New clinical grading system for chronic GVHD predicts duration of systemic immunosuppressive treatment and GVHD-specific and overall survival.

We investigated outcomes according to a new clinical grading system for chronic graft-versus-host disease (chronic GVHD) in 38 patients who developed chronic GVHD after an allogeneic hematopoietic stem cell transplantation. We categorized the patients into three grade groups, namely, grade I, grade II and grade III, according to the presence of three risk factors: extensive skin involvement, thrombocytopenia (TP) and progressive type of onset. Sixteen patients were classified into grade 1, 19 into grade II and three into grade III. The probability of withdrawal of systemic immunosuppression (IST) at 1, 2 and 3 years was 61, 76 and 87%, respectively. Patients with grades 2 or 3 chronic GVHD had prolonged duration of systemic IST compared to grade 1 (P=0.043). The probability of GVHD-specific survival (GSS) at 5 years was 52%. Twenty-two of 38 patients with chronic GVHD were still alive and the estimated 3-year overall survival (OS) rate was 60%, whereas that for the group with chronic GVHD grade I and grade II+III was 64 and 48% (P<0.05). Multivariate analysis showed that prior occurrence of acute GVHD, chronic GVHD grade, serum bilirubin over 1.5 mg/dl, date of diagnosis of chronic GVHD (day 150) and transplantation-risk factor were independent prognostic factors for GSS and OS.

IMVP-16/Pd followed by high-dose chemotherapy and autologous stem cell transplantation as a salvage therapy for refractory or relapsed peripheral T-cell lymphomas.

The present study aimed to analyse the treatment outcome of IMVP-16/Pd (ifosfamide, methotrexate, etoposide and prednisone) followed by high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with peripheral T-cell lymphomas (PTCLs) who were previously treated with CHOP. Since 1995, 32 PTCL patients were treated with IMPV-16/Pd. Nine of 32 patients achieved a response (5 demonstrating complete response (CR) and 4 partial response), with an overall response rate of 28.1% (95% onfidence interval 0.12-0.45). Considering histopathologic subtypes, 3 of 4 relapsed natural killer (NK)/T-cell lymphoma patients (75%) achieved CR, but only 1 of 6 in non-NK/T-cell lymphoma patients (16.7%) achieved CR (P = 0.19). Six of 9 IMVP-16/Pd sensitive patients underwent HDC/ASCT. Three of them relapsed after 3, 4 and 15 months, respectively, of HDC/ASCT. Estimated 3-year overall survival and progression-free survival rates were 14.2% and 12.2%, respectively. Multivariate analysis revealed that responsiveness to first-line CHOP was a significant prognostic factor (P < 0.05). These results indicate that IMVP-16/Pd followed by HDC/ASCT appears to be an effective salvage regimen, especially for NK/T-cell lymphoma.

Detection and identification of pyrovalerone and its hydroxylated metabolite in the rat.

Detection and identification of pyrovalerone and its metabolite, a hydroxylated product, are described. Their identities were confirmed by comparing their mass spectra and gas chromatographic retention times with those of the synthetic standards. The analytical method of pyrovalerone and its metabolite in biological samples was developed. The detection limit of the two compounds was 5 ng/mL, and the standard curves were linear in the concentration range of 10-5000 ng/mL. The single dose kinetics of pyrovalerone and the metabolite in rat urine and plasma were studied (n = 3). The calculated first half-life time of pyrovalerone in rat plasma was 0.34 h, and the second half-life time was 1.50 h. The half-life time of the metabolite was 0.39 h. The two products were detected in rat urine up to 18 h after a single oral administration and are suggested as screening target compounds in dope analysis.

Identification of new urinary metabolites of famprofazone in humans.

Urinary metabolites of famprofazone following oral administration in humans were identified by gas chromatography-mass spectrometry with electron impact-ionization and comparison with the spectra and retention times of authentic standards. The metabolites were determined following selective derivatization with N-methyl-bis-trifluoroacetamide (MBTFA) and N-methyl-N-trimethyl silyl trifluoroacetamide (MSTFA). Famprofazone was rapidly and extensively metabolized by N-dealkylation, beta-hydroxylation, and p-hydroxylation. The major metabolite, representing approximately 15% of the dose, was methamphetamine. The other metabolites, which were present in minor amounts, were amphetamine, norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, p-hydroxyamphetamine, p-hydroxymethamphetamine, and p-hydroxydemethyl famprofazone.

Biologic characteristics of bone marrow-derived mesenchymal stem cells from a patient with thalassemia syndrome.

INTRODUCTION: Mesenchymal stem cells (MSCs) are capable of self-renewal and differentiating morphologically and functionally into several mesenchymal tissues. There have been contrasting data on whether MSCs are altered in various hematologic disorders. METHODS: We isolated bone marrow (BM)-derived MSCs from a patient with thalassemia syndrome to compare phenotypic and functional characteristics to those from normal healthy donor. RESULTS: No differences were observed between MSCs from thalassemia syndrome (T-MSCs) and those from normal healthy donor in terms of morphology, phenotype, karyotype, multidifferentiation capacity. In mixed lymphocyte reaction, T-MSCs strongly inhibited the proliferation of allogeneic T cells in association with reduced proportion of CD3(+), CD4(+), and CD8(+) cells. Furthermore, the fraction of Treg cells was increased under the culture with T-MSCs, suggesting that T-MSCs exert normal immunomodulatory function. In addition, T-MSCs expressed hematopoietic cytokines and supported hematopoiesis, which was comparable to those from normal BM-derived MSCs. CONCLUSION: T-MSCs exhibited normal phenotype, karyotype as well as normal immunomodulatory function, and autologous MSCs from patients with thalassemia syndrome may be an attractive source of stem cell in terms of hematopoietic support as well as immunomodulatory activity.

Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma.

BACKGROUND: This nonrandomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. PATIENTS AND METHODS: Patients with histologically proven, metastatic gastric adenocarcinoma, aged 18-70 years, performance status zero to two, no prior chemotherapy, and with signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day 1, and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, which was repeated every 2 weeks. RESULTS: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24-69). In total, 386 cycles were administered with a median of nine cycles per patient (range 1-12 cycles) and 45 of 48 patients were assessable for treatment response. An independent review of tumor responses resulted in overall response rate of 66.7% (95% confidence interval=53.4% to 80.0%) by intent-to-treat analysis with one complete response and 31 partial responses. The median survival of all patients was 14.8 months and the median time to progression was 9.6 months. Most common grade 3/4 toxic effects were neutropenia (12% of all cycles) and emesis (8% of all cycles). Grade 2 peripheral neuropathy occurred in five patients. One (2%) patient had severe tumor bleeding and five (10%) patients experienced grade 3 diarrhea. CONCLUSIONS: The modified FOLFOXIRI combination chemotherapy showed a very promising preliminary antitumor activity and was generally well tolerated as a first-line treatment of patients with metastatic gastric cancer.

Three-week schedule of irinotecan plus cisplatin in patients with previously untreated extensive-stage small-cell lung cancer.

Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m-2 was administered on days 1 and 8 and cisplatin 60 mg m-2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0-82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer.