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Biomedical subjects

J Riggert

Publications and source records attributed to J Riggert.

At least 37 records · Page 2Linked to original sources
PubMed1999

Low- versus high-dose radioimmunotherapy with humanized anti-CD22 or chimeric anti-CD20 antibodies in a broad spectrum of B cell-associated malignancies.

Both CD22 and CD20 have been used successfully as target molecules for radioimmunotherapy (RAIT) of low-grade B cell non-Hodgkin's lymphoma. Because both CD20 and CD22 are highly expressed relatively early in the course of B cell maturation, and because its expression is maintained up to relatively mature stages, we studied the potential of the humanized anti-CD22 antibody, hLL2, as well as of the chimeric anti-CD20 (chCD20) antibody, rituximab (IDEC-C2B8), for low- or high-dose (myeloablative) RAIT of a broad range of B cell-associated hematological malignancies. A total of 10 patients with chemorefractory malignant neoplasms of B cell origin were studied with diagnostic (n = 5) and/or potentially therapeutic doses (n = 9) of hLL2 (n = 4; 0.5 mg/kg, 8-315 mCi of 131I) or chCD20 (n = 5; 2.5 mg/kg, 15-495 mCi of 131I). The diagnostic doses were given to establish the patients' eligibility for RAIT and to estimate the individual radiation dosimetry. One patient suffered of Waldenström's macroglobulinemia, eight patients had low- (n = 4), intermediate- (n = 2) or high- (n = 2) grade non-Hodgkin's lymphoma, and one patient had a chemorefractory acute lymphatic leukemia, after having failed five heterologous bone marrow or stem cell transplantations. Three of these 10 patients were scheduled for treatment with conventional (30-63 mCi, cumulated doses of up to 90 mCi of 131I) and 7 with potentially myeloablative (225-495 mCi of 131I) activities of 131I-labeled hLL2 or chCD20 (0.5 and 2.5 mg/kg, respectively); homologous (n = 6) or heterologous (n = 1) stem cell support was provided in these cases. Good tumor targeting was observed in all diagnostic as well as posttherapeutic scans of all patients. In myeloablative therapies, the therapeutic activities were calculated based on the diagnostic radiation dosimetry, aiming at lung and kidney doses < or = 20 Gy. Stem cells were reinfused when the whole-body activity retention fell below 20 mCi. In eight assessable patients, five had complete remissions, two experienced partial remissions (corresponding to an overall response rate of 87%), and one (low-dose) patient had progressive disease despite therapy. In the five assessable, actually stem-cell grafted patients, the complete response rate was 100%. Both CD20 and CD22 seem to be suitable target molecules for high-dose RAIT in a broad spectrum of hematological malignancies of B cell origin with a broad range of maturation stages (from acute lymphatic leukemia to Waldenström's macroglobulinemia). The better therapeutic outcome of patients undergoing high-dose, myeloablative RAIT favors this treatment concept over conventional, low-dose regimens.

Adolescent↗
PubMed1998

Quality and safety of platelet apheresis concentrates produced with a new leukocyte reduction system.

OBJECTIVES: Contaminating white blood cells (WBC) in apheresis platelet concentrates (PC) can cause a variety of adverse effects after platelet transfusion. To obtain PCs with low WBC contamination, a new leukoreduction system (LRS) utilizing 'fluidized particle bed' technology has recently been introduced. METHODS: We prospectively examined the effect of LRS apheresis on the donor, the quality of the resulting PCs (n = 120), and the platelet increment in the corresponding recipients. Conventionally prepared apheresis PCs served as control group (n = 27). Platelet glycoproteins were examined by flow cytometry. RESULTS: In LRS apheresis, we observed no serious adverse effects on the donors, but the postdonation absolute lymphocyte counts were reduced from 1,787 +/- 505/microliter to 1,405 +/- 383/microliter (p < 0.001). Comparable results were seen in non-LRS donors. The collection efficiency of the LRS procedures was 50.0 +/- 7.6%, resulting in a yield of 4.3 +/- 1.0 x 10(11) platelets/PC. In flow cytometry, platelet glycoproteins in LRS PCs were not elevated: mean fluorescence of CD62 (6 +/- 4) or CD63 (9 +/- 3) in comparison with non-LRS PCs (mean fluorescence of CD62: 7 +/- 4, CD63: 8 +/- 3). Median leukocyte contamination of the LRS PCs was 0.41 x 10(5) (range 0.07-8.5) WBCs/unit. In 43 recipients, the 24-hour corrected count increments after transfusion of LRS PCs (12,530 +/- 8,761) were essentially the same as those of 20 recipients of non-LRS PCs (13,133 +/- 9,812; p = 0.75). CONCLUSIONS: LRS apheresis appears to be a safe procedure, which produced effective PCs with few contaminating leukocytes. With new apheresis technology, filtration of PCs may become superfluous.

