Faculty of Medicine
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Item type:Publication, Special Conditions in Venous Thrombembolism - Case Series(Macedonian Academy of Sciences and Arts/Walter de Gruyter GmbH, 2019-10-01); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Special Conditions in Venous Thrombembolism – Case Series(Macedonian Academy of Sciences and Arts, 2019-10-01); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Posterior Reversible Encephalopathy Syndrome (PRES) in Children Undergoing Allogeneic Stem Cell Transplantation(Македонска академија на науките и уметностите, Одделение за медицински науки = Macedonian Academy of Sciences and Arts, Section of Medical Sciences/Walter de Gruyter GmbH/Walter de Gruyter GmbH/Walter de Gruyter GmbH, 2019-05-01); ; ; ; Posterior reversible encephalopathy syndrome (PRES) is one of the most serious complication after allogeneic stem cell transplantation in paediatric setting. It is most commonly reported as adverse event of immunosuppressive strategies during transplantation. We present a case of a 7 years old girl with myelodysplastic syndrome (MDS) treated with allogeneic stem cell transplantation (ASCT) at our department. Diagnosis of PRES was confirmed by imaging techniques during the first month after transplant and it was very likely connected with cyclosporine neurotoxicity. The aim of this article is to present our first experience in diagnosing and treating PRES in paediatric stem cell transplantation. Our experience showed that PRES is one of the reasons for higher transplant related mortality in children. Early prediction of factors contributing to PRES and closely monitoring of patient's vital signs, especially blood pressure, neurological status and vision are the main contributors for challenging the patient with another immunosuppressive agent that has less neurological toxicity. Still studies have to be initiated to confirm the influence of PRES on transplant outcome. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, ADMINISTRATION OF G-CSF AND CHEMOTHERAPY IN PATIENTS WITH LYMPHOMA AND MYELOMA OPTIMIZED SUCCESSFUL MOBILIZATION OF HEMATOPOETIC PROGENITOR CELLS FOR AUTOLOGOUS BLOOD STEM CELL TRANSPLANTATION(2007); ; ; ; Introduction. Hematopoetic stem cell mobilization and collection have been optimized in numerous clinical trials, but significant proportion of patients mobilize an insufficient number of hematopoetic stem cell, resulting in an inadequate graft. Classical strategies for peripheral blood stem cell mobilization include administration of growth factors, mainly G-CSF alone or in combination with marrow suppressive chemotherapy. The administration of a combination of chemotherapy and cytokines G-CSF is associated with a significantly increased efficacy of stem cell mobilization compared with either modality alone. Method. The aim of this study was to evaluate the efficacy of G-CSF preceded by chemotherapy (cyclophosphamide 4g/m sq for 1 dose) for hematopoetic progenitor cell mobilization for lymphoma and myeloma patients. We started G-CSF as a fixed dose 480MU SQ every day as soon as the leukocyte counts began to rise after chemotherapy induced myelosupression. Leukapheresis was commenced at the time when leukocyte count rose up to 1000/uL, and repeated for 2-4 consecutive days until target number of CD34+ cell, at least 2×106/kg was collected. Results. 39 (male to female, 21:18, age range 21-65, lymphoma 25, myeloma 14) underwent a total of 86 courses of leukapheresis for hematopoetic progenitor cell collection prior to autologous transplantation from April 2002 through October 2006. The target amount of marrow was harvest in all patients. All the patients achieved good engraftment after autologous transplantation. The mean days required for WBC count to be over 1,000/uL was 8-16 days. Patient’s age, sex, underlying malignancy, exposure to chemotherapy before mobilization did not show any statistically significant correlation. Conclusion. We can conclude that chemotherapy followed by G-CSF administration is an effective way for mobilization of hematopoetic progenitor cell and verified itself as a good mobilization method. