Key Points• An improvement of 4-year OS for acute and lymphoma types of ATL was observed in comparison with that of the 1991 report.• The prognosis of the smoldering type ATL was worse than expected from the 1991 report.Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes caused by human T-lymphotropic virus type I. Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation have been introduced since the previous Japanese nationwide survey was performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded; 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types, respectively, remained. The median survival times were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52%, respectively, for acute, lymphoma, chronic, and smoldering types. The number of patients with allogeneic hematopoietic stem cell transplantation was 227, and their median survival time and OS at 4 years after allogeneic hematopoietic stem cell transplantation was 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory, despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison with the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also noted that the prognosis of the smoldering type was worse than expected. (Blood. 2015;126(24):2570-2577 Introduction Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-1). 1-3Southwestern Japan is one of the most endemic areas for the malignancy, along with the Caribbean basin, Central and South America, and Western Africa. The Japan Clinical Oncology Group-Lymphoma Study Group proposed 4 clinical subtypes, namely, acute, lymphoma, chronic, and smoldering, based on nationwide surveys of patients with ATL who were newly diagnosed from 1983 to 1987 (1991 database). 4 Moreover, patients with the chronic type are further divided into 2 categories by the presence of any unfavorable prognostic factors, defined by levels of blood urea nitrogen (BUN) or lactate dehydrogenase (LDH) at higher than the upper limit of normal or having albumin levels lower than the lower limit of normal. Patients with acute, lymphoma, and chronic type with unfavorable prognostic factors, and those with chronic type without unfavorable prognostic factors and with smoldering type, are categorized as having aggressive and indolent There is an Inside Blood Commentary on this article in this issue.The publication costs of t...

The ATL-PI is a promising new tool for identifying patients with acute- and lymphoma-type ATL at different risks.

Compressional magnetic pulsations with irregular waveforms and periods longer than 150 s (here termed Pi 3) have been studied by using data from Active Magnetospheric Particle Tracer Explorers Charge Composition Explorer (AMPTE/CCE) and GOES 5 and 6 in the dayside magnetosphere and compared with signatures on the ground at low latitudes by using data from Kakioka station (L = 1.25). On the ground, the pulsations appear in the horizontal component. A study of 17 such concurrent events during a 2‐month period in 1986 reveals the following pulsation characteristics. (1) The peak‐to‐peak amplitudes in space (δBT) and on the ground (δH) are comparable and are in the range of 0.5–7 nT. (2) On the ground the pulsations can be seen at all local times, even at midnight, while at geostationary orbit they are observed only on the dayside with a clear amplitude maximum at noon. (3) The pulsations on the ground lag those observed by CCE near local noon, and the lag increases as the local time separation between CCE and the ground station increases. The time lag is 1–2 min longer when the ground station is on the nightside than when it is on the dayside. (4) The time lag between pulsations observed at geostationary orbit and near noon by CCE varies systematically with local time and is about 2 min per 6 hours of local time separation. These observations indicate that some nightside pulsations in the Pi 3 band have dayside origins. The position dependence of the pulsation amplitude can be explained well by changes in the magnetopause current, which are in turn presumably caused by changes in the solar wind dynamic pressure. The time lags observed in space are consistent with signal propagation in the MHD fast mode, but the variation in space‐ground time lags with ground station local time must be attributed to another mechanism.

