Comparison of prognostic scores in transplant-ineligible patients with peripheral T-cell lymphoma not otherwise specified and angioimmunoblastic T-cell lymphoma: a retrospective study from the national hospital organization in Japan.

We retrospectively analyzed the risk factors for outcomes among patients with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS, n = 100) and angioimmunoblastic T-cell lymphoma (AITL, n = 128) who did not receive hematopoietic stem cell transplantation between 2008 and 2018. We designed a comparison of prognostic scores specifically for PTCL-NOS and AITL. The international prognostic index (IPI) was useful for investigating the risk factors associated with outcomes among transplant-ineligible patients with PTCL-NOS (Harrell's c-statistic 0.715) and AITL (c-statistic 0.615). The prognostic index for T-cell lymphoma (PIT), modified PIT, and the International Peripheral T Cell Lymphoma Project for overall survival (OS) seemed to identify separate prognostic groups, based on visual assessment of Kaplan-Meier curves. However, better c-statistics (>0.7) were only found for the IPI score for OS in PTCL-NOS. Strategies that carefully select PTCL patients with higher IPI scores may help to identify individuals suitable for novel therapies.

Efficacy and Safety of the Modified EPOCH Regimen (Etoposide, Vincristine, Doxorubicin, Carboplatin, and Prednisolone) for Adult T-cell Leukemia/Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: We retrospectively analyzed patients with untreated aggressive adult T-cell leukemia/lymphoma who received the modified EPOCH (mEPOCH) regimen. PATIENTS AND METHODS: Patients received up to 6 mEPOCH cycles. Etoposide (50 mg/m2/day), doxorubicin (10 mg/m2/day), and vincristine (0.4 mg/m2/day) were each given as a continuous 96-hour infusion on days 1 to 4. Prednisolone (40 mg/m2/day) was given intravenously or orally on days 1 to 4 and then tapered and stopped on day 7, and carboplatin (dose calculated for each patient individually using Calvert's formula according to a target under the curve of 3 mg/mL/min) was given as a 2-hour intravenous infusion on day 6. RESULTS: In 103 patients, overall response rate and complete response rate were 58% and 25%, respectively. With a median follow-up of 8.9 months, the median survival time was 9.8 months (95% confidence interval, 7.2-13.9 months). The median progression-free survival (PFS) was 4.2 months (95% confidence interval, 3.4-5.7 months). Patients who completed ≥ 4 cycles experienced significantly better overall survival and PFS compared with those who completed < 4 cycles. Twenty-eight patients underwent allogeneic hematopoietic stem cell transplantation after mEPOCH and demonstrated significantly prolonged overall survival and PFS compared with those who did not undergo transplantation. CONCLUSION: The mEPOCH regimen is effective with tolerable adverse effects and may be an alternative treatment option for adult T-cell leukemia/lymphoma.

Phase II study of dose-adjusted gemcitabine, dexamethasone, cisplatin, and rituximab in elderly relapsed diffuse large B-cell lymphoma patients.

High-dose chemotherapy and autologous stem cell transplantation (ASCT) are too toxic for elderly patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Therefore, effective and tolerable regimens for elderly patients are urgently needed. The present phase II study assessed the efficacy and safety of dose-adjusted therapy with gemcitabine, dexamethasone, cisplatin, and rituximab (GDP-R) in this population. ASCT-ineligible elderly patients with relapsed or refractory DLBCL received dose-adjusted GDP-R in each 28-day cycle for up to six cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete response (CR) rate, progression-free survival (PFS), and safety. Thirty-three patients were enrolled and received dose-adjusted GDP-R. The median age was 75 years (range: 68-87 years). The ORR was 82.8% (90% confidence interval [CI], 67.1-93.0%), with a CR rate of 58.6% (90% CI, 41.7-74.1%). At a median follow-up of 20.9 months, the 2-year PFS rate was 46.8% (90% CI, 30.7-61.5%) and the 2-year overall survival rate was 63.2% (90% CI, 45.8-76.3%). The most frequently observed grade 4 adverse events were neutropenia (63.6%), thrombocytopenia (57.6%), and lymphocytopenia (39.4%). Dose-adjusted GDP-R is a promising salvage regimen for ASCT-ineligible elderly patients with relapsed DLBCL after rituximab-containing chemotherapy and warrants further investigation.

