ABSTRACT
Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for a positive hepatitis panel, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777-0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.
ABSTRACT
Daily intake of extracellular vesicles (EVs) derived from fish (f-EVs) may contribute to health maintenance by reducing cardiovascular risk. However, their physicochemical and biological properties remain unclear. In this study, we compared the physical characteristics (size, zeta potential, and free fatty acid composition) and biological characteristics (cell proliferation) of f-EVs with those of EVs derived from mammals (m-EVs). In the physical characteristic analysis, f-EVs derived from Pagrus major (PMS-EVs) and Seriola quinqueradiata (SQS-EVs) had a negatively charged and a positively charged group and higher levels of unsaturated fatty acids, unlike m-EVs. In the biological characteristic analysis for f-EVs, SQS-EV enhanced the human umbilical vein endothelial cell proliferation via vascular endothelial growth factor receptor 2, fibroblast growth factor receptor 1, or platelet-derived growth factor ß. These data suggest that SQS-EVs have unique functions compared with other EVs. To the best of our knowledge, this is the first study to show that SQS-EVs act positively on human cells.
Subject(s)
Extracellular Vesicles , Vascular Endothelial Growth Factor A , Animals , Humans , Human Umbilical Vein Endothelial Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism , Signal Transduction , Extracellular Vesicles/metabolism , Cell Proliferation , Mammals/metabolismABSTRACT
OBJECTIVE: This multicentre, phase 2, randomized, controlled study of allogeneic haematopoietic stem cell transplantation (allo-HSCT) recipients compared the immunogenicity of two anti-pneumococcal vaccine regimens: four doses of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) (3+1+1 experimental group), and three doses of PCV13 followed by PPSV23 (3+0+1 group). METHODS: Allo-HSCT recipients without active graft-versus-host disease at enrolment were eligible. The primary endpoint was the IgG response rate (≥0.20 mg/mL) for all eight measured serotypes at 5 months after the PPSV23 booster. RESULTS: Seventy-two recipients were randomized, and seventy recipients who received over one PCV13 dose were analysed. The mean ages were 47.2 years (standard deviation, 14.4) in the 3+1+1 group (n = 35) and 49.0 years (standard deviation, 14.3) in the 3+0+1 group (n = 35). There was no significant difference in the overall IgG response rate at 5 months after the PPSV23 booster between the 3+1+1 and 3+0+1 groups (100% (26/26) vs. 93% (27/29), respectively, relative risk (RR): 1.07; 95% confidence interval (CI): 0.97-1.19). This rate was high immediately before the PPSV23 booster in the 3+1+1 group (100% (26/26) compared with 81% (21/26), respectively, RR: 1.24; 95% CI: 1.03-1.49), but this difference disappeared 1 month after the PPSV23 booster (100% (26/26) vs. 97% (28/29), respectively, RR: 1.04; 95% CI; 0.97-1.11). No serious adverse events leading to study dropout occurred. DISCUSSION: We were not able to determine the efficacy of the experimental arm based on the IgG response rate at 5 months after the PPSV23 booster in allo-HSCT recipients.
Subject(s)
Hematopoietic Stem Cell Transplantation , Pneumococcal Infections , Humans , Middle Aged , Streptococcus pneumoniae , Vaccines, Conjugate , Double-Blind Method , Antibodies, Bacterial , Pneumococcal Vaccines , Immunoglobulin G , Hematopoietic Stem Cell Transplantation/adverse effects , Pneumococcal Infections/prevention & controlABSTRACT
The purpose of this study was to investigate Karnofsky performance status (KPS) scores and visual analogue scale (VAS) scores to explain which domains in the standardized self-reported quality of life (QOL) are instrumental for long-term hematopoietic stem cell transplantation (HSCT) survivors. We conducted a nationwide cross-sectional questionnaire study on 221 survivors with allogeneic-HSCT in 28 pediatric centers. Patient-reported QOL was assessed at a single time point using the 36-item Short-Form Survey (SF-36), the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and VAS scores. KPS scores were significantly correlated with both physical and role component summary scores of the SF-36, while the VAS provided by the patient (VASpt) was significantly correlated with the mental component summary score of the SF-36 and many subscales of the FACT-BMT. The VAS provided by the participants' attending physician (VASdoc) was correlated well with KPS scores. A VASpt score more than 40% lower than KPS scores suggested mental health problems. In conclusion, KPS scores might be considered as an indicator for physical and role/social components and VASpt score as an indicator for mental components and HSCT-specific QOL.