For the oncogenesis of many malignancies, it is crucial to prevent the shortening of the telomeres by the action of telomerase. In this study, clinical data and disease outcomes were analyzed in conjunction with the telomerase activity (TA) and telomere length (TL) of peripheral blood mononuclear cells. The study was carried out in 22 patients with adult T-cell leukemia (ATL) (7 chronic and 15 acute types) and in 13 asymptomatic human T-lymphotropic virus type 1 (HTLV-1) carriers. The mean values of TA in acute and chronic type patients were 13.8 and 1.6 total product generated (TPG) units, respectively, as determined by telomeric repeat amplification assays. The mean TA values in HTLV-1 carriers and healthy volunteers were 1.8 and 0.7 TPG, respectively. The mean TA value in acute type patients was significantly higher than in the three other subject groups. The mean TL values in patients with acute and chronic types were 5.39 and 4.38 Kb, respectively, while the mean TL values in HTLV-1 carriers and healthy volunteers were 7.69 and 7.06 Kb, respectively. The mean TL values in all ATL patients and in non-ATL subjects were 5.2 and 7.3 Kb, respectively. The former value is significantly shorter than the latter (p < 0.01). Neither TA nor TL of ATL cells showed any significant association with the number of ATL cells, serum soluble interleukin-2 receptor, or serum lactate dehydrogenase in the peripheral blood of acute type patients. This suggests that the levels of TA and TL did not reflect the ATL tumor load. The median survival period of acute ATL patients with high TA and shortened TL was 0.47 years, however, which was significantly shorter than that of acute ATL patients with low TA and normal TL (4.21 years) (p < 0.002). These data suggest that high TA and shortened TL were associated with poorer prognosis, and that TA and TL may be novel markers for the prognosis of ATL patients.

1582 Background: Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1). HTLV-1 is endemic to the southwestern region of Japan, Caribbean basin, Central and South America, and western Africa. A previous report by the Japan Clinical Oncology Group-Lymphoma Study Group (JCOG-LSG) identified five prognostic factors: advanced performance status (PS), high lactic dehydrogenase (LDH), age of 40 years or older, total involved lesions, and hypercalcemia, based on an analysis of 854 patients with newly diagnosed ATL registered between 1983 and 1987. The JCOG-LSG then proposed 4 clinical subtypes: acute, lymphoma, chronic, and smoldering types. In general, the prognosis of acute and lymphoma type ATL is similarly very poor, whereas that of the chronic and smouldering types is better. It has come to the attention of clinicians that there are diverse clinical courses and treatment outcomes among patients with acute and lymphoma type ATL. Therefore, it is necessary to establish a prognostic index (PI) for a risk-adapted approach and improving the quality of clinical trials. The aim of this study was to develop the first PI for acute and lymphoma type ATL (ATL-PI). Patients and Methods: We conducted a nationwide retrospective survey of ATL patients who were newly diagnosed between January 2000 and December 2009, and 1,270 patients with acute and lymphoma type were registered. Fully eligible 807 individuals excluding patients who have received allogeneic hematopoietic stem cell transplantation were used for this analysis, and randomly split the dataset into training (n=404) and validation (n=403) samples. We applied a multivariable fractional polynomial model using continuous variables, and then developed the simplified one using dichotomizing variables. Results: The overall median survival time (MST) for 807 patients was 7.7 months. The Ann Arbor stage (I - II vs. III - IV), performance status (0–1 vs. 2–4), and the three continuous variables of age, serum albumin, and soluble interleukin-2 receptor (sIL-2R) were identified as independent prognostic factors in the training sample. Using these variables, a prognostic model was devised to identify three groups at different levels of risk. In the validation sample, MSTs were 3.6, 7.3, and 16.2 months for patients at high, intermediate, and low risk, respectively (p<0.0001). ATL-PI = 0.65 (if Stage = III or IV) + 0.35 (if PS > 1) + 0.016 × Age (years) − 0.36 × Albumin (g/dL) + 0.37 × log10 (sIL2R (U/mL)) To make the scoring system simpler and clinically practicable, we also simplified the original ATL-PI by dichotomizing age at 70 years, serum albumin at 3.5 g/dL, and sIL-2R at 20,000 U/mL and subsequently fitted a multivariate Cox model based on these dichotomizations in the training sample. Then, we derived a simplified ATL-PI as follows: Simplified ATL-PI = 2 (if Stage = III or IV) + 1 (if PS > 1) + 1 (if Age > 70) + 1 (if Albmin < 3.5) + 1 (if sIL2R > 20,000) The scores from 0 to 2 were categorized into low risk group, 3 and 4 into intermediate risk, and from 5 to 6 into high risk group. This classification yielded a good separation of OS curves (p<0.0001), and high concordance to the original ATL-PI in the validation sample. Conclusion: We identified 5 prognostic factors in acute and lymphoma type ATL using a multivariable fractional polynomial model, and further simplified it with minimal loss of the original index. The ATL-PI enables us to distinguish 3 different groups by predicting OS at the time of diagnosis. The ATL-PI, the first PI for acute and lymphoma type ATL, may be a promising platform in consideration of the choice of optimal treatment by risk-stratification and for well-controlled clinical trials. Disclosures: No relevant conflicts of interest to declare.

