Peter Grundtvig Sørensen

Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

In vivo tissue characterization by measurement of T1- and T2-relaxation processes is one of the greatest potentials of magnetic resonance imaging (MRI). This may be especially useful in the evaluation of bone marrow disorders as the MRI-signal from bone marrow is not influenced by the overlying osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the patients MRI was done at the time of diagnosis and during follow-up of chemotherapy and related to bone marrow biopsies taken within three days of the MRI. At the time of diagnosis T1-relaxation time was increased two to three times in the patients (range 0.7-3.0 sec.) compared to the controls (range 0.38-0.60 sec.). No significant difference was seen in the T2-relaxation process. In relation to chemotherapy T1 decreased towards the normal range in the patients who obtained complete remission, whereas T1 remained prolonged in the patients who did not respond successfully to the treatment. The results indicate that MRI may be a non-invasive clinically useful tool in the evaluation of acute leukaemia especially as a follow-up control of chemotherapy.

Increased Urinary Albumin Excretion Rate in Breast Cancer Patients

A high frequency of slightly increased urinary albumin excretion (UAE) has been reported in patients with malignancies. Earlier studies have indicated a prognostic significance of UAE in some malignant diseases. We measured urinary albumin in 24-h urine samples in 44 patients with newly diagnosed early breast cancer and in 22 patients with relapse of metastatic breast cancer disease. The prevalence of microalbuminuria ( > or = 20 microg/min) was 20.5% in patients with early breast cancer and 54.5% in patients with metastatic disease. Median UAE was significantly higher in patients with metastatic breast cancer compared with the early breast cancer group (20.5 microg/min vs. 9.2 microg/min; p < 0.01). In patients with metastatic breast cancer, univariate survival analysis revealed a significantly lower survival rate in patients with microalbuminuria compared with the normoalbuminuric group (p <0.001). The present study demonstrates a high frequency of microalbuminuria in patients with breast cancer. Increased UAE was most prevalent in patients with metastatic disease. Our results also suggest that UAE may be a prognostic marker in metastatic breast cancer. Further prospective studies with a larger number of patients and controls are needed to test the validity of these observations.A high frequency of slightly increased urinary albumin excretion (UAE) has been reported in patients with malignancies. Earlier studies have indicated a prognostic significance of UAE in some malignant diseases. We measured urinary albumin in 24-h urine samples in 44 patients with newly diagnosed early breast cancer and in 22 patients with relapse of metastatic breast cancer disease. The prevalence of microalbuminuria (]20 mg/min) was 20.5% in patients with early breast cancer and 54.5% in patients with metastatic disease. Median UAE was significantly higher in patients with metastatic breast cancer compared with the early breast cancer group (20.5 mg/min vs. 9.2 mg/min; pB0.01). In patients with metastatic breast cancer, univariate survival analysis revealed a significantly lower survival rate in patients with microalbuminuria compared with the normoalbuminuric group (pB0.001). The present study demonstrates a high frequency of microalbuminuria in patients with breast cancer. Increased UAE was most prevalent in patients with metastatic disease. Our results also suggest that UAE may be a prognostic marker in metastatic breast cancer. Further prospective studies with a larger number of patients and controls are needed to test the validity of these observations.

Mediators of inflammation correlate with microalbuminuria in patients with non‐Hodgkin's lymphoma

Summary. Recent studies have demonstrated a high frequency of minor glomerular leakage of albumin in cancer patients. Pathogenic mechanisms of increased urinary albumin excretion (UAE) in malignancies remain to be clarified. We have attempted to identify whether microalbuminuria in lymphoma patients is associated with inflammatory mediators and the acute‐phase response. UAE, urinary excretion of β2‐microglobulin and IgG, and serum levels of interleukin 6 (IL‐6), tumour necrosis factor alpha (TNF‐alpha) and C‐reactive protein (CRP) were determined in 113 patients with newly diagnosed non‐Hodgkins lymphoma. We demonstrated a high frequency of microalbuminuria (≥ 20 μg/min) and UAE correlated strongly with serum levels of CRP, IL‐6 and TNF‐alpha. UAE, CRP, IL‐6 and TNF‐alpha were significantly higher in patients with advanced disease stage, B symptoms and in high‐risk patients according to the International Prognostic Index. Urinary excretion of β2‐microglobulin was unaffected in patients with increased UAE. However, UAE was significantly correlated with urinary excretion of IgG, suggesting an altered size selectivity of the glomerular filtration barrier. This is the first study that shows a direct correlation between microalbuminuria and proinflammatory cytokines in malignancies, indicating a pathogenic relationship between inflammation and glomerular leakage of albumin. Future efforts should focus on the pathophysiological cause–effect mechanisms and larger studies are needed to confirm the clinical significance of UAE.

