PubMed Health⌕ Search

Biomedical subjects

M Beksaç

Publications and source records attributed to M Beksaç.

At least 37 records · Page 2Linked to original sources

Randomised unicenter trial for comparison of three regimens in de novo adult acute nonlymphoblastic leukaemia.

Various regimens have been explored in the treatment of acute nonlymphoblastic leukaemia (AML), but so far none has been shown to be superior. Here we report on a comparison of three widely used protocols defined by Berman (Group 1), MRC AML 10 (Group 2), and Arlin (Group 3). Group 1 includes cytosine arabinoside (Ara-C) (100 mg/m2/d, days 1-7) and idarubicin (Ida) (12 mg/m2/d, days 1-3) for induction, and Ara-C (200 mg/m2/d, days 1-6) and Ida (15 mg/m2/d, day 1) twice for consolidation. Group 2 includes Ara-C (200 mg/m2/d, days 1-10), daunorubicin (Dnc) (50 mg/m2/d, days 1, 3, 5) and etoposide (VP16) (100 mg/m2/d, days 1-5) for induction. The first consolidation therapy consisted of the same schedule except for Ara-C given on days 1-8. The second consolidation regimen consisted of Ara-C (200 mg/m2/d, days 1-8), VP16 (100 mg/m2/d, days 1-5) and amsacrine (100 mg/m2/d, days 1-5). Mitoxantrone (Mitox) (10 mg/m2/d, days 1-5) and Ara-C (200 mg/m2/d, days 1-3) were given as the third consolidation therapy. Group 3 was identical to Group 1 except for Ida being replaced with Mitox. During the study period 99 patients were enrolled and 34 were allocated randomly to Group 1, 36 to Group 2, and 29 to Group 3. Except for age distribution all patients' characteristics were similar between the groups. As there were more elderly patients in Group 1, time to complete remission (CR) was longer in this group as they needed more second induction. Induction deaths were 9.7%, 12.9% and 14.8% in Groups 1, 2 and 3, respectively. Patients in Group 2 received a higher amount of Ara-C compared with the other groups (P < 0.001). After a median follow-up period of 45 months (1-67 for survivors) an advantage in Group 1 was observed. Relapse-free survival (RFS) was better in Group 1 (P = 0.014) at 3 years. Fourteen of the patients were transplanted (11 allografts, 3 autografts). When patients with transplants were excluded, overall survival was longer in Group 1 both at 3 years and 5 years (P = 0.05). In conclusion, despite patient advanced age and lower dose of Ara-C, the idarubicin-containing treatment was superior to the other regimens.

Adolescent↗

Acquired ichthyosis associated with chronic graft-versus-host disease following allogeneic peripheral blood stem cell transplantation in a patient with chronic myelogenous leukemia.

Acquired ichthyosis (AI) has rarely been described following bone marrow transplantation (BMT). We report a 29-year-old male, who underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) for chronic myelogenous leukemia, and who developed AI associated with chronic graft-versus-host disease (cGVHD). Both of these disorders were treated successfully with cyclosporin A. We conclude that AI may be related to an autoimmune process on the basis of cGVHD, and dermathopathologic evaluation must be performed in patients with skin changes suggesting AI following allogeneic bone marrow transplantation.

Adult↗

Incidence of tuberculosis after bone marrow transplantation in a single center from Turkey.

Tuberculosis (TB) is generally seen in immunodeficient states and its incidence would be expected to increase after hematopoietic stem cell transplantation (SCT), particularly in the allogeneic setting. However, recent reports from developed countries did not support this hypothesis. Turkey is one of the countries where the disease is endemic. Over a period of 10 years two cases of TB among 120 allogeneic and 65 autologous bone marrow or peripheral blood SCT were encountered. The first patient was a 42-year-old male with acute nonlymphoblastic leukemia (ANLL) who underwent allogenic SCT from his HLA-identical sister in first remission. His early post transplant period was unremarkable and showed no clinical acute or chronic graft versus host disease (GVHD). His chest X-ray and CT scan revealed alveolar infiltrate of the left apical lobe one year after the procedure and sputum showed acid-fast bacilli, later identified as Mycobacterium tuberculosis. He was put on combination chemotherapy. He is now well and disease-free 30 months after transplant with no complaints of pulmonary TB. The second patient with chronic phase CML underwent allogeneic peripheral SCT from his HLA-identical sister. He suffered from grade II acute and extensive chronic GVHD partially treated with immunosuppressive therapy. He showed pulmonary TB 15 months after transplantation. He is still on combination chemotherapy. Although our numbers are small, the annual incidence of TB after SCT is 1.1% (2/185) which is nearly 30 to 40 times higher than the incidence of TB in the general Turkish population. In other words, an immunosuppressive state after allogenic SCT seems to increase the risk of TB in Turkey. In conclusion, TB should be considered in the differential diagnosis of unexplained infections after SCT, especially in countries, where the disease is endemic.

