ALBERT

Description: This paper presents an ice classification algorithm based on combined active and passive microwave radiometer data in Lützow-Holm Bay (LHB), East Antarctica. The ice classification algorithm is developed based on the threshold values of an advanced scatterometer (ASCAT) and advanced microwave scanning radiometer 2 (here, AMSR2). These values are calculated via the features of various ice types, including open ice, first-year (FY) ice, multi-year (MY) ice, MY ice including icebergs (MY IB), ice shelves, coastal ice sheets, and inland ice sheets. To verify the validity of the ice classification algorithm, the algorithm results are compared with visual observation data and satellite imagery. Except for the flaw polynya and area with surface melting, the FY ice, MY ice, and the ice shelf areas estimated here using the proposed ice classification algorithm match those discernible from the verification data. Inter-annual changes in the areal extents of FY ice, MY ice, and the ice shelves are investigated here using the proposed ice classification algorithm. Investigation of MY ice and ice shelf areas revealed that the breakup of MY ice induced a breakup of an ice shelf. A comparison of the FY ice and MY ice areas showed the replacement of these ice types. The proposed ice classification algorithm can detect ice breakup events as quantitative changes in the distribution and ice type. In future work, we plan to classify sea ice in other sea ice areas, applying the proposed algorithm throughout the Antarctic region.

Description: Introduction. Diffuse large B-cell lymphoma (DLBCL) represents the largest entity of non-Hodgkin lymphoma. In spite of a remarkable improvement in the treatment of DLBCL patients, considerable proportion of the patients fail to cure. 18F-FDG PET/CT is routinely performed for staging and monitoring of DLBCL. Metabolic heterogeneity (MH) calculated using the PET images potentially reflects heterogeneities of glucose metabolism, blood flow, fibrosis, and hypoxia. While high MH at diagnosis predicts poor prognosis of primary mediastinal large B-cell lymphoma (PMBCL) and other malignancies (Ceriani L, Blood. 2018), the prognostic significance of MH in newly diagnosed DLBCL remains to be clarified. Recently, we reported that high total metabolic tumor volume (TMTV) 150cm3 or more predicts poor prognosis of newly diagnosed DLBCL after R-CHOP-like treatment (Senjo H, Cancer Med. 2019). In the current study, we explored the impact of MH in baseline PET-CT on prognosis of newly diagnosed DLBCL and also tested if MH could be correlated with TMTV in baseline PET-CT. Methods. We retrospectively evaluated the impacts of MH at diagnosis on overall survival (OS) and event free survival (EFS) in 86 patients with newly diagnosed DLBCL treated with R-CHOP-like regimens at Sapporo Hokuyu Hospital (training cohort). MH was determined using the area under curve of cumulative standardized uptake value-volume histogram (AUC-CSH) method, as previously described (Ceriani L, Blood. 2018). In patients with multiple lesions of lymphoma, the lesion with the highest TMTV was selected for MH evaluation. The results were verified in the independent validation cohort of 64 patients treated at Aiiku Hospital. The study procedures were in accordance with the Helsinki Declaration and institutional ethical guidelines, and were approved by the institutional review boards. Results. ROC curve analysis determined the optimal cutoff value of AUC-CSH as 0.481 for separating patients with EFS failure at 24 months, and therefore we defined AUC-CSH 〈 0.481 and ≥ 0.481 as MH high and MH low, respectively. In the training cohort (n=86), there was no significant difference in the patient characteristics between the MH low and high groups except the significantly higher incidence of bone marrow involvement in the MH low group compared to the MH high group (23.3% vs 0%, P=0.00108). Importantly, both OS and EFS were significantly lower in patients with high MH than in those with low MH [5-year OS (5-yr OS); 89.5% vs 61.2%, P=0.0122, 5-year EFS (5-yr EFS); 73.1% vs 51.1%, P=0.0327] (Figure A). In a univariate analysis, TMTV ≥150cm3 and high MH were associated with poor 5-yr OS and EFS. Pearson's correlation tests demonstrated no correlation between MH and TMTV [R2=0.137 P=0.208] (Figure B). A multivariate analysis that included MH and all factors in NCCN-IPI; age, LDH, clinical stage, ECOG PS and major organ involvement, demonstrated that age 〉 70 and high MH were independently associated with poor 5-yr OS (age; HR, 6.03; 95% CI, 1.63 to 22.3, P=0.00699, MH; HR, 5.68; 95% CI, 1.46 to 22.1, P=0.0121). We performed an additional multivariate analysis including both MH and TMTV. We found that both MH and TMTV persisted as independent prognostic factors in this multivariate analysis (MH; HR, 7.20; 95% CI, 1.49 to 34.7, P=0.014, TMTV; HR, 29.60; 95% CI, 2.93 to 300.0, P=0.00411; log-rank, Table). Combined with TMTV, MH stratified patients into three distinguishable prognostic groups; MH low/TMTV low with 5-yr OS 94.7% and 5-yr EFS 87.9%, MH low/TMTV high or MH high/TMTV low with 5-yr OS 77.7% and 5-yr EFS 61.0%, and MH high/TMTV high with 5-yr OS 45.7% and 5-yr EFS 31.5% (Figure C). In the validation cohort (n=64), we confirmed high MH predicted worse prognosis [5-yr OS; 68.6% vs 37.1%, P = 0.0254, 5-yr EFS; 57.3% vs 32.6%, P=0.0375] (Figure D). MH was not correlated with TMTV in the validation cohort either, and a combination of MH and TMTV again stratified the patients into three distinctive prognostic groups (Figures E and F). In the univariate analysis, MH was again associated with poor 5-yr OS and EFS. In the multivariate analysis, MH was associated with poor 5-yr OS. Altogether, we validated that prognostic values of MH in the patients with newly diagnosed DLBCL. Conclusion. High MH predicts worse prognosis in the patients with newly diagnosed DLBCL independently of NCCN-IPI and was not correlated with TMTV. Baseline MH is a novel prognostic biomarker in DLBCL. Figure Disclosures Teshima: Novartis: Honoraria, Research Funding.

