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記述言語：英語   出版者・発行元：Pediatric Blood and Cancer  

DOI： 10.1002/pbc.30706

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DOI： 10.1182/blood-2023-178288

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DOI： 10.1182/blood-2023-183059

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DOI： 10.1182/blood-2023-189160

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Haematologica  

DOI： 10.3324/haematol.2022.282513

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Haematologica  

DOI： 10.3324/haematol.2022.282385

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3324/haematol.2023.283636

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出版者・発行元：Tetrahedron Letters  

Highly strained diaza[1.1.1] and [1.1.1.1]paracyclophanes were synthesized using Smiles rearrangement (paracyclophane is hereafter abbreviated as PCP). Smiles rearrangement allowed the synthesis of compounds with bridging groups, which could not be obtained using the previously reported Chapman rearrangement method. The two synthetic methods are complementary to each other and therefore useful for the synthesis of diaza[1n]PCP. However, in Chapman rearrangement, the diaza[1.1.1]PCP precursor is a rigid molecule and the precursor could not be synthesized. In contrast, the Smiles rearrangement uses a PCP-precursor rearrangement with low distortion; thus, [1.1.1]PCP can be obtained. Furthermore, the syntheses of 1a and 2 can be performed on a gram scale. However, due to their low solubility, the molecular structure could not be confirmed by crystallographic analysis; therefore, these structures were optimized by DFT calculations and discussed.

DOI： 10.1016/j.tetlet.2023.154762

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare autosomal recessive inborn error of immunity (IEI) characterized by eczematous dermatitis, elevated serum IgE, and recurrent infections, comprising a seemingly hyper-IgE syndrome (HIES). DOCK8 deficiency is only curable with allogeneic hematopoietic cell transplantation (HCT), but the outcome of HCT from alternative donors is not fully understood. Here, we describe the cases of two Japanese patients with DOCK8 deficiency who were successfully treated by allogeneic HCT from alternative donors. Patient 1 underwent cord blood transplantation at the age of 16 years, and Patient 2 underwent haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide at the age of 22 years. Each patient received a fludarabine-based conditioning regimen. Their clinical manifestations, including refractory molluscum contagiosum, promptly improved post-HCT. They achieved successful engraftment and immune reconstitution without serious complications. Alternative donor sources such as cord blood and haploidentical donors can be options for allogeneic HCT for DOCK8 deficiency.

DOI： 10.1007/s12185-023-03613-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Acute graft-versus-host disease (aGVHD) is a challenging complication of allogeneic hematopoietic stem cell transplantation, and alternative therapies for patients showing inadequate response to steroids are limited. Vedolizumab, an anti-α4β7 integrin antibody widely used for treating inflammatory bowel diseases, has recently been studied in adult patients with steroid-refractory intestinal aGVHD. However, few studies have examined its safety and effectiveness in pediatric patients with intestinal aGVHD. We report the case of a male patient with intestinal late-onset aGVHD treated with vedolizumab. He underwent allogeneic cord blood transplantation for warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome and developed intestinal late-onset aGVHD 31 months after transplantation. The patient was refractory to steroids; however, vedolizumab was initiated 43 months after transplantation (at the age of 7 years) and the symptoms of intestinal aGVHD were alleviated. Additionally, favorable endoscopic findings were observed, such as reduction of erosion and regenerative epithelial growth. We also evaluated the efficacy of vedolizumab in 10 patients with intestinal aGVHD (9 from the literature review and the present case). Six patients (60%) showed an objective response to vedolizumab. No serious adverse events were observed in any patients. Vedolizumab is a potential treatment option for steroid-refractory intestinal aGVHD in pediatric patients.

DOI： 10.1007/s12185-023-03590-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatric Neurology  

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. Methods: We investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. Results: Patient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. Conclusion: We treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.

