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Emin Kansu

Publications and source records attributed to Emin Kansu.

At least 19 recordsLinked to original sources
PubMed2006

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma.

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.

Adolescent↗
PubMed2006

Improvement of chronic pulmonary graft-vs-host disease manifesting as bronchiolitis obliterans organizing pneumonia following extracorporeal photopheresis.

Despite use of combined immunosuppressive agents, prognosis of patients developing pulmonary manifestations of chronic graft-vs-host disease (cGVHD) following allogeneic stem cell transplantation (SCT) still remains poor. We present a male patient who developed pulmonary cGVHD in the form of bronchiolitis obliterans organizing pneumonia (BOOP) following allogeneic SCT for acute myelogenous leukemia. The patient developed progressive course despite use of a combination of immunosuppressive agents including high-dose prednisone, cyclosporin-A, and mycophenolate mofetil in addition to steroid-related complications. A remarkable clinical response to extracorporeal photopheresis (ECP) was observed, allowing minimization of immunosuppressive therapy and discontinuation of cyclosporin-A. Pulmonary functions and carbon monoxide diffusion capacity (DLCO) gradually improved and stabilized, but did not return to pretransplant baseline levels.

Adult↗
PubMed2005

Possible association between Budd-Chiari Syndrome and gemtuzumab ozogamicin treatment in a patient with refractory acute myelogenous leukemia.

Gemtuzumab ozogamicin (GO; CMA-676; Mylotarg) is a chemotherapeutic agent approved for the treatment of CD33-positive acute myelogenous leukemia in patients of age 60 years or older after first relapse. Hepatic veno-occlusive disease has been reported to develop as a late complication of gemtuzumab ozogamicin treatment. A patient who developed Budd-Chiari Syndrome with hepatic vein thrombosis following treatment with GO is presented. This complication has not been previously reported, and it deserves to be considered as a possible adverse effect of gemtuzumab ozogamicin.

Aged↗
PubMed2005

Ifosfamide, idarubicin, and etoposide in relapsed/refractory Hodgkin disease or non-Hodgkin lymphoma: a salvage regimen with high response rates before autologous stem cell transplantation.

To achieve long-term disease-free survival, high-dose therapy and autologous stem cell transplantation (ASCT) is the current standard approach in patients with relapsed or refractory Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL). Because chemosensitivity is a significant factor in determining transplantation eligibility, it is critical to select a salvage chemotherapy regimen that has the potential to induce a high response rate with low nonhematologic toxicity. In this phase II study, 49 patients with relapsed or refractory HD (n = 22) and NHL (n = 27) with a median age of 42 years were treated with an IIVP salvage regimen consisting of ifosfamide, idarubicin, and etoposide. Twenty-seven percent of the patients had primary refractory disease, whereas 22% and 51% had early and late relapses, respectively. As analyzed by intention to treat, 16 patients (33%) achieved complete remission and 21 patients (43%) achieved a partial response, leading to an overall response rate of 76% (63% in NHL and 91% in HD). In the univariate analysis, diagnosis (HD versus NHL), remission duration before the initiation of IIVP, disease bulk, increased lactate dehydrogenase, and the presence of "B" symptoms were significant factors affecting the response achieved by the IIVP regimen. Of 37 responders, 31 (84%) underwent high-dose therapy and transplantation. The probability of 4-year overall survival (OS) and event-free survival (EFS) in this group of patients who underwent ASCT was 67.7% and 49.1%, respectively. When compared with the patients who achieved a partial response, patients who achieved complete remission with the IIVP regimen had a significantly higher probability of 4-year EFS (67.3% versus 30%; P = .016) and 4-year OS (92.3% versus 39.2%; P = .003). In patients with HD, 4-year EFS and 4-year OS were 54.9% and 70.6%, respectively, without a significant difference with respect to the survival rates obtained in patients with NHL (43.6% and 63.6%, respectively). Common side effects observed during 102 cycles of therapy were grade 3 to 4 neutropenia (62%) and thrombocytopenia (58%). The IIVP regimen is a highly effective salvage regimen for patients with relapsed or refractory HD or NHL who are candidates for ASCT. Furthermore, the degree of response to IIVP predicts the posttransplantation outcome. However, close follow-up is necessary because of a high incidence of grade 3 to 4 hematologic toxicity.

