Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD). METHODS: Fifteen patients who received allogeneic hematopoietic stem transplantation for leukemia and developed acute GVHD were enrolled. We determined serum concentrations of BAFF and APRIL at the onset of the first clinical manifestation of GVHD by enzyme-linked immunosorbent assay. RESULTS: Nine patients had grade 2 acute GVHD, and 6 had grade 3-4 acute GVHD. The BAFF serum concentration was higher in patients with grade 3-4 acute GVHD (1,093.42 in grade 2 vs. 2,171.99 pg/mL in grade 3-4), although the difference was not significant (P=0.077). However, the ratio of BAFF serum concentration to absolute lymphocyte count (ALC) (BAFF/ALC) was significantly higher in patients with grade 3-4 acute GVHD (P=0.045). The APRIL serum concentration and APRIL/ALC ratio showed similar results (P=0.077 and P=0.013, respectively). CONCLUSION: Patients with grade 3-4 acute GVHD had higher BAFF/ALC and APRIL/ALC ratios than patients with grade 2 acute GVHD. These findings suggest that B cells might play an important role in the development of acute GVHD, and that the BAFF and APRIL concentrations in serum might be significant predictive factors for estimating the severity of acute GVHD. Their clinical significance should be further evaluated in a larger patient populationope

Nine-Year Survival of Lymphoblastic Lymphoma Patients

This study aimed to analyze the overall survival period of adult lymphoblastic lymphoma patients treated with various therapeutic regimens, and to assess the determinants affecting survival outcome. Twenty-five adult patients with lymphoblastic lymphoma who had been treated at Severance Hospital, Yonsei University College of Medicine, Seoul, Korea from June 1996 to June 2005 were analyzed retrospectively. As an initial remission induction chemotherapy, the hyper-CVAD regimen was performed in eight patients, the Stanford/Northern California Oncology Group (NCOG) regimen in five, the CAVOP regimen in four, the m-BACOP regimen in three, and the CHOP regimen in one patient. Patients were divided into two groups according to their therapeutic modalities. Twenty patients received conventional chemotherapy alone and five received subsequent PBSCT after conventional chemotherapy. Four patients of the PBSCT group underwent autologous PBSCT and one underwent allogeneic PBSCT. The overall response rate was 80% (60% showing a complete response, 20% showing a partial response) and the relapse rate was 73.3%. The overall survival (OS) rate was 55.1% at 1 year, 31.5% at 5 years, and 23.6% at 9 years. The disease-free survival (DFS) rate was 46.7% at 1 year and 30.0% at 7 years. The 5-year OS rate in relation to the regimens was 60% with the Stanford/NCOG regimen, 50% with the CAVOP regimen, and 33.3% with the m-BACOP regimen. The patients treated with the hyper-CVAD regimen had an 18.2% 2-year OS rate, and other patients with CHOP or COPBLAM-V expired early in their course. The OS rate in patients treated with conventional chemotherapy alone was 19.8%, whereas patients treated with subsequent PBSCT after chemotherapy showed 50% overall survival (p = 0.25). The age at presentation influenced the outcome of the patients (p = 0.01). The Stanford/NCOG regimen is an effective initial choice of therapy for lymphoblastic lymphoma patients, and is superior to the hyper-CVAD regimen in complete response rate and overall survival rate (p = 0.36). Addition of PBSCT after chemotherapy may be needed for achieving optimal outcomes

Clinical Outcomes and Prognostic Factors of Up-Front Autologous Stem Cell Transplantation in Patients with Extranodal Natural Killer/T Cell Lymphoma

AbstractLimited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy

An Unusual Case of Spontaneous Remission of Hodgkin's Disease after a Single Cycle of COPP-ABV Chemotherapy Followed by Infectious Complications

Advanced Hodgkin's disease is usually treated with six or more cycles of combination chemotherapy. Spontaneous regression of the cancer is very rarely reported in patients with Hodgkin's disease. We present an unusual case of a patient with Hodgkin's disease who experienced complete remission with a single cycle of chemotherapy, followed by pneumonia. The case was a 36-year-old man diagnosed with stage IVB mixed cellularity Hodgkin's disease in November 2000. After treatment with one cycle of COPP-ABV (cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine) chemotherapy without bleomycin, the patient developed interstitial pneumonia and was cared in the intensive care unit (ICU) for two months. Follow-up chest computerized tomography (CT), performed during the course of ICU care, revealed markedly improved mediastinal lymphomatous lesions. Furthermore, follow-up whole body CT and 18-fluorodeoxyglucose positron emission tomography showed complete disappearance of the lymphomatous lesions. Four years later, the patient is well and without relapse. This report is followed by a short review of the literature on spontaneous regression of Hodgkin's disease. To the best of our knowledge, this is the first case report of spontaneous remission of Hodgkin's disease in Korea

A Successful Treatment of Relapsed Primary CNS Lymphoma Patient with Intraventricular Rituximab Followed by High-Dose Chemotherapy with Autologous Stem Cell Rescue

