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S Serke

Publications and source records attributed to S Serke.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma.

We investigated peripheral blood progenitor cell (PBPC) mobilization by disease-specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine patients, five females and four males, aged 12-51 years, pretreated by one to nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization followed by G-CSF at 5 microg/kg/day. PBPC were collected by 19 conventional-volume aphereses (8-12 l) with one to four procedures in individual patients. Leukaphereses started on median day 15 (range 13-18) from the first day of mobilization chemotherapy at medians of 25.8 x 10(3) WBC/microl (6.8-46.9), 3.5 x 10(3) MNC/microl (1.1-8.8), 122 x 10(3) platelets/microl (72-293) and 30.7 CD34+ cells/microl (6.7-207.8). Cumulative harvests resulted in medians of 4.6 x 10(8) MNC/kg (3.0-6.4), 2.9 x 10(6) CD34+ cells/kg (1.1-11.1) and 12.0 x 10(4) CFU-GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8-15) for ANC >0.5 x 10(3)/microl and 14 days (8-27) for platelets >20 x 10(3)/microl. One patient, who received 1.6 x 10(6) CD34+ cells/kg, exhibited delayed ANC recovery on day +37 and failed to recover platelets until hospital discharge on day +55. We conclude that in patients with metastatic STS, who are pretreated by standard chemotherapy, PBPC can be mobilized by a further course of STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses result in PBPC autografts that can serve as hematopoietic rescue for patients scheduled for HDCT.

Adolescent↗
PubMed1998

Circulating CD34-expressing cells: German Proficiency Testing Survey.

Determination of absolute numbers of CD34-expressing cells is critical in the setting of peripheral blood stem and progenitor cell transplantation/reinfusion. The diagnostic value of the parameter, CD34-expressing cells/microliter, has been validated. A survey of CD34-expressing cells has been integrated into a series of flow cytometry proficiency testing surveys (reticulocytes, lymphocytes, leukemia, and lymphoma) that we have established in Germany. Commercially available, modified, stabilized myeloblastic leukemia cells (KG1a cell line) spiked at different numbers into two normal blood samples were sent out, and report forms were returned from 50 of 58 participants. With a predicted percentage of CD34-expressing cells of 0.5% (sample A) and of 0.25% (sample B), the respective mean values analyzing data from 44 participants returning the completed forms were 0.49% (sample A) and 0.29% (sample B). The coefficients of variation were 57% and 83%, respectively. Engineered samples based on normal blood and on commercially available stabilized modified KG1a cells seem to be reliable material for external quality assessment surveys of CD34-expressing cells.

Antigens, CD34↗
PubMed1998

Analysis of CD34-expressing cells in clinical practice.

The flow cytometric determination of haemopoietic cells defined as CD34-expressing cells has greatly added to the improvement of the management of harvesting circulating haemopoietic cells for subsequent autologous reinfusion in the setting of high-dose chemo/(radio)-therapy. Additionally, this flow cytometric determination has replaced, in some institutions, the in-vitro culture test for CFU-GM as the measure to estimate the haemopoietic potential of the cells to be reinfused/transplanted.

Antigens, CD34↗
PubMed1997

De novo malignancies after liver transplantation using tacrolimus-based protocols or cyclosporine-based quadruple immunosuppression with an interleukin-2 receptor antibody or antithymocyte globulin.

BACKGROUND: Although conventional immunosuppression after liver transplantation consists of cyclosporine A (CsA), steroids, and azathioprine, recently introduced protocols entail CsA-based quadruple induction protocols or tacrolimus-based combinations. These protocols aim to reduce the rejection rate and the considerable morbidity related to the side effects of additional immunosuppressive treatment, but have not yet been analyzed regarding their long term de novo neoplastic risk. METHODS: From September 1988 to May 1994, 500 liver transplantations were performed in 458 patients. The median follow-up was 50 months (range, 0.3-97 months) for all patients. Conventional triple therapy was implemented in 25 patients, CsA-based quadruple induction therapy using an antilymphocyte globulin preparation (ATG) in 190 patients, an interleukin-2 receptor antibody (BT563) in 141 patients, and tacrolimus-based dual or triple immunosuppression in 102 patients. The different protocols were evaluated in four randomized and two nonrandomized prospective trials. RESULTS: De novo neoplasias were detected in 33 patients (7.2%) and were comprised of lymphomas (n = 7), skin malignancies (n = 8 lesions in 7 patients), intraepithelial neoplasias of the cervix uteri (n = 7), breast carcinoma (n = 3), lung carcinoma (n = 3), and other malignancies (n = 6). The incidence of de novo neoplasias did not differ in the different trial arms. Only a positive T-crossmatch and a low CD4+/CD8+ ratio in patients receiving CsA-based immunosuppression demonstrated a significant correlation with the development of a de novo tumor in a multivariant logistic regression analysis. CONCLUSIONS: The development of de novo neoplastic diseases after liver transplantation with the use of CsA-based quadruple induction protocols or tacrolimus-based regimens for immunosuppresion was assessed over the long term. Recently introduced immunosuppressive protocols did not alter the posttransplant de novo tumor rate. Patients with a low CD4+/CD8+ ratio during CsA-based therapy or a positive T-crossmatch were identified to be at an increased risk for the development of a de novo malignancy.

