14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluate... more 14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluated the efficacy and toxicity of miniautologous transplantation of LAK in cytokine pretreated patients (pts) with metastatic RCC. Methods: Between May 1998 and July 2005, 29 pts (23M/6F) with metastatic RCC were included. All patients were pretreated with cytokine-based therapy (9 pts with interferon alfa, 9 pts with interferon alfa+5FU+IL-2, 10 pts with interferon alfa+5-FU and 1 patient with IL-2). Median age was 58 years (range 49–71). Patients were assigned into three prognostic groups according to MSKCC prognostic criteria for 2nd line treatment (Motzer et al., 2004). Six, seventeen and six pts had 0, 1 and 2–3 risk factors, respectively. Median number of metastatic sites was 2 (range 1–6). 9 pts had liver, 12 bone and 2 patients had cerebral metastases. Median time from cytokine treatment to LAK therapy was 9 months (range 0–41). Periferal blood stem cells (PBSC) were isolated. Part ...
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
The recent development of reduced intensity conditioning and allotransplantation (RICT) has opene... more The recent development of reduced intensity conditioning and allotransplantation (RICT) has opened a new way to assure engraftment of donor cells while reducing early transplant-related mortality. We evaluated the combination of high-dose therapy and autologous peripheral blood stem cells transplantation (APBSCT) followed by RICT to extend the benefit of allografting procedures in de novo multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51 years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony-stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6 patients developed chronic GVHD; 4 patients developed CMV antigenemia and were treated pre-emptively with ganciclovir. No transplant related mortality was shown. Response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF); when IF was negative, patients were classified in complete remission (CR) and when it remained positive, near CR (nCR). After a median follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and progression-free, respectively. Overall, the CR + nCR rate after dose-reduced allograft was enhanced from 26.7 to 73.3%. A correlation not statistically significant between GVHD and remission was found. In conclusion, an up-front tandem strategy with a very low reduced intensity-conditioning regimen for allografting following autografting is feasible and induces high CR/nCR rate in MM.
A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggress... more A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a part of firstline therapy. Forty-seven patients younger than 65 years with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL) or alk-negative anaplastic large cell lymphoma (ALCL) underwent ASCT between July 1997 and November 2005. Patients with DLBCL and alk-negative ALCL had 2 or 3 age-adjusted International Prognostic Index risk factors. All patients were transplanted after MACOP-B induction therapy followed by 2 courses of DHAP and myeloablative chemotherapy BEM or CBV. The complete response rate to the high-dose therapy was 79% with an estimated 5-year progression-free survival of 66%. At a median follow-up of 35 months (range, 16 to 112 months) the estimated overall survival at five years was 59%. There were 4 treatment-related deaths. Twenty-nine of 47 patients remain in complete remission. Our results confirm the efficacy of high-dose therapy with ASCT during first-line treatment of patients with poor-prognosis aggressive lymphoma, with substantial number of patients cured by using this treatment approach.
Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as ... more Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as an active component of the mature ribosome. The introduction of nucleotide changes (e. g., by site-directed mutations) clearly offers the most promising tool for elucidating the function of ribosomal RNA.
Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and im... more Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and improved tolerance in comparison with high-dose chemotherapy plus PBSC in poor risk germ cell tumors. The aim of this study was to confirm the effectivity and tolerance of this regimen in clinical practice. Twenty-five consecutive patients, 9 previously untreated with poor prognosis and 16 relapsed, were treated with 1.6 VIP or 1.9 VIP+PBSC. A relative dose intensity of 1.6 VIP was used in 14 patients and 11 patients received the intensity of 1.9 VIP. Clinical response was achieved in 56% of patients. Fifty-eight percent of patients have survived more than 1 year and 44% more than 2 years. No significant difference was noted between previously treated and untreated patients, as well as between the patients on 1.6 VIP and 1.9 VIP, with the exception of improved 1-year survival of patients on 1.9 VIP. One of four cisplatin-refractory patients achieved durable partial remission with a normal ...
We describe the implementation, optimization, sensitivity determination and first clinical result... more We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared highly informative in our patients population. In 21 sex-mismatched donor recipient pairs we used the Amelogenin locus to distinguish the X and Y chromosome. In sixty-three out of these 100 patients chimerism was regularly analyzed from blood samples taken at various time points after SCT with the median follow up of 17 months. Complete chimerism (CC), maintained over the whole follow-up period, was detected in 24 (38, 1%), stable and decreasing mixed chimerism (MC) in 28 (44, 4%) and increasing MC in 11 patients (17, 5%). Patients with CC, stable and decreasing MC showed a significantly better (p 0,005) overall survival rate (0, 81), compared to those with increasing MC (0, 24). These results demonstrate that STR-based chimerism monitoring with sensitivity above 1% and high informativity (98, 7% of donor recipient pairs) is necessary in establishing the origin of engrafted cells after an allogeneic SCT, in detecting graft rejection and that it may contribute in identifying patients with imminent leukemia relapse.
Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by... more Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by the bcr/abl gene rearrangement. Allogeneic transplantation of stem cells (SCT) is a routinely used treatment method of patients with this diagnosis and remains the only curative mode of treatment. From January 1990 to December 2002, 78 patients with CML underwent allogeneic transplantation and were examined at the Department of Genetics in the National Cancer Institute in Bratislava. Using conventional cytogenetic and FISH 6 patients (7.7%) showed additional chromosomal changes before SCT. These patients had statistically worse post transplantation prognosis compared to the patients without additional changes before SCT (mean survival in month+/-standard error (58.08 (+/-6.70) vs. 5.17 (+/-0.98), p-value=0.001), patient mortality (67% vs. 31%)). In addition five other variables were evaluated for transplant outcome, namely, patient's age at the time of transplantation, sibling or no...
Dear Editor, We have observed the spontaneous tumour regression in four patients (breast cancer, ... more Dear Editor, We have observed the spontaneous tumour regression in four patients (breast cancer, Hodgkin's disease, nonHodgkin's lymphoma and Ewing's sarcoma) who had relapsed/progressed after highdose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (ASCT).1 Patients' blood counts strongly resembled the blood counts in aplastic anaemia (aplastic anaemia (AA)like syndrome). Moreover, some of these patients' morphology of the bone marrow trephine biopsies was identical to the AA picture. It should be noted that in some patients who were treated by conventional chemotherapy only, a similar phenomenon has been observed, too (Lakota J, unpublished observation). In a provoking paper,2 the authors proposed that the autoimmune (antitumour) activity against present malignancy also operates against haematopoietic stem cells. The final clinical and laboratory pattern in these patients is present as acquired aplastic anaemia (AA). This pathophysiol...
14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluate... more 14593 Background: Prognosis of patients with metastatic renal carcinoma remains poor. We evaluated the efficacy and toxicity of miniautologous transplantation of LAK in cytokine pretreated patients (pts) with metastatic RCC. Methods: Between May 1998 and July 2005, 29 pts (23M/6F) with metastatic RCC were included. All patients were pretreated with cytokine-based therapy (9 pts with interferon alfa, 9 pts with interferon alfa+5FU+IL-2, 10 pts with interferon alfa+5-FU and 1 patient with IL-2). Median age was 58 years (range 49–71). Patients were assigned into three prognostic groups according to MSKCC prognostic criteria for 2nd line treatment (Motzer et al., 2004). Six, seventeen and six pts had 0, 1 and 2–3 risk factors, respectively. Median number of metastatic sites was 2 (range 1–6). 9 pts had liver, 12 bone and 2 patients had cerebral metastases. Median time from cytokine treatment to LAK therapy was 9 months (range 0–41). Periferal blood stem cells (PBSC) were isolated. Part ...
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled... more Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
The recent development of reduced intensity conditioning and allotransplantation (RICT) has opene... more The recent development of reduced intensity conditioning and allotransplantation (RICT) has opened a new way to assure engraftment of donor cells while reducing early transplant-related mortality. We evaluated the combination of high-dose therapy and autologous peripheral blood stem cells transplantation (APBSCT) followed by RICT to extend the benefit of allografting procedures in de novo multiple myeloma (MM) patients. Fifteen subjects with stage III MM (median age 51 years, range 40-57) received high dose melphalan (200 mg/m(2)) followed by APBSCT previously collected after cyclophosphamide (4 g/m(2)) and granulocyte colony-stimulating factor (G-CSF). After 3-4 months from APBSCT, the patients underwent RICT, consisting of fludarabine 30 mg/m(2) + cyclophosphamide 300 mg/m(2) on days -4, -3, and -2. Acute graft-versus-host disease (GVHD) occurred in 2 patients; 6 patients developed chronic GVHD; 4 patients developed CMV antigenemia and were treated pre-emptively with ganciclovir. No transplant related mortality was shown. Response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF); when IF was negative, patients were classified in complete remission (CR) and when it remained positive, near CR (nCR). After a median follow up of 44 months post APBSCT, 100 and 43% of patients are still alive and progression-free, respectively. Overall, the CR + nCR rate after dose-reduced allograft was enhanced from 26.7 to 73.3%. A correlation not statistically significant between GVHD and remission was found. In conclusion, an up-front tandem strategy with a very low reduced intensity-conditioning regimen for allografting following autografting is feasible and induces high CR/nCR rate in MM.
