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S Serke

Publications and source records attributed to S Serke.

At least 55 records · Page 3Linked to original sources
PubMed1995

Autografting with blood progenitor cells: predictive value of preapheresis blood cell counts on progenitor cell harvest and correlation of the reinfused cell dose with hematopoietic reconstitution.

One hundred and nine patients suffering from various malignancies underwent 285 apheresis procedures for PBPC collection. A median of two leukaphereses (range: 2-5) resulted in median numbers of 4.6 x 10(8) MNC/kg, 14.1 x 10(4) CFU-GM/kg, and 6.0 x 10(6) CD34+ cells/kg. Preleukapheresis peripheral blood CD34+ cells correlated significantly with collected CD34+ cells/kg (r = 0.94; p < 0.0001) and with CFU-GM/kg (r = 0.52; p < 0.0001). A value > 4 x 10(4) CD34+ cells/ml was highly predictive for a collection yield > 2.5 x 10(6) CD34+ cells/kg harvested by a single leukapheresis. Sixty patients were evaluated for hematologic reconstitution and engrafted in a median time of 10 days for WBC > 1.0 x 10(9)/l (range: 7-21 days), 10 days for ANC > 0.5 x 10(9)/l (7-20) and 11 days for PLT > 20 x 10(9)/l (7-62). Reinfused CD34+ cells/kg correlated significantly with hematologic engraftment (r = 0.44-0.52 and p < 0.006-0.001) as well as CFU-GM/kg (r = 0.36-0.44 and p < 0.007-0.001). A progenitor cell dose > 2.5 x 10(6) CD34+ cells/kg or > 8.0 x 10(4) CFU-GM/kg led to a significantly faster recovery for WBC, ANC, and PLT when compared with patients receiving < 2.5 x 10(6) CD34+ cells/kg or < 8.0 x 10(4) CFU-GM/kg. We conclude that rapid hematopoietic engraftment after high-dose therapy and PBPC reinfusion correlates well with a progenitor cell dose > 2.5 x 10(6) CD34+ cells/kg or > 8.0 x 10(4) CFU-GM/kg, and that above a preleukapheresis threshold of 4 x 10(4) CD34+ cells/ml a PBPC autograft containing > 2.5 x 10(6) CD34+ cells/kg can be collected by a single leukapheresis. We suggest that patients recovering from myelosuppression should be monitored for CD34+ cells in serial blood samples to determine the course of circulating hematopoietic progenitor cells. This issue will help to define the optimal time point to start apheresis and to predict a PBPC autograft harvested by a single leukapheresis, which will lead to rapid and stable hematopoietic reconstitution following transplantation.

Adolescent↗
PubMed1995

Tumorous manifestation of hairy cell leukemia after long-term treatment with interferon alpha.

Tumorous-manifestation of hairy cell leukemia in a patient treated with IFN alpha for 7 years is described. After this time, while the patient still was in hematological remission, a tumorous involvement of the lung by hairy cells developed and was successfully treated by surgery. No differences in the phenotype of hairy cells in the lung tumor, in the bone marrow, or in the blood could be detected.

Bone Marrow↗
PubMed1995

Propagation of large numbers of cells of a human mixed-lineage T-lymphoid/myeloid.

Previously, a subset of T cells co-expressing the myeloid antigen CD33 has been described in patients with acute myelogenous leukaemia. However, normal lymphocytes have been viewed as not expressing the CD33 antigen. We have developed culture conditions which allow for the rapid expansion of CD3+CD33+ cells from patients with myeloid leukaemia as well as normal individuals. The protocol for cellular expansion includes the addition of interferon-gamma on day 0, interleukin-1, interleukin-2 and a monoclonal antibody against CD3 on day 1 to peripheral blood lymphocytes. Using this protocol, total cell number increased more than 600-fold within 16 d of culture. Cells could be kept in culture for more than 6 months. Cells of the CD3+CD33+ phenotype increased to 15.2 +/- 4.6% using this protocol after 16 d in culture. These cells have been characterized by flow cytometry and have been found to express the alpha, beta T-cell receptor, co-express the CD2, CD5, CD7 and HLA-DR antigens and did not express CD14 or CD15 antigens. Cells of the CD3+CD33+ phenotype were unable to lyse tumour cells as determined in a 51Cr release assay. In patients with chronic myeloid leukaemia. CD3+CD33+ cells seem to be negative for expression of bcr/abl transcript in contrast to CD33- cells. Our data suggest that CD3+CD33+ cells do exist in peripheral blood from normal individuals.

Antigens, CD↗
PubMed1995

Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: a randomized comparison.