Antigens, Human Platelet↗
PubMed1997

Frequency and causes of refractoriness in multiply transfused patients.

The use of leukocyte-depleted blood components has become the standard therapy for multiply transfused patients during the past few years, as a measure to reduce the frequency of alloimmunization and refractoriness. We assessed frequency and causes of refractoriness, defined as a repeated 24-h post-transfusion platelet count below 20,000/microliters, in 145 consecutive patients who received three or more single-donor platelet concentrates during a 1-year period. Flow-cytometric detection of anti-platelet antibodies and a glycoprotein-specific ELISA were applied for the diagnosis of alloimmunization. Forty patients (27.6%) had at least one episode of refractoriness. In 25 of these 40 patients (62.5%), nonimmune factors (fever, sepsis, coagulopathy, splenomegaly) alone were the cause. In 15 refractory patients alloantibodies were detected. In seven patients (17.5%), alloimmunization alone caused an inadequate transfusion response, while in eight refractory patients (20.0%) alloimmunization and fever or sepsis were present. HLA antibodies were detected in 17 patients (11.7%); three patients (2%) had platelet-specific antibodies in addition to HLA antibodies; in two patients panreactive platelet antibodies were detectable. All 17 patients had a history of previous transfusions or pregnancy. We did not observe primary immunization in patients transfused exclusively with filtered (leukodepleted) blood products. Our data suggest that alloimmunization in patients with a negative risk history can be prevented by the exclusive use of leukodepleted blood components.

Antigens, Human Platelet↗
PubMed1997

Prestorage inline filtration of whole blood for obtaining white cell-reduced blood components.

BACKGROUND: Preliminary studies have indicated that the inline filtration of whole blood is a feasible method of obtaining white cell (WBC)-reduced packaged red cells (RBCs) and WBC-reduced fresh-frozen plasma (FFP) while using only one filter. STUDY DESIGN AND METHODS: An inline WBC-reduction filter, specially designed for this purpose and integrated in a "top-top" system, was used in the preparation of 24 units of WBC-reduced RBCs (RBC-F) and FFP (FFP-F) in each of two transfusion centers (Vienna and Göttingen). Twelve conventionally prepared units of RBCs (RBC-C) and FFP (FFP-C) served as controls. WBC contamination was assessed in each unit with the Nageotte chamber. Several coagulation measures were evaluated by using standardized test systems. RESULTS: The median WBC contamination in RBC-F was 27,000 per unit in Vienna and 50,000 in Göttingen. In FFP-F, the median WBC contamination was 13,000 (Vienna) and 31,000 (Göttingen) per unit. Coagulation factors I, V, VIII, and XI in FFP-F were not different from those in FFP-C. In addition, markers for the activation of coagulation and fibrinolysis--that is, factor XIIa, prothrombin fragments, thrombin-antithrombin complexes and fibrinogen degradation products--were not greater in FFP-F. CONCLUSION: Blood components prepared from inline-filtered whole blood meet the standards for WBC-reduced RBCs and FFP. The protein profile of FFP-F is not altered, and markers for the activation of coagulation and fibrinolysis show no increase.

Blood Coagulation Factors↗
PubMed1997

Comparison of CD34+ cell numbers and colony growth before and after cryopreservation of peripheral blood progenitor and stem cell harvests: influence of prior chemotherapy.

