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Von Bahr L.,Karolinska Institutet | Von Bahr L.,Karolinska University Hospital | Batsis I.,George Papanicolaou Hospital | Moll G.,Karolinska Institutet | And 7 more authors.
Stem Cells | Year: 2012

Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to <1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a "hit and run" mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy. © AlphaMed Press.

Vlachos D.,Aristotle University of Thessaloniki | Iakovou E.,Aristotle University of Thessaloniki | Keramydas C.,Aristotle University of Thessaloniki | Anagnostopoulos A.,George Papanicolaou Hospital
Operational Research | Year: 2012

Allogeneic hematopoietic stem cell transplantation is a relative new treatment method for a wide range of diseases including hematopoietic malignancies, immunodeficiency disorders, metabolic diseases and genetic disorders. Umbilical Cord Blood (UCB) is a modern and effective source of hematopoietic stem cells with increasing usage throughout the world. Thus, the establishment and operation of public UCB banks has emerged as a common practice all over the world. In Greece, the development of such a UCB bank network is still in its infancy. This paper presents the development of a methodology for estimating the required inventory level of UCB units in Greece (bank size), in order to ensure an adequate probability that a Greek patient finds a Human Leukocyte Antigen (HLA)-compatible unit/donor (with a match at least for 4 out of 6 HLA histocompatibility antigens). To this end, we have adopted a Monte Carlo simulation approach. The available histocompatibility data include detailed genotypes of 8,500 Greeks. These data were fed into the system simulation model to emulate a UCB bank operation. The results of the simulation process reveal that an inventory of 10,000 cryopreserved UCB units could ensure a 4 out of 6 HLA matching for a Greek patient with a probability exceeding 95%. The determination of the bank size is a strategic, pivotal decision; thus, the proposed methodology provides the input for the National Healthcare System to decide on developing or not an UCB Bank (along with its designing parameters). © 2010 Springer-Verlag.

Samalidou M.,George Papanicolaou Hospital | Samalidou M.,Aristotle University of Thessaloniki | Bougiouklis D.,George Papanicolaou Hospital | Vyzantiadis T.-A.,Aristotle University of Thessaloniki | And 6 more authors.
Experimental Biology and Medicine | Year: 2015

Liposomal amphotericin B, voriconazole, and caspofungin are currently used for systemic and severe fungal infections. Patients with malignant diseases are treated with granulocyte-colony stimulating factor (G-CSF) for the recovery of granulocytes after chemotherapy or hematopoietic cell (HC) transplantation. Since they have a high incidence of fungal infections, they inevitably receive antifungal drugs for treatment and prophylaxis. Despite their proven less toxicity for various cell types comparatively with amphotericin B and the decrease in the number of leukocytes that has been reported as a possible complication in clinical studies, the effect of liposomal amphotericin B, voriconazole, and caspofungin on HCs has not been clarified. The present study aimed to examine the in vitro and in vivo effect of these three modern antifungals on HCs. Colony-forming unit (CFU) assays of murine bone marrow cells were performed in methylcellulose medium with or without cytokines and in the presence or absence of various concentrations of liposomal amphotericin B, voriconazole, and caspofungin. In the in vivo experiments, the absolute number of granulocytes was determined during leukocyte recovery in sublethally irradiated mice receiving each antifungal agent separately, with or without G-CSF. In vitro, all three antifungal drugs were nontoxic and, interestingly, they significantly increased the number of CFU-granulocyte-macrophage colonies in the presence of cytokines, at all concentrations tested. This was contrary to the concentration-dependent toxicity and the significant decrease caused by conventional amphotericin B. In vivo, the number of granulocytes was significantly higher with caspofungin plus G-CSF treatment, higher and to a lesser extent higher, but not statistically significantly, with voriconazole plus G-CSF and liposomal amphotericin B plus G-CSF treatments, respectively, as compared with G-CSF alone. These data indicate a potential synergistic effect of these antifungals with the cytokines, in vitro and in vivo, with subsequent positive effect on hematopoiesis. © 2015, © 2015 by the Society for Experimental Biology and Medicine.

Sakellari I.,George Papanicolaou Hospital | Mallouri D.,George Papanicolaou Hospital | Batsis I.,George Papanicolaou Hospital | Apostolou C.,George Papanicolaou Hospital | And 13 more authors.
Leukemia and Lymphoma | Year: 2015

Optimal conditioning remains a challenge in lymphomas. We designed a regimen consisting of Busulfex, etoposide and melphalan (BuEM). We retrospectively analyzed the outcome of patients conditioned with carmustine, etoposide, cytarabine and melphalan (BEAM) or BuEM in matched-pair analysis on a planned 2:1 ratio. Eighty-seven patients treated with BEAM who fulfilled the matching criteria were randomly selected. Two-year progression-free survival/overall survival (PFS/OS) were 63.2%/76.7% for BEAM vs. 65.6%/79.8% for BuEM after 64.7 and 42.7 months, respectively. Furthermore, marginally better PFS and OS were noted in Hodgkin lymphoma (HL) after BuEM. In multivariate analysis, PFS was superior in HL, chemosensitive disease and complete remission post-transplant. BEAM correlated with faster engraftment, reduced infections, less mucositis and liver toxicity, and BuEM with less need for blood cell and platelet transfusions and granulocyte colony-stimulating factor administration. In conclusion, BuEM was well tolerated and equally highly efficacious as BEAM for non-Hodgkin lymphoma and offered marginally significantly improved PFS and OS in HL with acceptable toxicity and zero mortality. © 2015 Informa UK, Ltd.

Sakellari I.,George Papanicolaou Hospital | Barbouti A.,George Papanicolaou Hospital | Bamichas G.,George Papanicolaou Hospital | Mallouri D.,George Papanicolaou Hospital | And 9 more authors.
Bone Marrow Transplantation | Year: 2013

Chronic kidney disease (CKD) has been related to allogeneic haematopoietic cell transplantation (HCT) as a late effect caused by a variety of factors. We retrospectively evaluated the development of CKD in 230 patients, aged 34 (5-65) years, who had undergone allogeneic HCT for haematological disease, using sibling or unrelated donors and myeloablative or reduced conditioning regimens. Pre-HCT glomerular filtration rate (GFR) was within normal limits (108±28 mL/min/1.73 m 2) in patients who did not develop CKD and 95±24 mL/min/1.73 m 2 in those with CKD postHCT, while the GFR 12 months post transplant declined to 104±26 and 69±19 mL/min/1.73 m 2, respectively. CKD incidence was 20.4%, with a median time of development of 6 (3-18) months post transplant. On multivariate analysis, risk factors for CKD were the presence of chronic GVHD (cGVHD; P=0.001), unrelated donor transplantation (P=0.008), post-transplant event of acute kidney injury (AKI) (P=0.002) and older age (P=0.002). In long-term survivors stable significant predictors for CKD were older age at transplantation, cGVHD and AKI. CKD did not influence non-relapse mortality. In our study, cGVHD emerges as an important cause of kidney injury in HCT survivors, regardless of administration of nephrotoxic agents. © 2013 Macmillan Publishers Limited All rights reserved.

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