Survival and prognostic factors after initiation of treatment in Waldenstrom's macroglobulinemia.

BACKGROUND: Waldenstrom's macroglobulinemia (WM) is an unusual lymphoplasmacytoid lymphoma characterized by the presence of a serum monoclonal immunoglobulin M. Although several studies have evaluated possible prognostic factors of this disease, few have focused on the survival and prognosis of symptomatic patients after the initiation of treatment. PATIENTS AND METHODS: Our study included 122 previously untreated patients with a median age of 67 years who required systemic treatment. Multiple variables were analyzed for their prognostic value on survival after initiation of treatment using univariate and Cox regression multivariate analysis. RESULTS: The median overall survival was 106 months. Pretreatment factors associated with shorter survival were age >/=65 years, splenomegaly, B-symptoms (weight loss, fever or night sweats), hemoglobin <10 g/dl, platelets <100 x 10(6)/dl, albumin <3.5 g/dl and bone marrow lymphoplasmacytic infiltrate >/=50%. In the multivariate analysis, the two variables with independent prognostic value were age >/=65 years and hemoglobin <10 g/dl. Furthermore, we were able to divide our patients into three risk groups based on the presence of two, one or none of these two adverse prognostic factors. The median survival times in the high-, intermediate- and low-risk groups were 46 months, 107 months and 172 months, respectively (P <0.0001). DISCUSSION: Our findings suggest that advanced age and anemia appear to be the two dominant prognostic factors for survival after initiation of treatment in patients with WM. These two readily available parameters can stratify the patients into three distinct subgroups and may help the selection of appropriate treatment.     

Early benefit from structured care with atorvastatin in patients with coronary heart disease and diabetes mellitus

This is a prospective evaluation of the effect of structured care of dyslipidemia with atorvastatin (strict implementation of guidelines) versus usual care (physician's standard of care) on morbidity and mortality of patients with coronary heart disease (CHD) and diabetes mellitus (DM). From 1600 consecutive CHD patients randomized to either form of care in the GREek Atorvastatin and CHD Evaluation Study (GREACE), 313 had DM: 161 in the structured care arm and 152 in the usual care arm. All patients were followed up for a mean of 3 years. In the structured care group, patients were treated with atorvastatin to achieve the National Cholesterol Education Program (NCEP) low-density lipoprotein cholesterol (LDL-C) treatment goal of <2.6 mmol/L (100 mg/dL). Primary endpoints were all-cause and coronary mortality, coronary morbidity, and stroke. In the structured care group, 156 patients (97%) were taking atorvastatin (10-80 mg/day; mean, 23.7 mg/day) throughout the study; the NCEP LDL-C treatment goal was reached by 150 patients (93%). Only 17% (n=26) of the usual care patients were on long-term hypolipidemic drug treatment and 4% (n=6) reached the NCEP LDL-C treatment goal. During the study, 46 of 152 (30.3%) CHD patients with DM on usual care experienced a major vascular event or died versus 20 of 161 (12.5%) patients on structured care; relative risk reduction (RRR) 58%, p<0.0001. RRR for all-cause mortality was 52%, p=0.049; coronary mortality 62%, p=0.042; coronary morbidity 59%, p<0.002; and stroke 68%, p=0.046. Event rate curves started deviating from the sixth treatment month and the RRR was almost 60% by the 12th month. RRRs remained at that level until the end of the study, when they became statistically significant. The cost/life-year gained with structured care was estimated at 6200 US dollars. In CHD patients with DM, structured care of dyslipidemia with atorvastatin to achieve the NCEP LDL-C treatment goal, reduces all-cause and coronary mortality, coronary morbidity, and stroke by more than one half within a 3-year period, in comparison to usual care. Clinical benefit is manifested as early as the sixth month of treatment.     

Impaired generation of bone marrow CD34-derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a stem cell disorder characterized by ineffective haematopoiesis and blood cytopenias. The present study investigated the potential of bone marrow CD34(+) progenitors in MDS patients to proliferate and differentiate into dendritic cells (DCs) in a cytokine-supplemented liquid culture system and analysed the status of blood DC subsets in these patients. CD34(+) progenitors had low potential to generate DCs in vitro, as the number of DCs obtained from one CD34(+) cell was significantly lower compared with controls (median value 0.2 vs. 4, P = 0.003). In patients, the survival and proliferation of CD34(+) cells in culture was not correlated to the degree of apoptosis. Phenotypically and functionally CD34(+)-derived DCs were similar in MDS patients and normal subjects. The percentage of both circulating DC subsets in patients was extremely diminished compared with controls (myeloid DC: 0.10 +/- 0.10% vs. 0.35 +/- 0.13%, P < 0.001; plasmacytoid DC: 0.11 +/- 0.10% vs. 0.37 +/- 0.14%, P < 0.001). In cases with the 5q deletion both CD34-derived DCs and blood DCs harboured the cytogenetic abnormality. Our results indicate that, in MDS, the production of DCs is affected by the neoplastic process resulting in ineffective 'dendritopoiesis' with low blood DC precursor numbers. This quantitative DC defect probably contributes to the poor immune response against infectious agents and to the escape of the malignant clone from immune recognition with disease progression towards acute leukaemia.     