BACKGROUND: Quantitative determination of hematopoietic progenitor cells is a major issue in peripheral blood progenitor and stem cell collection and transfusion, although the extent is still an object of discussion. STUDY DESIGN AND METHODS: In 116 leukapheresis collections from 42 patients, immunophenotyping for CD34+ cells, evaluation of in vitro proliferative capacity by a colony-forming unit-granulocyte-macrophage (CFU-GM) assay, and viability assessment by trypan blue exclusion were performed before and after storage in liquid nitrogen at -196 degrees C. RESULTS: Before storage, the median number of CD34+ cells was 1.46 x 10(6) (range, 0.01-54.05 x 10(6)) per kg of body weight (BW). There was no significant difference between precryopreservation and postcryopreservation numbers. The median number of CFU-GM was 2.25 x 10(5) (range, 0.02-157.49 x 10(5)) per kg of BW before cryopreservation and significantly (p < 0.001) lower, 0.83 x 10(5) (range, 0-220.36 x 10(5)) per kg of BW, after cryopreservation. The correlation coefficient of prestorage and poststorage values was 0.92. The median ratio of poststorage and prestorage values was 42.3 percent (0-304.8%). Male patients who underwent intense chemotherapy (> 5 cycles) showed a significantly lower ratio of postcryopreservation and precryopreservation CFU-GM values than other patients (p = 0.0047). A strong linear correlation was determined between the number of CD34+ cells per kg of BW and the number of CFU-GM per kg of BW before and after cryopreservation. A viability below 50 percent predicted a high loss of in vitro proliferative capacity, while a viability above 50 percent did not correlate with a high ratio of CFU-GM from after and before cryopreservation. CONCLUSION: A good correlation between the variables used for characterization of peripheral blood progenitor cells--the number of CD34+ cells and the number of CFU-GM--was observed. Viability assessment by trypan blue exclusion does not seem to be a substitute for assays evaluating in vitro proliferative capacity.

Adult↗
PubMed1997

A multicenter evaluation of the routine use of a new white cell-reduction apheresis system for collection of platelets.

BACKGROUND: Residual white cells (WBCs) cause serious side effects in platelet transfusion. An in-line WBC-reduction system based on fluidized particle bed technology was recently developed as a modification of an existing plateletpheresis system. STUDY DESIGN AND METHODS: In an investigational phase, three flow profiles were evaluated using prototype software in five centers, each using their standard conditions. In the confirmatory phase, the released software was tested in three centers. WBCs were counted in two full Nageotte grids (dilution 1-in-5). RESULTS: With the prototype software, WBC levels were always below 1 x 10(6) per procedure (median, 25,000/procedure; n = 314). One profile proved to be superior to the other two with respect to platelet yield and residual WBCs, and it was incorporated in the released WBC-reduction system, together with a built-in process control. Median residual WBCs in these WBC-reduction system components not rejected by the process control were 19,000 per procedure (n = 211/225 total), with 99.5 percent of the platelet components having less than 1 x 10(6) WBCs. CONCLUSION: The protocol selected in the initial phase, now available as a WBC-reduction system, results in platelet concentrates with very low residual WBC levels. This satisfies even the most stringent criteria for WBC reduction in platelets, without the platelet loss typically seen with conventional fiber filtration.

Blood Platelets↗
PubMed1997

[Quality control in producing thrombocytapheresis preparations with minimal leukocyte contamination].

Passenger white blood cells (WBC) in platelet concentrates (PC) produced by apheresis can cause a variety of adverse effects in recipients after platelet transfusion. With new technologies (LRS, leukocyte reduction system), the preparation of PC with a low WBC contamination is possible without consecutive filtration. In a prospective examination, we compared the effect of LRS apheresis on the donor, the quality of the resulting PC (n = 120), and the platelet increment in the corresponding recipients with conventionally prepared PC (n = 27). In LSR apheresis, no serious adverse effects on the donors were observed, but the post-donation absolute numbers of lymphocytes were reduced from 1,787 +/- 505/microliter to 1,402 +/- 383/microliter (p < 0.001). Comparable results were observed in non-LRS donors. The collection efficiency of the LRS procedures was 50.0 +/- 7.6%, resulting in a yield of 4.25 +/- 1.03 x 10(11) platelets/PC. Flow cytometric examination concerning the expression of platelet glycoproteins in LRS PC showed no elevation in mean fluorescence of CD 62 (6 +/- 4) or CD 63 (9 +/- 3) in comparison to non-LRS PC (mean fluorescence CD 62: 7 +/- 4, CD 63: 8 +/- 3). Median leukocyte contamination of the LRS PC was 0.41 x 10(5) (range 0.06-8.5 x 10(5)) WBC/unit. In 43 recipients, the 24-hour corrected count increments (CCI) after transfusion of LRS PC (12,530 +/- 8,761) showed no significant differences when compared with the CCI in 20 recipients of non-LRS PC (13,133 +/- 9,812, p = 0.75). LRS apheresis seems to be safe procedure, resulting in PC with low WBC contamination, which causes adequate CCI values after transfusion.