Antibodies, Monoclonal↗
PubMed1997

Imprecision of counting CFU-GM colonies and CD34-expressing cells.

Determinations of committed haemopoietic progenitor cells, namely CFU-GM (colony-forming unit-granulocyte/macrophage) and of CD34-expression haemopoietic cells as assessed by multiparameter flow cytometry are routine diagnostic tools in haemopoietic cell therapy. Generally, the tests are used to optimise the timing and management of cytapheresis and to assess the engraftment potential of the harvested cells. Both measurements, however, are at best surrogate markers, as an adequate routine test which effectively assesses the short- and long-term repopulating haemopoietic cell is not available. Nonetheless, cell threshold doses have been established. Above these thresholds rapid engraftment is almost invariable but below these thresholds the outcome is variable. In this study we have focussed on the imprecision in counting haemopoietic cells, as assessed as CFU-GM and as CD34-expressing cells. The data on both tests have been analysed from six European institutions. The coefficient of variation in CFU-GM colony counting was about 30%, whereas the coefficient of variation in flow cytometric counting of CD34-expressing cells was about 10%. These data suggest that the technical imprecision in enumerating progenitor cells, particularly CFU-GM, at low levels, might make a major contribution to the clinical variability observed after transplantation of sub-threshold progenitor cell dose.

Antigens, CD34↗
PubMed1997

Two subsets of peripheral blood plasma cells defined by differential expression of CD45 antigen.

The purpose of this study was to optimize the flow cytometric determination of circulating normal and malignant plasma cells (PC). We investigated peripheral blood (PB) samples of 65 patients with multiple myeloma or monoclonal gammopathy of unknown significance and 47 control subjects using CD38, CD45, B-B4, CD56, VLA-4, VLA-5 and CD19 monoclonal antibodies (MoAbs). Mono- or polyclonality was determined by staining of intracellular kappa and lambda light chains. Two subpopulations of PBPC were distinguished by differential expression of CD45. CD45 positive (CD45+) PC showed a more immature morphology and were detected in all groups. They were polyclonal in the control subjects and either poly- or monoclonal in the myeloma patients. In contrast, CD45 negative (CD45-) PBPC only occurred in myeloma patients and were consistently monoclonal, their presence being significantly associated with high disease activity (P < 0.001). Although detection of CD45- PBPC using CD38 or B-B4 MoAbs lead to similar results. CD45+ PBPC often were recognized to a lesser extent by B-B4 than by CD38 MoAbs. In conclusion, normal and malignant circulating PC can reliably be identified using CD38 and CD45 MoAbs. CD45 expression separates PBPC into two subsets of which the CD45- one only occurs in myeloma patients.

ADP-ribosyl Cyclase↗
PubMed1997

Peripheral blood progenitor cell collection during hematopoietic recovery following autologous blood progenitor cell transplantation.

