研究者詳細 - 嶋　晴子

Combined Tyrosine Kinase Inhibitors and Chemotherapy Based on Minimal Residual Disease in Children With Ph+ Acute Lymphoblastic Leukemia: A Phase 2 Single-Arm Trial, JCCG ALL-Ph13

Sato A., Kodama Y., Kawasaki H., Ohki K., Oshima K., Deguchi T., Hashii Y., Iijima-Yamashita Y., Yonezawa S., Imamura C.K., Shima H., Sakaguchi H., Kato K., Kato M., Hiramatsu H., Ito E., Yamamoto M., Inoue A., Sakaguchi K., Kosaka Y., Hasegawa D., Kiyokawa N., Kada A., Saito A.M., Manabe A., Horibe K., Shimada H.

Pediatric Blood and Cancer 73 （ 4 ） 2026年04月

ISSN 15455009

　概要を見る

Background: Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph<sup>+</sup> ALL) have a poor prognosis. In Ph+ALL04, allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR) was indicated for all patients, and was performed in those who remained in CR at the scheduled time of transplantation, with 4-year event-free survival (EFS) and overall survival (OS) rates of 54% (95% confidence interval [CI]: 38%–68%) and 78% (95% CI: 62%–88%), respectively. Procedure: The Japan Children's Cancer Group conducted ALL-Ph13, a multicenter single-arm Phase 2 clinical trial, to improve outcomes and reduce HSCTs by using chemotherapy with tyrosine kinase inhibitors (TKIs) guided by minimal residual disease (MRD). The primary endpoint was the 3-year EFS rate. Results: Between 2013 and 2017, 41 of 43 enrolled patients with Ph<sup>+</sup> ALL aged 1–19 years were eligible. Imatinib was started on Day 15 of induction and switched to dasatinib if MRD-positive after consolidation IB. TKIs were administered until the end of maintenance treatment (Week 104), with temporary discontinuation due to the severity of nonhematological adverse events and resumption at 80% of the original dose. When MRD was positive after the three HR blocks, HSCT was performed. Following four sepsis-related deaths, the protocol was amended in 2016, after which no such deaths occurred. Six patients (15%) underwent HSCT in the first CR, one per protocol indication and five without. The 3-year EFS and OS rates were 65% (95% CI: 48%–78%) and 85% (95% CI: 70%–93%), respectively. As several relapses occurred beyond 3 years, the 5-year EFS and OS rates were also calculated: 48% (95% CI: 30%–64%) and 85% (95% CI: 70%–93%), respectively. Conclusions: Compared with Ph+ALL04, HSCT was substantially reduced in ALL-Ph13 while maintaining comparable outcomes. Further optimization of treatment, particularly the duration of TKI administration, is needed to maintain long-term EFS.
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Favorable outcomes of de novo advanced phases of pediatric chronic myeloid leukemia in the tyrosine kinase inhibitor era

Yoshikawa T., Ishida H., Watanabe A., Yuza Y., Shima H., Ito M., Sakurai Y., Keino D., Ichimura T., Kato K., Osugi Y., Sunami S., Shinoda K., Imamura T., Koh K., Okimoto Y., Tono C., Shimada H., Tanizawa A.

International Journal of Hematology 122 （ 1 ） 117 - 127 2025年07月

ISSN 09255710

　概要を見る

Chronic myeloid leukemia (CML) is a rare disease during childhood, and accelerated phase (AP) and blast phase (BP) CML, also called advanced phases, are even rarer. We retrospectively collected and analyzed clinical data of children younger than 20 years with de novo advanced-phase CML between 1996 and 2017 in Japan. Median follow-up time was 8.9 years for AP-CML (n = 15) and 3.7 years for BP-CML (n = 32). The 5-year overall survival (OS) was 93.3% for AP-CML, and 100.0% for patients who received tyrosine kinase inhibitors (TKIs) in first-line therapy (n = 10). Four of the ten patients who received TKIs in first-line therapy remained in molecular remission without transplantation (median follow-up 5.5 years). The 5-year OS of patients with BP-CML was 79.0%, and most patients received chemotherapy before transplantation, with regimen selection based on blast immunophenotype. Furthermore, among patients who received transplantation after TKI therapy, the 5-year OS was 100.0% for AP and 84.8% for BP. In conclusion, our study confirmed excellent outcomes in children with de novo advanced-phase CML, especially in the TKI-era.
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Management of children and adolescents with chronic myeloid leukemia in chronic phase: International pediatric chronic myeloid leukemia expert panel recommendations

Millot F., Ampatzidou M., Moulik N.R., Tewari S., Elhaddad A., Hammad M., Pichler H., Lion T., Tragiannidis A., Shima H., An W., Yang W., Karow A., Farah R., Luesink M., Dworzak M., Sembill S., De Moerloose B., Sedlacek P., Schultz K.R., Kalwak K., Versluys B., Athale U., Hijiya N., Metzler M., Suttorp M.

Leukemia 39 （ 4 ） 779 - 791 2025年04月

ISSN 08876924

　概要を見る

The treatment strategy for children and adolescents with chronic myeloid leukemia in the chronic phase (CML-CP) has evolved from allogeneic hematopoietic stem cell transplantation (HSCT) to tyrosine kinase inhibitors (TKIs). With the advent of next-generation TKIs and new targeted therapies in the CML field, an international pediatric CML expert panel provides recommendations based on the medical literature (including previous pediatric guidelines), national standards, and treatment principles used in adults with CML-CP. Recommendations include diagnosis of the disease and details on managing the initial steps of care of children and adolescents with newly diagnosed CML-CP, including complications such as leukostasis. The treatment recommendations are based on the initiation of therapy with a first- or second-generation TKI according to the allocated European Treatment and Outcome Study (EUTOS) long-term survival score risk group of the patient. The subsequent steps are based on the results of recommended monitoring which can justify a switch to another TKI or a drug in development if there is resistance or toxicity. The panel also provides recommendations regarding the discontinuation criteria for TKIs in children and adolescents in sustained deep molecular response. Allogeneic HSCT is not recommended as the first-line of treatment for children with CML-CP but is to be considered in case of progression to the advanced phase or failure of several lines of treatment. The present treatment and management recommendations are intended to provide advice to clinicians in view of optimizing the care and the outcome of children and adolescents with CML-CP.
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Sex education to an adolescent male with Down syndrome in a single-mother family in Japan

Saito A., Sato T., Shima H., Yamagishi H., Narumi S., Ishii T., Hasegawa T.

Pediatrics International 67 （ 1 ） 2025年01月

ISSN 13288067
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Refractory Burkitt Lymphoma With False-positive and False-negative Mass Detected on Positron Emission Tomography-computed Tomography After Chemotherapy

Shima H., Takaki T., Ito J., Iwabuchi Y., Nakazawa A., Shimada H.

Journal of Pediatric Hematology Oncology 45 （ 7 ） E915 - E916 2023年10月

ISSN 10774114

　概要を見る

A 4-year-old boy with an abdominal mass extending from the spleen to the lower umbilicus was diagnosed with Burkitt lymphoma stage III. Because the fluorodeoxyglucose uptake on positron emission tomography (PET)-computed tomography of the residual splenic tumor remained elevated, splenectomy was performed. The PET-positive area was composed of inflammatory infiltrates, whereas the PET-negative area was composed of a viable tumor surrounded by necrotic or dying tumor cells. The residual tumor may have been false-negative for PET because of its poor proliferative potential. In this case, the comparison of PET-computed tomography and pathologic findings demonstrates the simultaneous presence of a false-positive inflammatory lesion and a false-negative residual tumor.
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