Abstract. To identify the propagation mode of ULF waves in the magnetosphere, observational determination of their amplitude and phase structure is necessary. Despite the fact that Pc 3 pulsations are observed at various latitudes, no systematic studies of the phase and amplitude structure of Pc 3 over a wide range of latitudes have been done. Using magnetic field data from the Western Pacific magnetometer array centered at 210 ø geomagnetic longitude and from the Geotail satellite, we present the latitudinal structure of a Pc 3 pulsation event that occurred on October 17-18, 1992. During this event, Geotail was located in the dayside magnetosphere at a radial distance of -8 Re and observed tailward propagating fast-mode magnetosonic waves in the Pc 3 band [Takahashi et al., 1994b]. Pulsations observed at the ground stations, also on the dayside, exhibit dynamic spectra similar to those observed from Geotail. Spectral analyses of the ground data reveal that the pulsations are often coherent from L -1 to L -6. Furthermore, the phase of the pulsations varies with L in a complex manner: at low-latitude stations in the L range between 1.1 and 2.9, there is little phase delay; at a high-latitude station (L -5.5) the phase relative to low latitudes is -180ø; and at an equatorial station (L = 1.01), the phase relative to low latitudes is -150 ø . The pulsation amplitude is at an overall maximum at the highest-latitude station of the magnetometer array, but two additional maxima occur at L -1 and L -2.1. We discuss these observations in terms of MHD wave propagation effects in the magnetosphere.

In 1998, a consensus meeting was held in Miyazaki, Japan, to develop an approach to management of febrile neutropenia (FN). The K-HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study. Patients who developed fever with neutrophil counts <1,000/µL were randomized to receive either a single antibiotic, cefepime or one of the carbapenems, or a combination of cefepime and an aminoglycoside. Patients who became afebrile within the first 3 days were continued on the same treatment. Patients who remained febrile were switched to a combination regimen if they were randomized to receive a single agent, and patients on combination medication were changed from cefepime to another cephalosporin. A total of 165 patients were entered into the trial. One hundred fifty-three patients were evaluable for response. The average age was 52 years, and 70% of the patients had acute leukemia. Severe neutropenia, defined as <100/µL at the time of FN, was seen in 62% of the patients on entry and during the course of treatment 71% of patients experienced neutrophil counts of <100/µL. Microbiologically documented infection was seen in 6.5% for monotherapy, and 10.5% for a combination treatment, and fever of unknown origin occurred in 75.3% and 59.2% of the patients in each regimen, respectively. Excellent to good response was seen in two-thirds of the patients in all treatment groups. Adverse events were minimal, and three early deaths were observed at days 9, 16, and 16 among patients treated with a single antibiotic and three in the combination regimen group at days 14, 15, and 20. These results indicate that cefepime or a carbapenem alone is as effective as a combination of cefepime and an aminoglycoside for treating FN. Am. J. Hematol. 71:248-255, 2002.

In this study, we demonstrate a polarization sensitive pixel for a complementary metal-oxide-semiconductor (CMOS) image sensor based on 65-nm standard CMOS technology. Using such a deep-submicron CMOS technology, it is possible to design fine metal patterns smaller than the wavelengths of visible light by using a metal wire layer. We designed and fabricated a metal wire grid polarizer on a 20 × 20 μm(2) pixel for image sensor. An extinction ratio of 19.7 dB was observed at a wavelength 750 nm.