Wilms' Tumor 1 Gene Expression Using a Standardized European LeukemiaNet-Certified Assay Compared to Other Methods for Detection of Minimal Residual Disease in Myelodysplastic Syndrome and Acute Myelogenous Leukemia after Allogeneic Blood Stem Cell Transplantation

Overexpression of the Wilms' tumor 1 (WT1) gene is informative in many patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) and is measurable in peripheral blood (PB). Despite these advantages, WT1 has not broadly been established as a marker for minimal residual disease (MRD) monitoring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to limited patient numbers, differing sample sources, and nonstandardized in-house methods. To estimate the value of WT1 as an MRD marker, we serially quantified PB WT1 expression using a standardized European LeukemiaNet-certified assay in 59 patients with AML and MDS after allo-HSCT. We compared its performance with routine methods such as chimerism, XY-fluorescence in situ hybridization (FISH), disease-specific cytogenetic, and molecular analyses, which were accessible in 100%, 34%, 68%, and 37%, respectively. Twenty-four patients (41%) relapsed within a median of 126 days after allo-HSCT, and 20 of them showed at least 1 elevated WT1 value above the validated cutoff. The other 35 patients (59%) remained in complete remission, and only 1 patient had a transient increase in WT1 expression. This reflects a sensitivity of 83% and a specificity of 97% for WT1 and appears to be favorable compared with the sensitivities and specificities observed for chimerism (33% and 91%), XY-FISH (67% and 73%), cytogenetic (33% and 77%), and molecular (78% and 85%) analyses. Further supporting its predictive impact, elevated WT1 expression prompted an earlier BM biopsy and consecutively the diagnosis of relapse in 62% of patients. The results of this real-life experience imply that PB WT1 expression is measurable by a standardized assay and predicts imminent relapse after allo-HSCT with high sensitivity and specificity in most patients with AML and MDS.     

Imaging evidence of early brain tissue degeneration in patients with vanishing white matter disease: a multimodal MR study

To find imaging signs of active degenerative processes in vanishing white matter disease (VWM), six VWM patients and six matched controls underwent MR examinations. The data were analyzed with modified Scheltens scales for morphological findings and determined quantitatively for apparent diffusion coefficient (ADC). Single-voxel MR spectra were acquired at the parietal white matter and analyzed with LCModel. Typical VWM brain lesions were found in all patients accompanied by proton diffusion abnormalities: Increased ADC appeared in brain regions with severe myelin destruction in all patients, and reduced ADC in two of six younger patients in remaining white matter adjacent to the lesions or at the borders around the lesions, who had a short history of the disease (≤ 1 year). The MR spectroscopy revealed reductions of NAA, Cho, and Cr, which correlate to the grade of white matter abnormalities. An increase of myo-inositol as marker of reactive gliosis was missing. Thus, restricted proton diffusion was evident in younger VWM patients with short history of disease, which in combination with lack of reactive gliosis may reflect early white matter degeneration in VWM. The multimodal MR methods are useful for characterizing such tissue degeneration in brain in vivo.     

Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis

In a retrospective study, 43 patients with dysplastic neoplasms of the bone marrow (myelodysplastic syndromes and myelodysplastic/myeloproliferative-overlap neoplasms) associated with marked (grades 2–3) fibrosis were examined. Histopathologic and morphologic findings as well as cytogenetic and molecular results were correlated with clinical endpoints. Multilineage dysplasia (34 of 43 patients, 79 %) and hypercellular bone marrow (64 %) were found in most patients. In ten of 35 patients, poor risk karyotypes according to the International Prognostic Scoring System (IPSS) were recorded. The JAK2 V617F mutation was detected in four of 30 patients (13 %), and the KIT D816V mutation was found in two of 30 patients (6 %). Patients were mainly treated with palliative drugs and best supportive care. After an observation time of 1–41 (median 21) months, ten of 43 patients (23 %) had developed a secondary acute leukemia. The median survival of all 43 patients was 21.4 months (range 1.8–88.2 months). Of all prognostic parameters examined, the blast cell count at diagnosis was found to be a most reliable and most predictive marker concerning survival and leukemia progression. This confirms previous studies in dysplastic bone marrow neoplasms without fibrosis.     

Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting: follow-up results of a randomized study

A combined antiplatelet treatment with ticlopidine and aspirin has been accepted as standard pharmacological regimen after coronary artery stenting. No data of a randomized trial are available on ticlopidine monotherapy. This prospective, randomized monocenter trial investigates the role of ticlopidine monotherapy versus combined antiplatelet therapy with ticlopidine and aspirin in unselected patients undergoing coronary artery stenting. After successful placement of 378 coronary artery stents, two hundred and forty-three consecutive patients were randomly assigned to receive antiplatelet therapy with 2 x 250 mg ticlopidine (121 patients) or a combination of 2 x 250 mg ticlopidine plus 100 mg aspirin (122 patients) daily. The primary endpoint included the absence of death, cardiac events and vascular access-site complications during the in-hospital phase. Angiographic and clinical assessment was repeated at the 3-month follow-up exam. Two hundred and thirty-seven patients (97.5%) were free from cardiac and non-cardiac events. Stent thromboses were seen in 2 patients of the combined treatment group, while none were observed in the monotherapy group. No statistically significant differences were found between the 2 groups regarding the primary endpoint. Angiography performed in 210 patients (86.4%) at follow-up revealed a restenosis rate of 29.4% in the combined treatment group and 27.8% in the monotherapy group. Monotherapy with ticlopidine is as safe and effective as a combined regimen of ticlopidine plus aspirin after coronary artery stenting in an unselected patient population. These results need to be confirmed in a larger multicenter trial.     

Autoimmune disorders in two patients with myelodysplastic syndrome and 5q deletion

Autoimmune diseases occurring concurrently with myelodysplastic syndrome (MDS) with deletion del(5q) including band q31 are very rare and have only been reported twice in the medical literature. We present two additional cases, one patient with del(5q) and trisomy 21 who suffered from rheumatoid arthritis and one patient with isolated del(5q) and autoimmune hemolytic anemia. Both patients had mild leukopenia and severe transfusion-dependent anemia. The rheumatoid arthritis was treated with antirheumatics without additional immunosuppressive medication. Autoimmune hemolytic anemia was controlled with long-term steroid administration. This patient developed additional trisomy 21, 2 years after the initial diagnosis of del(5q). Contrary to previous reports on autoimmune disorders in MDS mentioning improvements of hematological function in response to steroid administration, neither of our patients had a hematological improvement under corticosteroids.     

Recurrent myocardial ischemia due to riding left main coronary artery bifurcation thrombus--noninterventional therapy with glycoprotein blocker and thrombolysis.

BACKGROUND: Acute coronary syndrome (ACS) comprises different manifestations of coronary artery disease. Angiograms performed at the time of an ACS may present different coronary morphologies; mostly there are acute vessel occlusions, ruptured atherosclerotic plaques, or thrombotic lesions that require reperfusion therapy. In the presence of intracoronary thrombi localized in the left main coronary artery, the clinical situation is challenging. Hemodynamic situation, symptoms, and rhythm status may change immediately and entail high mortality. Catheter-based therapy and surgical revascularization are associated with a high mortality rate. A noninterventional approach may be chosen in patients with stable hemodynamics and reestablished perfusion. METHODS AND PATIENT: We describe a patient with acute ST-elevation myocardial infarction with chest pain and stable hemodynamics. Angiography revealed a large thrombus in the left main coronary artery bifurcation with ostial subtotal narrowing of the circumflex and left anterior descending artery. However, coronary perfusion was maintained. Immediate treatment with the glycoprotein IIb/IIIa inhibitor abciximab was performed. The patient became asymptomatic. Angiography the next day showed no change in thrombus formation, so abciximab infusion was prolonged. Initial elevated enzymes decreased to normal values. Three days later the patient developed a new unstable angina with newly elevated cardiac enzymes. At this time, a thrombolytic agent was administered. Angiography 2 days later demonstrated normal coronaries. CONCLUSION: This case demonstrates the impact of intracoronary thrombi on repetitive myocardial ischemia and the effectiveness of a noninterventional pharmacological approach for the treatment of acute myocardial infarction due to intracoronary thrombus even in the left main coronary bifurcation.