Induction bortezomib in Al amyloidosis followed by high dose melphalan and autologous stem cell transplantation: a single institution retrospective study.

INTRODUCTION/BACKGROUND: High-dose melphalan (HDM) followed by autologous stem cell transplant (ASCT) for light chain amyloidosis (AL) was performed in 31 patients at Oregon Health and Science University between 2005 and 2012. Fifteen patients had cardiac involvement. PATIENTS AND METHODS: Patients received melphalan 200 mg/m(2) or dose-adjusted HDM (100-140 mg/m(2)) depending on high risk features. Thirteen patients proceeded directly to ASCT after diagnosis, 12 patients received a bortezomib-containing regimen, and 6 received a variety of other induction regimens. RESULTS: The day 100 treatment-related mortality was 9.6%. Overall hematologic (ORR) and organ response rates (OR) in the whole cohort after ASCT were 77% and 58%. ORR and OR in the bortezomib pretreated group were 92% and 75% vs. 69% and 54% in the group that received no pretreatment. The median time to maximum hematologic response after ASCT was reduced in the group that received bortezomib induction (3 vs. 14 months). Overall cardiac response rate was 60%; 100% in patients pretreated with bortezomib and 43% in those without induction treatment. With a median follow-up of 2.9 years, the 3-year progression-free and overall survival rates in the entire cohort were 66% and 73% and in those with cardiac involvement, 73% and 80%. CONCLUSION: We observed that bortezomib-based induction is well tolerated in patients with and without cardiac involvement and suggest that this approach be studied in prospective multi-institutional trials.

High levels of soluble serum hemojuvelin in patients with congenital dyserythropoietic anemia type I.

OBJECTIVE: Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders with ineffective erythropoiesis and secondary hemochromatosis. Inappropriate suppression of hepcidin and high levels of growth differentiation factor 15 (GDF15) have been described in CDA I and II patients, probably contributing to secondary hemochromatosis. Hemojuvelin (HJV) is an important regulator of serum hepcidin, while soluble form of HJV (s-HJV) competitively down-regulates hepcidin. METHODS: We determined the soluble hemojuvelin (s-HJV) levels in 17 patients with CDA I and in 17 healthy volunteers (HV) and looked for correlations with other parameters of iron overload and erythropoiesis. RESULTS: Significantly higher levels of s-HJV were found in patients (2.32 ± 1.40 mg/L) compared with healthy volunteers (0. 69 ± 0.44 mg/L) (P = 0.001). Western blot analysis confirmed the presence of high levels of s-HJV in CDA I patients. s-HJV positively correlated with serum ferritin, erythropoietin, soluble transferrin receptor, and GDF15 and negatively correlated with hepcidin to ferritin ratios. CONCLUSIONS: We for the first time documented high levels of serum s-HJV in CDA I patients, suggesting that it may contribute to iron loading pathology in CDA I and eventually in other anemias with ineffective erythropoiesis.

Left ventricular geometric abnormality screening in hypertensive patients using a hand-carried ultrasound device.

The authors assessed the validity of a hand-carried cardiac ultrasound device operated by an internal medicine resident for left ventricular geometric abnormalities (LVGAs) in mild hypertensive patients. LVGAs were diagnosed when at least one of the following was present: left ventricular mass index exceeding 125 g/m(2) and 110 g/m(2) for men and women, respectively; intraventricular septum thickness > or = 10 mm; posterior wall thickness > or = 10 mm; and left ventricular end-diastolic diameter > or = 5.3 mm. For validation, a cardiologist performed standard echocardiography in all patients. A total of 85 patients completed both echocardiographic studies. LVGAs were diagnosed in 19 (22.4%) cases, 18 of which were confirmed by standard echocardiography. Standard echocardiography did not detect any case of LVGA among the hand-carried cardiac ultrasonography LVGA-negative patients. The sensitivity and specificity of the resident's examination were 100% and 98.78%, respectively. Agreement between the two studies was 99% (kappa 0.97, 95% confidence interval). Hand-carried cardiac ultrasonography may be used as a screening tool for LVGA in hypertensive patients.

Agranulocytosis at first presentation of autoimmune hepatitis type-1.

Autoimmune hepatitis (AIH) is a progressive, chronic disease of unknown cause with varying presenting symptoms, ranging from no symptoms through nonspecific symptoms to fulminant hepatic failure. Although nonspecific hematologic abnormalities in AIH may occur, a case of agranulocytosis (<100 neutrophils/microL) associated with a flare of AIH and suspected to be of autoimmune origin was recently reported. Increased levels of suppressing cytokines had been previously reported in bone marrow samples of patients with AIH type-1 (AIH-1). These changes could be related to induction of apoptosis or interference with differentiation and proliferation of the myeloid lineage, hence, playing a meaningful role in the pathogenesis of agranulocytosis in patients with AIH-1. Here, we report a patient with agranulocytosis at first presentation of AIH-1. On the basis of the patient's diagnostic evaluation, response to administered therapy, and the review of the literature, we suggest several possible mechanisms relating to bone marrow cytokine milieu changes, in addition to autoimmune pathogenesis, that could explain this phenomenon.

Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I.

Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders characterized by ineffective erythropoiesis and increased iron absorption. To determine whether growth differentation factor 15 (GDF15) hyper-expression is associated with the ineffective erythropoiesis and iron-loading complications of CDA type I (CDA I), GDF15 levels and other markers of erythropoiesis and iron overload were studied in blood from 17 CDA I patients. Significantly higher levels of GDF15 were detected among the CDA I patients (10 239 +/- 3049 pg/mL) compared with healthy volunteers (269 +/- 238 pg/mL). In addition, GDF15 correlated significantly with several erythropoietic and iron parameters including Hepcidin-25, Ferritin, and Hepcidin-25/Ferritin ratios. These novel results suggest that CDA I patients express very high levels of serum GDF15, and that GDF15 contributes to the inappropriate suppression of hepcidin with subsequent secondary hemochromatosis.

Fiber-optic biosensor to assess circulating phagocyte activity by chemiluminescence.

We describe herein the construction of a novel computerized multi-sample temperature-controlled luminometer for a fiber array-based biosensor to monitor circulating phagocyte activity. It can perform simultaneously integral measurements of chemiluminescence emitted from up to six samples containing less than 0.5 microl whole blood while the samples and detector do not change their position during the measurement cycle. The optical fibers in this luminometer are used as both light guides and solid phase sample holders. The latter feature of the instrument design simplifies the assessment process of both the extra-cellular and the intra-cellular parts of the phagocyte-emitted chemiluminescence using the same system. We describe some examples or proof of principle for the use of the biosensor. This new technology may find use in a wide range of analytical luminescence applications in biology, biophysics, biochemistry, toxicology and clinical medicine.