DOI： 10.1016/j.pediatrneurol.2023.03.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Human leukocyte antigen (HLA) mismatched unrelated donor transplantation is associated with an increased risk of graft-versus-host disease, graft failure, and infection, which increases post-transplant morbidity and mortality. In this single-center retrospective study, outcomes were evaluated in 30 consecutive children who underwent bone marrow transplantation (BMT) from HLA 1 allele-mismatched (HLA 7/8-matched) unrelated donors with rabbit anti-thymocyte globulin (rATG) as graft-versus-host disease (GVHD) prophylaxis. The 3-year overall survival (OS), event-free survival (EFS), and GVHD-relapse-free survival rates were 91.7% (95% CI 70.5%–91.9%), 88.3% (95% CI 67.5%–96.1%), and 73.9% (95% CI 52.4%–86.8%), respectively. Grade II–IV and III–IV acute GVHD occurred in 10 (33%) and 2 (7.0%) patients, respectively. The 3-year cumulative incidence of chronic GVHD was 7.8%. No fatal viral infections occurred. The study results show the feasibility of HLA 7/8-matched unrelated BMT with ATG to achieve favorable outcomes and acceptable GVHD, especially for patients who lack a fully matched donor.

DOI： 10.1007/s12185-023-03571-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Anti-thymocyte globulin (ATG) is widely used to reduce acute and chronic graft-versus-host disease (a/cGVHD), one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). As the removal of alloreactive T cells by ATG may also reduce the graft-versus-leukemia effect, the question of whether ATG use affects relapse incidence and survival outcomes in acute leukemia patients with pre-transplant bone marrow residual blasts (PRB) remains controversial. Here, we evaluated the impact of ATG on transplant outcomes in acute leukemia patients with PRB (n = 994) who underwent HSCT from HLA 1-allele mismatched unrelated donors (MMUD) or HLA 1-antigen mismatched related donors (MMRD). In MMUD with PRB (n = 560), multivariate analysis demonstrated that ATG use significantly decreased grade II–IV aGVHD (hazard ratio [HR], 0.474; P = 0.007) and non-relapse mortality (HR, 0.414; P = 0.029) and marginally improved extensive cGVHD (HR, 0.321; P = 0.054) and GVHD-free/relapse-free survival (HR, 0.750; P = 0.069). We concluded that ATG had different effects on transplant outcomes using MMRD and MMUD, and its use would be beneficial to decrease a/cGVHD without increasing non-relapse mortality and relapse incidence in acute leukemia patients with PRB following HSCT from MMUD.

DOI： 10.1007/s12185-023-03563-5

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記述言語：英語   出版者・発行元：Healthcare (Switzerland)  

Background: Depression is frequently seen among pregnant women. This is called antenatal depression (AND). Aim: Our aim was to identify clusters of AND and its core symptoms. Methods: The Patient Health Questionnaire-9 (PHQ-9), Pregnancy-Unique Quantification of Emesis and Nausea (PUQE-24), and Nausea and Vomiting of Pregnancy Quality of Life Questionnaire (NVP-QOL) were distributed to 382 pregnant women with a gestational age of 10 to 13 weeks who were attending antenatal clinics. The two PHQ-9 subscale scores were entered into a 2-step cluster analysis. The PHQ-9 items’ capacity to identify AND were examined in terms of the area under curve (AUC) of a receiver operating characteristic (ROC) analysis. The selected symptom items were examined for their diagnostic capability in terms of the graded response model (GRM) in the item response theory (IRT) analysis. Results: Three clusters emerged. Cluster 3 scored highly in the scores of the two PHQ-9 subscales and the two emesis scales. In the ROC, five items showed an AUC > 0.80. The GRM identified four items with high information: ‘loss of interest’, ‘depressed mood’, ‘self-esteem’, and ‘poor concentration’. Conclusions: The core symptoms of antenatal depression were four non-somatic symptoms; particularly, ‘depressed mood’ and ‘loss of interest’. AND did not exist alone, but was accompanied by nausea and vomiting. Hence, we propose a new category: emesis–depression complex among pregnant women.

DOI： 10.3390/healthcare11101494

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Pediatric Hematology/Oncology  

Differential diagnosis of juvenile hemochromatosis along with hemolytic anemia is often difficult. We report a 23-year-old woman with macrocytic hemolytic anemia with iron overload. The patient showed high serum ferritin and transferrin saturation and low serum transferrin and ceruloplasmin. We also noticed stomatocytes in her blood smear, which was confirmed by scanning electron microscopy. Target gene sequencing identified a mutation in PIEZO1 (heterozygous c.6008C>A: p.A2003D). This mutation was reported previously in a family with dehydrated hereditary stomatocytosis (DHS1, [OMIM 194380]), but in the current case, it was identified to be a de novo mutation. We underscore DHS1 in the differential diagnosis of iron overload associated with non-Transfused hemolytic anemia in children and young adults.

