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A Spyridonidis

Publications and source records attributed to A Spyridonidis.

13 recordsLinked to original sources
PubMed2005

Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation.

Both conventional chimerism analysis (CCA) and lineage-specific chimerism analysis (LCA) have potential pitfalls as diagnostic means for the detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). Therefore, the present study examines the results of both methods in order to determine how predictive consecutive evaluations were, with respect to the risk that the patient would relapse during post-transplant follow-up and with respect to responsiveness to immunomodulatory treatment. A total of 168 individuals with acute myeloid leukemia (AML) (n = 137) and myelo dysplastic syndrome (n = 31) were investigated with CCA and LCA at mean intervals of 24 days (range: 11-116). The median follow-up after myeloablative aHCT was 22 months (range: 4-49). Of 168 patients, 65 experienced a clinical relapse after aHCT. CCA and LCA were comparatively sensitive and specific for relapse at the intervals of chimerism testing employed in this study. Of 32 patients, 10 who were offered donor lymphocyte infusions (DLI) treatment for increasing (n = 29) or stable (n = 3) mixed chimerism (MC) achieved at least transitory CC. The observation that all patients with increasing MC relapsed despite DLI treatment (54%) or withdrawal of immune suppression (24%) indicates that novel strategies to deal with rapidly evolving relapse in AML patients, such as shortening of chimerism monitoring intervals, need to be evaluated.

Cell Lineage↗
PubMed2004

Evidence for a graft-versus-mast-cell effect after allogeneic bone marrow transplantation.

Mast cell leukemia (MCL) is a rare form of aggressive mastocytosis with a reported median survival below 6 months. Casuistic reports suggest the effectiveness of allogeneic bone marrow transplantation (BMT) for MCL. However, these reports lack clear evidence for a graft-versus-mast-cell (GvMC) effect. We prospectively investigated the GvMC at different time points after allogeneic BMT and donor-lymphocyte infusions (DLI). Samples were gathered from a patient with MCL treated with allogeneic BMT from an unrelated HLA identical donor. Parameters for detection of a GvMC effect included flow cytometrical analysis of mast cell (MC) populations in peripheral blood and BM, BM smear and histology, chimerism analysis of flow cytometrically sorted BM CD117+/CD34- MC and testing for anti-mast cell reactivity of donor lymphocytes by interferon (IFN)-gamma ELISPOT. DLIs reduced MC from 5 to 0.5%. MC chimerism analysis demonstrated a complete recipient genotype after BMT, suggesting that the persistent mastocytosis was part of residual neoplastic disease. At 3.7 years after BMT, there is some evidence for relapse. In summary, BMT and DLIs attenuated the mastocytosis from an aggressive to an indolent form and may have improved the patients' prognosis. The in vitro data of our study indicate for the first time the existence of a GvMC effect.

Adult↗
PubMed2004

Donor lymphocyte infusions for multiple myeloma: clinical results and novel perspectives.

Donor lymphocyte infusions (DLIs) provide effective therapy for patients with various hematological malignancies who have relapsed after allogeneic hematopoietic stem cell transplantation (HSCT). In patients with multiple myeloma (MM), DLIs can induce response rates of 40-52%. DLIs were employed as treatment for MM relapse or as prophylaxis for relapse in MM patients undergoing allo-HSCT. The clinically most relevant treatment-related morbidity with DLIs is the occurrence of graft-versus-host disease (GVHD). Secondly, graft failure and the immune escape of extramedullary plasmocytoma have been reported. The fact that previous clinical reports have documented graft-versus-myeloma (GVM) activity without GVHD suggests that at least two distinct immunocompetent cell populations mediating GVHD and/or GVM may exist. Further characterization of the effector cells such as T cells and/or NK cells and their targets may help to clarify the immune response that mediates the GVM effect. This review considers the results of clinical approaches with DLI for MM, with emphasis on strategies to prevent GVHD while preserving the GVM effect. Furthermore, currently investigated molecular antigenic targets for the GVM effect such as MM-specific idiotypic determinant of immunoglobulin variable regions, several PRAME epitopes and antigenic structures encoded by cancer germline-specific genes as candidates for immunotherapy trials are discussed.

Female↗
PubMed2002

Paraneoplastic cerebellar degeneration and nephrotic syndrome preceding Hodgkin's disease: case report and review of the literature.