Clinical significance of urinary albumin excretion in patients with non-Hodgkin's lymphoma

Slightly increased urinary albumin excretion rates (UAE) have been reported in patients with various types of human cancer. We measured UAE in 24 h urine samples from 48 untreated patients with non‐Hodgkins lymphoma at diagnosis. In patients with a pretreatment UAE 20 μg/min, post‐treatment value of UAE was determined following completion of the last treatment. The median UAE was 15.0 μg/min and the prevalence of microalbuminuria (UAE 20 μg/min) was 39.6%. Increased UAE was significantly associated with Ann Arbor stage, performance status, serum lactate dehydrogenase (LDH) level, and the International Prognostic Index (IPI). The median posttreatment value of UAE was significantly lower than the pretreatment value (P < 0.0001). Our data suggest a clinical and prognostic significance of UAE in patients with non‐Hodgkins lymphoma.

In vivo measurements of the T1 relaxation processes in the bone marrow in patients with myelodysplastic syndrome. A magnetic resonance imaging study

Nine patients with myelodysplastic syndrome (MDS) were examined with magnetic resonance imaging and in vivo T1 relaxation time measurements of the vertebral bone marrow in a 1.5 tesla whole body scanner. Two patients underwent transformation to acute myeloid leukemia and were evaluated at follow-up examinations. At the time of diagnosis the T1 relaxation times of the vertebral bone marrow were significantly prolonged compared with normal values. The T1 relaxation times of the vertebral bone marrow in patients with MDS showed significantly lower values compared with patients with acute leukemia and did not differ from patients with polycythemia vera.

Prolonged bone marrow T1-relaxation in patients with polycythemia vera.

In vitro as well as in vivo studies have shown prolonged T1 relaxation times in patients with acute leukemia. The mechanism behind this finding is not known. In order to evaluate if this was specific for leukemia we examined eight patients with polycythemia vera, representing a condition with a rather benign bone marrow neoplasia. In this group of patients we found prolonged T1 relaxation times but normal T2 relaxation times. This may indicate that the prolonged T1 relaxation time seen in leukemic bone marrow is not due to the malignant cell per se.

Prolonged T1 Relaxation of the Hemopoietic Bone Marrow in Patients with Chronic Leukemia

Eleven patients with chronic leukemia (7 with chronic lymphocytic leukemia and 4 with chronic myeloid leukemia) were evaluated with magnetic resonance (MR) imaging and T1 relaxation time measurements by use of a 1.5 tesla whole body MR scanner. Bone marrow biopsies were obtained from the posterior iliac crest (within 72 hours of the MR examination) in order to provide data on bone marrow cellularity and differential counts. The patients with chronic leukemia all showed a significant prolongation of the T1 relaxation times compared with the normal range for hemopoietic bone marrow.

Magnetic resonance imaging of the bone marrow following treatment with recombinant human erythropoietin in patients with end-stage renal disease.

We used magnetic resonance imaging (MRI) to study vertebral bone marrow in hemodialysis patients during treatment with recombinant human erythropoietin (rHuEPO). We found changes in T1 relaxation times and image contrast within 14 days after starting treatment, before any response was seen in the hemoglobin concentration in peripheral blood. The increase in T1 relaxation times, together with earlier reported changes observed with localized magnetic resonance spectroscopy, indicate an alteration in cellular composition of the hemopoietic bone marrow with an increase in the amount of hemopoietic active tissue. MRI may be a useful, non-invasive way of evaluating bone marrow response to different modes of rHuEPO administration and dosage.

