Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet

We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first-and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

The anomaly in the candidate microlensing event PA-99-N2

The light curve of PA-99-N2, one of the recently announced microlensing candidates toward M31, shows small deviations from the standard Paczynski form. We explore a number of possible explanations, including correlations with the seeing, the parallax effect, and a binary lens. We find that the observations are consistent with an unresolved red giant branch or asymptotic giant branch star in M31 being microlensed by a binary lens. We find that the best-fit binary lens mass ratio is similar to1.2x10(-2), which is one of the most extreme values found for a binary lens so far. If both the source and lens lie in the M31 disk, then the standard M31 model predicts the probable mass range of the system to be 0.02-3.6 M-circle dot (95% confidence limit). In this scenario, the mass of the secondary component is therefore likely to be below the hydrogen-burning limit. On the other hand, if a compact halo object in M31 is lensing a disk or spheroid source, then the total lens mass is likely to lie between 0.09 and 32 M-circle dot, which is consistent with the primary being a stellar remnant and the secondary being a low-mass star or brown dwarf. The optical depth (or, alternatively, the differential rate) along the line of sight toward the event indicates that a halo lens is more likely than a stellar lens, provided that dark compact objects comprise no less than 15% (or 5%) of halos.

High-efficiency low-voltage-stress Class-EF PA with extended maximum operating frequency

The Class-EF power amplifier (PA) introduced recently has a peak switch voltage much lower than the well-known Class-E PA. However, the value of the transistor output capacitance at high frequencies is typically larger than the required Class-EF optimum shunt capacitance. As a result, softswitching operation that minimizes power dissipation during OFF-to-ON transient cannot be achieved at high frequencies. A novel Class-EF topology with transmission-line load network proposed in this paper allows the PA to operate at much higher frequencies without trading the other figures of merit. Closed-form formulations are derived to simultaneously satisfy the Class-EF impedances requirement at fundamental frequency, all even harmonics, and the first two odd harmonics as well as to provide matching to 50O load. © 2011 Institut fur Mikrowellen.

Hydroclimatic shifts in northeast Thailand during the last two millennia - the record of Lake Pa Kho

The Southeast Asian mainland is located in the central path of the Asian summer monsoon, a region where paleoclimatic data are still sparse. Here we present a multi-proxy (TOC, C/N, δ¹³C, biogenic silica, and XRF elemental data) study of a 1.5m sediment/peat sequence from Lake Pa Kho, northeast Thailand, which is supported by 20 AMS ¹⁴C ages. Hydroclimatic reconstructions for Pa Kho suggest a strengthened summer monsoon between BC 170-AD 370, AD 800-960, and after AD 1450; and a weakening of the summer monsoon between AD 370-800, and AD 1300-1450. Increased run-off and a higher nutrient supply after AD 1700 can be linked to agricultural intensification and land-use changes in the region. This study fills an important gap in data coverage with respect to summer monsoon variability over Southeast Asia during the past 2000 years and enables the mean position of the Intertropical Convergence Zone (ITCZ) to be inferred based on comparisons with other regional studies. Intervals of strengthened/weaker summer monsoon rainfall suggest that the mean position of the ITCZ was located as far north as 35°N between BC 170-AD 370 and AD 800-960, whereas it likely did not reach above 17°N during the drought intervals of AD 370-800 and AD 1300-1450. The spatial pattern of rainfall variation seems to have changed after AD 1450, when the inferred moisture history for Pa Kho indicates a more southerly location of the mean position of the summer ITCZ.

Recurrence of Philadelphia chromosome-positive leukemia in donor cells after bone marrow transplantation for chronic granulocytic leukemia

Allogeneic bone marrow transplantation has been shown to be a very effective therapy for Chronic Granulocytic Leukemia with long term disease free survivals in excess of 60%. Relapse rates remain low at 15% following histocompatible sibling transplants and lower rates following matched unrelated donor grafts. Relapse rates however, are higher if BMT is carried out in transformation or blast crisis. Leukemic relapse in donor cells following transplantation for CGL is a rare event. The occurrence of donor leukemia however, may be under reported as accurate and sensitive investigation of the origin of relapsed leukemia following BMT requires DNA based technologies. A possible mechanism of donor leukemia in CGL is transfection of donor cells with the chimeric gene which is unique to this disease. It is possible that the malignant cells found in transformed or blast crisis of CGL may have a greater potential to transfect donor haematopoietic material. Careful evaluation of the incidence of donor leukemia using molecular biology methods may elucidate the frequency of this event following BMT for CGL.