Regression of uterine cervical diffuse large B-cell lymphoma transformed from mucosa-associated lymphoid tissue lymphoma subsequent to Chlamydia trachomatis eradication.

A 37-year-old-woman was referred to our center after her uterine cervix health screening presented abnormal findings. We performed a biopsy of the uterine cervix to examine for cervical dysplasia, and diagnosed a diffuse large B-cell lymphoma transformed from mucosa-associated lymphoid tissue (MALT) lymphoma of the cervix. The patient presented with concurrent chlamydial cervicitis and received eradication therapy for Chlamydia trachomatis. Four months later, the CD20 positive abnormal lymphocyte disappeared and complete remission was achieved. MALT lymphoma is considered to correlate with infection and inflammation. Particularly, the relationship between gastric MALT lymphoma and Helicobacter pylori is well known. MALT lymphoma of the uterine cervix is rare, and its relationship with C.trachomatis infection is unknown. Further studies are warranted to investigate this association.

[Alveolar rhabdomyosarcoma of unknown origin mimicking acute leukemia at the initial presentation].

A 14-year-old boy presented with a short history of general fatigue. Laboratory examination of the peripheral blood revealed white blood cells 11,300/microl, hemoglobin 10.4 g/dl, platelets 45,000/microl, fibrinogen < 50 mg/dl, fibrin/fibrinogen degradation products 536 microg/ml and lactate dehydrogenase 1,684 U/l. A bone marrow aspirate contained 89.6% of undifferentiated tumor cells. A hematological malignancy was suspected and the patient was treated with idarubicin and cytarabine. However, further examination revealed that tumor cells were positive for CD56 and lacked lineage markers of lymphoid or myeloid cells. They were positive for PAS, HHF35 and desmin, and negative for MPO. Reverse transcriptase polymerase chain reaction demonstrated PAX3/FKHR fusion transcripts, confirming the diagnosis of alveolar rhabdomyosarcoma. Radiological examination revealed only one enlarged lymph node being 1.5 cm in diameter at the paraaortic region in the abdomen, and failed to find a primary tumor. After three courses of chemotherapy containing etoposide, cyclophosphamide, pirarubicin, cisplatin and vincristine, tumor cells were eradicated from the bone marrow. The patient received an allogeneic bone marrow transplantation eight months after diagnosis, although he died of hepatic veno-occlusive disease on day 21. Alveolar rhabdomyosarcoma often develops in older children and younger adults, and its bone marrow infiltration may mimic acute leukemia.

A simplified estimation of loss of life expectancy (LLE) using rectangular approximation method.

In order to evaluate the effects of short exposure period using a simple methodology, a plain rectangular approximation method to estimate loss of life expectancy (LLE) was devised and applied to evaluate cancer risk. The posed risk was expressed as the time of LLE, which is proportional to the period and concentration of exposure. This method assumes a rectangular survival curve and a flat cancer risk for all ages. In the survival curve, the survival rate of the population studied declined due to the risk such that the new survival curve became a trapezoid. The area difference between the initial rectangle and the trapezoid was converted to an LLE value. Lifetime exposure to the acceptable level concentration (ALC), which is equivalent to a 10(-5) lifetime cancer risk, gave the base LLE, which was calculated to be 210 min. Exposure to the ALC between the ages of 20 and 25 years resulted in an LLE of 18.9 min, which is 9.0% of the base risk. One minute of exposure to carcinogens at 1000 x ALC is equivalent to an LLE of 0.0075 min. Considering that the ALC of benzene is 2 microg/m(3), 1 min of exposure to 267 mg/m(3) benzene is equal to 1 min of LLE, which is as toxic as "smoking tobacco."

Correlation of low-volatile organic chlorine (LVOCl) and PCDD/Fs in various municipal waste incinerators (MWIs).

