Biomedical subjects

M Beksac

Publications and source records attributed to M Beksac.

At least 19 recordsLinked to original sources

PubMed2006

International uniform response criteria for multiple myeloma.

New uniform response criteria are required to adequately assess clinical outcomes in myeloma. The European Group for Blood and Bone Marrow Transplant/International Bone Marrow Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system. Categories for stringent complete response and very good partial response are added. The serum free light-chain assay is included to allow evaluation of patients with oligo-secretory disease. Inconsistencies in prior criteria are clarified making confirmation of response and disease progression easier to perform. Emphasis is placed upon time to event and duration of response as critical end points. The requirements necessary to use overall survival duration as the ultimate end point are discussed. It is anticipated that the International Response Criteria for multiple myeloma will be widely used in future clinical trials of myeloma.

Humans↗

PubMed2006

Evaluation of the effect of transplant-related factors and tissue injury on donor-derived hepatocyte and gastrointestinal epithelial cell repopulation following hematopoietic cell transplantation.

The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.

Adolescent↗

PubMed2005

Low-dose cytosine arabinoside (LD-AraC) vs LD-AraC plus granulocyte/macrophage colony stimulating factor vs LD-AraC plus Interleukin-3 for myelodysplastic syndrome patients with a high risk of developing acute leukemia: final results of a randomized phase III study (06903) of the EORTC Leukemia Cooperative Group.

In this randomized phase III study of the EORTC Leukemia Cooperative Group, patients with myelodysplastic syndromes (MDS) with 10-30% bone marrow blasts and hematopoietic failure were treated with low-dose cytosine arabinoside (LD-AraC) (2 x 10 mg/m2/day subcutaneously (s.c.) days 1-14) either alone or in combination with rhGM-CSF or interleukin-3 (IL-3) both given s.c. at a dose of 150 microg/day from day 8 to 21. A total of 180 evaluable patients with a median age of 65 years and refractory anemia with an excess of blasts (RAEB, n = 107) or RAEB in transformation (RAEBt, n = 73) were randomized. There were no differences among the three treatment regimens with respect to numbers of courses applied or treatment delays. Hemorrhage occurred in approximately 40% in all arms, whereas infection rates were higher in the granulocyte/macrophage colony stimulating factor (GM-CSF)- or IL3-containing arm. The overall response rate was 38.6% with no statistically significant difference among the three arms. In summary, a substantial proportion of patients had achieved relatively durable responses in all the three arms. No influence of either growth factor was detected on the grade of cytopenia. Thus, the combination of LD-AraC with GM-CSF or IL-3 cannot be recommended for routine use in a high-risk MDS population.

Acute Disease↗

PubMed2003

Role of pretransplant interferon-alpha(IFN) treatment in the outcome of stem cell transplantation (SCT) from related donors in chronic myelogenous leukemia (CML): results from three Turkish transplant centers.

Since transplantation cannot be performed immediately after the diagnosis of chronic myelogenous leukemia (CML), interferon treatment is usually required. This study aims to analyze the effects of interferon-alpha (IFN) treatment on allogeneic stem cell transplantation (SCT) outcome. A total of 106 patients aged 16-47 years and transplanted from HLA-identical sibling donors for CML in chronic phase (CP) were evaluated. In all, 48 had received IFN-alpha for a median duration of 5 months (1-18 months) until a median of 1 month prior to transplantation. Of the patients, 50 have received bone marrow transplant (BMT) whereas 56 have received peripheral blood stem cells (PBSCT) between 1991 and 1999 in three major transplant centers in Turkey. Patient characteristics in both groups were similar. More hematological responders were present in the IFN(+) patients (P=0.0001). No difference was found in engraftment kinetics. The incidences of acute or chronic graft-versus-host disease (GVHD), relapse and graft failure were similar in all patients regardless of stem cell source. Overall survival (OS) and disease-free survival (DFS) at 2 years were similar for both IFN(+) or (-) patients following SCT. With multivariate analysis, pretransplant IFN-alpha use, stem cell source, transplant year and CD34+ cell content were not found to be risk factors for OS. In conclusion, prior IFN exposure did not impair BMT or PBSCT outcome.