Adult↗
PubMed1996

Risk of hepatitis C virus (HCV) transmission by anti-HCV-negative blood components in Austria and Germany.

In order to estimate the residual risk of transfusion-transmitted HCV infection, we have analyzed data from transfusion centers in Austria (Vienna) and Germany (Göttingen) from 1990 to 1995. In Vienna, the seroprevalence (RIBA-confirmed third-generation anti-HCV tests) was 0.28% in first-time donors (FTD) and the incidence of seroconversion in repeat donors (RD) was 0.049 (per 100 person years) from 1994 to 1995. In Göttingen, the prevalence of a PCR-confirmed positive third-generation anti-HCV test was 0.22% in FTDs and the incidence was 0.093 (per 100 persons years). A continuous decline of the rate of anti-HCV-positive donations and donors was observed with first- and second-generation anti-HCV tests in the years 1990-1994. The introduction of the third-generation anti-HCV test resulted in increased numbers of anti-HCV positive repeat donors, mainly due to false-positive results. Only 9% of anti-HCV-positive repeat donors were either PCR positive or RIBA positive or or indeterminate. Based on a mathematical model which takes (a) the window period, (b) the false-negative rate of anti-HCV tests, and (c) human and operational errors into consideration, we have calculated the residual risk of HCV infection. We used a window period of 74 days, a sensitivity of 98%, and an error rate of .1%. The residual risk (for third-generation anti-HCV test-negative blood components) was calculated to be 1:9000 (95% confidence interval 1:16390-1:6210) and 1:4800 (95% confidence interval 1:40000-1:1320) for Vienna and Göttingen, respectively, in 1994 and 1995. Since this conservative approach does not take the impact of ALAT screening into account, the actual risk is probably lower.

Adult↗
PubMed1996

Flow cytometric detection of platelet-reactive antibodies and application in platelet crossmatching.

BACKGROUND: Alloimmunization against HLA or platelet antigens can cause refractoriness to platelet transfusions in multiply transfused patients. Crossmatching of platelet concentrates is effective in overcoming this problem. STUDY DESIGN AND METHODS: A flow cytometric assay was used for simultaneous detection of lymphocyte-reactive and platelet-reactive antibodies in a single sample using fluorescein isothiocyanate-labeled anti-IgG. This assay was compared with the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay in selected sera containing HLA and platelet antibodies. In a further study, this assay was compared with lymphocytotoxicity test results from thrombocytopenic patients, for whom platelet concentrates were ordered. The results of both assays were then correlated with the 1-hour corrected count increment, with a corrected count increment greater then 7500 considered as an adequate transfusion response. RESULTS: The results of the MAIPA and flow cytometric assay in detecting platelet-reactive antibodies correlated well (p<0.0001, r = 0.84). The sensitivity and specificity of the flow cytometric assay in detecting platelet-reactive antibodies were 94.7 and 96.3 percent, when the MAIPA assay was taken as a reference. In unselected sera from patients, the sensitivity and specificity of the flow cytometric assays were, respectively, 72.7 and 91.7 percent in detecting lymphocyte-reactive antibodies and 70.6 and 77.7 percent in detecting platelet-reactive antibodies, when the lymphocytotoxicity test was used as a reference. With regard to an adequate transfusion response, the sensitivities and efficiencies were 20.0 and 82.1 percent, 33.3 and 84.3 percent, and 70.0 and 88.6 percent for the lymphocytotoxicity test and the lymphocyte-reactive and platelet-reactive flow cytometric assays, respectively. CONCLUSION: Flow cytometric crossmatching appears to be an effective method of detecting platelet-reactive antibodies that may affect the success of platelet transfusions. This procedure is well-suited for routine conditions and can be performed within 2 hours.