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, MOBILIZATION OF PERIPHERAL BLOOD PROGENITORS IN MULTIPLE MYELOMA. HOW TO DEAL WITH HARD TO MOBILIZE MYELOMA PATIENTS-SIX YEARS CENTER EXPERIENCE(2007); ; ; ; Peripheral blood progenitor cells (PBPCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are still used to support myeloablative therapy of multiple myeloma during the autologous setting. Variables having an impact on the ability to collect PBPC include age, month’s prior previous chemotherapy, mobilization regimen and platelet count at the time of mobilization. Myeloma patients with low mobilizing capacity indicate the need of evaluating alternative mobilizing regimens. We analyzed 25 patients with MM that underwent PBPC mobilization at Department of hematology, University Clinical Center Skopje. Pts received Cyclophosphamide (3gr/m2) followed by daily G-CSF (10 mcg/kg). In 15 pts we experienced a significant WBC nadir on median day +6, and began pheresis in recovered WBC up to 5.0×109/L on day +8 (median). Good mobilizers reached at least 2×106/kg CD34+ cells with median 3 (ranges 1-6) apheresis procedures. In 9 MM patients we registered low mobilizing capacity. Remobilizing procedure was preformed with single G-CSF in a dose of 20 mcg/kg in a 5 days regimen. All remobilized patients reached sufficient CD34+/kg count with median 2 (ranges 1-4) aphaeresis procedures. In statistical data in both groups of good and hard to mobilize MM pts we followed several variables concerning the platelet count on day 1 of aphaeresis which correlated with the ability to collect over 5×106 CD34+cells/kg (p<0,001), age of patients < 60 yrs and >60yrs (p<0,001) and previously received chemotherapy cycles of 5 pts (27%) who started aphaeresis on median day +14 (p<0,001) in the Cy/G-CSF group. We can conclude that the 5 day regimen of single G-CSF in increased daily dose showed effective with efficient yields results for median 2 day leukopheresis procedure, well tolerated with possibility for mobilization in outpatient basis. This approach, if confirmed on larger series of myeloma patients could open new opportunities in stem cell mobilization for poor or non-mobilizers. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Influence of filgrastim mobilization of HLA identical familiar healthy stem cell donor in allogenic transplant setting(2010); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Efficacy, complication rates and cost-effectiveness of chemotherapy + G-CSF and single agent C-CSF as mobilizing regimens for autologous PBSC: analysis of 125 patients with hematological malignancies(2010); ; ; ; Mobilized PBSC have largely replaced conventional, unprimed BM as source during the autologous transplant setting, because of a faster hematopoietic reconstitution, less transfusion requirements, less infective complications and earlier hospital discharge. Choosing the optimal mobilizing regimen is the goal for achieving the suffi cient amount of PBSC for autologous transplant. G-CSF is the standard agent commonly administered undergoing PBPC mobilization and collection in a dose of 10 micro/gr in a 4 days regimen. The additional chemotherapy to G-SCF is still associated with higher rate of hemorrhagic cystitis, prolonged neutropenia, infective complications, secondary malignancies and other toxicities. Therefore in this study we evaluated the effi cacy, complication rates and cost-effectiveness of chemotherapy + G-CSF versus single agent C-CSF as mobilizing regimens. We analyzed 125 patients with haematological malignancies (49 AML in fi rst remission, 26 HD, 30 MM, 16 NHL, 4ALL) who underwent mobilization of PBSC in our centre and the attempt to reach 2 × 10(6)/kgCD34 cells. In 6% of patients adequate cell dose was not reachable and overall failure rate of mobilization of 17,5%. Furthermore 15.6% failed to harvest the optimal 4 × 10(6)/kgCD34 + cells with > 1 aphaeresis attempt. The analysis of factors contributing in this effect in the univariante analysis were: > 2 lines of previous chemotherapy and neutropenic events (P = 0,002 and P = 0,005), those also remained signifi cant in the multivariate analysis (RR:4,4 and 6,2). No differences have been noticed between the diagnostic groups of patients. The mortality rate was 2% (intracranial bleeding