Autologous transplantation in patients with relapsed or high-grade follicular lymphoma provides long term disease-free survival and best median duration of response

The best treatment option for patients with relapsed or high-grade follicular lymphoma (FL) is unknown. In spite of major advances in the therapy for FL, disease-free survival remains short, and median time to progression is just over a year. Autologous stem cell transplantation in patients with relapsed FL is safe and appears to improve disease-free survival. In an attempt to examine whether autologous stem cell transplantation provides long-term disease control in patients with relapsed or high-grade FL, we retrospectively evaluated our experience and analyzed the outcomes of autologous stem cell transplantation in patients with FL from 1991 to 2003. Seventeen men and seven women (n=24) of median age 47.5 years (range 28–64 years) were treated. Three patients with high-risk FL were in first remission. Twenty-one patients were salvaged after relapse with second-line chemotherapy. Of these, 14 were in CR at the time of transplantation, and seven patients were transplanted with active disease. Bone marrow was used in six patients as the source of stem cells prior to 1995 and peripheral blood stem cells were used in 18 patients. Twenty-three of 24 patients engrafted (96%). Median time for neutrophil recovery was 11.5 days (range 9–35 days) and 15 days (range 10–40 days) for platelets. Median duration of follow-up was 6 years (range 7 months–8 years). Of the 24 patients, six have died—with one patient death due to transplant-related pulmonary complications. Overall survival (OS) and disease-free survival (DFS) of all evaluable patients were 71.6 and 40%, respectively. Median duration of response was 4.3 years. OS and DFS in patients transplanted in CR were 80 and 57%, respectively. For those transplanted with disease, a complete response was achieved in 43% of patients, with the OS and DFS of 57 and 19%, respectively. Disease status at transplantation was not a significant variable for survival (p>0.3). Three patients developed moderate to severe treatment-related toxicity, two with grade III mucositis and one with life-threatening infection. When these results are compared with historical controls or patients treated with other modalities, autologous stem cell transplantation appears to be providing the longest disease-free survival and best duration of response.     

Could Vitamin D Supplements Be a New Therapy for Heart Failure? Possible Pathogenic Mechanisms from Data of Intervention Studies

Vitamin D deficiency may play a role in the pathogenesis of chronic heart failure (HF), but whether giving patients supplements to raise vitamin D into the normal range improves their survival is not clear. It has been demonstrated that vitamin D deficiency is common in patients with HF, especially the elderly, in obese and in dark skinned people, and that low vitamin D levels are associated with adverse outcome. The epidemiological data have been confirmed by experimental data, which show that knockout mice for the vitamin D receptor developed myocardial hypertrophy and dysfunction. Data from interventional studies are scarce and discordant, and more research is urgently needed to confirm whether add-on supplementation therapy with vitamin D has a role in the management of patients with chronic HF.     

Endometriosis-associated infertility: GDF-9, AMH,and AMHR2 genes polymorphisms

Purpose

The purpose of this paper is to determine whether there is a correlation between polymorphisms in the growth differentiation factor-9 (GDF-9) gene and anti-Müllerian hormone (AMH) gene and its receptor, AMHR2, and endometriosis-associated infertility.

Methods

This is a case-control study to evaluate whether there is a correlation between polymorphisms in the GDF-9 gene (SNPs determined by direct sequencing), AMH gene, AMHR2 (both SNPs determined by genotyping using TaqMan Allelic Discrimination), and endometriosis-associated infertility. The study included 74 infertile women with endometriosis and 70 fertile women (tubal ligation) as a control group.

Results

Patient age and the mean FSH levels were similar between the infertile with endometriosis and fertile without endometriosis groups. The frequency of genotypes between the groups for GDF-9 gene polymorphisms did not show statistical significance, nor did the AMHR2 gene polymorphism. However, the AMH gene polymorphism did show statistical significance, relating the polymorphic allele with infertility in endometriosis.

Conclusions

We demonstrate that an SNP in the AMH gene is associated with infertility in endometriosis, whereas several SNPs in the GDF-9 gene and the – 482A G SNP in the AMHR2 gene were found to be unrelated.

     

Perceived and measured levels of exertion of patients with chronic back pain exercising in a hydrotherapy pool

OBJECTIVE: To investigate the efficacy of using ratings of perceived exertion (RPEs) to regulate exercise intensity for patients with chronic back pain while they undergo hydrotherapy. DESIGN: Experimental study. SETTING: Hydrotherapy pool in the United Kingdom. PARTICIPANTS: Twenty-six patients (16 women, 10 men) with chronic low back pain of more than 12 months in duration. All were referred for hydrotherapy after attending a back pain triage clinic. INTERVENTIONS: Not applicable.Main outcome measures Borg Ratings of Perceived Exertion Scale; heart rate expressed as a percentage of age-predicted maximum heart rate, computed from readings using heart rate monitors; Oswestry Disability Questionnaire; and pain score from a visual analog scale. RESULTS: At workloads below 55% of age-predicted maximum heart rate, great variability was found in the relation between RPE and exercise intensity. However, for workloads between 55% and 85% of age-predicted maximum heart rate, RPE had a strong correlation with relative exercise intensity during hydrotherapy. CONCLUSIONS: At workloads sufficient to induce an aerobic training response, and yet be safe for patients with chronic back pain, RPE was an accurate predictor of exercise intensity. At lower intensities, back and leg pain may exert a mediating influence. Further investigation is needed to determine the exact relation between back pain, exercise type, and RPE at low exercise intensities.     

Tumor necrosis factor-alpha in liver transplantation and resection. No evidence for a key role in ischemia-reperfusion injury.

Experimental studies have shown that liver ischemia-reperfusion induces Kupffer cell activation and tumor necrosis factor-alpha (TNF alpha) release. The aim of this work was to determine whether severe hepatic ischemia and subsequent reperfusion triggers TNF alpha release in man. Serum TNF alpha was measured before and 3, 10, 30, 60, 120 min after revascularization and postoperatively at day 1 and 2 in 11 patients with orthotopic liver transplantation (group 1) and 4 patients with liver resection with vascular occlusion (group 2). In group 1, TNF alpha levels decreased during the first few minutes of reperfusion, then increased slightly to peak at 120 min (40 +/- 13 pg/ml). Primary non-function occurred in 1 patient in whom low peroperative levels of TNF alpha levels were measured. In group 2, no significant changes in TNF alpha levels were observed. These data, in a small number of patients: (a) show that hepatic ischemia-reperfusion does not result in major TNF alpha production; (b) do not support a primary pathogenic role for TNF alpha in damage after ischemia-reperfusion in humans.