A patient presented with symptoms of cerebellar degeneration and nephrotic syndrome. A work-up at that time failed to reveal an underlying disease; however, 20 months later Hodgkin's disease was diagnosed. Hodgkin's lymphadenopathy developed 2 wk after prednisone therapy for the nephrotic syndrome had been discontinued. Systemic polychemotherapy resulted in complete remission of both Hodgkin's disease and nephrotic syndrome, while the neurological deficit persisted. Patients with unexplained cerebellar degeneration and/or nephrotic syndrome demand extensive evaluation for the presence of Hodgkin's disease, and steroid therapy may delay diagnosis.

Adrenal Cortex Hormones↗
PubMed2001

Paraneoplastic polyneuropathy preceding the diagnosis of Hodgkin's disease and non-small cell lung cancer in a patient with concomitant Borrelia burgdorferi infection.

A patient with painful peripheral neuropathy is presented, whose symptoms were thought to result from an infection with Borrelia burgdorferi sensu lato. Investigations of the cerebrospinal fluid for signs of inflammation and borrelial antibodies were negative, and the patient did not benefit from repeated antibiotic treatment. Electrophysiologic studies and sural nerve biopsy showed axonal neuropathy consistent with a paraneoplastic syndrome. Further workup revealed mediastinal Hodgkin's disease (HD; nodular sclerosing subtype) Ann Arbor stage II and non-small cell cancer of the lung (stage T1N0M0). Surgical resection of the lung cancer and combined chemo- and radiotherapy for HD resulted in complete remission of both malignancies. While the preexisting neurologic symptoms persisted during treatment, neurography showed some improvement of the distal nerves. During radiation therapy the patient developed transient left-sided brachial plexopathy. This case illustrates that the diagnosis of borreliosis in patients with isolated painful peripheral neuritis cannot be based solely upon positive IgG titers and supports the requirement for a thorough workup for an underlying--potentially curable--disease. In addition, singular pulmonary lesions in the setting of HD should be suspected to have a separate cause.

Adult↗
PubMed1999

Proliferation and survival of mammary carcinoma cells are influenced by culture conditions used for ex vivo expansion of CD34(+) blood progenitor cells.

Malignant cell contamination in autologous transplants is a potential origin of tumor relapse. Ex vivo expansion of CD34(+) blood progenitor cells (BPC) has been proposed as a tool to eliminate tumor cells from autografts. To characterize the influence of culture conditions on survival, growth, and clonogenicity of malignant cells, we isolated primary mammary carcinoma cells from pleural effusions and ascites of patients with metastatic breast cancer and cultured them in the presence of stem cell factor (SCF), interleukin-1beta (IL-1beta), IL-3, IL-6, and erythropoietin (EPO), ie, conditions previously shown to allow efficient ex vivo expansion of CD34(+) BPC. In the presence of serum, tumor cells proliferated during a 7-day culture period and no significant growth-modulatory effect was attributable to the presence of hematopoietic growth factors. When transforming growth factor-beta1 (TGF-beta1) was added to these cultures, proliferation of breast cancer cells was reduced. Expansion of clonogenic tumor cells was seen in the presence of SCF + IL-1beta + IL-3 + IL-6 + EPO, but was suppressed by TGF-beta1. Cocultures of tumor cells in direct cellular contact with hematopoietic cells showed that tumor cell growth could be stimulated by ex vivo expanded hematopoietic cells at high cell densities (5 x 10(5)/mL). In contrast, culture under serum-free conditions resulted in death of greater than 90% of breast cancer cells within 7 days and a further decrease in tumor cell numbers thereafter. In the serum-free cultures, hematopoietic cytokines and cellular contact with CD34(+) BPC could not protect the tumor cells from death. Therefore, ex vivo expansion of CD34(+) BPC in serum-free medium provides an environment for efficient purging of contaminating mammary carcinoma cells. These results have clinical significance for future protocols in autologous progenitor cell transplantation in cancer patients.

Antigens, CD34↗
PubMed1998

Purging of mammary carcinoma cells during ex vivo culture of CD34+ hematopoietic progenitor cells with recombinant immunotoxins.