Adolescent↗

PubMed2002

In vivo use of all-trans retinoic acid prior to induction chemotherapy improves complete remission rate and increases rhodamine 123 uptake in patients with de novo acute myeloid leukemia.

All-trans retinoic acid (ATRA) is used in the treatment of acute promyelocytic leukemia. Because ATRA has effects (increase in apoptosis, suppression of bcl-2), it has also been used for the treatment of other French-American-British (FAB) subtypes of acute myelogenous leukemia (AML). To find out the in vivo and in vitro effects of ATRA in AML, we analyzed 37 patients with de novo AML. Twenty-seven patients received ATRA before remission-induction (RI) treatment (ATRA group). Results were compared to a control group (10 patients) that received induction without ATRA during the same time period. Bone marrow or peripheral blood samples were collected from all patients on d 0 and 4. The immunphenotype, myeloperoxidase (MPO), reac tion and the efflux uptake of rhodamine 123 (Rh123) were analyzed on myeloblasts in these samples. In the myeloblasts from patients treated with ATRA, the uptake of Rh123 was increased significantly (p = 0.026) from d 0 to d 4, and all other parameters remained unaltered. ATRA administration increased the complete remission (CR) rate (88%, 22/25 vs 55%, 5/9) significantly (p = 0.042). Logistic regression analysis revealed that ATRA administration was the important factor in CR, among other potential factors including age, white blood count, bcl-2 expression, and the uptake and efflux of Rh123 (p = 0.05). Estimated disease-free survival and overall survival were similar between these two groups (43% vs 37.5% and 51.2% vs 37.5%, respectively). In conclusion, ATRA treatment prior to RI treatment may improve the CR rate in patients with de novo AML, which seems to be related to its beneficial effect on multidrug resistance.

Acute Disease↗

PubMed2001

Frequent demonstration of human herpesvirus 8 (HHV-8) in bone marrow biopsy samples from Turkish patients with multiple myeloma (MM).

In order to investigate the frequency of HHV-8 in MM patients from another geographic location, we obtained fresh bone marrow (BM) biopsies from Turkish patients with MM (n = 21), monoclonal gammopathy of undetermined significance (MGUS) (n = 2), plasmacytoma (n = 1) with BM plasma cell infiltration, various hematological disorders (n = 6), and five healthy Turkish controls. The frequency of HHV-8 was analyzed by polymerase chain reaction (PCR) in two independent laboratories in the USA and in Turkey. Using fresh BM biopsies, 17/21 MM patients were positive for HHV-8 whereas all five healthy controls, and six patients with other hematological disorders were negative. Two patients with MGUS, and one patient with a solitary plasmacytoma were also negative. The data from the two laboratories were completely concordant. Also using primer pairs for v IRF and v IL-8R confirmed the results observed with the KS330233 primers. Furthermore, sequence analysis demonstrated a C3 strain pattern in the ORF26 region which was also found in MM patients from the US. Thus, HHV-8 is present in the majority of Turkish MM patients, and the absence of the virus in healthy controls further supports its role in the pathogenesis of MM.

Biopsy↗

PubMed2001

Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914).