Antibodies, Monoclonal↗
PubMed1996

Effect of storage conditions on the CD34+ counts in flow cytometric analysis after anticoagulation of samples with EDTA.

The transplantation of peripheral blood precursor cells (PBPC) is becoming of interest for autografting patients with a wide variety of haematological and other malignancies. For rapid quality control of PBPC apheresis products, flow cytometry is applied to quantify the number of CD34+ events. We studied the effect of different storage conditions on the number of CD34+ counts in EDTA-anticoagulated aliquots of PBPC grafts. Within 24 h, CD34+ signals decreased when samples were stored at room temperature (RT, 20 +/- 2 degrees C) compared to the results obtained directly after cytapheresis. The signal rate equalled or exceeded the baseline values after 24 h when aliquots were deposited at room temperature and subjected to agitation. Storage at 4 degrees C revealed no significant changes. These data indicate that quality control of PBPC samples by flow cytometry significantly depends on storages time, temperature and other conditions like the agitation of the specimen.

Adolescent↗
PubMed1996

[Immunologic effects of blood donation].

The effects of blood transfusion and blood donation on the immune system are still unclear. In a prospective study we investigated the effect of blood and blood component donation on several immunologic parameters. Lymphocyte subsets and cytokine levels were determined in 25 repeat whole-blood donors (RD), 25 plateletpheresis donors (PD), and 20 autologous blood donors (AD). First-time donors (FTD, n = 20) served as controls. Lymphocyte subsets and cytokines were determined using standard methods. Leukocytes, T-suppressor cells and natural killer (NK) cells were decreased in RD and PD when compared to FTD. Additionally, NK cells decreased with repeat donations in AD. No significant differences of cytokines in the different groups or during repeat autologous donations were observed.

Adult↗
PubMed1995

Risk of human immunodeficiency virus (HIV) transmission by anti-HIV-negative blood components in Germany and Austria.

In order to estimate the residual risk of transfusion-transmitted HIV infection we have analyzed the data from two transfusion centers in Austria (Vienna) and Germany (Göttingen) from 1985 to 1994. In Vienna, an incidence of 1:42,000 positive anti-HIV tests in repeat donors and a prevalence of 1:7000 in first-time donors were found in 1993. In Göttingen, the indicence was 1:67,000 and the prevalence 1:7900 from 1985 to 1993. Based on a mathematical model which takes (a) the window period and (b) the false-negative rate of anti-HIV tests, as well as (c) human and operational errors into consideration, we have calculated the residual risk of HIV infection. The residual risk (third generation anti-HIV test) was found to be 1:520,000 (95% confidence interval 1:1340,000-1:210,000), and 1:900,000 (95% confidence interval 1:2340,000-1:380,000) for Vienna and Göttingen, respectively, in 1993. Look-back studies from 1985 till 1994 revealed transfusion-transmitted HIV infections in three recipients (for 1.9 million donations in Vienna) and one recipient (for 160,000 donations in Göttingen) of blood components. Based on our model, as well as on prevalence and incidence rates of HIV infection, it is also possible to predict the efficacy of additional measures introduced to further decrease the risk of transfusion-transmitted HIV infection through blood components.

Austria↗
PubMed1995

Flow cytometric analyses of the subclasses of red cell IgG antibodies.