DOI： 10.1097/MPH.0000000000002639

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記述言語：英語   出版者・発行元：American Journal of Hematology  

DOI： 10.1002/ajh.26874

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記述言語：英語   出版者・発行元：Healthcare (Switzerland)  

Insomnia is associated with adverse outcomes in women in the perinatal period; thus, the assessment of insomnia is important for pregnant women. The Insomnia Severity Index (ISI) is an instrument used globally to assess the severity of insomnia. However, its factor structure and structural invariance for pregnant women have not been studied. Therefore, we aimed to conduct factor analyses to search for the best model to fit its structural invariance. A cross-sectional study with the ISI was conducted at one hospital and five clinics in Japan from January 2017 to May 2019. A set of questionnaires was administered on two occasions with a one-week interval. The study included 382 pregnant women ranging in gestational age from 10 to 13 weeks. One week later, 129 participants answered the retest. After exploratory and confirmatory factor analyses, the measurement and structural invariance between parity and two time points was tested. The two-factor structure model showed an acceptable fit for the ISI in pregnant women (χ2 (12) = 28.516, CFI = 0.971, RMSEA = 0.089). The model also showed satisfactory measurement and structure invariance between parity and time points. The findings indicate that the ISI’s use would be appropriate for pregnant women as a two-factor subscale of “severity” and “impact”, regardless of the parity or time point. The ISI’s factor structure may vary by subject; hence, it is necessary to confirm the measurement and structural invariance of the subject for whom the ISI will be used. Furthermore, interventions that focus not only on total scores and cutoff points but also on the phenomenon of subscales should be considered.

DOI： 10.3390/healthcare11081194

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatrics International  

DOI： 10.1111/ped.15557

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記述言語：英語   出版者・発行元：Healthcare (Switzerland)  

Background: Many pregnant women experience impairments in social, occupational, or other important functioning. Aim: This study aimed to confirm measurement and structural invariance of the Sheehan Disability Scale (SDS) and its validity during early pregnancy. Design: Longitudinal study with two observations. Methods: Questionnaires were distributed to pregnant women attending antenatal clinics at gestational weeks 10–13. Of 382 respondents, 129 responded to the SDS again 1 week later. Results: Confirmatory factor analysis shows good fit with the data: χ2/df = 0, comparative fit index (CFI) = 1.000, standardized root mean square residual (SRMR) = 0, and root mean square error of approximation (RMSEA) = 0.718. There is acceptable configural, measurement, and structural invariance of the factor structure between primiparas and multiparas as well as between two observation occasions. The Pregnancy–Unique Quantification of Emesis and Nausea, Patient Health Questionnaire-9, and Insomnia Severity Index subscales explain 47% of the variance in SDS scores. Conclusion: Perinatal health care professionals should pay more attention to the difficulties and disabilities that pregnant women face.

DOI： 10.3390/healthcare10122514

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Clinical Immunology  

Purpose: The aim of this study is to evaluate the usefulness of T cell receptor excision circle (TREC) and/or kappa-deleting recombination excision circle (KREC) measurements integrated with diagnostic next-generation sequencing (NGS) analysis using a severe combined immunodeficiency (SCID) newborn screening (NBS) program. Methods: TREC and/or KREC values were measured in 137,484 newborns between April 2017 and December 2021 using EnLite TREC (n = 80,791) or TREC/KREC kits (n = 56,693). For newborns with positive screening results, diagnostic NGS analysis was performed with a 349-gene panel to detect genetic mutations associated with primary immunodeficiencies (PIDs). Results: A total of 145 newborns (0.11%) had abnormal TREC and/or KREC values, and a genetic diagnosis was established in 2 patients with SCID (1 in 68,742 newborns) (IL2RG-SCID and reticular dysgenesis) and 10 with non-SCID PIDs with T and/or B cell deficiencies (1 in 13,748 newborns) using NGS analysis. Furthermore, TREC values of 2849 newborns were measured and confirmed the significant correlation between the results of both TREC and TREC/KREC kits (P < 0.001) and naïve T cell counts. Conclusions: We performed the first large-scale TREC and TREC/KREC NBS programs in Japan. Our NBS programs followed by the diagnostic NGS analysis for newborns with abnormal TREC and/or KREC values are useful for the early identification and rapid molecular evaluation of not only SCID but also different non-SCID PIDs.