Adult↗
PubMed2005

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.

Adult↗
PubMed2005

Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto's thyroiditis.

Hashimoto's thyroiditis is the most frequent autoimmune thyroid disease. L-thyroxine therapy can reduce the incidence and alleviate the symptoms of this disease. The aim of this study was to evaluate the effects of prophylactic L-thyroxine treatment on clinical and laboratory findings of patients who were euthyroid at the time of diagnosis. Thirty-three patients who had diagnosis of euthyroid Hashimoto's thyroiditis were randomized to two groups, one group received prophylactic L-thyroxine treatment and the other was followed-up without treatment. Initial thyroid function tests, autoantibodies, ultrasonography, fine needle aspiration biopsy and peripheral blood lymphocyte subsets were similar in the two study groups. After 15 months of L-thyroxine treatment, there was a significant increase in free T4 and a significant decrease in TSH and anti-thyroglobulin antibody anti-thyroid peroxidase antibody levels. CD8+ cell counts increased in both groups, CD4/CD8 levels decreased significantly because of the increase in CD8+ cell count levels. Though there was no change in cytological findings, ultrasonography showed a decrease in thyroid volume in L-thyroxine receiving patients whereas an increase was detected in patients who were followed without treatment. In conclusion, prophylactic thyroid hormone therapy can be used in patients with Hashimoto's thyroiditis even if they are euthyroid.

Adult↗
PubMed2005

Successful salvage with high-dose sequential chemotherapy coupled with in vivo purging and autologous stem cell transplantation in 2 patients with primary refractory mantle cell lymphoma presenting in the leukemic phase.

We report the results of an aggressive salvage regimen in 2 patients with advanced-stage leukemic-phase mantle cell lymphoma who were refractory to previous conventional therapies. We combined multiple phases of a cytoreductive regimen including rituximab and sequential high-dose treatment with autologous stem cell transplantation (ASCT). The regimen consisted of a debulking phase with fludarabine, idarubicin, high-dose cytarabine, and high-dose methotrexate; a mobilization and in vivo purging phase with rituximab, cyclophosphamide, and granulocyte colony-stimulating factor; high-dose sequential chemotherapy with etoposide, mitoxantrone, and melphalan followed by ASCT; and, finally, posttransplantation consolidation with rituximab for treatment of minimal residual disease. With this regimen, these 2 refractory patients with multiple poor prognostic factors are in complete remission at 41 and 42 months following transplantation. Although the fact that these 2 patients are still in remission beyond 3 years after ASCT is encouraging, we need a longer follow-up to comment on their long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

A randomized trial of continuous infusion versus bolus mitoxantrone in combination with cytarabine in newly diagnosed patients with acute myeloblastic leukemia.