BACKGROUND AND OBJECTIVES: Peripheral blood progenitor cells (PBPC) are increasingly used for autologous transplantation after high-dose radio/chemotherapy in patients suffering from cancer. PBPC are usually collected after mobilization with conventional-dose chemotherapy plus growth factor. However, it is conceivable to perform leukapheresis for the second autograft during recovery of hematopoiesis after the first course of HDCT/ABPCT. MATERIALS AND METHODS: We treated two patients this way. In the first, with germ cell cancer, six 12-liter leukaphereses yielded 1.8 x 10(6) CD34+ cells/kg after mobilization with cis-platinum, etoposide and ifosfamide (PEI) plus granulocyte colony-stimulating factor (G-CSF). The second patient, with relapsed Hodgkin's disease, underwent PBPC collection after treatment with dexamethasone, carmustine, etoposide, cytarabine and melphalan (DexaBEAM) plus G-CSF. Due to excellent mobilization, 8.5 x 10(6) CD34+ cells/kg were collected by one 12-liter leukapheresis. Both patients then underwent PBPC collection during hematopoietic recovery following HDCT and ABPCT. RESULTS: In patient 1, following HDCT and ABPCT, three 12-liter aphereses resulted in 0.7 x 10(6) CD34+ cells/kg. In patient 2, also after HDCT and ABPCT, a second autograft with 3.2 x 10(6) CD34+ cells/kg was harvested by a single 10-liter apheresis. No adverse effects were seen in either patient during apheresis following ABPCT. To our knowledge this is the first report dealing with PBCT collection during hematopoietic recovery following HDCT and ABPCT. CONCLUSIONS: (1) PBPC harvesting is feasible and well tolerated in this setting. (2) In appropriate patients with efficient PBPC mobilization after conventional-dose chemotherapy, a further PBPC autograft can be collected during recovery of hematopoiesis after ABPCT, serving as a rescue for a second course of HDCT.

Adult↗
PubMed1997

Recent progress on the role of Axl, a receptor tyrosine kinase, in malignant transformation of myeloid leukemias.

Receptor tyrosine kinases (RTK) play an important role in the signal transduction of normal and malignant cells. There are different families of RTKs which are mainly characterized by differences in the ligang-binding extracellular domains. Axl (or UFO/Ark) is the first member of a new class of RTK with two fibronectin type III domains and two immunoglobulin-like domains present at the extracellular domain. The axl-gene has been isolated by means of gene transfection studies using DNA of patients with chronic myelogeneous leukemia. For a previous and the present study, we used a sensitive reverse-transcriptase polymerase chain reaction assay to detect axl's mRNA in cells from normal and malignant hematopoietic tissue. Axl's mRNA expression was mainly detected in myelo-monocytic cells, whereas much weaker transcription was seen in lymphatic cells and in lymphatic leukemias. In normal bone marrow, axl was heavily transcribed in marrow stromal cells. Further, we analysed Axl protein expression using monoclonal antibody M50 in peripheral stem cell harvests; in most harvests, no co-expression of CD34 and Axl was detected. However, in one patient with AML in complete remission, Axl was co-expressed on 80% of the CD34-positive population. These data show that axl is preferentially expressed in monocytes and stromal cells. Furthermore, a fraction of CD34-positive progenitor cells may express Axl. The exact mechanism for transformation of myeloid progenitor cells through Axl, however, remains to be determined.

Flow Cytometry↗
PubMed1996

Expression of class I, II and III epitopes of the CD34 antigen by normal and leukemic hemopoietic cells.

Peripheral blood samples from 115 consecutive patients and bone marrow samples from 9 healthy donors were studied for percentages of CD34-expressing cells, quantitative expression of various CD34 epitopes as defined by fluorescence mean channel, and mutual inhibition of the different CD34 monoclonal antibodies detecting the various CD34 epitopes. The study focused only on samples from patients with presumably elevated numbers of CD34-expressing cells, due to the nature of the disease. Samples from patients with chronic myeloproliferative syndromes, acute leukemias from nonhematological cancer patients during mobilization with filgrastim, and normal bone marrow samples were studied. Elevated numbers of CD34-expressing cells (> 0.04% of all nucleated cells) were detected in 111 of 124 patients. An almost identical expression of CD34 epitopes as detected by phycoerythrin-conjugated monoclonal antibodies QBEND-10, 8G12, and ICH3 were detected, whereas expression of the IMMU409 epitope was detected in only a few samples (19 of 111). Reactivity of IMMU-133 was almost identical to that of QBEND-10. Reactivity of BIRMA-K3, the only CD34 monoclonal used in this study, but not described in previous workshops, was almost identical to that of 8G12. From studies on mutual inhibition of binding, two families of CD34 epitopes are defined. The first family is comprised of QBEND-10, IMMU-133, My-10, and ICH-3, and the second one is comprised of only 8G12 and BIRMA-K3.

Antigens, CD34↗
PubMed1996

In-vitro clonogenicity of mobilized peripheral blood CD34-expressing cells: inverse correlation to both relative and absolute numbers of CD34-expressing cells.

