Volker Witt - Academia.edu (original) (raw)

Papers by Volker Witt

Transfusion and Apheresis Science, 2019

The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis proc... more The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis procedures in more than 12,000 patients. The aim of this study was to evaluate functional health and quality of life (QoL) in patients during apheresis treatment. Material and methods: : Estimates of health condition (HC) were made in 40,445 and of QoL in 22112 apheresis procedures. This study focused on a 10-step graded evaluation of HC (scale from: 'bedridden, unable to eat' to a level of 'athletic competition') and self-assessment of QoL (scale from: worst ever '0' to best ever '10'). Data were compared in relation to various apheresis procedures and if the patient underwent the first or subsequent apheresis procedure. Results: : Of the patients treated with plasma exchange (PEX) with centrifugation technique (n = 15787) 10% were 'bedridden, unable to come out of bed' while for patients treated with plasma filtration technique (n = 1018) the percentage was 27%. During the first procedure these figures were 16% and 30%, respectively. Self-estimates of QoL were graded 'zero' or '1' in 1.6% of patients during the first apheresis procedure; At the first contact patients undergoing PEX graded like this in 4.3%. Conclusion: : Many of the patients undergoing apheresis treatment have poor HC and QoL at the start of therapy. Of all therapeutic apheresis procedures patients undergoing PEX had the lowest score of QoL.

Transfusion and Apheresis Science, 2014

Transfusion and Apheresis Science, 2017

The WAA apheresis registry was established in 2003 and an increasing number of centers have since... more The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Vox Sanguinis, 2016

Our post‐thaw cell recovery rates differed substantially in interlaboratory comparisons of identi... more Our post‐thaw cell recovery rates differed substantially in interlaboratory comparisons of identical samples, potentially due to different temperatures during cell staining.

Transfusion and Apheresis Science, 2016

Apheresis with different procedures and devices are used for a variety of indications that may ha... more Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/ asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

Transfusion and Apheresis Science, 2012

Transfusion and Apheresis Science, 2010

Background: Phlebotomy (P) is currently the standard therapy for patients with hemochromatosis (H... more Background: Phlebotomy (P) is currently the standard therapy for patients with hemochromatosis (HH). Per procedure 500 ml whole blood is removed until the serum ferritin level is 50 mg/L and/or transferin saturation is below 50%. Depending on the initial ferritin levels this requires 20-100 P's over a period of 6 to 24 months. Thereafter P frequency is reduced to 3-6 times a year. Recently therapeutic erythrocytapheresis (TE) has become a new therapeutic modality. With TE, up to 1000 ml erythrocytes per procedure can be removed, compared to 250 ml erythrocytes per P. Thus TE potentially offers a more efficient method to remove iron overload with less procedures in a shorter time period. Aim: To compare TE and P. The primary objective: the number of treatment procedures to reach the ferritin target level of ≤50 mg/L. The secondary objectives: duration of therapy and costs. Methods: A prospective randomized clinical trial among newly diagnosed HH patients (homozygote for C282Y). Statistical analysis: Univariate analysis by two-sided t-test. Adjustments for observed differences in initial ferritin level were done by logistic regression analysis. Uncertainty intervals (2.5th and 97.5th percentiles) for the mean differential costs were obtained by the bootstrap method. Cost-analysis: Not only costs related to the treatment of P and TE but also costs related to loss of productivity were collected. Direct costs of both P and TE contained the personnel, material and equipment costs and were calculated by the Sanquin Blood Bank financial department. In addition, costs resulting from productivity losses were calculated according to the friction cost method. Overhead costs related to the Blood bank were allocated to the direct costs as an overall percentage of 50%. No discounting was applied since all costs occurred within one year. All costs are presented in euro's for the year 2009. Results: 38 patients were included. Both treated groups consisted of 19 patients. The baseline anthropometrics and laboratory characteristics were similar among the treatment groups. Only the baseline serum ferritin levels were significantly lower in the TE group (mean 1104 mg/l; SD 677) compared to the P group (mean 1666 mg/l; SD 912). Univariate t-test showed that in the TE group the mean number of treatments required to reach a serum ferritin level of 50 mg/l was one third of the number of treatments needed in P group (9 vs 27; p ≤ 0.05) (Table 1). Multivariate logistic regression analysis shows a decline in the reduction factor of the number of treatments to 2.17 (CI 95% 1.23-3.80) when adjusted for the baseline serum ferritin levels, and a decline to 2.60 (CI 95% 1.1-6.14) when also body weight was include in the model. The total treatment costs for P €4.438 (SD €599) are higher compared to those of TE €3005 (SD €444), although the difference is not statistically significant. The total costs consists of the treatment costs

