ALBERT

Description: We report here for the first time a case of “decitabine-induced differentiation syndrome” in a patient (pt) with acute myeloid leukemia (AML). The cytosine analog decitabine, after incorporating into DNA, irreversibly binds DNA methyltransferase (DNMT) enzymes where cytosine residues are targeted for methylation. This allows replication of unmethylated DNA with subsequent re-expression of genes previously silenced by promoter methylation. It has been suggested that decitabine at low doses may have differentiating effects, as compared to cytotoxic effects at higher doses. A previous phase I trial demonstrated clinical activity of low dose decitabine in patients with myeloid malignancies (Issa, et al., Blood 2004). Given the close relationship of DNA methylation and histone deacetylation in modulating gene expression, we are currently conducting a phase I trial (OSU 0336) of low dose decitabine (15mg/m2 IV over 1 hour on days 1–10) alone (step 1) or in combination with escalating doses of the histone deacetylase inhibitor valproic acid (step 2) in AML. An 82 year old male pt with untreated, secondary AML (65% bone marrow blasts, 95% marrow cellularity) was enrolled on step 1 of the study and given 15mg/m2/day of decitabine for 10 consecutive days. At the time of initiation of therapy, the pt had a white blood cell (WBC) count of 8,700/uL with absolute neutrophil count (ANC) of 1,500/uL and absolute blast count (ABC) of 3,200/uL. At day 11, the pt had WBC 1,000/uL with ANC of 450/uL and ABC of 150/uL and was clinically well. However, at day 17, he presented with cough and shortness of breath, without fever. WBC had risen to 18,700/uL with ANC of 11,000/uL and ABC of 750/uL. The patient developed worsening hypoxia and required mechanical ventilation. Chest radiograph demonstrated diffuse interstitial infiltrates, but bronchoscopy and lavage (on day 18 and repeated on day 24) did not identify an infectious etiology. Due to clinical concern for a differentiation syndrome similar to the “retinoic acid syndrome” occurring in acute promyelocytic leukemia patients treated with all-trans-retinoic-acid (ATRA), the pt was started on dexamethasone 10mg IV q12 hours beginning on day 18, in addition to broad spectrum antimicrobial coverage. Peripheral blood smears during the following week showed evidence of myeloid differentiation, and by day 25 no circulating blasts were found (WBC 4,300/uL, ANC 3,000/uL) while the overall clinical condition improved. The pt was finally extubated on day 38 but within 24 hours required emergent re-intubation due to nasogastric feeding aspiration and died at day 53. In summary, these preliminary data support the biological activity of low dose decitabine in AML and suggest that clinical precautions similar to those implemented for the “retinoic acid syndrome” in ATRA-treated APL should be considered in decitabine-treated AML when myeloid differentiation and rising neutrophil counts are observed.

Description: By the beginning of winter 2000/2001, a mysterious stratospheric aerosol layer had been detected by four different Arctic lidar stations. The aerosol layer was observed first on November 16, 2000, at an altitude of about 38 km near Søndre Strømfjord, Greenland (67°N, 51°W) and on November 19, 2000, near Andenes, Norway (69°N, 16°E). Subsequently, in early December 2000, the aerosol layer was observed near Kiruna, Sweden (68°N, 21°E) and Ny-Ålesund, Spitsbergen (79°N, 12°E). No midlatitude lidar station observed the presence of aerosols in this altitude region. The layer persisted throughout the winter 2000/2001 at least up to February 12, 2001. In November 2000, the backscatter ratio at a wavelength of 532 nm was up to 1.1, with a FWHM of about 2.5 km. By early February 2001, the layer had sedimented from an altitude of 38 km to about 26 km. Measurements at several wavelengths by the ALOMAR and Koldewey lidars indicate the particle size was between 30 and 50 nm. Depolarisation measurements reveal that the particles in the layer are aspherical, hence solid. In the mid-stratosphere, the ambient atmospheric temperature was too high to support in situ formation or existence of cloud particles consisting of ice or an acid-water solution. Furthermore, in the year 2000 there was no volcanic eruption, which could have injected aerosols into the upper stratosphere. Therefore, other origins of the aerosol, such as meteoroid debris, condensed rocket fuel, or aerosols produced under the influence of charged solar particles, will be discussed in the paper. Trajectory calculations illustrate the path of the aerosol cloud within the polar vortex and are used to link the observations at the different lidar sites. From the descending of the layer and calculated sedimentation rates, the mean downward motion of air within the polar vortex was estimated to about 124 m/d between 35 and 30 km, with higher values at the edge of the vortex.

Description: Measurements taken in the framework of the Ground-Based Measurements and Campaign Database Subgroup (GBMCD) of the Atmospheric Chemistry Validation Team (ACVT) are compared to selected preliminary results of scientific algorithms to determine atmospheric parameters from measurements of SCIAMACHY. Presented are comparisons with algorithms to determine NO2 total column, CH4 and CO total columns, ozone profiles from limb and detection of PMCs. NO2 total columns are compared with three ground-based DOAS stations. Three algorithms to determine CH4 and CO total columns are compared with FTIR measurements taken at Kiruna, Ny-Ålesund and Jungfraujoch. First limb ozone profiles are compared with ozone sondes from Ny-Ålesund, Hohenpeißenberg, and Neumayer station (Antarctica) and Lidar measurements from Lauder. A method for detecting polar mesospheric clouds from limb measurements is compared to the observation of noctilucent clouds with the UBonn Lidar at the Esrange near Kiruna. All results show the potential of SCIAMACHY to detect the anticipated and even further products.