Subject(s)
Hematopoietic Stem Cell Transplantation , Quality of Life , Child , Humans , Karnofsky Performance Status , Cross-Sectional Studies , Visual Analog Scale , Survivors , Hematopoietic Stem CellsABSTRACT
PURPOSE: Advances in allogeneic hematopoietic cell transplantation (allo-HCT) have resulted in a growing number of transplant survivors; however, long-term survivors are at risk of developing late complications, and published guidelines recommend screening of this population. We conducted a single-center prospective study to evaluate the adherence to and usefulness of recommended screenings at a long-term follow-up (LTFU) clinic. METHODS: We included consecutive patients who received allo-HCT at our center from 2014, as well as post-HCT patients visiting our outpatient clinic. Visits and screenings were planned at 3 months, 6 months, and 1 year after allo-HCT, and annually thereafter. Outcomes were reported by physicians including the incidence of findings at each screening that led to interventions. RESULTS: Among the 216 participants, 95% visited the LTFU clinic, and 94% completed planned screenings. However, the rate of secondary cancer screenings targeting high-risk subjects was lower (38% to 68%). The overall percentage of screening results leading to interventions was 4.5%, with higher percentages (> 10%) for bone density testing, ophthalmological examinations, dental assessment, upper gastrointestinal endoscopy, and colonoscopy, with two patients diagnosed with secondary cancers. CONCLUSIONS: Although the overall screening rate was high, it should be possible to improve the detection rate of late complications by decreasing screening failures, especially the screening for secondary cancers limited for high-risk survivors. A nationwide effort to educate HCT survivors and health practitioners using standardized nationwide LTFU tools may be effective, along with the development of institutional, local, and nationwide networks to maintain effective follow-up systems.
Subject(s)
Hematopoietic Stem Cell Transplantation , Feasibility Studies , Follow-Up Studies , Humans , Prospective Studies , SurvivorsABSTRACT
A nationwide cross-sectional survey was conducted in long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT) in childhood to investigate the effect of chronic graft-versus-host disease (cGVHD) on quality of life (QOL) and differences in QOL assessments between raters. QOL was evaluated by a visual analogue scale (VAS). Assessments were compared between the survivor, guardian, and attending pediatrician for those aged 15 years or younger, and between the survivor and attending pediatrician for those aged 16 years or older. For cGVHD, severity scores were obtained by organ and their association with the VAS score was analyzed. The average pediatrician-rated VAS score was higher than that of other raters for both patient age groups (< 15 years and > 16 years). By organ, involvement of the skin, digestive organs, and joints in GVHD affected the VAS scores. A high joint score was associated with a low VAS score, and conversely, a high lung score was associated with a low pediatrician-rated VAS score. Our results indicate that differences between raters must be considered when evaluating QOL of HSCT survivors, because patients appeared to experience grater inconvenience and difficulties due to joint GVHD than their pediatricians perceived.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation/mortality , Quality of Life , Survivors , Transplantation, Homologous/mortality , Visual Analog Scale , Adolescent , Age Factors , Child , Chronic Disease , Cross-Sectional Studies , Female , Humans , Japan , MaleABSTRACT
In allogeneic hematopoietic cell transplantation (allo-HCT), investigator-based clinical variables have been used for pretransplantation prognostic prediction, risk adjustment, and post-transplantation long-term screenings. Although several studies have investigated the prognostic significance of pretransplantation patient-reported outcomes (PROs) and longitudinal trends in PROs after allo-HCT, few have assessed these outcomes using the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) and EuroQol 5 Dimension (EQ-5D) index. The present study used 18 items from the SF-12 and EQ-5D index to evaluate the prognostic impact of pretransplantation quality of life (QOL) on allo-HCT outcomes and longitudinal changes in QOL in allo-HCT recipients. This single-center prospective study included consecutive patients who underwent