Transfusion and Apheresis Science, 2008

Seventy-five centers from many countries have applied for a login code to the WAA apheresis regis... more Seventy-five centers from many countries have applied for a login code to the WAA apheresis registry. Fifteen centers from 7 countries have been actively entering data at the internet site from 2003 until 2007. We report on data from the registry so far. This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 2013 patients (12,448 procedures) have been included. A median of 6 treatments have been performed (range 1-140). Mean age 51 years (range 1-94 years; 45% women). Seven percent of the patients were &amp;lt; or = 21 years and 4% were &amp;lt; or = 16 years. The purpose of the apheresis procedure was therapeutic in 67% and retrieval of blood components in 33%. Main indications: neurological and hematological diseases, lipid apheresis and stemcell collection (autologous, and some allogeneic). Blood access: peripheral vessels (71%), central dialysis catheter through jugular (6.5%) or subclavian veins (6.7%), femoral vein (8%) and AV fistula (4%). ACD was used for anticoagulation in 73% of the procedures. Albumin was mainly used as replacement fluid. Adverse events (AE) were registered in 5.7% of the procedures. AE was graded as mild (2.5%), moderate (2.7%) or severe (0.5%). No death occurred due to treatment. The procedures were interrupted in 2.6%. Most frequent AEs were blood access problems (29%), tingling around the mouth (20%), hypotension (18%), and urticaria (9%). There were significant differences between the centers regarding mild and moderate AEs. Data indicate that centers using continuous infusion of calcium had fewer AEs. There was a limited number of severe AEs. Centers use various standard procedures for apheresis. By learning from the experience of others the treatment quality will improve further. In the near future, an update of the registry will enable more extensive evaluation of the data.

Onkologie, 2000

BACKGROUND: Methods for clinical-scale selection of CD34-positive hematopoietic stem and progenit... more BACKGROUND: Methods for clinical-scale selection of CD34-positive hematopoietic stem and progenitor cells have facilitated allogeneic transplants using HLA-mismatched healthy donors. We examined different approaches to purify mobilized CD34+ cells, focusing on yield, purity, and viability of the selected cells and T-cell depletion levels. METHODS: Sixty-seven CD34-positive selections were performed for a total of 37 allogeneic transplantations, 23 of which from HLA-haploidentical donors. The selection devices were the Isolex((R)) 300i (v. 1.12) used alone (n =13) or with the SuperMACS (n = 29); the CliniMACS (n = 3); and the Isolex 300i (v. 2.0b1). The latter was used for CD34-positive selection (n = 7) and combined CD34+/CD4 8 19-negative selections (n =15). DNAse was included to reduce cell clumping. RESULTS: With the Isolex 300i (v. 1.12), the median CD34+-cell recovery increased from 51% (without DNAse) to 61% (15 mg DNAse) and 70% (7.5 mg). DNAse (5 mg) was used for 22 selections with the Isolex (v. 2.0b1) without cell clumping. CD34-positive cell purity, yield, and viability, as well as the degree of CD3 depletion varied with the selection device and procedure used. CONCLUSION: With regard to all of the above-mentioned parameters, the best results were obtained with the Isolex 300i (v. 2.0b1). Values achieved for CD34-positive cells were 98% for purity, 50-60% for yield, and > 96% for cell viability; T-cell depletion was 4.5 to > 5 log. The automated and closed system provides target cells that are free of both magnetic particles and murine monoclonal antibody. Copyright 2000 S. Karger GmbH, Freiburg

Transfusion Medicine and Hemotherapy, 2021

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive diseas... more Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased...

Cytotherapy, 2008

Background Human cytomegalovirus (HCMV) infection remains a major cause of morbidity and mortalit... more Background Human cytomegalovirus (HCMV) infection remains a major cause of morbidity and mortality in immunocompromised patients undergoing allogeneic stem cell transplantation (SCT). In the case of HCMV reactivation, the well-defined detection of virus-specific effector cells in patients might positively impact antiviral treatment. Methods We examined blood samples from healthy volunteers serologically typed for HCMV IgG. Based on multicolor flow cytometry analysis, we addressed HCMV-specific CD8 ' effector T lymphocytes using HCMV-specific tetramers for the respective major histocompatibility complex (MHC) class I type. As a second approach, we employed the cytokine secretion assay (CSA), which allows the indirect detection of target-specific CD4 ' and CD8 ' T cells via their interferon (IFN)-g secretion upon HCMV pp65 in vitro stimulation. Results We hypothesized the detection of HCMV-specific lymphocytes in 50% of healthy Caucasians that were IgG-seropositive for HCMV. In terms of specificity, both assays showed comparably good results (specificity 100%, confidence interval 95%). Regarding sensitivity, both assays met the zero hypothesis. However, with 45/52 (86.5%) the tetramer technology was superior to the CSA, which detected 34/52 (65.4%) based on CD8 ' T cells and 41/52 (78.8%) based on both CD4 ' and CD8 ' T cells. Discussion A good correlation was observed between both assays, although the tetramers addressed only CD8 ' HCMV-specific T cells, whereas IFN-g secretion was detected on all T-cell types. Disadvantages of the CSA are the time-consuming stimulation, the extensive cell washing steps and the fact that the target cells are detected indirectly. The analysis with tetramers is rapid and reliable but their general use is hampered because of the restriction to a few HLA types.