Medium- and low-volatile organic chlorine (M/LVOCl) and PCDD/Fs in flue gas from various municipal waste incinerators (MWIs) were monitored. The sample for M/LVOCl was collected in an adsorption tube which was thermally desorbed and the amount of chlorine was measured by atomic emission spectrometry (AES) detection using radiofrequency helium plasma. The helium plasma excited chlorine having an optical emission line of 837.6 nm was monitored. The MVOCl and LVOCl were organic chlorine groups whose boiling points (bp) ranged from 70-120 degrees C and 170-270 degrees C, respectively. The compounds having bp 120-170 degrees C were distributed in two tubes. LVOCl correlated well with PCDD/Fs (ng/Nm3, r=0.81) in a wide range of 0.01-100 ng/Nm3 of PCDD/Fs, while the correlation of LVOCl vs. TEQ was less related (r=0.69). These results agreed with the fact that LVOCl monitored the amount of organic chlorine without molecular structure information, which is critical to toxicity. Since the bp of LVOCl was not identical with that of PCDD/Fs, the regression was effected by the conditions of the gas treatment devices. Because most data of 2001 were collected just after the installation of PCDD/Fs in MWIs, the regression of 2001 was slightly different from that of 2002-2003. Eliminating these initial unsteady data, the regression of LVOCl vs. PCDD/Fs became better, giving r= 0.86. Besides having PCDD/Fs as surrogates, M/LVOCl is valuable as a versatile element-selective organic chlorine monitor to improve thermal process control.

Estimation and control of atmospheric emissions of chloroform and dichloromethane due to laboratory activity.

In Japanese universities, the management of chemical reagents has become an important issue in preserving the environment and the health of students and researchers. It is thus necessary to estimate the levels of chemical emissions into the environment and to measure working-environment chemical levels in laboratories. However, there are many laboratories in universities using many chemical reagents for their own needs. Hence, it is difficult for universities to quantitate the amount of chemicals on campus, and there is a lack of information about laboratory environment chemical levels. In this study, the material balance of chloroform and dichloromethane (DCM) in Kyoto University was examined, and the emission rates of chloroform and DCM were estimated to be 37-50% and 50-70%, respectively. These chemicals were thought to be volatilized mainly through reduced-pressure distillation. However, it was found that there was a loss of chemicals due to volatility, which researchers were unaware of, such as that during solvent recovery under reduced pressure and volatilization from containers of organic waste liquid. On the other hand, working-environment chemical levels were measured in several laboratories which used chloroform and DCM frequently. Even in such laboratories, the average concentrations of these chemicals were approximately 1 ppm at most measurement points.

Solidification and stabilization of fly ash from mixed hazardous waste incinerator using ordinary Portland cement.

Fly ash samples from a mixed hazardous waste (MHW) incinerator were subjected to solidification and stabilization (S/S) studies using ordinary Portland cement (OPC) as the binder. Additives (i.e., activated carbon and rice husk) were also homogenized with the binder and waste to determine the effectiveness of the immobilization of heavy metals. The toxicity characteristics leaching procedure (TCLP), Japanese Leaching Test (JLT-13) and the American Nuclear Test 16.1 (modified) ANS 16.1 were used to gauge the leaching of heavy metals from the solidified matrixes. Compressibility strength of the solidified matrixes was also tested using the American Standard Testing Material (ASTM) test procedure for the compressive strength of hydraulic cement mortars.

Influence of particle size preparation of MSW incineration residues on heavy metal leaching behavior in leaching tests.

This study examines the influence of particle size preparation on leaching tests of heavy metal leaching behavior of municipal solid waste (MSW) incineration fly ash and MSW melting slag. The MSW incineration fly ash and melting slag were divided into 2-3 fractions by sieving. The metal contents of the respective fractions were determined and the representativeness of the samples was verified. Differences in the metal contents of the fractions with different particle sizes were significant for MSW incineration fly ash. Therefore, particle size preparation by sieving should not be done prior to these leaching tests. In contrast, differences in metal contents of different particle sizes of melting slag were not significant. Therefore, sample fractions with identical metal contents are obtainable by sieving. The metal leaching quantities by the Japanese Leaching Test Method No. 19 (JLT-19) depend on the chemical stability and particle size preparation of slag. The modified basicity, [(CaO+MgO+Na(2)O+K(2)O) / (SiO(2)+Al(2)O(3))], is useful as an index of the chemical stability of slag.

Polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) and monobromo-polychlorinated dibenzo-p-dioxins/dibenzofurans (MoBPXDD/Fs) in the atmosphere and bulk deposition in Kyoto, Japan.

Polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) and monobromo-polychlorinated dibenzo-p-dioxins/dibenzofurans (MoBPXDD/Fs) in atmosphere, bulk atmospheric deposition and soil in Kyoto, which is an urban city in Japan, were measured. Decabromodiphenyl ether (D(10)BDE, BDE-209) was detected in relatively high concentrations compared to other PBDE congeners in most samples. Similar results, in which D(10)BDE was predominantly detected, were reported in other studies in Japan. However, these homologue profiles differ from those of studies conducted in North America. The partitioning of semivolatile organic compounds between atmospheric gas phase and particulate-associated phase is an important factor in their environmental behavior. In this study, atmospheric particulate phase fraction (f(P)) of the brominated compounds increased with increasing bromine number, and f(P) was higher in samples collected in winter than in those collected in summer. Moreover, f(P) of PBDFs and MoBPXDFs was higher than that of PCDFs with the same halogen number. These results agree well with expectations from the vapor pressure of the brominated compounds and PCDD/Fs. Among the brominated compounds in the atmosphere, the level of MoBPXDD/Fs correlates positively with that of PCDD/Fs. This relationship has been previously observed in waste incineration samples. These results suggest that one of the sources of MoBPXDD/Fs in the atmosphere is incineration byproduct. The level of PBDD/Fs seems to correlate positively with that of PBDEs. This relationship suggest that the PBDD/Fs in the atmosphere relate to PBDEs, which is an impurity of PBDE products, or formed by the manufacture or combustion of plastics containing PBDEs.

Waste wood recycling as animal bedding and development of bio-monitoring tool using the CALUX assay.

Animal bedding made of waste wood samples from seven different plants in Japan were chemically analyzed in terms of persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs), coplanar polychlorinated biphenyls (Co-PCBs), drin compounds, chlordane compounds and various inorganic toxic compounds (Cr, Cu, As, B, Cd and Pb) to investigate the chemical characteristics and levels of contamination. Further investigation was conducted to determine the success of applying the Chemically Activated Luciferase Expression (CALUX) bioassay to the waste wood samples in combination with a cleanup procedure for the detection of dioxin-like compounds in order to develop the CALUX bioassay as a rapid and cost-effective screening/monitoring method and a contributive tool to risk management in the waste wood recycling process. For the cleanup procedure, crude extracts from wood samples were prepared by dimethylsulfoxide (DMSO)/n-hexane extraction, and then the extracts were processed by silica gel-44% sulfuric acid reflux treatment at 70 degrees C for 60 min to yield the bioassay fractions. The presence of POPs and inorganic toxic compounds were confirmed in most of the litter samples. In particular, Co-PCBs in one sample (litter dust) showed a high concentration level (1200000 pg/g, 240 pg TEQ/g), suggesting the potential for contamination from demolition waste. The CALUX assay-determined TEQs (CALUX-TEQs) were significantly high in the sample after DMSO/n-hexane extraction, probably due to labile aryl hydrocarbon receptor (AhR) ligands such as PAHs; however, they were remarkably reduced through a single silica gel-44% sulfuric acid reflux treatment. The ratio between CALUX-TEQ values and WHO toxicity equivalent values (WHO-TEQ) obtained by congener-specific chemical analysis ranged from 0.058 to 22 and show comparatively good agreement. Underestimation in some samples, however, was observed where WHO-TEQ values of Co-PCBs contributed greatly to total WHO-TEQ values. Reasons for this gap could be lower CALUX assay-determined relative potencies (REPs) than the WHO-TEFs for these congeners or AhR-antagonistic effects of non dioxin-like PCBs which coexist at higher concentration than Co-PCBs. The CALUX assay is proposed as a promising application in the recycling process of wooden materials.

Congener-specific intake fractions for PCDDs/DFs and Co-PCBs: modeling and validation.