allo-HCT at our center between October 2014 and September 2016. All participants were followed up until October 2017. The SF-12 and EQ-5D index were administered to assess patient-reported QOL before allo-HCT and at 3 months, 6 months, 1 year, and 2 years after allo-HCT when participants visited the long-term follow-up clinic. Longitudinal trends in the QOL-adjusted means were estimated using linear mixed-effects, adjusting for pretransplantation covariates and reasons for missing QOL data. Among 157 patients who underwent allo-HCT, 145 (92%) were registered in this study, and 143 with available QOL data were analyzed. The median pretransplantation scores were 45.3 for the SF-12 physical component score (PCS), 55.6 for the mental component score (MCS), 38.8 for the role/social component score (RCS), 70.0 for the visual analog scale (VAS), and 49.0 for the EQ-5D index. Overall survival (OS) was significantly improved in patients with higher pretransplantation scores on the PCS, RCS, and EQ-5D index, and multivariable analyses showed that the median pretransplantation RCS was significantly associated with OS after allo-HCT (hazard ratio, 3.66; P = .003). The longitudinal trends in the SF-12 score showed that the PCS was improved at 2 years after allo-HCT and was comparable to the normative score for the general population. The MCS remained comparable to or higher than the normative score after allo-HCT. The RCS improved significantly beginning at 6 months after allo-HCT but remained lower than the normative score at 2 years. The VAS and EQ-5D index values showed a drop at 3 months after allo-HCT. Patient-reported QOL assessed by 18 questions on the SF-12 and EQ-5D predicted prognosis, and may be used as a prognosticator to determine treatment strategies, including preparative regimens. Although we experienced a certain amount of patient attrition in the longitudinal follow-up of QOL data, we demonstrated characteristic trajectories of QOL in different domains after adjusting for background covariates and reasons for the lack of QOL data.
Subject(s)
Hematopoietic Stem Cell Transplantation , Quality of Life , Health Surveys , Humans , Prognosis , Prospective StudiesABSTRACT
Halorhodospira (Hlr.) halochloris is a unique phototrophic purple bacterium because it is a triple extremophile-the organism is thermophilic, alkalophilic, and halophilic. The most striking photosynthetic feature of Hlr. halochloris is that the bacteriochlorophyll (BChl) b-containing core light-harvesting (LH1) complex surrounding its reaction center (RC) exhibits its LH1 Qy absorption maximum at 1016 nm, which is the lowest transition energy among phototrophic organisms. Here we report that this extraordinarily red-shifted LH1 Qy band of Hlr. halochloris exhibits interconvertible spectral shifts depending on the electrostatic charge distribution around the BChl b molecules. The 1016 nm band of the Hlr. halochloris LH1-RC complex was blue-shifted to 958 nm upon desalting or pH decrease but returned to its original position when supplemented with salts or pH increase. Resonance Raman analysis demonstrated that these interconvertible spectral shifts are not associated with the strength of hydrogen-bonding interactions between BChl b and LH1 polypeptides. Furthermore, circular dichroism signals for the LH1 Qy transition of Hlr. halochloris appeared with a positive sign (as in BChl b-containing Blastochloris species) and opposite those of BChl a-containing purple bacteria, possibly due to a combined effect of slight differences in the transition dipole moments between BChl a and BChl b and in the interactions between adjacent BChls in their assembled state. Based on these findings and LH1 amino acid sequences, it is proposed that Hlr. halochloris evolved its unique and tunable light-harvesting system with electrostatic charges in order to carry out photosynthesis and thrive in its punishing hypersaline and alkaline habitat.
Subject(s)
Bacterial Proteins/metabolism , Bacteriochlorophylls/metabolism , Ectothiorhodospiraceae/metabolism , Extremophiles/metabolism , Light-Harvesting Protein Complexes/metabolism , Amino Acid Sequence , Hydrogen Bonding , Molecular Conformation , Peptides/metabolism , Photosynthesis , Protein Binding , Static Electricity , ThermodynamicsABSTRACT
BACKGROUND: Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures. CASE PRESENTATION: A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae. CONCLUSION: We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.