Patients with multiple myeloma (MM) refractory to alkylating agents frequently express P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype. We have conducted a randomized phase II/III study of the MDR reversal agent cyclosporin A combined with VAD (vincristine, doxorubicin, dexamethasone) compared with standard VAD in patients with MM stage IIA/IIIA who were refractory to or progressive after treatment with alkylating agents. Out of 81 patients who were randomized, 75 were eligible and evaluable: 34 in the VAD + cyclosporin A arm versus 41 in the VAD arm. Toxicities of grade 2-3 were observed more often with VAD + cyclosporin A than with VAD only: nausea (30% versus 8%, P = 0.015), mucositis (18% versus 5%, P = 0.13), infection (45% versus 35%, P = 0.50). The treatment results were similar in the two arms: 53% versus 49% responded [95% CI (-18.5%, 26.9%)]. The median progression-free survival (PFS) was 8.6 months (VAD + cyclosporin A) versus 5.8 months (VAD): [log rank P = 0.16, hazard ratio = 0.71, 95% CI (0.44, 1.15)], and median overall survival was 13 months versus 14.6 months [log rank P = 0.89, hazard ratio = 0.96, 95% CI (0.62, 1.72)]. The cause of death was progressive disease (85%), toxicity (10%) or other (5%). Bone marrow analysis performed in 23 patients showed that the response rate was 67% in Pgp-positive versus 55% in Pgp-negative patients. Cyclosporin A combined with VAD is relatively well tolerated. There is no effect of cyclosporin A on the overall response rate, PFS and overall survival with VAD.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Human herpesvirus 8 open reading frame 26 and open reading frame 65 sequences from multiple myeloma patients: a shared pattern not found in Kaposi's sarcoma or primary effusion lymphoma.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, has been implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease, and recently multiple myeloma (MM). DNA sequence analyses of HHV-8 suggest that multiple HHV-8 strains exist. We extracted DNA from 24 patients with MM and 3 patients with monoclonal gammopathy of undetermined significance and compared HHV-8 open reading frames (ORFs) 26 and 65 sequences with those derived from patients with KS, PEL, and two HHV-8-positive PEL cell lines KS-1 and BC-1. ORF26 sequence data suggest that MM patients are consistently carriers of HHV-8 strain subtype C3. All MM patients also consistently revealed either a single bp deletion or substitution at position 112197 in ORF65. This unique alteration is not present in patients with KS or PEL or in PEL cell lines. It occurs in the portion of ORF65 that is known to be responsible for a serological response to HHV-8.

Amino Acid Sequence↗

PubMed1999

Differences in liver pathology and clinical outcome between two patients with hepatitis B virus and graft versus host disease.

Our two patients undergoing allogeneic bone marrow transplantation (AlloBMT) had both Hepatitis B virus (HBV) and graft-versus-host disease (GVHD). In the first patient, liver enzymes elevated three months after AlloBMT, and GVHD was diagnosed. Two weeks after the diagnosis of GVHD, HBsAg appeared in his serum. At that time, liver biopsy was not able to discriminate two disorders, but his sequential liver biopsies disclosed GVHD. Despite the patient was treated with cyclosporin A (CsA), he died for chronic GVHD. In contrast to the first patient, the second patient had HBsAg prior to GVHD. His liver enzymes deterioration was detected in the first month after AlloBMT, and reached the highest level in the third month while withdrawing CsA. In the fifth month he developed scleradermatous skin changes, and skin biopsy revealed chronic GVHD, whereas concurrent liver biopsy revealed chronic active hepatitis. This observation showed that immunosuppressive conditions such as GVHD or its prophylaxis may affect the appearance of liver pathology caused by HBV, which depends on the time of GVHD development, and the duration and depth of GVHD prophylaxis.

Adult↗

PubMed1998

Cord blood transplantation (CBT) in hemoglobinopathies. Eurocord.

Patients with beta-thalassemia (Hbeta th) and sickle cell anemia (SCA) can be treated with bone marrow transplantation. Stem cells from cord blood have several theoretical advantages, however, the place of cord blood transplant for hemoglobinopathies has not yet been established. We report here the EUROCORD experience of 10 patients (Hbeta th = 7, SCA = 3) transplanted with related cord blood.

Anemia, Sickle Cell↗

PubMed1998

Serum erythropoietin levels in patients with leukemia on cytostatic treatment.