Background: Intensified treatment protocols have improved survival of pediatric oncology patients... more Background: Intensified treatment protocols have improved survival of pediatric oncology patients. However, these treatment protocols are associated with increased treatment-related morbidity requiring admission to pediatric intensive care unit (PICU). We aimed to describe the organizational characteristics and processes of care for this patient group across PICUs in Europe. Methods: A web-based survey was sent to PICU directors or representative physicians between February and June 2021. Results: Responses were obtained from 77 PICUs of 12 European countries. Organizational characteristics were similar across the different countries of Europe. The median number of PICU beds was 12 (IQR 8-16). The majority of the PICUs was staffed by pediatric intensivists and had a 24/7 intensivist coverage. Most PICUs had a nurse-to-patient ratio of 1:1 or 1:2. The median numbers of yearly planned and unplanned PICU admissions of pediatric cancer patients were 20 (IQR 10-45) and 10 (IQR 10-30, res...

Journal of Clinical Oncology, 2014

3096 Background: Cancer immunotherapy (CIT) based on Dendritic Cells (DC) is developing into a mo... more 3096 Background: Cancer immunotherapy (CIT) based on Dendritic Cells (DC) is developing into a more mature therapy option as clinical trials progress. Our approach involves the microbial danger mol...

Journal of Cellular and Molecular Medicine, 2008

Bone Marrow Transplantation, 2004

HLA-mismatched family members may represent an important cell source for patients that require st... more HLA-mismatched family members may represent an important cell source for patients that require stem cell transplantation but lack both a matched sibling donor and a closely matched unrelated donor. We report the outcome of 19 transplantations from HLA two-or three-loci mismatched parental donors in which 14 pediatric patients with hematological malignancies or other disorders, received a median of 21.5 ؋ 10 6 (range, 5.4-58) highly purified CD34 ؉ peripheral blood stem cells (PBSC), as well as 4.7 ؋ 10 4 (range, 0.4-12) donor T cells per kg body weight. T cell depletion was performed using a two-step CD34positive selection on two different magnetic beads devices. Ten of 14 patients presented with rapid myeloid engraftment. The four patients who presented with graft failure (two nonengraftments, two rejections) received a second stem cell graft and one a third. Graft rejection was detected early by polymerase chain reaction (PCR) analysis of FACS-sorted T cells. Eight of the 14 patients are still alive after a median observation period of 15.6 months (range, 3-31.3) with full donor chimerism in all hematopoietic cell lineages. No acute organ graft-versushost disease (GVHD) and no chronic GVHD have occurred. One patient experienced relapse of leukemia. We conclude that transplantation of allogeneic PBSC from haploidentical donors will open new perspectives for pediatric patients for whom an HLA-matched stem cell graft is not available. Close monitoring of recipient and donor hematopoiesis might be of clinical value, to recognize early engraftment or rejection.

Bone Marrow Transplantation, 1999

Children with high risk malignancies are usually given permanent (Hickman-type) tunneled silicone... more Children with high risk malignancies are usually given permanent (Hickman-type) tunneled silicone rubber central venous catheters (silicone CVCs) for the administration of chemotherapy. In the past, these children received an additional short-term polyurethane dialysis CVC for stem cell apheresis. To avoid placement of an additional short-term CVC, we started in 1995 to use pre-existing silicone CVCs for PBPC harvests. From May 1996 to February 1999 we evaluated 165 harvests in 37 children and 14 young adults (16-28 years) treated with high-dose chemotherapy and stem cell support, comparing CD34 + cell harvest efficiency, catheter tolerability, and complications in three different approaches to vascular access. Pre-existing silicone CVCs (64%) or peripheral venous cannulae (15%) were the first choice for venous access. Only when these failed were polyurethane CVCs (21%) used. No significant difference was seen between these three groups, even after dividing the silicone CVC group (105 harvests in 32 patients) into three subgroups according to weight and age. The most frequent problems were citrate toxicity (n = 33), mechanical obstruction inside (n = 9) and outside the cell separator (n = 2), decreased draw line flow in silicone CVCs (n = 7), decreased draw line flow in peripheral venous cannulae (n = 6), and one occlusion in a polyurethane CVC. Pre-existing CVCs and peripheral venous cannulae functioned efficiently when used as a draw line in 79% of the apheresis procedures without significantly reducing single harvest efficiency or catheter tolerability. Consequently, the risks and costs associated with the placement of a dialysis CVC could be avoided in the majority of cases.