Urinary albumin excretion is a predictor of response to treatment and disease progression in low-grade non-Hodgkin's lymphoma

Slightly increased urinary albumin excretion (UAE) is frequently found in patients with malignant diseases and is associated with adverse prognostic factors. In the present study, the main objective was to elucidate the role of UAE as predictor of response to treatment and time to progression in low-grade non-Hodgkins lymphoma. We included 52 patients with newly diagnosed follicular lymphoma grade 1 and 2. Pre- and post-treatment median UAE level was 17.5 and 12.0 microg/min, respectively (P < 0.01). Significantly more patients with a pre-treatment UAE below the median level were in CR after treatment (P < 0.05). Patients with a clinical response to treatment had a significantly lower frequency of UAE above the median post-treatment level (P < 0.05). UAE at the time of progression increased to a significantly higher level compared with the post-treatment level (26.5 vs. 16.0 microg/min; P < 0.0001). Median response duration and progression-free survival were significantly longer in patients with a post-treatment UAE below the median level (P < 0.001 and P < 0.0001, respectively). In conclusion, we found elevated UAE to be a highly sensitive indicator of clinical behavior in newly diagnosed low-grade lymphoma. Both response to treatment and time to progression were predicted by levels of UAE. Further studies are needed to confirm the clinical implications of UAE in lymphoma patients.Slightly increased urinary albumin excretion (UAE) is frequently found in patients with malignant diseases and is associated with adverse prognostic factors. In the present study, the main objective was to elucidate the role of UAE as predictor of response to treatment and time to progression in low-grade non-Hodgkins lymphoma. We included 52 patients with newly diagnosed follicular lymphoma grade 1 and 2. Pre- and post-treatment median UAE level was 17.5 and 12.0 μg/min, respectively (P < 0.01). Significantly more patients with a pre-treatment UAE below the median level were in CR after treatment (P < 0.05). Patients with a clinical response to treatment had a significantly lower frequency of UAE above the median post-treatment level (P < 0.05). UAE at the time of progression increased to a significantly higher level compared with the post-treatment level (26.5 vs. 16.0 μg/min; P < 0.0001). Median response duration and progression-free survival were significantly longer in patients with a post-treatment UAE below the median level (P < 0.001 and P < 0.0001, respectively). In conclusion, we found elevated UAE to be a highly sensitive indicator of clinical behavior in newly diagnosed low-grade lymphoma. Both response to treatment and time to progression were predicted by levels of UAE. Further studies are needed to confirm the clinical implications of UAE in lymphoma patients.

DBCG trial 89B comparing adjuvant CMF and ovarian ablation: Similar outcome for eligible but non-enrolled and randomized breast cancer patients

Introduction. A cohort of premenopausal patients with primary hormone receptor positive breast cancer was prospectively identified to be eligible for the DBCG 89B trial. We perform a long-term follow-up and evaluate the external validity of the trial. Material and methods. Following registration in a population-based registry, patients were invited to be randomized to ovarian ablation (OA) versus nine courses of three-weekly cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The same procedures were used in all patients, including report forms, central review, querying, and analysis of data. Multivariate analysis was used to adjust for differences in base-line characteristics. Results. Participation in the randomization varied according to center and time period. One thousand six hundred and twenty eight eligible patients were registered and 525 randomized in the DBCG 89B trial. Median estimated follow-up was 9.5 years for disease-free survival and 12.1 years for overall survival. Non-enrolled patients had a disease-free and overall survival similar to randomized patients. Within 5 years of surgery, results were similar following OA and CMF, but disease-free survival was significant inferior with OA more than five years after surgery, adjusted hazard ratio 1.38 (95% CI 1.03 to 1.85; p=0.03). This convened ten years after surgery to an inferior survival with OA, and the adjusted hazard ratio was 2.37 (95% CI 1.43 to 3.91; p<0.01). Discussion. This prospective cohort study indicates that eligible patients not participating in the DBCG 89B trial had a similar disease-free and overall survival as participants. Survival was similar after OA and CMF in the first ten years, but became inferior in the OA group 10 or more years after surgery.