Cardiovascular magnetic resonance for the diagnosis and management of heart failure with preserved ejection fraction

Heart Failure Reviews - Heart failure with preserved ejection fraction (HFpEF) is characterized by an impaired ventricular filling resulting in the development of dyspnea and other HF symptoms....     

Ticlopidine-induced aplastic anemia: two new case reports,review, and meta-analysis of 55 additional cases

Ticlopidine-induced aplastic anemia (TIAA) is considered very uncommon. We present two new cases, and we review 55 additional cases from the literature. The first case concerns a 70-year-old man who developed severe aplastic anemia 7 weeks after treatment with 500 mg of ticlopidine daily. The patient sustained a severe septic episode, was treated with antibiotics and GM-CSF, and recovered the 14(th) day after ticlopidine withdrawal. The second was an 82-year-old man receiving ticlopidine for 2 years when, during a febrile episode, he was found neutropenic with marrow aplasia. Ticlopidine withdrawal and treatment with antibiotics, transfusions, and G-CSF helped him to recover. When the data of the 57 patients are evaluated, a reversible direct cytotoxic effect of ticlopidine on the pluripotent/bipotent hematopoietic progenitor stem cell is proposed. It is estimated that the real incidence if TIAA is higher, and many cases, initially presented as agranulocytosis +/- thrombocytopenia, might be true aplastic anemias, not proven by marrow aspiration or trephine biopsy. There is no effective monitoring to prevent this side effect. Recombinant growth factors appear not to help in shortening the neutropenic period.     

Open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate mesh: gross and pathologic assessment of the inguinal area at reoperation for recurrence

Purpose

Our group tried to test the hypothesis of using a totally absorbable material for open inguinal hernia repair. However, the increased incidence of recurrences alleviated our initial enthusiasm regarding the technique. The purpose of the present study was to attain both gross and microscopic data that could at least in part justify the hernia repair failure from a patient included in our initial pilot study and was re-operated for recurrence.

Methods

A 65-year-old male patient was diagnosed clinically with a recurrence 24 months after open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate mesh. The patient was operated for the recurrence upon our group on July 2012. The gross appearance of the inguinal area as well as the degree of chronic inflammation provoked by the used mesh as depicted by the pathologic analysis of specimens obtained intraoperatively were assessed.

Results

An open tension-free repair with the use of a non-absorbable mesh under spinal anesthetic was undertaken. Intraoperatively, after the division of the external oblique aponeurosis, only minor fibrotic reaction was observed a finding that was additionally confirmed pathologically.

Conclusion

Polyglycolic acid/trimethylene carbonate mesh used for inguinal hernia repair was associated with a minimal inflammatory host reaction in the inguinal area at 3 years verified both grossly and microscopically.     

Treatment of anemia in low-risk myelodysplastic syndromes with amifostine. In vitro testing of response

Amifostine (AMF) promotes in vitro growth and survival of hematopoietic progenitors. In this study we evaluated the efficacy of AMF in the treatment of anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible predicting value for response to AMF therapy of two types of in vitro clonogenic assays. Two different doses of AMF, 300 mg/m2 (group A, 11 patients) or 400 mg/m2 (group B, 16 patients), were studied. AMF was given three times weekly for 3 weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two cycles of treatment. Partially or nonresponding patients of group A received 400 mg/m2 AMF and were reevaluated. An increase of hemoglobin (Hb) values of more than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks were defined as a complete response (CR) while an increase of Hb values of 1-2 g/dl or a 50% decrease in transfusion requirements was considered as a partial response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the initial dose and one of the nine that received 400 mg/m2 AMF achieved a PR. In group B, three out of 16 (18.7%) patients achieved a PR; the overall response rate in both groups was 22.2%. In group A, bone marrow progenitor assay was performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU-E) were increased in six out of 11 (54.5%) patients, and this increase preceded the rise in Hb levels in three of them. In group B, a clonogenic assay was performed in 11 out of 16 patients before AMF treatment. In vitro results after pretreatment with 500 microM amifostine confirmed the response of two MDS patients that achieved a PR. No response in vitro was observed in all eight nonresponding patients and in one PR patient. The lack of response in the clonogenic assays predicted for nonresponse to treatment with a predictive power of 91.8%. We conclude that 300 mg/m2 is an adequate initial treatment for low-risk MDS patients and both clonogenic assays have a strong predicting value for response to treatment.