Subject(s)
Campylobacter Infections , Campylobacter fetus/isolation & purification , Ceftriaxone/administration & dosage , Foodborne Diseases , Meningitis, Bacterial , Meropenem/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Anti-Bacterial Agents/administration & dosage , Campylobacter Infections/blood , Campylobacter Infections/cerebrospinal fluid , Campylobacter Infections/diagnosis , Campylobacter Infections/drug therapy , Diagnosis, Differential , Drug Therapy/methods , Drug-Related Side Effects and Adverse Reactions/diagnosis , Female , Foodborne Diseases/complications , Foodborne Diseases/diagnosis , Foodborne Diseases/drug therapy , Foodborne Diseases/microbiology , Humans , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Treatment OutcomeABSTRACT
Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms-EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants.
Subject(s)
Dimethylallyltranstransferase/metabolism , Eucommiaceae/enzymology , Hemiterpenes/biosynthesis , Latex/biosynthesis , Plant Proteins/metabolism , Plants, Genetically Modified/enzymology , Dimethylallyltranstransferase/chemistry , Dimethylallyltranstransferase/genetics , Eucommiaceae/genetics , Hemiterpenes/chemistry , Latex/chemistry , Models, Molecular , Molecular Weight , Mutation , Plant Proteins/genetics , Plants, Genetically Modified/genetics , Protein Conformation , Structure-Activity RelationshipABSTRACT
We conducted a cross-sectional observational study investigating socioeconomic status among Japanese survivors of pediatric hematopoietic stem cell transplantation (HCT) and the impact of chronic graft-versus-host disease (cGVHD) on socioeconomic outcomes, which are topics not well explored in the previous research. We collected data on socioeconomic outcomes from 442 HCT survivors through a questionnaire and obtained demographic and clinical information from their attending physicians and a national database between February 2013 and November 2014. We used logistic regression analysis to examine the relationship between cGVHD and socioeconomic outcomes in allogeneic HCT (allo-HCT) survivors. Most survivors did not experience socioeconomic problems. Nevertheless, allo-HCT survivors with cGVHD aged 8-15 years had poorer economic status (p = 0.013), and allo-HCT survivors with cGVHD aged ≥ 16 years were more likely to have never married (p = 0.034) and less likely to have more than a high school education (p = 0.023), compared with allo-HCT survivors without cGVHD. Thus, cGVHD in Japanese allo-HCT survivors was a risk factor for economic difficulties for those aged 8-15 years, and for never marrying and low educational achievement in those aged ≥ 16 years.
Subject(s)
Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Survivors/statistics & numerical data , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Japan/epidemiology , Odds Ratio , Outcome Assessment, Health Care , Public Health Surveillance , Socioeconomic Factors , Transplantation, Autologous , Transplantation, Homologous/adverse effectsABSTRACT
We investigated the efficacy and safety profiles of 4-weekly docetaxel for castration-resistant prostate cancer. Patients treated with ≥2 courses of docetaxel chemotherapy (median, 70 mg/m2) between 2008 and 2018 were included. Among 125 Japanese men, 40 (32.0%) and 85 (68.0%) were treated with 3-weekly and 4-weekly regimens, respectively. In the 4-weekly regimen, the risks of progression, treatment failure, and any-cause mortality were comparable to those in the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. These data suggest that the 4-weekly regimen may be an acceptable option for selected patients.
Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Docetaxel/adverse effects , Docetaxel/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Antineoplastic Agents/administration & dosage , Asian People , Docetaxel/administration & dosage , Humans , Kaplan-Meier Estimate , Male , Prognosis , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Treatment Failure , Treatment OutcomeABSTRACT
An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been established. Three prospective multicenter phase II studies were conducted, in which 142 patients older than 54 years (median age, 61 years; range 55-70 years) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received a myeloablative dose of intravenous busulfan (ivBu, 12.8 mg/kg) along with fludarabine (180 mg/m2) ± low dose total body irradiation for allo-HSCT between September 2009 and February 2013. A total of 103 AML and 39 MDS patients including 21 related bone marrow (BM) or peripheral blood (PB), 50 unrelated BM, and 71 unrelated cord blood (UCB) transplantation were enrolled. Grade 3 or greater toxicities were observed in 105 patients. Neutrophil engraftment was achieved in 70 out of the 71 related PB/BM or unrelated BM recipients, and 61 out of the 71 UCB recipients. The cumulative incidence rates of relapse and non-relapse mortality after 2 years were 24.0 and 24.1%, respectively. The overall and event-free survival rates at 2 years were 53.3 and 47.4%, respectively. The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality in older adults who underwent allo-HSCT with any donor source.