and sepsis). The statistical analysis preformed for analyzed patients transplanted with single G-CSF as mobilizing regimen, compared with the chemotherapy + G-CSF group showed P < 0,0001 for febrile days, microbiological positive isolates, days of hospital stay, transfusion requirements. The median cost of PBSC collection in the Chemotherapy + G-CSF group was E 8550 (E220-10110) compared with the G-CSF group alone E3110 (E2200-4120) that showed P < 0,0001. Taking these results in consideration for the potential candidates for ASCT, transplant centers should consider the use of less myelosupressive agents or dose reduction strategies for the mobilization and autologous stem cell procurement. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Validation of the predictive power of the hematopoietic cell transplantation co-morbidity index, performance status for non-relapse mortality and long-term survival after autologous transplantation in patients with hematological malignancies(2010); ; ; ; The hematopoietic cell transplantation comobrbidity index (HCTCI) was developed as a sensitive tool to capture pretransplant comorbidities among transplant recipients which will have infl uence on non relapse mortality (NRM) and overall posttransplant survival (OS). HCT-CI has not been widely validated among autologous recepients. We retrospectivelly evaluated if HCT-CI and karnofsky performance status (PS) and other readily available pretransplant variables concerning pretransplant mobilization strategies can predict the outcome of autologous recipients in our transplant center. We stratifi ed outcomes among 120 consecutive adult autologous recipients (47 AML in fi rst remission, 24 HD, 27 MM, 16 NHL, 4ALL). HCT-CI risk was low in 10 (12%), intermediate in 22 (27%) high in 45 (55%) and undetermined in 5 (6%). Two year OS was 45% (95%CI: 24–64%), 55% (95%CI: 40–68%) and 42% (95%CI: 24–64%) in the low, intermediate and high-risk HCT-CI groups respectively. Two year NRM was 36% (95% CI: 17–36%), 26% (95% CI: 15–39%) and 30% (95% CI: 22–39%) in the low, intermediate and high-risk HCT-CI groups respectively. The multivariate analysis revealed that HCT-CI failed in prediction of OS and NRM but KPS (< 90%) was a strong predictor of NRM as an independent predictor. The variables concerning mobilization of stem cells (chemotherapy with G-CSF versus G-CSF alone and the dose of infused CD34 + > 4,0 × 106/kg and < 4.0 × 106/kg in the three risk HCT-CI groups revealed that patients with HCTCI score > 3 and intermediate and high risk disease that received < 4.0 × 106/kg had 2 year NRM <30% and OS<45%, as well the patients mobilized with chemotherapy + G-CSF showed lower NRM in the HCT-CI > 3 (intermediate and high risk disease). To determine the validity of HCT-CI, KPS and weather to include the the independent variables concerning the mobilization strategy and stem cell dose that we analyzed, a multi-center collaboration is necessary to produce an adequately powered validation study for risk stratifi cation of autologous recipients. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, First step towards Macedonian donor registry-mobilization of HLA-identical familiar healthy stem cell donor in allogeneic transplant setting(2011); ; ; ; Mobilized peripheral blood stem cells (PBSC) from healthy donors have become an increasingly used alternative to bone marrow for allogeneic transplantation. Granulocyte colonystimulating factor (G-CSF) –primed peripheral stem cells harvesting may result in a graft with increased mononuclear cells collected, increased progenitor cell dose and potential for more rapid engraftment resulting in improved survival. Filgrastrim is not only known to mobilize CD34+ progenitor cells but acts as a pleiotropic immune modulator. So, systematic donor follow-up in healthy donors is needed. The aim of this study is to evaluate safety and feasibility of G-CSF primed hematopoietic peripheral stem cells in familiar HLA-identical donors. The follow-up focused on clinical and laboratory testing including reports of adverse event after the mobilization. Granulocyte colony-stimulating factor (G-CSF) is administrated in 56 healthy donors to reach suffi cient mobilization in the period 