Mitoxantrone (MTZ) has been shown to be effective in the treatment of newly diagnosed acute myeloblastic leukemia (AML). The objective of this randomized study was to evaluate the impact of mode of administration of MTZ on the response and recurrence rates in newly diagnosed patients with AML and to compare the toxicity patterns associated with bolus and continuous infusion (CI) of MTZ. From March 1987 to March 1994, 40 newly diagnosed patients with AML were randomized to receive either bolus or CI-MTZ, administered for 3 days at 10 mg/m2/day in combination with CI-cytarabine for 7 days at 100 mg/m2/day. Patients achieving complete remission (CR) received two consolidation cycles followed by monthly maintenance cycles, aiming a total of 12 cycles of chemotherapy. Fifteen patients (75%) in the bolus arm and 16 patients (80%) in the CI arm achieved CR. There were no significant differences in rates of early death and time to myeloid recovery between the two groups. After 11 years from the initiation of the study, median disease-free survival (DFS) in bolus and CI groups were 19 and 29 months after a median follow-up of 10 and 14 months, respectively. DFS rates at 10 years were 16.7% in the bolus group and 28.6% in the CI group (p = 0.36). Overall survival (OS) rates during the same period were 10.7 and 21.3% in the bolus and CI groups, respectively (p = 0.26). No relapse was observed in either group after 4 years. In patients younger than 40 years of age, DFS and OS were found to be significantly longer in the CI arm (p = 0.02 and p = 0.03, respectively). Mild asymptomatic cardiotoxicity associated with a decrease of 10 to 20% in the ejection fraction occurred in a patient in CI-MTZ arm and in two patients in the bolus arm. None of these patients showed any evidence of cardiac failure during their subsequent follow-up. Grade III-IV alopecia (p = 0.05) and grade I-II hepatotoxicity (p = 0.01) were more frequent in the CI arm. A tendency for higher frequency of grade III-IV nausea was observed in the bolus arm (9 vs. 3%, p = 0.10). As a conclusion, bolus and CI administration of MTZ were equally effective and tolerated well. Development of new anti-leukemia agents with novel treatment approaches is still needed to improve the high relapse rates in patients with AML who do not have an HLA-matched donor.

Adolescent↗
PubMed2004

Effect of interferon beta-1a on serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in relapsing remitting multiple sclerosis patients. One year follow-up results.

There is emerging evidence that matrix metalloproteinases (MMPs) might be involved in blood brain barrier (BBB) breakdown in multiple sclerosis. A group of natural tissue inhibitors of metalloproteinases (TIMPS) regulates proteolytic activity to prevent tissue damage. TIMP-1 and MMP-9 are known to be secreted as heterodimers and TIMP-1 preferentially functions to inhibit MMP-9 activity. In this present study, the effects of IFNbeta-1a on serum MMP-9 and TIMP-1 were evaluated longitudinally during a one-year period. The MMP-9 levels showed no significant changes while TIMP-1 levels gradually and significantly increased during 3rd and 6th months of therapy compared with pretreatment levels.

Adult↗
PubMed2004

The pathophysiology of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) still remains the most significant complication after allogeneic hematopoietic stem cell transplantation. The disease usually appears after day 100 and is characterized by signs and symptoms similar to autoimmune diseases. The pathophysiology of chronic GVHD is poorly understood because of the lack of highly satisfactory animal models and basic studies in patients. It has not been clearly determined whether the disease is a distinct entity or a continuation of acute GVHD. In experimental and clinical studies of chronic GVHD, thymic atrophy, lymphocyte depletion, and autoantibody formation have been described. Conditioning regimens and acute GVHD may disrupt thymic function and dysregulate the negative selection process of potentially autoreactive T-lymphocytes. Disruption of thymic apoptosis and failure to eliminate the majority of self-reactive lymphocytes may lead to impairment of lymphocyte homeostasis and self tolerance. Expansion and effector functions of autoreactive T-cells will then promote autoreactive B-cell activation and production of autoantibodies with target-organ damage. Chronic GVHD requires continuous CD4+ T-cell help for B-cells and is known as T-helper 2 (Th2) disease. Murine models have demonstrated the roles of interleukin (IL)-12 and IL-18 in chronic GVHD. IL-12 may cause an increase in donor CD8+ cytotoxic T-cells leading to conversion of chronic GVHD to an acute form. In contrast, IL-18 prevents chronic GVHD by decreasing numbers of CD4+ (Th2) cells and host-reactive B-cell activation and reducing alloantigen-specific immune response. Mouse and human cellular genomics coupled with advances in cell biology in donor-recipient tolerance will improve our understanding of transplantation immunology and may offer new approaches to the challenge of ameliorating chronic GVHD.

Animals↗