Tumor cells have been found in autologous hematopoietic cell transplants used after high-dose chemotherapy. To specifically eliminate contaminating mammary tumor cells during ex vivo expansion of CD34+ hematopoietic progenitor cells, we used recombinant immunotoxins (ITs) directed against cell-surface antigens expressed on mammary carcinoma cells. ITs were expressed from fusion cDNAs combining a single-chain antibody fragment (scFv) directed against the Erb-B2 or epidermal growth factor (EGF) receptors with a truncated Pseudomonas exotoxin A fragment devoid of its cell-binding domain. CD34+ hematopoietic progenitor cells did not express Erb-B2 and EGF receptors as detected by Western blotting. Ex vivo expansion of total hematopoietic cells or of colony-forming cells from CD34+ progenitors in the presence of stem-cell factor (SCF), interleukin-1 (IL-1), IL-3, IL-6, and erythropoietin (Epo) was not affected when ITs were added to the cultures. In contrast, MDA-MB 453 and MCF-7 mammary carcinoma cells were depleted in a dose- and time-dependent manner by more than 3 log in coculture with CD34+ cells over a period of 7 days in the presence of 100 to 1,000 ng/mL of anti-Erb-B2 IT. This included elimination of the subpopulations with regrowth potential. Similarly, addition of either anti-Erb-B2 or anti-EGF receptor ITs to primary breast cancer cells isolated from patients with metastatic disease resulted in elimination of cytokeratin-positive cells in seven of seven samples. ITs are highly efficient and convenient to use for the depletion of mammary tumor cells during ex vivo expansion of hematopoietic progenitor-cell autografts.

ADP Ribose Transferases↗
PubMed1998

Minimal residual disease in autologous hematopoietic harvests from breast cancer patients.

The increasing use of high-dose chemotherapy with autologous hematopoietic transplantation for the treatment of solid malignancies has raised concern about the role of tumor cells contaminating the grafts. Minimal residual disease (MRD) in autologous grafts has became a dynamic and intensively studied field in oncology. This review discusses the current status of MRD in breast cancer autografts and presents existing data on detection methodology, clinical relevance, biologic characteristics and purging techniques.

Antineoplastic Agents↗
PubMed1997

Transforming growth factor-beta 1 delays formation of granulocyte-macrophage colony-forming cells, but spares more primitive progenitors during ex vivo expansion of CD34+ haemopoietic progenitor cells.

Ex vivo culture and expansion of autologous haemopoietic transplants has been developed to improve tumour cell purging and accelerate haemopoietic reconstitution by transplantation of increased progenitor cell numbers. We studied the effect of the negative haemopoietic regulator, transforming growth factor beta-1 (TGF-beta 1) on primitive precursors during ex vivo expansion of CD34+ cells. When added directly to methylcellulose colony-forming assays, TGF-beta 1 potently suppressed the development of granulocyte-macrophage colonies from CD34+ enriched peripheral blood progenitor cells (80-90% inhibition). In contrast, expansion of total nucleated cells and granulocyte-macrophage colony-forming cells (GM-CFC) from CD34+ progenitors in liquid culture in the presence of stem cell factor (SCF), interleukin (IL)-1 beta, IL-3, IL-6 and erythropoietin (EPO) was inhibited to 32-65% of control culture levels within 14 d when TGF-beta 1 was added, and still produced an average 3.3-fold absolute amplification of GM-CFC. The inhibitory effect of TGF-beta 1 on GM-CFC generation was reversed when it was washed out on day 6 of ex vivo expansion cultures, and total numbers of GM-CFC generated from expansion cultures then reached levels of untreated controls by day 16. Long-term bone marrow culture-initiating cell (LTCIC) numbers were preserved, at least at input levels, over a culture period of 14 d both in control and TGF-beta-1-treated expansion cultures. These findings suggest that TGF-beta 1, a cytokine which induces apoptosis or terminal differentiation in a number of malignant cell types, may be added to ex vivo expansion cultures without loss of primitive cells from autologous haemopoietic transplants.

Apoptosis↗
PubMed1996

Hematopoietic cell proliferation and differentiation.

The use of colony-stimulating factors to stimulate hematopoietic cell proliferation and differentiation in vivo is under still increasing investigation, particularly in the field of stem cell transplantation. This review discusses recently published results and tries to extrapolate lines of future development from the achievements reached to date.

Animals↗