Overcoming minimal residual disease using intensified conditioning with medium-dose etoposide, cyclophosphamide and total body irradiation in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults

BACKGROUND AIMS: An intensified conditioning regimen incorporating medium-dose etoposide (VP16) is an option for patients with acute lymphoblastic leukemia (ALL). However, the prognostic impacts of the addition of VP16 to cyclophosphamide (CY) and total body irradiation (TBI) in patients with Philadelphia chromosome-positive (Ph+) ALL with regard to minimal residual disease (MRD) status have not been elucidated. METHODS: The authors retrospectively compared the outcomes of patients with Ph+ ALL who underwent allogeneic transplantation following VP16/CY/TBI (n = 101) and CY/TBI (n = 563). RESULTS: At 4 years, the VP16/CY/TBI group exhibited significantly better disease-free survival (DFS) (72.6% versus 61.7%, P = 0.027) and relapse rate (11.5% versus 21.1%, P = 0.020) and similar non-relapse mortality (16.0% versus 17.2%, P = 0.70). In subgroup analyses, the beneficial effects of the addition of VP16 on DFS were more evident in patients with positive MRD status (71.2% versus 48.4% at 4 years, P = 0.022) than those with negative MRD status (72.8% versus 66.7% at 4 years, P = 0.24). Although MRD positivity was significantly associated with worse DFS in patients who received CY/TBI (48.4% versus 66.7%, P < 0.001), this was not the case in those who received VP16/CY/TBI (71.2% versus 72.8%, P = 0.86). CONCLUSIONS: This study demonstrated the benefits of the addition of VP16 in Ph+ ALL patients, especially those with positive MRD status. VP16/CY/TBI could be a potential strategy to overcome the survival risk of MRD positivity

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL

High-temperature and starvation tolerances of juvenile Japanese Spanish mackerel Scomberomorus niphonius

Japanese Spanish mackerel Scomberomorus niphonius is a target species for stocking, but its biological characteristics at the juvenile stage are not well understood. Here, we investigated the high-temperature and starvation tolerances of hatchery-reared juveniles in captivity. We used juveniles of approximately 40 mm standard length, the size of juveniles released into the field. The upper incipient lethal temperature (50% lethal water temperature) was estimated to be 31.8 °C, higher than the maximum sea surface temperature in the field (approximately 29 °C). The critical thermal maximum was 34.8 °C, whereas it was 36.1 °C when juveniles were preliminarily acclimated to 31 °C for 24 h. Juveniles died from 3 to 11 days under nonfeeding conditions at 20 °C, but from 2 to 7 days at 27 °C. This information is expected to contribute to the development of the production of juvenile Japanese Spanish mackerel.This study was partly supported by JSPS KAKENHI Grant Number 19K06207

Theoretical Study of the Transpore Velocity Control of Single-Stranded DNA

The electrokinetic transport dynamics of deoxyribonucleic acid (DNA) molecules have recently attracted significant attention in various fields of research. Our group is interested in the detailed examination of the behavior of DNA when confined in micro/nanofluidic channels. In the present study, the translocation mechanism of a DNA-like polymer chain in a nanofluidic channel was investigated using Langevin dynamics simulations. A coarse-grained bead-spring model was developed to simulate the dynamics of a long polymer chain passing through a rectangular cross-section nanopore embedded in a nanochannel, under the influence of a nonuniform electric field. Varying the cross-sectional area of the nanopore was found to allow optimization of the translocation process through modification of the electric field in the flow channel, since a drastic drop in the electric potential at the nanopore was induced by changing the cross-section. Furthermore, the configuration of the polymer chain in the nanopore was observed to determine its translocation velocity. The competition between the strength of the electric field and confinement in the small pore produces various transport mechanisms and the results of this study thus represent a means of optimizing the design of nanofluidic devices for single molecule detection

Features in Vibrational Spectra Induced by Ar-Tagging for H₃O⁺Ar_<i>m</i>, <i>m</i> = 0–3

Understanding the spectral features for solvated hydronium has been hindered due to the strong and complex vibrational couplings that lead to broad bands in the aqueous phase. In this work, utilizing <i>ab initio</i> vibrational calculations, we determine how the vibrational couplings induced by the Ar microsolvation in H₃O⁺Ar_<i>m</i> <i>m</i> = 0–3 affect the observed spectra. With theoretical peak intensities and peak positions, we assign the experimental spectra. We also show that an increase in the number of Ar atoms results in an anticooperative blue shifting in the Ar-tagged OH stretching bands. This change in peak position of the OH stretching fundamental modulates the Fermi resonance with the bending overtone. This is observed as a distinct doublet feature at 3200 cm^–1 with varying intensities for H₃O⁺Ar₂ and H₃O⁺Ar₃. The coupling between the in-plane rotation of the hydronium and the bending modes of H₃O⁺ leads to the existence of a strong association bands around 1900 cm^–1

PROPOSALS FOR METHODS TO IMPROVE THE ENVIRONMENT OF THE AMAGASAKI CANAL, FOCUSING ON TROPHIC LEVEL OF Tridentiger obscurus

本研究では，チチブの栄養段階に着目して，尼崎運河の環境改善の方法について調査研究を行った．その結果，チチブは付着藻類を起点とする底生系の食物連鎖の上位にあり，またチチブを食する大型魚類の存在も示唆された．そこで，環境改善策として，積極的にチチブを保全し，運河内に過剰にある栄養塩をより多くの生物に利用されるようにすることを考えることができた．実際にチチブの保全のためのすみかを作成し，現地実験をした結果，適当なすみかの創出には，空隙がコウロエンカワヒバリガイによって閉塞されないような工夫が必要であることがわかった．This study focused on fish species to investigate methods for improving the environment of the Amagasaki Canal. Analysis of the food web revealed that a benthic fish species Tridentiger obscurus has an important role in transferring energy from primary producers to organisms at higher trophic levels. The result suggest that protection of the bottom dwelling T. obscurus is effective for improving the environment of the canal by making excessive nutrients ingestible for other organisms. When artificial shelters for T. obscurus was set in the canal, a large amount of mussel Xenostrobus securi attached to the shelter. The result insists that further improvements are needed to prevent clogging by the shells and make shelters available for T. obscurus

Phase separation in ion bombarded FeNi Invar alloys

Studies of the effects of ion bombardment on the phase equilibria and ordering of FeNi alloys with 30.6 and 39.5 at. % Ni were performed. The FeNi samples were bombarded with Ne, Ar, and Kr at different doses and temperatures, and analyzed using the conversion electron Mössbauer spectroscopy (CEMS) technique with 57Fe. The changes in the CEMS spectra of Fe69.4Ni30.6 and Fe60.5Ni39.5 alloys, bombarded with Ne and Ar, indicate a phase separation, but no evidence of ordering. The Kr bombardment does not produce any change, however samples of 39.5 at. % Ni already showing phase separation returned to the single phase state after Kr irradiation. Our results give strong evidences of a prevalence of displacement mixing for bombardment with heavier ions, and of radiation enhanced diffusion for bombardment with lighter ions