2000-2010. The donors were characterized as follows: 43 years median; female 60% of the donors. G-CSF was administrated in the dose 10g/kg of donor weight in fi ve day and PBSC collections started on the fi fth day using COBE Spectra cell separator. The aim was to collect mononuclear cells 2x108/kg of recipient weight. Three donors were mobilized twice (for second transplant). Aphaeresis needed to reach target number of CD34+ cells were: 1 apherese in 50%, more than two apherese need in only 1 patient. The most frequent adverse event that was noted by patients was bone pain associated with increasing number of white blood cells. Better mobilization and higher PBSC yield correlated signifi cantly with younger age. Four years after G-CSF –primed peripheral stem cells harvesting, a young female 48 years old was diagnosed with acute myeloblastic leukemia. Four years ago when she was 44 years old, she donated for her HLA identical sister with acute myeloblastic leukemia. G-CSF is safe and very effective for PBSC mobilization in our group of healthy donors. This method allows certain collections of suffi cient numbers of progenitors in virtually all healthy donors. We demonstrated that fi lgrastim mobilization for peripheral blood stem collection is effective and result with successful engraftment in all the recipients. Daily injection of 10g/kg of G-CSF and fi rst aphaeresis preformed at day 5 seems to be the best strategy to obtain the CD34+ cell count for an allogeneic hematopoietic stem cell graft. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Adverse events related to PBPC collection and mobilization for autologous transplantation in 10 years’ experience: procedures, efficiency, variables related to collection and safety profile(2011); ; ; ; Objectives: We tried to evaluate the effi ciency, safety and risk factors of aphaeresis procedures used for autologous PBPC collections in a 10-year period in our transplant center. Thrombocytopenia, hypotension and citrate related adverse effects were evaluated as different biological variables. Material and methods: A total of 155 patients with hematological malignancies were analyzed (57 AML in fi rst remission, 33 HD, 37 MM, 20 NHL, 4ALL) that underwent mobilization of PBPC. The patients were mobilized either with CTX 3gr/m² + G-CSF 10mcg/kg starting or VP-16 (2gr/m²)+G-CSF 10mcg/ kg. Collections of PBSC were performed using Cobe spectra Baxter CS3000 aphaeresis system. Target of collection was >2, 0x10(6)/kg CD34+. The procedure was initiated when leukocyte count reached to 5x10(9)/L. Results: Both regimens were effective in the progenitor cell mobilization and almost 84% of analyzed patients reached at least 2x10(6)/kg CD34+ cells with median 3 (ranges 1-6) aphaeresis procedures. In 6% of patients adequate cell dose was not reachable and overall failure rate of mobilization of 17, 5%. Furthermore 15.6% failed to harvest the optimal 4x10(6)/ kgCD34+cells with >1 aphaeresis attempt. 48% patients in the CT/G-CSF group initiated aphaeresis on day 9, 34% on day 8 and 31% on day 10. Good mobilizers (GM) experienced at least one adverse event during aphaeresis compared with the no- GM. The percentage of absolute CD34+ before aphaeresis correlated with CD34+/cells/kg collected (R2=0, 62). The median of blood volume processed for body weight and the median time of aphaeresis was 7215ml (980ml-13450ml) in 202 min for GM and 8054ml (1450ml-14659ml) and 207min or no-GM. No correlation was found between CD34+/kg and volume processed. High correlation was found between the number of CD34+/kg and volume processed in the GM subject that reached the target of CD43+cells/kg only with one aphaeresis procedure (R2=0,87) We can conclude that the mobilizing regimens were adequate to achieve PBSC harvest in 84% of pts in our center that underwent autologous transplantation. The optimal approach to remobilization strategy remains unclear. Also we did not observe any signifi cant difference between GM and no-GM subjects in the adverse effect manifestation in reaching the CD34+cells/kg target, concerning the number of cells and volume processing. Maybe volume reducing of aphaeresis technique in future will shorten the time of achieving CD34+ target in GM subject.