Intake fractions (iFs) for emissions to air, water, and soil for 17 PCDDs/DFs and 12 Co-PCBs were calculated with a level III multimedia model and a food-chain exposure model in succession. The two integrated models were tested by comparing the predicted and measured concentrations in the environment and by comparing intakes through food. Measurement-based iFs were also calculated and compared with the model-based iFs. The air concentrations predicted by the fate model were close to the median of the observed concentrations, whereas the predicted soil and water concentrations were one-third to one-tenth the observed concentrations. This difference was large in case of PCDDs and Co-PCBs, which was explained by the past pollution such as commercial PCB products and PCDD impurities in chloronitrofen (CNP) and pentachlorophenol (PCP). For fish, the predicted and observed exposures agreed well each other. For meat and milk, the predicted exposures were about 10 times the observed exposures for PCDDs/DFs, whereas the predicted and observed values agreed well for Co-PCBs. When the model was modified to consider feeding of fish meal to livestock and geographic bias in feed-grass production, the predicted congener profile was comparable to the measured profile. The comparison also suggested that chickens should be modeled separately from other terrestrial livestock. The model-based iFs for air emission of OCDD and 2378-TCDD were 0.001% and 0.1%, respectively. The iFs of most Co-PCBs were higher than those of PCDDs/DFs. These iF differences suggest the importance of the fate factor in assessing emissions of the 29 congeners.

Enantioselective Lewis acid-catalyzed Mukaiyama-Michael reactions of acyclic enones. Catalysis by allo-threonine-derived oxazaborolidinones.

allo-Threonine-derived O-aroyl-B-phenyl-N-tosyl-1,3,2-oxazaborolidin-5-ones 1g,n catalyze the asymmetric Mukaiyama-Michael reaction of acyclic enones with a trimethylsilyl ketene S,O-acetal in high enantioselectivity. A range of alkenyl methyl ketones is successfully employed as Michael acceptors affording ee values of 85-90% by using 10 mol % of the catalyst. The use of 2,6-diisopropylphenol and tert-butyl methyl ether as additives is found to be essential to achieve high enantioselectivity in these reactions. The effects of the additives are discussed in terms of the retardation of an Si(+)-catalyzed racemic pathway, which seriously deteriorates the enantioselectivity of asymmetric Mukaiyama-Michael reactions. A working model for asymmetric induction is proposed based on correlation between catalyst structures and enantioselectivities.

Monitoring minimal residual disease in patients with MLL-AF6 fusion transcript-positive acute myeloid leukemia following allogeneic bone marrow transplantation.

Acute myeloid leukemia (AML) patients with chromosome 11q23 abnormalities or MLL rearrangements have a poor prognosis when treated with conventional chemotherapy. However, the efficacy of allogeneic bone marrow transplantation (BMT) for this type of leukemia is not yet clear. We describe 2 MLL-AF6 fusion transcript-positive AML patients treated with allogeneic BMT who were monitored for minimal residual disease (MRD) by reverse transcriptase polymerase chain reaction. Although long survival or cure of this type of AML is rarely reported, 1 patient had durable remissions. Fusion transcripts disappeared in 1 patient but not in the other, even after the graft-versus-host disease effect was increased by the discontinuation of immmunosuppressive therapy. This is the first report of MRD and the probability of graft-versus-leukemia effects following BMT in AML patients who are MLL-AF6 fusion transcript positive.

Clinical significance of telomerase activity in multiple myeloma.

BACKGROUND: The clinical course of patients with multiple myeloma varies, and therefore it is important to evaluate the disease state. We studied the telomerase activity of myeloma cells as a possible prognostic factor in such patients. METHODS: Twenty five samples from patients with multiple myeloma were studied. We purified myeloma cells in bone marrow samples according to the expression of surface antigens, CD38 and CD45. CD38+/CD45- or dim cells had morphologic characteristics of myeloma cells, with a purity exceeding 95%. The telomerase activity of myeloma cells was determined by a polymerase chain reaction-based telomeric repeat amplification protocol assay. Ki-67 positivity of the purified cells was determined by flow cytometry using anti-Ki-67 antibody. The relationship between telomerase activity and prognostic factors was also examined. RESULTS: A significantly high degree of telomerase activity was detected in subjects with a serum beta2-microglobulin level > or = 6 mg/dL or at Stage III (P = 0.002). The serum C-reactive protein, lactate dehydrogenase, and creatinine levels did not correlate with the telomerase activity, but this activity did significantly correlate with Ki-67 positivity and the percentage of plasma cells in the bone marrow (r = 0.561, P = 0.004, and r = 0.397, P = 0.049, respectively). The patients with high levels of telomerase activity were thus found to have a significantly short survival time after sampling (P = 0.035). CONCLUSIONS: The measurement of the telomerase activity in myeloma cells was found to be a reliable marker for the proliferating capacity and tumor mass in myeloma patients. The telomerase activity of myeloma cells may therefore be useful as a prognostic factor.