A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggress... more A single center, retrospective analysis evaluating the outcome of patients with poor-risk aggressive non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT) as a part of firstline therapy. Forty-seven patients younger than 65 years with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL) or alk-negative anaplastic large cell lymphoma (ALCL) underwent ASCT between July 1997 and November 2005. Patients with DLBCL and alk-negative ALCL had 2 or 3 age-adjusted International Prognostic Index risk factors. All patients were transplanted after MACOP-B induction therapy followed by 2 courses of DHAP and myeloablative chemotherapy BEM or CBV. The complete response rate to the high-dose therapy was 79% with an estimated 5-year progression-free survival of 66%. At a median follow-up of 35 months (range, 16 to 112 months) the estimated overall survival at five years was 59%. There were 4 treatment-related deaths. Twenty-nine of 47 patients remain in complete remission. Our results confirm the efficacy of high-dose therapy with ASCT during first-line treatment of patients with poor-prognosis aggressive lymphoma, with substantial number of patients cured by using this treatment approach.
Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as ... more Ribosomal RNA serves as the backbone in ribosomal assembly and also, at least to some degree, as an active component of the mature ribosome. The introduction of nucleotide changes (e. g., by site-directed mutations) clearly offers the most promising tool for elucidating the function of ribosomal RNA.
Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and im... more Intermediate high dose VIP (etoposide, ifosfamide, cisplatin) achieved comparable efficacy and improved tolerance in comparison with high-dose chemotherapy plus PBSC in poor risk germ cell tumors. The aim of this study was to confirm the effectivity and tolerance of this regimen in clinical practice. Twenty-five consecutive patients, 9 previously untreated with poor prognosis and 16 relapsed, were treated with 1.6 VIP or 1.9 VIP+PBSC. A relative dose intensity of 1.6 VIP was used in 14 patients and 11 patients received the intensity of 1.9 VIP. Clinical response was achieved in 56% of patients. Fifty-eight percent of patients have survived more than 1 year and 44% more than 2 years. No significant difference was noted between previously treated and untreated patients, as well as between the patients on 1.6 VIP and 1.9 VIP, with the exception of improved 1-year survival of patients on 1.9 VIP. One of four cisplatin-refractory patients achieved durable partial remission with a normal ...
We describe the implementation, optimization, sensitivity determination and first clinical result... more We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared highly informative in our patients population. In 21 sex-mismatched donor recipient pairs we used the Amelogenin locus to distinguish the X and Y chromosome. In sixty-three out of these 100 patients chimerism was regularly analyzed from blood samples taken at various time points after SCT with the median follow up of 17 months. Complete chimerism (CC), maintained over the whole follow-up period, was detected in 24 (38, 1%), stable and decreasing mixed chimerism (MC) in 28 (44, 4%) and increasing MC in 11 patients (17, 5%). Patients with CC, stable and decreasing MC showed a significantly better (p 0,005) overall survival rate (0, 81), compared to those with increasing MC (0, 24). These results demonstrate that STR-based chimerism monitoring with sensitivity above 1% and high informativity (98, 7% of donor recipient pairs) is necessary in establishing the origin of engrafted cells after an allogeneic SCT, in detecting graft rejection and that it may contribute in identifying patients with imminent leukemia relapse.
Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by... more Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by the bcr/abl gene rearrangement. Allogeneic transplantation of stem cells (SCT) is a routinely used treatment method of patients with this diagnosis and remains the only curative mode of treatment. From January 1990 to December 2002, 78 patients with CML underwent allogeneic transplantation and were examined at the Department of Genetics in the National Cancer Institute in Bratislava. Using conventional cytogenetic and FISH 6 patients (7.7%) showed additional chromosomal changes before SCT. These patients had statistically worse post transplantation prognosis compared to the patients without additional changes before SCT (mean survival in month+/-standard error (58.08 (+/-6.70) vs. 5.17 (+/-0.98), p-value=0.001), patient mortality (67% vs. 31%)). In addition five other variables were evaluated for transplant outcome, namely, patient's age at the time of transplantation, sibling or no...
Dear Editor, We have observed the spontaneous tumour regression in four patients (breast cancer, ... more Dear Editor, We have observed the spontaneous tumour regression in four patients (breast cancer, Hodgkin's disease, nonHodgkin's lymphoma and Ewing's sarcoma) who had relapsed/progressed after highdose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (ASCT).1 Patients' blood counts strongly resembled the blood counts in aplastic anaemia (aplastic anaemia (AA)like syndrome). Moreover, some of these patients' morphology of the bone marrow trephine biopsies was identical to the AA picture. It should be noted that in some patients who were treated by conventional chemotherapy only, a similar phenomenon has been observed, too (Lakota J, unpublished observation). In a provoking paper,2 the authors proposed that the autoimmune (antitumour) activity against present malignancy also operates against haematopoietic stem cells. The final clinical and laboratory pattern in these patients is present as acquired aplastic anaemia (AA). This pathophysiol...
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