Description: Abstract 1532 The current standard initial treatment for APL is all-trans retinoic acid (ATRA) and anthracycline with or without citarabine, followed by ATRA maintenance. Although the treatment has greatly improved clinical outcomes of APL, a considerable proportion of patients still undergo disease relapse, requiring salvage therapy with such as arsenic trioxide (ATO). GO, an anti-CD33 monoclonal antibody conjugated with calicheamicin, is also highly effective on APL. Highly homogeneous expression of CD33, potential efficacy of calicheamicin and lower expression of P-glycoprotein on APL cells explain the high potency of GO on APL. We report here on the efficacy of GO monotherapy against relapsed/refractory APL in a post-marketing surveillance study of GO in Japan. All patients who were treated with GO alone were obligatorily registered into a post-marketing surveillance study run by Wyeth Japan, Co. Ltd. under the guidance of the Pharmaceutical and Medical Devices Agency. We obtained permission to access patients' data from each institution and Pfizer Japan, Co. Ltd. The survey items included adverse events, treatment outcome, overall survival (OS) and relapse-free survival (RFS). Clinical and biological characteristics were analyzed in APL and compared by chi-square test or Fisher's exact test for categorical data, and Wilcoxon rank-sum test for continuous data. OS and RFS were estimated by the Kaplan-Meier method in APL, and then compared to those from the simultaneous post-marketing study in acute myeloid leukemia (AML) by the log-rank test. Between 2005 and 2008, 27 relapsed/refractory APL patients were enrolled in this surveillance. Of these, two patients were excluded from analysis because of insufficient data, while 726 AML patients were enrolled and 503 were evaluable. Twelve (48%) and 2 (9%) APL patients who were treated with GO alone achieved CR and CRp, respectively, while 42 (8%) and 41 (8%) of AML achieved CR and CRp, respectively. Remission duration of first CR and number of relapses influenced CR rates, but previous usage of ATO and age did not in APL. OS and RFS at 2 years were 63% and 71% in APL, and 14% and 20% in AML, respectively. These were shown in figures. OS and RFS in APL were better than those in AML (P