The prognosis for patients with primary central nervous system (CNS) lymphoma (PCNSL) who relapse after the initial response is usually poor. A standard treatment for relapsed PCNSL has not yet been identified because of the heterogeneity of the therapies employed and the lack of large, prospective clinical trials. We describe a 46-year-old relapsed PCNSL patient who was successfully treated with intraventricular applications of rituximab to minimize neurotoxicity, 2 cycles of salvage chemotherapy with etoposide, ifosfamide, and cytarabine (VIA) regimen and high-dose chemotherapy with autologous stem cell rescue. The high-dose chemotherapy consisted of bischloroethylnitrosourea, etoposide, cytarabine, and melphalan (BEAM) regimen. Partial remission was detected after intraventricular rituximab therapy and the patient has been in complete remission without evidence of neurotoxicity for 28 months after high-dose chemotherapy with autologous stem cell rescue. This case indicates a new appropriate treatment guideline in relapsed PCNSL patient after initial intensive chemo-radiotherapy

High Dose Chemotherapy and Autologous Stem Cell Transplantation in Non-Hodgkin's Lymphoma: an Eight-Year Experience

Autologous stem cell transplantation (ASCT) is commonly used in relapsed or refractory non-Hodgkin's lymphoma (NHL). Several trials report the role of ASCT for high risk patients. We evaluated the results and the prognostic factors influencing the therapeutic effects on the patients who were treated with high dose chemotherapy (HDC) and autologous peripheral stem cell transplantation. We analyzed the data of 40 cases with NHL who underwent ASCT after HDC. Twenty-four patients had high-risk disease, 12 cases sensitive relapse, and two cases resistant relapse or primary refractory each. The median age of patients was 34 years (range, 14-58 years). The median follow-up duration from transplantation was 16 months (range, 0.6-94 months). Estimated overall survival and progression-free survival at 5 years were 40% and 30%, respectively. Poor prognostic factors for survival included older age (≥ 45 years), poor performance status in all patient analysis, and a longer interval between first complete remission and transplantation in high risk patients. In high risk NHL patients, transplantation should be done early after first complete remission to overcome chemo-resistance

Differential Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Thioacetamide-Induced Chronic Liver Injury

Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA)-induced liver fibrogenesis. Chronic liver injury was induced with TAA (200 mg/kg i.p.) for 4 or 7 weeks in male Sprague-Dawley rats. Hepatic injury and fibrosis were assessed by hematoxylin-eosin (H&E) staining, and collagen deposition was confirmed by Sirius Red staining. The level of hepatic injury was quantified by serological analysis. The transcriptional and translational levels of α-smooth muscle actin (α-SMA), MMPs, and TIMPs in the liver were measured by Western blotting, RT-PCR, and immunohistochemistry. MMP, TIMP, and α-SMA were observed along fibrotic septa and portal spaces around the lobules. TAA treatment increased transcription of both MMPs and TIMPs, but only TIMPs showed increased translation. The dominant expression of TIMPs may regulate the function of MMPs to maintain liver fibrosis induced by TAA

Melatonin receptor 1 B polymorphisms associated with the risk of gestational diabetes mellitus

<p>Abstract</p> <p>Backgrounds</p> <p>Two SNPs in <it>melatonin receptor 1B </it>gene, <it>rs10830963 </it>and <it>rs1387153 </it>showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in <it>MTNR1B </it>may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes.</p> <p>Methods</p> <p>A total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two <it>MTNR1B </it>polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by <it>x</it>²models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding <it>P </it>values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed.</p> <p>Results</p> <p>We found significant associations between the two genetic variants and GDM, <it>rs10830963</it>, with a corrected <it>P </it>value of 0.0001, and <it>rs1387153</it>, with the corrected <it>P </it>value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that <it>rs10830963 </it>might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses.</p> <p>Conclusion</p> <p>There have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of <it>MTNR1B </it>and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.</p

Treatment of Hodgkin's Disease: A Twenty-Year Follow-up of Patients at a Center in Korea

Hodgkin's disease (HD) is a hematologic malignancy which shows common features regardless of race, but racial differences may be considered with certain clinical characteritcs. HD in Korea shows somewhat different characteristics when compared to cases in Western countries. We evaluated the clinical and histopathologic characteristics of HD, the outcomes of various chemotherapy regimens, and prognostic factors of HD in Korea. One hundred and five patients with initial histopathologic diagnosis of Hodgkin's disease were retrospectively reviewed 20 years after diagnosis at Yonsei University College of Medicine. Nodular sclerosis was the most common histopathogic subtype (41%) and mixed cellularity was nearly as common (40%). The overall complete remission rate (CR) was 87.6%. The disease-free survival (DFS) and overall survival (OS) rate were 79.2% and 84.8% at 5-years, 70% and 79.2% at 10- and 20-years. There were no significant differences in CR rate and DFS, but OS rates were significantly higher in m-BACOP and ABVD regimen. Univariate analysis revealed that age, B-symptom, ECOG scale, Ann Arbor stage, international prognostic index, and serum β2-microglobulin level were significant prognostic factors for both DFS and OS. Multivariate analysis demonstrated that age, B symptoms, and ECOG scale were significant prognostic factors for OS only. In conclusion, the survival rates of HD patients in our center were superior to those of previous reports in Korea and Western countries. Considering the higher OS rate and decreased incidence of side effects, the ABVD regimen may be recommended for the initial treatment of Hodgkin's disease