Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/bjh.19980

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Authorship：Lead author   Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Pediatric ALK-positive anaplastic large cell lymphoma is a rare subtype of non-Hodgkin lymphoma, and approximately 30% of patients relapse following treatment with conventional chemotherapy. Alectinib monotherapy has demonstrated excellent activity in relapsed and refractory ALCL, but its role as a maintenance therapy after hematopoietic cell transplantation is unclear. We experienced a relapse case of pediatric ALK-positive ALCL with central nervous system involvement treated with alectinib maintenance therapy following cord blood transplantation. The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.

DOI： 10.1007/s00277-024-06000-7

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Language：English   Publishing type：Research paper (scientific journal)  

Cytomegalovirus (CMV) infection is a major complication of hematopoietic stem cell transplantation (HSCT). Previous studies in adults demonstrated that letermovir prophylaxis for 100 d after HSCT reduces the occurrence of CMV infection; however, studies in children are limited. In this study, we aimed to examine the incidence of CMV infection in children who underwent allogeneic HSCT with prophylactic letermovir therapy. A single-center retrospective study was conducted among patients aged ≤17 who underwent allogeneic HSCT. We compared the cumulative incidence of CMV infection, mainly monitored by pp65-antigenemia, after HSCT between patients with and without letermovir prophylaxis (10-12 or 5-6 mg/kg/d when co-administered with cyclosporine) using Gray's test. We analyzed 79 patients with a median follow-up period of 126 d. The median age of these patients was 8.3 years (Interquartile range, 3.7-12.4). Prophylactic letermovir was used in 25 patients. Twenty-five patients developed CMV infection, and the cumulative incidence was 38.9% (95% confidence intervals, 25.0-52.5). The cumulative incidence of CMV infection was not significantly different between the letermovir and no-letermovir groups (33.1 vs. 36.6%, p = 0.228). Meanwhile, the cumulative incidence of CMV infection up to 100 d following HSCT was significantly lower in the letermovir group than in the no-letermovir group (8.0 vs. 32.8%, p = 0.026). Most patients experienced no noticeable adverse effects associated with letermovir; however, one patient discontinued letermovir because of nausea and anorexia. In conclusion, the results of this study suggest that letermovir prophylaxis against CMV infection may be effective in children without severe adverse effects.

DOI： 10.1248/bpb.b24-00217

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Objective

This study primarily focused on the diagnostic interval (DI), defined as the duration from the onset of leukemic symptoms to diagnosis. We investigated whether a prolonged DI is associated with the outcomes of pediatric leukemia.

Methods

We retrospectively collected data of children with newly diagnosed pediatric leukemia at Okayama University Hospital from January 2007 to December 2022. Survival analyses were conducted using Kaplan–Meier methods, and an unadjusted analysis to compare differences in survival was performed using the log‐rank test.

Results

In total, 103 children with leukemia were included in the analysis. The median DI was 20 days (interquartile range, 9.5–33.5 days). A prolonged DI (≥30 days) demonstrated no association with either 5‐year event‐free survival (70.1% for <30 days and 68.3% for ≥30 days, p = .99, log‐rank test) or overall survival (84.7% for <30 days and 89.4% for ≥30 days, p = .85, log‐rank test).

Conclusions

A prolonged DI was not associated with the survival of children with leukemia. If a precise classification of leukemia biology is provided for pediatric patients, a prolonged DI may have little impact on the prognosis of these patients.

DOI： 10.1111/ejh.14162

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Transfusion Medicine and Cell Therapy  

DOI： 10.3925/jjtc.69.605

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Language：English  

A three-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ALL) presented with an osteolytic lesion in his right upper arm. Tyrosine kinase inhibitors (TKIs) such as imatinib and dasatinib are an essential component throughout the course of treatment for Ph+ALL. However, TKIs are reported to affect the bone metabolism. In the treatment course of the current patient, the osteolytic lesion quickly improved despite the continuous use of TKIs, even during the concomitant use of corticosteroids. This suggests that TKIs can be safely given with concomitant corticosteroids to children with Ph+ALL, even when osteolytic lesions are present.

DOI： 10.18926/AMO/65757

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1002/pbc.30108

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Language：English  

Among patients with transient abnormal myelopoiesis (TAM) associated with Down syndrome, approximately 20% die within 6 months from multiorgan failure, especially liver fibrosis. We experienced three children with TAM who had low white blood cell counts but increased bilirubin levels. Here, we discuss the detailed clinical courses of these patients, including the pathological findings of liver biopsies. Our cases, together with previous literature, suggest that liver biopsy can be performed safely and provides useful information, especially regarding disease activities, and that low-dose cytarabine is a reasonable option to prevent early death in TAM patients with liver dysfunction.