DOI： 10.1007/s10875-022-01335-0

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出版者・発行元：Psychiatry and Clinical Neurosciences Reports  

Aim: The Nausea and Vomiting of Pregnancy Quality of Life (NVP QOL) Questionnaire is a self-report measure of health-related QOL for nausea and vomiting during pregnancy. This study determines the best fitting factor structure for the NVP QOL Questionnaire and explores its measurement invariance in terms of observation time and parity. Methods: A test–retest study of pregnant women was conducted at Gestational Weeks (GWs) 10–13 (T1: N = 381) and 1 week later (T2: n = 128) at one hospital and five clinics with the NVP QOL and the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE). Exploratory and confirmatory factor analyses were performed to compare different factor structure models and evaluate measurement invariance of the best fitting model between two time points and between primiparas and multiparas. Concurrent validity of the NVP QOL was clarified by correlations with the PUQE, Sheehan Disability Scale, and other scales. Results: The one-factor model had the best fit. This factor structure model was acceptable up to the factor invariance level for two time points and up to the factor mean level for primiparas versus multiparas. Correlations between NVP QOL, PUQE, and Sheehan Disability Scale scores were strong. Women with higher NVP QOL scores were more likely to lose weight, have lower daily fluid intake, have reduced fluid and food intake since pregnancy began, and receive outpatient or inpatient treatment. Conclusion: The one-factor structure and measurement invariance of the NVP QOL at different times and parities were demonstrated, suggesting that the NVP QOL can be used to evaluate primiparas and multiparas in a longitudinal study.

DOI： 10.1002/pcn5.21

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Juvenile myelomonocytic leukemia (JMML) is a rare heterogeneous hematological malignancy of early childhood characterized by causative RAS pathway mutations. Classifying patients with JMML using global DNA methylation profiles is useful for risk stratification. We implemented machine learning algorithms (decision tree, support vector machine, and naïve Bayes) to produce a DNA methylation-based classification according to recent international consensus definitions using a well-characterized pooled cohort of patients with JMML (n = 128). DNA methylation was originally categorized into three subgroups: high methylation (HM), intermediate methylation (IM), and low methylation (LM), which is a trichotomized classification. We also dichotomized the subgroups as HM/IM and LM. The decision tree model showed high concordances with 450k-based methylation [82.3% (106/128) for the dichotomized and 83.6% (107/128) for the trichotomized subgroups, respectively]. With an independent cohort (n = 72), we confirmed that these models using both the dichotomized and trichotomized classifications were highly predictive of survival. Our study demonstrates that machine learning algorithms can generate clinical parameter-based models that predict the survival outcomes of patients with JMML and high accuracy. These models enabled us to rapidly and effectively identify candidates for augmented treatment following diagnosis.

DOI： 10.1038/s41598-022-18733-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.

DOI： 10.1038/s41598-022-14161-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatric Hematology and Oncology  

Microsatellite instability (MSI)-high status is associated with good responsiveness to immune checkpoint inhibitors. Although MSI-high status has been actively investigated in pediatric brain tumors, studies of other pediatric solid tumors are lacking. Among 334 consecutive pediatric patients with solid tumors, we retrospectively analyzed formalin-fixed paraffin-embedded tumor tissues of 36 of 74 patients (49%) who died of disease. We assessed the MSI status in these tissues using five multiplexed markers. The results revealed that none of the patients had an MSI-high status. These results indicate that MSI-high status is a rare event in pediatric patients with refractory/relapsed solid tumors. Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1998266.