Description: Background. Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma. High total metabolic tumor volume (TMTV) or total lesion glycolysis (TLG) calculated using 18F-FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18F-FDG PET/CT. Methods. In order to explore a surrogate marker for TMTV/TLG, we evaluated the correlations between the serum levels of soluble interleukin-2 receptor (sIL-2R) and TMTV/TLG in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. The study procedures were in accordance with the Helsinki Declaration and institutional ethical guidelines, conducted under the auspices of the institutional ethics committee, and approved by the institutional review boards. Results. In the training cohort(n=64), OS and EFS were significantly lower in patients with TMTV≥150cm3 than in those with less than 150cm3 [5-year OS; 84.0% vs 29.1%, P=0.000194, 5-year EFS; 71.4% vs 28.7%, P=0.000384]. We also found that TLG≥1500cm3 at diagnosis predicted significantly inferior OS and EFS[5-year OS; 84.0% vs 31.7%; P=0.000477, 5-year EFS; 70.2% vs 30.6%, P=0.00107].Pearson's correlation tests demonstrated highly significant positive correlations between sIL-2R and TMTV[R2=0.490; P=0.00004] and between sIL-2R and TLG[R2=0.543; P=0.00000357]. Serum sIL-2R≥1300 U/ml was a strong prognostic factor both for worse OS and EFS[5-year OS; 85.2% vs 25.9%, P=0.000035, 5-year EFS; 72.0% vs 26.8%, P=0.000076].In a univariate analysis, B symptom, LDH, sIL-2R, TMTV and TLG were associated with poor 5-year OS; and B symptom, LDH, PS, sIL-2R, TMTV and TLG were identified as poor prognostic factors for 5-year EFS. We performed multivariate analysis that included sIL-2R and all factors in NCCN-IPI; age, LDH, clinical stage, ECOG PS and major organ involvement. In this multivariate analysis, age and sIL-2R were independently associated with poor 5-year OS(age; HR, 4.44; 95% CI, 1.05 to 18.7, P=0.0424, sIL-2R; HR, 4.45; 95% CI, 1.04 to 19.1, P=0.0444). Another multivariate analysis that included TMTV and all factors for NCCN-IPI demonstrated that TMTV was an only independent prognostic factor for 5-year OS(HR, 3.87; 95% CI, 1.08 to 13.8; log-rank, P=0.0373).Subgroup analyses included the patients with NCCN-IPI High-Int and High(n=49) demonstrated that the cut off value of TMTV 150cm3 stratified treatment outcomes in this poor prognostic group [5-year OS; 75.0% vs 27.7%, P=0.0355, 5-year EFS; 66.7% vs 29.7%, P=0.0493]. Similar results were obtained using the cut-off value of sIL-2R 1300U/mL [5-year OS; 75.0% vs 25.9%, P=0.0182, 5-year EFS; 58.3% vs 29.7%, P=0.0499]. In the validation cohort(n=86), Kaplan-Meier curves showed that OS and EFS in patients with TMTV≥150cm3 was again lower than in those with TMTV