Adult↗

An artificial intelligent diagnostic system on differential recognition of hematopoietic cells from microscopic images.

Despite their advantages, none of the automated white blood cell differentiated counters have replaced the conventional microscopic evaluations of blood and bone marrow slides by hematologists. We have analyzed the smears of 39 patients and 8 control subjects to develop an artificial expert system that recognizes 16 different types of nucleated hematopoietic cells during the stages of differentiation. A charge coupled television camera and a special frame grabber were used for data acquisition, and 247 nucleated cell images were transferred from a microscope to an IBM 386 computer to be processed. One hundred sixty-five and 82 of these images were used for training and testing, respectively. Our system is composed of image processing and analysis (enhancement, thresholding/smoothing, edge detection), pattern recognition (feature extraction and classification with supervised artificial neural network), and expert system development. Image processing and analysis were used to obtain 13 cellular features to be used as the input parameters (neurons) of the artificial neural network. A supervised artificial neural network (back-propagation learning algorithm) was used in the classification of 16 different cells (output neurons of the neural network), which is the second step of pattern recognition. A confusion matrix has been developed to compare the similarities and dissimilarities between the differential recognitions of the hematologist and the expert system. The discriminatory power of the procedure is statistically significant: Q = (N - n.K)2/N.(K - 1) = 28.2. The sensitivity and the specificity of the expert system were 71.4% and 90.9%, respectively.

Bone Marrow↗

Incidence of graft vs host disease in allogeneic bone marrow transplantation in a single center study from Turkey.

Graft versus host disease (GVHD) is one of the obstacles encountered in allogeneic bone marrow transplantation (alloBMT) and has a direct impact on the transplant outcome and survival. In this report, we summarized the incidence of acute and chronic GVHD among 71 HLA matched and 9 HLA mismatched sibling alloBMTs performed for various hematological malignancies, mainly leukemias seen at Ibn-i Sina Hospital. Fifty-five were male and 25 were female Turkish patients. Median age was 29 (12-48). Cyclophosphamide(CY)+total body irradiation (TBI)(12), CY+total lymphatic irradiation (TLI)(6), busulfan (BU)+CY(58) and ALG/ATG+CY(4) were the regimens used for conditioning. Cyclosporin A (CsA)+short term methotrexate were given for GVHD prophylaxis except for two syngeneic transplants who both received only CsA. In 22 of the patients ABO and in 30 patients sex mismatched bone marrow was given. Thirty-one (38.8%) patients showed acute GVHD (grade I-II: 22, grade III-IV: 9) and 8 (11.6%) showed chronic GVHD. In HLA matched and mismatched patients acute GVHD incidence were 33.7% and 44.4% respectively. All of the HLA mismatched patients that showed acute GVHD were in advanced stage. Of the patients with acute GVHD, 28 (96.5%) disclosed skin, 22 (75.9%) hepatic and 14 (48.3%) gut involvement. In the chronic form three patients had mild limited, two limited, two moderate and one advanced GVHD. Seven of the patients were lost due to GVHD. To determine the graft versus leukemia effect of alloBMT, we compared the disease free survival (DFS) of the 68 leukemia patients. Although the patients who had grade I-II acute GVHD showed a better DFS than the patients who did not have acute GVHD, it did not reach to a significance (15.9 vs 13.6 months: p = 0.43).

Adolescent↗

HLA DR2: a predictive marker in response to cyclosporine therapy in aplastic anemia.