The determination of CD34-expressing cells by multiparameter flow cytometry is now widely used to estimate the reconstitution potential of cells harvested by cytapheresis for peripheral blood stem cell and progenitor cell transplantation. There is a correlation between the number of CD34-expressing cells collected and committed progenitor cells (CFU-GM and BFU-E) capable of forming colonies in vitro, but there is considerable variation in the proportion of CD34-expressing cells capable of clonogenic growth. The data in this study of 782 cytapheresis samples indicates that there is a negative correlation between the clonogenicity of the CD34-expressing cells and the absolute number or the proportion of CD34-expressing cells within the harvest. In 116 samples the proportion of CD34-expressing cells co-expressing the CD45-RA-antigen (a subset of CD34-expressing cells which includes virtually all clonogenic cells in terms of CFU-GM) was determined, but this did not help to identify the clonogenicity of a given sample. These findings may have clinical relevance, particularly when mobilization is judged to be relatively poor or when a good harvest is to be divided for multiple high-dose procedures.

Antigens, CD34↗
PubMed1996

Interference of blood leucocytes in the measurements of immature red cells (reticulocytes) by two different (semi-) automated flow-cytometry technologies.

Flow cytometrical methods have been introduced recently as an alternative to the enumeration of reticulocytes by microscopy. Two of these methods have gained widespread use in haematological practice; the multiparametric flow cytometer using thiazole orange staining (Retic-Count, FACScan) and the single-application reticulocyte counter using auramine-O staining (R-series, Sysmex). Several studies have emphasized the excellent correlations between microscopy and these techniques. The purpose of our study has been to examine the specificity of these automated devices with regard to cells classified as 'reticulocytes' and the effect that this may have on measures of reticulocyte maturity. Our results indicate that the specificity of reticulocyte measurements by both the Sysmex R-1000/-3000 and the Retic-Count system is relatively low. This is due to the presence of leucocytes amongst cells classified as reticulocytes. These leucocytes display intense staining with either dye, leading to an erroneous estimation of RMI (thiazole orange) and high fluorescence count (R-1000/-3000). This error is directly correlated with the leucocyte count. The basis for reticulocyte identification should be improved before automated estimation of reticulocyte maturation can be used in clinical practice.

Automation↗
PubMed1996

Impact of preleukapheresis cell counts on collection results and correlation of progenitor-cell dose with engraftment after high-dose chemotherapy in patients with germ cell cancer.

PURPOSE: To identify predictive factors for a good leukapheresis yield and to determine peripheral-blood progenitor cell (PBPC) dose requirements for rapid hematopoietic engraftment. PATIENTS AND METHODS: Seventy-one patients with germ cell cancer (GCC) underwent PBPC harvest for autologous transplantation following high-dose therapy. Aphereses were performed after chemotherapy during granulocyte colony-stimulating factor (G-CSF) administration. RESULTS: A median of two aphereses (range, two to five) resulted in 4.6 x 10(8) mononuclear cells (MNC)/kg, 15.7 x 10(4) colony-stimulating units granulocyte-macrophage (CFU-GM)/kg, and 6.0 x 10(6) CD34+ cells/kg. Peripheral blood MNC count correlated significantly with number of harvested CD34+ cells per kilogram (r = .49; P < .0001) and with CFU-GM count per kilogram (r = .35; P < .002). Circulating CD34+ cells from peripheral blood gave the best correlations to collected CD34+ cells per kilogram (r = .92; P < .0001), as well as to harvested CFU-GM per kilogram (r = .48; P < .0001). A preleukapheresis number of CD34+ cells greater than 4 x 10(4)/mL was highly predictive for a PBPC collection yield that contained more than 2.5 x 10(6) CD34+ cells/kg harvested by a single leukapheresis. After autologous transplantation, 41 patients were assessable for hematopoietic engraftment. They engrafted in a median time of 9 days (range, 7 to 18) to a WBC count greater than 1.0 x 10(9)/L, 10 days (range, 7 to 18) to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L, and 11 days (range, 7 to 62) to a platelet (PLT) count greater than 20 x 10(9)/L. Good correlations were seen between reinfused CD34+ cell count and recovery of WBC count, ANC, and PLT count, with r values of .65 (P < .001), .65 (P < .001), and .45 (P < .03), respectively. Patients reinfused with a PBPC dose greater than 2.5 x 10(6) CD34+ cells/kg recovered hematopoiesis in a significantly shorter time than patients who received less than 2.5 x 10(6) CD34+ cells/kg. CONCLUSION: Rapid hematopoietic engraftment can be achieved by a PBPC dose of greater than 2.5 x 10(6) CD34+ cells/kg. When circulating preleukapheresis CD34+ cell counts are greater than 4 x 10(4)/mL, a PBPC autograft that contains more than 2.5 x 10(6) CD34+ cells/kg can be collected by a single leukapheresis.

Adult↗