We report on flow cytometric IgG subclass determinations of red cell antibodies using polyclonal FITC-labeled antibodies. The limit of detection of this method was 1 ng anti-D per 1 x 10(7) red cells. The inter- and intra-assay coefficients of variance were 8.2 and 2.3%, respectively. In 8 newborns with a positive direct antiglobulin test (DAT) in the gel centrifugation test (GCT), due to ABO antibodies, IgG1 was detected in all and IgG2 additionally in 4 of these cases. In 5 severe cases of hemolytic disease of the newborn (HDN) due to anti-D, large amounts of IgG1 were found, and in 3 of these 5, IgG3 in combination with IgG1. In 8 mild or moderate HDN cases (4 anti-D, 2 anti-E, 1 anti-Fya, 1 anti-Jka), phototherapy sufficed, and IgG1 was the only antibody. In 7 adult patients with malignant lymphoma and a positive DAT (GCT), only small amounts of IgG1 red cell autoantibodies could be demonstrated by flow cytometry. In 5 further patients with malignant lymphoma, a positive DAT, and severe hemolytic anemia, large amounts of IgG1 autoantibodies were found and IgG3 was also present in 3 of these cases. Flow-cytometric determination of IgG subclasses may be a useful tool in immunohematology, since subclass determinations were possible in all of these cases. This method is suited for clinical routine and offers the possibility of sufficient standardization.

Adult↗
PubMed1995

Prestorage leukocyte depletion with in-line filtration of whole blood in comparison with blood component leukocyte depletion.

In-line filtration of blood components appears to be an effective method to reduce white-cell-induced adverse reactions. We have investigated whether whole blood filtration (WBF), prior to component preparation, is comparable with filtration of already prepared blood components (CF), i.e. the red cell concentrate (RCC) and fresh plasma. Conventionally prepared nonfiltered blood components served as a control. No significant differences for most parameters investigated were found between leukodepleted RCCs and plasma units prepared by CF or WBF. All filtered RCCs and plasma units (CF and WBF) had white blood cell contaminations < 1 x 10(5) per unit. Platelets were reduced in all filtered components: 95% in plasma and 99% in RCCs. Fresh-frozen plasma (FFP) prepared by CF and WBF had normal amounts of factors V, VIII, von Willebrand factor and thrombin-antithrombin-III complexes, whereas platelet factor 4 (PF-4) was slightly increased in FFP prepared by WBF. RCCs and plasma units prepared from filtered whole blood (n = 20) had a significantly greater volume (RCC: 288 +/- 19 ml; plasma: 274 +/- 20 ml) than conventionally prepared (n = 20) and filtered products (RCC: 257 +/- 19 ml, plasma: 259 +/- 19 ml). For early filtration of blood components, WBF prior to component preparation seems to offer an interesting technique for obtaining a leukocyte-depleted RCC and FFP.

Blood Cell Count↗
PubMed1994

[Leukocyte filtration of stored whole blood for preparation of components].

Prophylaxis of infection and alloimmunisation is the main reason for leucocyte depletion by filtration of blood components. The question is whether all red cell concentrates (RCC) should be filtered and whether plasma has to be filtered, too. For leucocyte-poor units whole blood was filtered before preparation using the 'top and bottom' system. These units of buffy-coat-poor RCC and plasma were compared with components filtered after preparation. Non-filtered RCCs and plasmas served as a control. By prefiltration of whole blood and filtration of components we obtained RCCs and plasmas with less than 1 x 10(5) leucocytes in every unit. In conclusion, leucocyte filtration before preparation seems to be an easy and cost-effective method in order to get two filtered components (RCC and plasma) with one filter.

Blood Component Transfusion↗
PubMed1994

[Flow cytometry analysis of IGG subclasses of auto- and alloantibodies in autoimmune hemolytic anemia and hemolytic disease of the newborn].

Red cell IgG antibodies capable of causing hemolytic disease of the newborn (HDN) or autoimmune hemolytic anemia (AIHA) have been analyzed concerning their IgG subclasses using flow cytometry. The results were always in agreement with those of the direct Coombs test. Anti-A and/or anti-B able to cause HDN belonged to the IgG1 subclass (4/8 cases) or to the subclasses IgG1 and IgG2 (4/8 cases). In 3 out of 4 cases of HDN caused by Rh antibodies the antibodies belonged to the subclasses IgG1 and IgG3. In patients with lymphoma but without AIHA, red cell autoantibodies were often found to be IgG1 only (n = 10), in low concentrations. In cases of acute AIHA in adults caused by IgG autoantibodies the subclass IgG3 was found in addition to IgG1 in 4/5 cases. In our opinion flow cytometry should become substantial for immunohematological diagnostics.

Adult↗