PURPOSE: To compare autologous bone marrow (BM) with peripheral-blood progenitor cells (PBPC) as hematopoietic rescue after high-dose chemotherapy (HDCT). PATIENTS AND METHODS: From January 1991 until April 1993, 47 consecutive patients with relapsed or refractory germ cell tumors were randomized to either BM harvest or collection of PBPC mobilized by chemotherapy plus granulocyte colony-stimulating factor (G-CSF). After additional conventional-dose salvage treatment, all patients received HDCT with carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 with either BM or PBPC rescue. RESULTS: Forty-six patients were assessable for hematologic reconstitution, and one patient died on day +4 before engraftment. Rescue using PBPC resulted in a significantly shorter recovery time to neutrophil counts more than 500/microL (10.0 v 11.0 days, P < .01), neutrophil counts more than 1,000/microL (10.0 v 12.0 days, P = .001), and platelet counts more than 20,000/microL (10.0 v 17.0 days, P < .01), as well as in fewer days to transfusion independence from RBCs (8.0 v 12.0, P < .05) and platelets (9.0 v 12.0, P < .01) and fewer days of intravenous (IV) antibiotics (9.0 v 11.0, P < .05). However, no statistical differences in transfusion requirements or in other clinical outcome variables were observed. Overall survival and event-free survival also were not different in the two study arms. CONCLUSION: We conclude that the use of PBPC mobilized by chemotherapy plus G-CSF results in sustained trilineage reconstitution after HDCT, which occurs more rapidly as compared with BM. The earlier hematologic reconstitution in patients with PBPC rescue significantly reduces the time to transfusion independence.

Adolescent↗
PubMed1994

Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis.

We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.

Base Sequence↗
PubMed1994

Overexpression of the Raf-1 proto-oncogene in human myeloid leukemia.

The Raf-1 protein, a cytoplasmic serine/threonine kinase, plays an important role in signal transduction pathways. In order to examine the role of Raf-1 in human myeloid leukemia, we determined raf-1 mRNA expression by Northern blot analysis in blast cell samples from 27 acute myeloid leukemia (AML) cases and peripheral blood mononuclear cells from six healthy donors. A normal raf-1 transcript size was detected in all cases investigated. However, overexpression of raf-1 mRNA was found in 2 of 27 AML cases, both of which were erythroleukemias (AML, FAB M6).

Acute Disease↗
PubMed1994

Characterization and measurement of CD34-expressing hematopoietic cells.

Because of availability of anti-CD34 monoclonal antibodies, multiparameter flow cytometry has become the tool of choice for determination of hematopoietic stem and progenitor cells. This report describes general techniques for quantitation and characterization of CD34-expressing cells by flow cytometry.

Adult↗
PubMed1994

[Flow cytometry quality control in stem cell separation].

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.

Colony-Forming Units Assay↗
PubMed1993

Positive selection of CD34+ cells: a short review of the immunoadsorption methods currently available for experimental and clinical use. Report on the "2nd European Workshop on stem Cell Methodology," Mulhouse, France, May 3-7, 1993.

At the "2nd European Workshop on Stem Cell Methodology," held in Mulhouse, France, on May 3-7, 1993, part of the meeting was dedicated to the positive selection of CD34+ cells. All devices that are currently in use, or will be available in the near future, were explained and practically demonstrated using human cell populations by scientists involved in their development. In this paper, a review of these methods is given in the form of a short description, together with the data presented in Mulhouse and available from the literature.

Antigens, CD↗
PubMed1993

Improved specificity of determination of immature erythrocytes (reticulocytes) by multiparameter flow-cytometry and thiazole orange using combined staining with monoclonal antibody (anti-glycophorin-A).

Applying thiazole orange stain and multiparameter flow-cytometry, immature erythrocytes, e.g., reticulocytes, can be discriminated from the mature erythrocytes by virtue of their higher RNA-content. One major problem of this method, however, consists in the inclusion of nucleated cells (leucocytes) and large RNA-containing platelets in the population defined by light scatter-patterns as erythrocytes. Due to the high intensity of staining with thiazole orange of all these cellular elements, all of them in the analysis are prone to be classified erroneously as reticulocytes. In order to classify elements in analysis properly as erythroid (reticulocytes+mature erythrocytes) or as non-erythroid (leucocytes+platelets), an alternative staining method is shown in this paper, consisting of thiazole orange combined to anti-glycophorin-A-PE-monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1993

[Mobilization of hematopoietic stem cells in peripheral blood by leukapheresis].

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.

Antigens, CD↗
PubMed1993

[Optimizing leukocytapheresis for collection of circulating hematopoietic stem- and precursor cells by multiparameter flow cytometry].

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.

Antigens, CD↗
PubMed1993

Fractionated total body irradiation and high-dose VP-16 with purged autologous bone marrow rescue for children with high risk relapsed acute lymphoblastic leukemia.

Twenty-two children with ALL in high risk second (n = 13), third or subsequent complete remission (n = 9) were treated with high-dose VP-16 60 mg/kg and fractionated total body irradiation (fTBI) 12 Gy, 2 x 2 Gy daily followed by autologous BM rescue. Prior to transplantation all patients had been treated according to intensive German BFM front-line or BFM relapse protocols. In all cases the marrow was purged using monoclonal antibodies attached to magnetic microspheres. All patients engrafted. There was no severe toxicity related to the pre-transplant high-dose chemoradiotherapy. Two patients died in the early course of transplantation from infections (Legionella and Aspergillus). Sixteen patients relapsed within 259 days (median 109 days); 13 died from leukemia. Four patients are alive in CR at a median of 1328 days with a Karnofsky score of 100%. The Kaplan-Meier estimation shows a probability of event-free survival (EFS) of 18% and a probability of relapse of 80%. Considering the otherwise poor prognosis of these children the results are acceptable although the high relapse rate is still disappointing. We conclude that high-dose VP-16 and fTBI combined with ABMT is a curative treatment for some children and should therefore be considered for those who lack an HLA-identical sibling donor. In future better therapy concepts are needed either in pre-transplant conditioning regimens or in post-transplant treatment schedules.

Adolescent↗