Subject(s)
Busulfan/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Transplantation Conditioning/methods , Age Factors , Aged , Busulfan/adverse effects , Clinical Trials, Phase II as Topic , Disease-Free Survival , Female , Humans , Infusions, Intravenous , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Prospective Studies , Radiation Dosage , Transplantation, Homologous , Treatment Outcome , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Whole-Body Irradiation/methodsABSTRACT
Reduced-intensity conditioning (RIC) has been facilitating allogeneic hematopoietic cell transplantation (allo-HCT) for patients originally considered ineligible for HCT with myeloablative conditioning. Fludarabine (Flu) with reduced doses of busulfan (Bu) (Flu + Bu) and Flu with reduced doses of melphalan (Mel) (Flu + Mel) are widely used RIC regimens for acute myeloid leukemia (AML). A nationwide retrospective study comparing clinical outcomes of adult patients with AML receiving first allo-HCT after RIC between 2001 and 2010 was performed. Cumulative incidences of relapse were not significantly different among the Flu + ivBu-based (FBiv), Flu + poBu-based (FBpo), and Flu + Mel-based (FM) groups (p = 0.29). Non-relapse mortality (NRM) was significantly lower in patients receiving FBiv compared with FBpo (p = 0.003) and FM (p < 0.001). On multivariate analysis, there was no significant difference in overall survival, but FM was associated with a significantly lower risk of relapse (hazard ratio (HR) = 0.65, 95% confidence interval (CI): 0.50-0.85, p = 0.002), higher NRM (HR = 1.60, 95% CI: 1.10-2.33, p = 0.013) and better leukemia-free survival (HR = 0.77, 95% CI: 0.63-0.95, p = 0.015) compared with FBiv. These results suggest that Flu + Mel has a more intense disease control potential and Flu + ivBu is less toxic than the other. Both RIC regimens provide similar survival outcomes and are effective and useful regimens for patients with AML who received allo-HCT.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Busulfan , Humans , Leukemia, Myeloid, Acute/therapy , Melphalan , Retrospective Studies , Transplantation Conditioning , Vidarabine/analogs & derivativesABSTRACT
Understanding of the impact of stem cell donation on donors' health-related quality of life (HRQOL) remains limited. A prospective observational study of eligible unrelated donors enrolled in the Japan Marrow Donor Program was conducted to compare HRQOL and adverse events (AEs) between peripheral blood stem cell (PBSC) and bone marrow (BM) donors. In total, 107 PBSC donors and 108 BM donors were enrolled. HRQOL scores for physical status were significantly lower in BM donors 1 week post-harvest (P < 0.001), but there were no significant differences between the two groups at baseline or 3 months post-harvest. PBSC donors were more likely to experience AEs before harvest (P < 0.001). However, at harvest, moderate-to-severe AEs were more common in BM donors (P = 0.001). After harvest, all grades of AEs were significantly higher in BM donors (P < 0.001). Among BM donors, a lower total physical score at baseline [odds ratio (OR) 1.21], female sex [OR 2.71], and young donors (OR 3.08) were risk factors for moderate-to-severe AEs at harvest, while among PBSC donors, only female sex (OR 4.86) was a risk factor. Our findings show better HRQOL during PBSC donation. These data help support decision-making by potential donors.