Anemia is the major stimulus for erythropoietin (Epo) secretion. Various studies have reported increase of Epo following chemotherapy. The mechanism of this phenomenon is not yet clarified. In this study, the serum Epo levels have been evaluated before, during (7 and 14 days), and after (day 25) chemotherapy in patients with acute myeloblastic leukemia (n = 13) and lymphoblastic leukemia (n = 4). As a control group, 12 healthy age-matched subjects were evaluated. Epo levels were high in untreated leukemia patients compared to controls and continued to increase following chemotherapy. There was no significant difference in post-treatment values of Epo as compared with pre-treatment levels. In patients with pre-treatment values of Hb < or = 9 g/dl, Epo levels were inversely correlated with Hb (r = 0.552; p < 0.05). This correlation disappeared during and following treatment. There was no correlation between Epo levels and hematological or biochemical parameters. Therefore, elevated levels of Epo regardless of anemia may be due to a response to tissue hypoxia or increased synthesis of Epo in liver or bone marrow.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Determination of in vitro drug sensitivity to a panel of cystostatic drugs and interferon alpha-2b in patients with renal cell carcinoma.

Fresh operative cells from 27 renal cell carcinomas (RCC) were cultured in vitro for the determination of in vitro drug sensitivity. Two samples were not culturable. Incubation was carried out in triplicate in the presence and absence of various concentrations of chemotherapeutic agents. Sensitivity of the tumour cells to interferon-alpha (IFN-alpha), cisplatin (CDDP), mitomycin C (MMC), vinblastine (VBL), doxorubicin (DOX), etoposide (ETOP), bleomycin (BLM), vincristine (VCR) were tested by a colorimetric assay using MTT. A preexposure viability over 75% was essential for in vitro drug sensitivity assay (IVDSA). Sensitivity was determined by a more than 50 +/- 2 SD% reduction from the control absorbance. All eight drugs in their low concentrations exhibited cell proliferation inhibition in 0-12% of RCCs. On the other hand, IFN-alpha in its higher concentration (60 IU/ml) was effective in 88% of RCCs. After IFN, CDDP was found to be the second most effective drug in its higher concentration (36% efficacy). The results indicate that IFN appears to be the most effective in vitro agent in our 25 RCCs and the clinical trials either as a monotherapy or multiple combinations of various agents should include IFNs for the treatment of RCC.

Adult↗

PubMed1997

In vitro drug sensitivity testing of human testicular germ cell tumours with cytostatic drugs and interferon alpha-2b.

In spite of the significant advances in the chemotherapy of germ cell neoplasms, some patients do not achieve disease-free status and ultimately die from their diseases. Therefore, it is reasonable to select the best chemotherapeutic agents in these patients by in vitro drug sensitivity assay (IVDSA) in order to apply the most effective agent in case of resistance to primary chemotherapy. Fresh operative cells from 12 testicular germ cell tumours (TGCT) were cultured in vitro. Sensitivity of the tumour cells to interferon-alpha (IFN-alpha), cisplatin, mitomycin C, vinblastine, doxorubicin, etoposide, bleomycin, vincristine (VCR) were tested by a colorimetric assay using MTT. A preexposure viability over 75% was essential for IVDSA. Sensitivity was determined by a more than 50 +/- 2 SD% reduction from the control absorbance. All eight drugs in their high concentrations exhibited cell proliferation inhibition in 83.3 +/- 100% of TGCT. But in low concentrations efficacy of IFN and VCR were found to be lower than the others (33.3% and 58.3%, respectively). The results indicated that although TGCT are highly sensitive to various agents IVDSA may help to identify the effective agents which might be necessary for second line chemotherapy in a small percentage of patients.

Adult↗

PubMed1997

Administration of MINE protocol in untreated patients with intermediate and high grade non-Hodgkin's lymphoma.

In recent years, more effective and less toxic treatment protocols have been developed to increase the cure rates in intermediate and high grade non-Hodgkin's lymphoma (NHL). This study was undertaken to investigate the efficacy and toxicity of MINE (ifosfamide, mesna, mitoxantrone and etoposide) combination chemotherapy in patients with intermediate and high grade NHL. Twenty-one patients (16 male, 5 female; age between 26 and 70 years) with NHL were included in the study. An overall response rate of 73% and complete response rate of 56% were achieved and survival rate for responding patients was 80% at the 48th month. Side effects including mild myelosuppression, nausea/vomiting and alopecia were observed. MINE combination seems to be effective and well tolerated without significant toxicity as a first-line therapy in patients with intermediate or high grade NHL.

Adult↗

PubMed1996