The effect of immunosuppressive agents on HLA DR2-aplastic anemia (AA) has recently been investigated by different groups. In the present report, we analyzed 40 Turkish AA patients, who received immunosuppressive therapy (IST) and 12 AA's who were transplanted from HLA matched siblings. HLA DR2 frequency was 0.442 and significantly higher in AA's when compared to an unrelated healthy control group (RR: 2.93, 95% confidence interval 1.48-5.77, P = 0.001. Patients received antithymocyte or antilymphocytic globulin (AT/LG) or AT/LG plus cyclosporine-A (CsA) or CsA alone. In DR2+ and DR2- patients overall response rates were 73.3 and 30%, respectively (P = 0.03). When patients were analyzed separately, CsA administration either alone or in combination with AT/LG gave favorable results in the DR2+ group (P = 0.02). In contrast AT/LG presence alone was shown to be inadequate.

Adolescent↗

Hepatitis B virus infection in allogeneic bone marrow transplantation.

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.

Adolescent↗

Use of high-dose chemotherapy plus granulocyte colony-stimulating factor for the salvage of refractory or resistant-relapse lymphoma patients without stem cell support.

The combination of cyclophosphamide (CY) and etoposide is synergistic, spares bone marrow stem cells and can be given repeatedly in high doses without stem cell support. Thirteen patients with non-Hodgkin's lymphoma (n = 8) or Hodgkin's disease (n = 5), received high-dose chemotherapy (HDC). Median age was 32 years (24-52). Male to female ratio was 10:3. All the patients were in advanced-stage. Karnofsky score prior to HDC was 60% (range 40-90). Six patients showed primary refractoriness and 7 had resistant relapse. HDC consisted of CY 1,500 mg/m2/day and etoposide 300 mg/m2/day, both for 4 days. rhG-CSF was started 24 h after the last dose of chemotherapy as a continuous intravenous infusion at a dose of 0.01 mg/kg/day and stopped when the leukocyte count reached 1 x 10(9)/1 on 3 consecutive days. Overall, 69% (9/13) of patients responded to HDC. Four achieved CR and 5 achieved PR. Two of the patients showed disease progression. The other 2 died during the early period of HDC. Neutrophil and platelet recovery after HDC were 8 (6-16) and 10 (4-14) days, respectively. The major nonhematological toxicities were nausea-vomiting (100%) and diarrhea (61%). The median follow-up was 204 (7-600) days. Two patients relapsed 48 and 185 days after HDC. Eight patients are still alive, 7 progression free. The progression-free survival is 220 (40-285) days. In conclusion, HDC + granulocyte colony-stimulating factor (G-CSF), without stem cell support seems to be promising in refractory or resistant relapse lymphoma patients bringing the need for randomized studies to show the cost effectiveness of HDC + G-CSF compared to HDC + autologous stem cell support.

Antineoplastic Combined Chemotherapy Protocols↗

Hemorrhagic cystitis as a complication of bone marrow transplantation.

Hemorrhagic cystitis (HC) is one of the most troublesome complications of bone marrow transplantation (BMT) and sometimes may be life-threatening. The etiology and prevalence of HC depends on the type of the transplant and the period after BMT. Here we report about 134 patients transplanted in a single center (89 allogeneic and 45 autologous) between May 1988 and August 1995. Forty-six patients (34.3%) had HC after BMT. Thirty-four (38%) alloBMT patients and 12 (27%) autoBMT patients had HC (p = 0.18). The onset of HC was 7 to 125 days after transplantation. The degree of HC was mild to moderate in 25 (28%) and severe in 9 (10%) allogeneic transplants. In autologous transplants, all of the episodes of HC were mild to moderate. Age, sex, diagnosis and the dosage of mesna used for prophylaxis were not correlated with the incidence of HC. In 36 of 46 (78.2%) patients HC occurred early and as a transient form. Ten (21.7%) were late and long-lasting. In 2 patients who had late starting and long-lasting HC after allogeneic BMT, electron microscopic examinations revealed virus-like structures in bladder epithelial cells.

Adolescent↗

Allogeneic peripheral blood stem cell transplantation: is there an increased risk of graft vs host disease in leukemia patients?