Bone Marrow Transplantation, 1998

A 2 year and 8 month old CMV-negative boy suffering from stage III neuroblastoma underwent ABMT i... more A 2 year and 8 month old CMV-negative boy suffering from stage III neuroblastoma underwent ABMT in first very good partial remission. He acquired early CMV infection on day +5, followed by consecutive graft failure and severe sepsis, and the clincial course deteriorated. Between days +16 and +21, he received seven leukocyte concentrates (LC) collected from a healthy, but CMV-IgG-seropositive relative stimulated with G-CSF (filgastrim, 5 g/kg/day). A median of 5.7 × 10 10 neutrophils/m 2 /day (range, 1.2-8.3) were transfused, corresponding to a T cell number of roughly 4 × 10 8 CD3 + cells/kg/day. After infusion of the LCs, PCR analysis became negative for CMV and the patient received his rescue bone marrow. One year after ABMT, he is in complete remission and in good clinical condition. Our results suggest that the T cells infused together with the irradiated leukocytes played a major role in eradicating the CMV infection in this patient.

Biology of Blood and Marrow Transplantation, 2014

Although the influence of transplanted bone marrow (BM) CD34þ cells on neutrophil engraftment (NE... more Although the influence of transplanted bone marrow (BM) CD34þ cells on neutrophil engraftment (NE) and transplantation outcomes has been discussed controversially, thresholds between 2 and 4 Â 10 6 /kg CD34þ cells are commonly accepted. This has substantial consequences for a donor in terms of BM volume to be collected, which frequently covers up to 15 to 20 mL/kg. As the BM CD34þ compartment contains varying fractions of CD34þ/CD19þ B lymphoid progenitors, we tested the hypothesis that the infused CD34þ/ CD45dim/CD19-/CD10-myeloid stem cells might reliably predict NE in 94 children who received BM from 37 HLA-identical sibling donors (MSD) and 57 matched unrelated donors after myeloablative conditioning. The grafts contained a median of 3.6 Â 10 6 /kg total CD34þ cells, which consisted of a median of 73% myeloid CD34þ cells and 27% B lymphoid progenitors. Grafts from donors <15 years old yielded significantly lower myeloid fractions compared with grafts from older donors (P < .001). All patients achieved sustained NE after median 20 (range, 11 to 40) days. By multivariate analysis, neither the number of total CD34þ cells (P ¼ .605) nor of myeloid CD34þ cells (P ¼ .981) correlated with NE, whereas transplantation from MSD (hazard ratio [HR] 3.51; P ¼ .019) and the administration of granulocyte colonyestimulating factor (HR 2.24; P ¼ .002) remained independent factors associated with earlier NE. Furthermore, neither total nor myeloid CD34þ cell quantities were associated with incidences of severe infections before NE (P ¼ .271 and P ¼ .132) or transplantation-related mortality (TRM) at day þ100 (P ¼ .294 and P ¼ .490). Taking into account that the number of transplanted total CD34þ or myeloid CD34þ cells does not seem to have a relevant impact on time to NE, sepsis rates, or TRM, the need of certain threshold cell numbers should be revisited, at least for pediatric MSD. Ó 2014 American Society for Blood and Marrow Transplantation. PATIENTS AND METHODS Patients and Transplantation Characteristics To eliminate confounding factors, such as reduced-intensity conditioning, ex vivo T cell depletion, and PBSC or cord blood grafts, 100 consecutive children and adolescents receiving unmanipulated BM after myeloablative conditioning between 2000 and 2012 were included in the analysis. Four patients who had received granulocyte transfusions before engraftment, 1 patient with overt relapse on day þ28, and 1 patient who died on day þ11 were excluded. The median recipient age was 11.7 years (range, 1.0 to 23.1 years). All patients were treated for hemato-oncological diseases, with acute lymphoblastic or myeloid leukemia accounting for the vast majority. Fifty-nine patients (63%) received a total body irradiationebased conditioning regimen and 35 (37%) received a busulfan-based chemotherapy,

$Research paper thumbnail of Compassionate use of bevacizumab (Avastin(R)) in children and young adults with refractory or recurrent solid tumors$

Annals of Oncology, 2007

The aim of this study was to evaluate feasibility and toxicity of bevacizumab (Avastin Ò), a mono... more The aim of this study was to evaluate feasibility and toxicity of bevacizumab (Avastin Ò), a monoclonal antibody directed against the vascular endothelial growth factor in children and young adults.