood donors, all living in Berlin or in the areas around, were tested for the presence of the Dia antigen on their red blood cells. All donors were Caucasians. RESULTS: Dia was found in 12 individuals (0.89%). CONCLUSIONS: We think that Dia is a low-frequency antigen in the European population. The admixture of Mongol genes following wars or migration is only of low or no importance.
Since 1992, the Fresenius cell separator AS-104 offers a single-needle option. The authors present data on their first experience with this new single-needle thrombocytapheresis system.
To improve the separation results of peripheral blood stem cells (PBSC), cytokines (GM-CSF, G-CSF or IL3) can be administered to patients. The most important prerequisites for successful PBSC separation are daily monitoring of CD-34-positive cells to determine the separation days and the use of optimized separation programs. To improve the performance of the cell separation, we increased the process volume to more than patients' blood volume and obtained increased MNC and CFU recoveries. In most cases, we collected more cells than the preseparation number of circulating cells. We therefore conclude that large-volume PBSC separation itself mobilizes hematopoietic progenitor cells.
Peripheral blood stem cells are an alternative to bone marrow-harvested stem cells. We report on the feasibility of predicting optimal timing for leukapheresis by means of blood monitoring for CD34-positive cells by flow cytometry. In addition to monitoring, determinations of CD34-positive cells also are predictive for the hemopoietic potency of cells harvested by leukapheresis, as close correlations of numbers of CFU-GM and of CD34-positive cells, respectively, in leukapheresis samples are determined. Our data are indicating that flow-cytometrical determinations of CD34-positive cells are helpful in the setting of blood stem cell harvesting by leukapheresis, both for optimal timing of the procedure and for real-time estimation of the hemopoietic potency of cells harvested.