Subject(s)
Bone Marrow , Health , Peripheral Blood Stem Cells , Quality of Life , Stem Cells , Tissue Donors , Tissue and Organ Harvesting/adverse effects , Age Factors , Female , Humans , Japan , Male , Prospective Studies , Risk Factors , Sex FactorsABSTRACT
The synergistic extraction of trivalent lanthanoid (Ln(III)) ions with 4-isopropyltropolone (Hipt) and 1,10-phenanthroline (phen) in o-dichrolobenzene (DCB) was investigated. The synergistic effect in DCB is more significant than that in toluene, and the polynuclear complexes found in toluene are not formed in DCB. Based on the 3-dimensional equilibrium analysis, the extracted species for La(III), Eu(III), and Lu(III) are found to be ion-pairs, such as Ln(ipt)2phen·ClO4 and Ln(ipt)2(phen)·ClO4 in the presence of NaClO4 as a salt, and the extraction constants of the respective species were determined. The simultaneous extraction of different lanthanoids in the present extraction system was demonstrated. The separation factors between lighter lanthanoids were larger than those with 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester, an excellent extractant for the separation of lanthanoid ions, in decane.
ABSTRACT
By evaluating risks of late mortality and causes of death among long-term survivors after autologous hematopoietic stem cell transplantation (HSCT) in Japan, we clarified what we should focus on during follow-up to reduce them. The study cohort included 6,780 patients who had survived for ≥2 years after the first autologous HSCT performed from 1974 to 2012 for hematological diseases. With a median follow-up of 6.0 years among survivors, overall survival probabilities at 5 and 10 years after HSCT were 92% and 83%, respectively. Eight hundred thirty deaths occurred: 451, recurrent primary diseases; 87, subsequent solid cancers; 57, subsequent hematological malignancies; 55, infections; 41, respiratory diseases; 19, cardiovascular diseases; 15, liver diseases; 10, neurological diseases; and 7, kidney/genitourinary diseases (Except small numbers of other causes and missing). According to the log-rank test, the risk of overall mortality was remarkably increased among HSCT recipients compared with the that in the general Japanese population (observed/expected ratio [O/E]=5.4; 95% confidence interval [CI], 5.0-5.8). The risks of cause-specific mortality increased with infection (O/E=6.8; 95% CI, 5.1-8.8), subsequent solid cancers (O/E=1.4; 95% CI, 1.1-1.7), subsequent hematological malignancies (O/E=14.3; 95% CI, 10.8-18.5), kidney/genitourinary diseases (O/E=3.4; 95% CI, 1.4-7.1), respiratory disease (O/E=9.0; 95% CI, 6.5-1.2), and liver diseases (O/E=2.6; 95% CI, 1.4-4.2). Long-term survivors after autologous HSCT are at an increased risk of death due to secondary cancers, infections, and any organ diseases as well as recurrence compared to the general population. When monitoring these patients in the outpatient clinic, it is important for physicians to predict a change in the patient's condition and to start treatment earlier.
ABSTRACT
The aim of this study was to determine whether impaired quality of life (QOL) persisted among patients who experienced resolved chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). Eligible participants were patients who were relapse-free for 3 years after allo-HCT who were age ≥16 years at the time of transplantation and age ≥20 years without relapse at the time of the survey. The Medical Outcomes Study's 36-Item Short-Form Survey (SF-36), the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and a visual analog scale (VAS) were administered to assess QOL. Physicians evaluated the current status of chronic GVHD at survey using National Institutes of Health (NIH) criteria, and pretransplantation characteristics and history of GVHD were extracted from the national transplant registry database. Patients without currently active GVHD but with a history of chronic GVHD were categorized as having "resolved GVHD." Of 1250 patients informed of the study, 1216 provided consent and 1130 were included in the final analysis. A total of 745 patients (66%) had currently active chronic GVHD, 149 (13%) had resolved chronic GVHD, and 236 (21%) never had chronic GVHD after allo-HCT. Multivariable analyses showed that compared with patients with resolved or no chronic GVHD, those with active chronic GVHD reported significantly poorer QOL. The QOL scores were similar in patients with resolved chronic GVHD and those without chronic GVHD. Greater between-group differences were observed in SF-36 Physical component and VAS scores in patients age ≥50 years, but the differences were not statistically significant. Our data indicate that only currently active chronic GVHD has a significant impact on physical, mental, and social QOL in allo-HCT survivors, whereas previous chronic GVHD does not impair QOL if it has been resolved.