Description: High costs of molecule-targeted drugs such as rituximab, ibritumomab and tositumomab have given rise to an economical issue for treating patients with non-Hodgkin’s lymphoma (NHL). Granulocyte colony-stimulating factors (G-CSF), which are also expensive, are widely used for treating neutropenia after chemotherapy. In Japan, lenograstim at 2 μg/kg (almost 100 μg/body) or filgrastim at 50 μg/m2 (almost 75 μg/body) is commonly administered for patients with NHL after chemotherapy. Therefore, cost-effectiveness is an important issue in treatment for NHL. Patients with advanced-stage NHL who needed chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen with or without rituximab were enrolled in this randomized cross-over trial to investigate the efficacy and safety of low-dose G-CSF. Half of the patients were administered 75 μg filgrastim in the first course after neutropenia and 50 μg lenograstim in the second course, and the other half were crossed over. Forty-seven patients were enrolled in this cross-over trial, and twenty-four patients completed the trial. Frequencies of leukocytopenia and neutropenia of grade 4 were similar in patients who received filgrastim courses and those who received lenograstim courses (p=0.6366 in leukocytopenia and p=0.2207 in neutropenia, respectively). Durations of leukocytopenia and netropenia of grade 4 in each treatment course were not different statistically (p=0.3892 in leukocytopenia and p=0.1476 in neutropenia, respectively), and each period of G-CSF administration in both courses was not different statistically (p=0.0676). Frequency of fever higher than 37.5 degrees (p=0.6826) and duration of fever (p=0.7455) were also not statistically different in the two treatment courses. Documented infection containing FN after chemotherapy was not statistically different (p=0.1213). Although the administration dose of G-CSF was not determined on the basis of body weight or body surface area, eight febrile patients were not administered insufficient dose of G-CSF. Therefore, compared with the standard-dose G-CSF course (filgrastim at 75 μg), there was no statistically increased frequency of antibiotic usage in the low-dose G-CSF course (lenograstim at 50 μg) (p=0.2199). The total cost of G-CSF in the low-dose G-CSF (lenograstim at 50 μg) course was significantly lower than that in the standard-dose G-CSF (filgrastim at 75 μg) course (p

Description: MALT1, BCL10 (B-cell lymphoma 10), and API2 (apoptosis inhibitor 2)-MALT1 are key molecules in mucosa-associated lymphoid tissue (MALT) lymphomagenesis. We previously reported that MALT1 and API2-MALT1 were localized only in cytoplasm, where we suggested that both molecules were likely to be active. In the study presented here, we further examined the localization-determining region by generating various mutants and were able to demonstrate that there were nuclear export signal (NES)-containing domains in the MALT1 C-terminal region. The use of leptomycin B, an NES-specific inhibitor, demonstrated that both MALT1 and API2-MALT1 were predominantly retained in the nuclei, indicating that these molecules were shuttling between nucleus and cytoplasm in an NES-dependent manner. It was also found that MALT1 was involved in the nuclear export of BCL10, which is originally localized in both nucleus and cytoplasm. These results correlate well with the nuclear BCL10 expression pattern in both t(1;14) and t(11;18) MALT lymphomas. The nucleocytoplasmic shuttling of MALT1 and BCL10 complex may indicate that these molecules are involved not only in the nuclear factor κB (NF-κB) pathway but also in other biologic functions in lymphocytes.

Description: We analyze sea-ice conditions along seven segments of the Northern Sea Route (NSR) over four time periods. We researched sea ice by segment, using data from the satellite microwave sensors SMMR, SSM/I and AMSR-E. The four analysis periods (periods I–IV: 1980–88, 1989–2001, 2002–06 and 2007–11, respectively) were determined based on changes in the extent of minimum sea ice throughout the Arctic Ocean. Sea ice showed a decreasing tendency from period I to period IV. For example, sea-ice area in period IV decreased compared to previous periods in the eastern East Siberian Sea and around Severnaya Zemlya, areas that had very high sea-ice concentrations in period I. Sea-ice area in the eastern East Siberian Sea decreased sharply during period III, whereas the Severnaya Zemlya area maintained a high ice concentration. In period IV, sea-ice coverage around Severnaya Zemlya was low, although it remained at 25% in the area east of Severnaya Zemlya, which is a key area for navigation. The proportion of multi-year (MY) ice drastically decreased after winter 2002, and only a small amount of MY ice existed in the winters of 2003–06. MY ice disappeared from the eastern East Siberian Sea after 2007. On the other hand, around Severnaya Zemlya the proportion of MY ice showed cyclic ups and downs between 1997 and 2008. Thus, the persistence of various types of sea ice varies according to region. The persistence of various types of sea ice around Severnaya Zemlya also varied each year.