Fifteen patients with hematological malignancies [9 acute nonlymphoblastic leukemia (ANLL), four chronic myelogenous leukemia (CML), two acute lymphoblastic leukemia (ALL)] received allogeneic peripheral blood stem cell transplantation (alloPBSCT) from HLA-identical sibling donors. Donors received 2.5-15 micrograms/kg/day of recombinant human granulocyte colony stimulating factor (rhG-CSF) for 5-10 days. Administration of rhG-CSF was well tolerated except for mild to moderate bone pain occurring in all the donors which was relieved by oral paracetamol. A total of 40 leukaphereses were performed for the 15 donors using the bilateral antecubital veins. None of the donors needed central venous line insertion. The median number of apheresis procedures for each patient was 3 (2-3). A median of 7.7 (4-38.2) x 10(8)/kg mononuclear cells, 35 (2.4-90.0) x 10(6)/kg CD34+ cells, 1.85 (0.45-4.8) x 10(8)/kg CD3 and 0.3 (0.16-1.01) x 10(8)/kg natural killer cells were given without any manipulation. Cyclosporin A (CsA) plus short-course methotrexate (MTX) (12 patients) and CsA alone (3 patients) were used for graft versus host disease (GVHD) prophylaxis. Median granulocyte and platelet engraftments were done on days 11 (10-31) and 16 (11-54) respectively. Grades II-IV GVHD occurred in 62% of the patients and grades III-IV in 15%. Twelve patients are still alive with full engraftment and disease-free. In conclusion, alloPBSCT is an alternative to allogeneic bone marrow transplantation, because of the ease of collection and rapid hematological recovery. However, there is a trend for increased acute GVHD in our leukemia patients compared to allogeneic bone marrow.

Adult↗

A case report of a patient who has pure red cell aplasia and rheumatoid arthritis.

Pure red cell aplasia (PRCA) as an extra-articular manifestation of rheumatoid arthritis (RA) is rare. In the present report a 40-year-old female patient, with a 4-year-history of severe anemia and pain in the small joints of the hands, was diagnosed as having PRCA by bone marrow (BM) examination. Antithymocyte globulin (ATG), methylprednisolone and cyclosporin A (CSA) were used for the treatment of PRCA. The patient's hematological values responded within 6 months but pre-existing arthralgia continued, although with some relief. The patient subsequently fulfilled the criteria for diagnosis of RA at the 16th month. A review of nine published case reports on the coexistence of PRCA with RA revealed the initial diagnosis as RA. In our case, as the initial symptoms and findings were not sufficient for the diagnosis of RA, we therefore conclude that PRCA preceded RA. Although CSA was curative in the treatment of PRCA it could not prevent the full diagnostic features of RA.

Adult↗

Peripheral T cell receptors alpha beta and gamma delta in patients with Hodgkin's lymphoma.

Antigen recognition by T cells is determined by an antigen specific T cell receptor (TCR). Two heterodimeric TCR structures associated with CD3 have been defined: TCR alpha beta and TCR gamma delta. TCR alpha beta and its function are well described but the role of TCR gamma delta in normal and lymphoproliferative disorders is not well established. In newly diagnosed or relapsed/refractory Hodgkin's disease (HD), a disease associated with defective T cell functions and increased sIL-2R, we determined levels of seven TCR alpha beta variable regions [beta V5(a), beta V5(b), beta V6(a), beta V12(a), alpha beta V(a), alpha V2(a)] and TCR gamma delta by using monoclonal antibodies (MCA). TCR gamma delta levels did not show any difference, but several variable regions of the TCR alpha beta differed when groups are compared with each other and the control group.

Adolescent↗

The clinical correlations of serum tumor necrosis factor-alpha in acute leukemias: a predictor of response and relapse?

The clinical correlations of serum tumor necrosis factor alpha (TNF-alpha), a cytokine which can be released from leukemic blasts, has not been extensively studied. We have analyzed serum TNF-alpha in 20 ANLL, one CML-myeloblastic crisis, and 14 ALL adult patients by using a commercial ELISA kit. Sterile serum samples were taken on day 0, day 7, during remission and relapse with a mean follow-up period of 4.2 (1-19) months. After a median of 7 days following chemotherapy, serum TNF-alpha decreased both in responding ANLL (p = 0.004) and ALL (p > 0.05) but remained high in refractory leukemias. Values on day 7 were significantly different between responding and refractory patients in both ANLL (p = 0.0027) and ALL (p = 0.0099). At relapse, serum TNF-alpha increased starting at a median of 3 months preceding clinical symptoms in ANLL (p = 0.002). However, the relapse of ALL coincided with a slight increase which was not significant (p > 0.05). Together these findings indicate that serum TNF-alpha can be used as an early predictor of clinical response and relapse in ANLL.

Acute Disease↗