DOI： 10.18926/AMO/65153

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Varicella-zoster virus (VZV) reactivation is a serious complication of hematopoietic stem cell transplantation (HSCT). Although low-dose acyclovir can prevent VZV reactivation after HSCT in adults, the efficacy of a dose of acyclovir lower than the recommended dose, such as 60-80 mg/kg/day in children, is unclear. In this study, we aimed to evaluate the incidence of VZV reactivation after HSCT during and after low-dose acyclovir administration for preventing VZV reactivation in children. METHODS: This single-center retrospective study included children aged ≤15 years who received oral acyclovir (at 15 mg/kg/day) to prevent VZV reactivation after HSCT. We examined the cumulative incidence of VZV reactivation after HSCT, during and after prophylactic acyclovir administration. RESULTS: Fifty-three eligible patients were included in this study, of whom 37 underwent allogeneic HSCT. The median duration of prophylactic acyclovir therapy was 264 days (range: 69-1140 days). VZV reactivation occurred in 13 patients (24.5%, 95% confidence interval [CI]: 14.9-37.6). The cumulative incidence of VZV reactivation 1 and 2 years after HSCT was 6.26% (95% CI: 1.60-15.5) and 20.9% (95% CI: 10.3-34.0), respectively. While only one patient developed VZV reactivation during the administration of prophylactic acyclovir, the cumulative incidence of VZV reactivation increased to 24.2% (95% CI: 12.5-38.0) 1 year after the cessation of acyclovir. CONCLUSION: Low-dose acyclovir (15 mg/kg/day) could be effective for preventing VZV reactivation after HSCT in children because VZV reactivation seldom occurs during the administration of 15 mg/kg/day acyclovir.

DOI： 10.1002/pbc.29979

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Language：English  

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A-rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A-MLLT3-rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A-MLLT3-rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre-post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.

DOI： 10.1111/cas.15380

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Language：English   Publishing type：Research paper (scientific journal)  

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. As overall cure rates of childhood ALL have improved, reduction of overall treatment intensity while still ensuring excellent outcomes is imperative for low-risk patients. We report the outcomes of patients treated following the standard-risk protocol from the prospective Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study, which was conducted between 2002 and 2008 for patients with newly diagnosed ALL aged 1-18 years. Of 1138 patients with B-cell precursor ALL, 388 (34.1%) were allocated to this protocol. Excellent outcomes were achieved despite the overall treatment intensity being lower than that of most contemporary protocols: 4 years event-free survival (EFS) was 92.3% and 4 years overall survival 98.2%. Patients with high hyperdiploidy (HHD) involving triple trisomy (trisomy of chromosomes 4, 10, and 17) or ETV6-RUNX1 had even better outcomes (4 years EFS 97.6% and 100%, respectively). Unique characteristics of this protocol include a selection of low-risk patients with a low initial WBC count and good early treatment response and reduction of cumulative doses of chemotherapeutic agents while maintaining dose density. In Japan, we are currently investigating the feasibility of this protocol while incorporating minimal residual disease into the patient stratification strategy.

DOI： 10.1007/s12185-022-03315-x

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/bjh.18068

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Authorship：Lead author   Language：English  

DOI： 10.1080/08880018.2021.1955059

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ped.15275

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J-GLOBAL

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Authorship：Lead author  

J-GLOBAL

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Language：English   Publishing type：Research paper (scientific journal)  

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

DOI： 10.1007/s00277-018-3554-8

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Patients with multi-system (MS)-type langerhans cell histiocytosis (LCH) show poor outcomes, especially congenital MS LCH cases were shown in high mortality rate. We experienced a congenital case of MS LCH with high risk organs, who needed intensive respiratory support after birth. Even though intensive chemotherapy was discontinued, this patient's lung LCH lesions gradually became reduced and his respiratory condition recovered; therefore, we restarted and completed maintenance chemotherapy. The patient maintained complete remission for more than 4 years after the end of chemotherapy. Our case suggests that congenital MS LCH even with severe organ involvement can be treated successfully with chemotherapy.

DOI： 10.18926/AMO/56459

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Acute megakaryoblastic leukemia in children without Down syndrome (non-DS AMKL) is considered to be a poor prognostic subtype in acute myeloid leukemia. Recently, some chimeric fusion genes were found in pediatric non-DS AMKL; therefore, we attempted to detect chimeric fusion genes RBM15-MKL1, CBFA2T3-GLIS2, and NUP98-KDM5A from 10 pediatric non-DS AMKL diagnostic samples using polymerase chain reaction and Sanger sequencing methods. Two samples were positive for RBM15-MKL1, four had CBFA2T3-GLIS2, and only one case had NUP98-KDM5A. Both RBM15-MKL1-positive patients showed long-term remission after chemotherapy. The eight RBM15-MKL1-negative patients received hematopoietic stem cell transplantation (HSCT). In four CBFA2T3-GLIS2-positive patients, three had HSCT without complete remission and two of themdied. Additional treatment stratification depending on chimeric fusion genes and development of new therapeutic drugs are required for non-DS AMKL.

DOI： 10.11406/rinketsu.60.99

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：English   Publisher：(一社)日本血液学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

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Language：Japanese   Publisher：(一社)日本血液学会-東京事務局  

J-GLOBAL

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Event date： 2024.3.16

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2024.3.16

Language：Japanese  

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Event date： 2023.10.13 - 2023.10.15

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2023.10.11 - 2023.10.14

Language：English   Presentation type：Poster presentation  

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Event date： 2021.11.25 - 2021.11.27

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2021.11.25 - 2021.11.27

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2021.11.25 - 2021.11.27

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2021.9.23 - 2021.9.25

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2020.11.20 - 2020.11.22

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.11.14 - 2019.11.16

Language：Japanese   Presentation type：Poster presentation  

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