DOI： 10.1080/08880018.2021.1998266

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Familial Cancer  

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40–44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

DOI： 10.1007/s10689-021-00268-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cancer Medicine  

Background: Patients with primary refractory and relapsed neuroblastoma have a poor prognosis since safe and effective chemotherapies for these patients are currently limited. The development of new chemotherapy regimens for these patients is imperative to improve survival outcomes. Methods: We retrospectively analyzed 40 patients with refractory (n = 36) or relapsed (n = 4) neuroblastoma who received irinotecan, etoposide, and carboplatin (IREC) as a second-line treatment. We evaluated their therapeutic response and the toxicity of IREC. We also assessed the impact of UGT1A1 gene polymorphisms, which are involved in irinotecan metabolism, on outcomes and toxicity. Results: A total of 112 cycles of IREC were administered to 40 patients with a median of 2 cycles per patient (range, 1–9). Six (15%) patients (UGT1A1 wild-type [n = 2] and heterozygous [n = 4]) showed objective responses, including partial response (n = 1), tumor shrinkage (n = 4), and improved findings on their MIBG scan (n = 1). Grade 4 neutropenia, grade 4 leukopenia, and grades 3–4 gastrointestinal toxicity were observed in 110 (98%), 88 (79%), and 3 (3%) cycles, respectively. There was no IREC-related mortality. Patients with UGT1A1 polymorphisms showed a higher frequency of grade 4 leukopenia, but these patients did not have increased treatment-related mortality or non-hematologic toxicity. Conclusions: IREC showed an objective response rate of 15% including 1 case with partial response. IREC was well tolerated regardless of UGT1A1 genotype. This study suggests that IREC is a promising second-line chemotherapy for refractory or relapsed neuroblastoma.

DOI： 10.1002/cam4.4529

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記述言語：日本語   出版者・発行元：(一社)日本小児血液・がん学会  

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blood Advances  

DOI： 10.1182/bloodadvances.2021006044

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Hematology  

Juvenile myelomonocytic leukemia (JMML) is a pediatric hematological malignancy with a poor prognosis. Although several case series have been published describing hematological and molecular responses to azacitidine (AZA) treatment in patients with JMML, the efficacy and safety profile of AZA is not well investigated, especially in Asian children and children undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 5 patients who received a total of 12 cycles (median 2 cycles) of AZA treatment in Japan. All five patients were boys and their ages at the time of treatment were 21, 23, 24, 26, and 46 months, respectively. All five patients tolerated AZA treatment, including four patients who received AZA after HSCT. Therapeutic toxicity with AZA was mostly limited to hematological toxicity. The only serious non-hematological adverse event was hyperbilirubinemia (grades III–IV) observed in a patient who received AZA after a second HSCT. Two out of five patients treated with AZA achieved a partial response (PR), while three patients treated for post-transplant relapse did not have an objective response. Future prospective studies should be conducted to develop combination therapies with AZA and other molecular targeted drugs for high-risk patients.

DOI： 10.1007/s12185-021-03248-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatrics International  

DOI： 10.1111/ped.15275

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Cell Transplantation  

Melphalan is widely used for hematopoietic stem cell transplantation (HSCT) conditioning. However, the relationship between its pharmacokinetic (PK) and transplantation outcomes in children has not been thoroughly investigated. We prospectively analyzed the relationship between melphalan area under the curve (AUC) and transplantation outcome and examined the development of a predictive model for melphalan clearance in children. This study included 43 children aged 0 to 19 years who underwent HSCT following a melphalan-based conditioning regimen from 2017 to 2021. In univariable analysis, high-melphalan AUC resulted in a significantly lower cumulative incidence of acute graft-versus-host disease and a higher cumulative incidence of thrombotic microangiopathy, although no significant difference was observed in survival. Regression analysis of a randomly selected derivation cohort (n = 21) revealed the following covariate PK model: predicted melphalan clearance (mL/min) = 6.47 × 24-h urinary creatinine excretion rate (CER, g/day) × 24-h creatinine clearance rate (CCR, mL/min) + 92.8. In the validation cohort (n = 22), the measured melphalan clearance values were significantly correlated with those calculated based on the prediction equation (R2 = 0.663). These results indicate that melphalan exposure may be optimized by adjusting the melphalan dose according to CER and CCR.

DOI： 10.1177/09636897221143364

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記述言語：英語  

開催年月日： 2022年6月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年2月

記述言語：日本語  

国名：日本国  

開催年月日： 2022年2月

記述言語：日本語  

国名：日本国