Myeloproliferative neoplasm harboring both monosomy 7 and an fusion gene: Proposal for a new disease entity.

Introduction: We present a case of a 9-year-old girl diagnosed with a myeloproliferative neoplasm (MPN) harboring both monosomy 7 and an ALK/ROS1 fusion gene.

Case Presentation: The neoplasm was resistant to conventional AML chemotherapy and required hematopoietic cell transplantation (HCT) to achieve remission.

Discussion: MPNs with monosomy 7 and ALK/ROS1 fusions occur in a wide age range of children and adults, and require HCT for long-term remission.

Surface-Enhanced Raman Scattering on Size-Classified Silver Nanoparticles Generated by Laser Ablation.

This study delved into the complex interplay between the nanostructural characteristics of nanoparticles and their efficacy in surface-enhanced Raman scattering (SERS) for sensitive detection of trace chemical substances. Silver nanoparticles were prepared for the SERS substrate by combining laser ablation, postannealing processes (up to 500 °C), and electrostatic mobility classification, allowing high-purity silver nanoparticles with controlling their sizes (40-100 nm) and aggregate structures. These nanoparticles were then inertially deposited on the substrates to create SERS-active surfaces, employing Rhodamine B as a probe to assess the impact of particle size, shape, and deposition density on SERS effectiveness.

Allogeneic Hematopoietic Cell Transplantation With Reduced Toxicity Conditioning for Pediatric B Lymphoid Malignancy.

Background: Conventional conditioning regimens for children with lymphoid malignancy undergoing allogeneic hematopoietic cell transplantation (HCT) are myeloablative and involve high-dose total body irradiation (TBI). Such regimens are associated with significant late complications.

Observations: Here, we used a reduced-toxicity conditioning regimen comprising fludarabine, cytarabine, melphalan, and low-dose TBI (FLAMEL) to treat 5 patients with lymphoid malignancy before HCT.

Analysis of overweight/obese pediatric patients with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study.

The dosage of chemotherapy drugs for overweight/obese children with acute myeloid leukemia (AML) has been empirically reduced based on ideal body weight (BW) in Japan to reduce the risk of adverse events. We investigated the associations between pre-therapeutic body mass index (BMI) and clinical outcomes among children with AML. A total of 280 children were divided into two groups based on the World Health Organization Child Growth Standards: a healthy-weight group (n = 254), and an overweight/obese group (n = 26).

Leukaemic cells expressing ETV6::FRK are sensitive to dasatinib in vivo.

ETV6::Fyn-related kinase (FRK), which is a Src family tyrosine-kinase-related fusion gene and firstly identified in our patient with paediatric high risk B cell precursor acute lymphoblastic leukaemia (B-ALL), has no evidence of efficacy of tyrosine kinase inhibitor in vivo. We performed functional analysis of ETV6::FRK to establish molecular targeting therapy and determined that dasatinib could abrogate proliferation activity of ETV6::FRK through the repression of FRK-STAT3/STAT5 pathway in vitro and significantly extended the survival time of the xenografted mice in vivo ( < 0.01).

Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan.

Purpose: Artemis is an exonuclease essential for V(D)J recombination and repair of DNA double-stranded breaks. Pathogenic variants in DCLRE1C encoding Artemis cause TBNK severe combined immunodeficiency (SCID), and patients with Artemis-deficient SCID (ART-SCID) require definitive therapy with allogeneic hematopoietic cell transplantation (HCT). Here we describe the clinical and genetic characteristics of patients with ART-SCID who were diagnosed in Japan from 2003 to 2022.

Targeting FLT3-specific chimeric antigen receptor T cells for acute lymphoblastic leukemia with KMT2A rearrangement.

CD19-specific chimeric antigen receptor T (CAR T) immunotherapy is used to treat B-cell malignancies. However, antigen-escape mediated relapse following CAR T therapy has emerged as a major concern. In some relapsed cases, especially KMT2A rearrangement-positive B-acute lymphoblastic leukemia (KMT2A-r B-ALL), most of the B-cell antigens are lost via lineage conversion to the myeloid phenotype, rendering multi-B-cell-antigen-targeted CAR T cell therapy ineffective.

[HLA-mismatched bone marrow transplantation with post-transplant cyclophosphamide for pediatric patients with aplastic anemia].

Post-transplant cyclophosphamide (PTCy) has improved the efficacy of HLA-mismatched hematopoietic cell transplantation (HCT) by decreasing the risk of graft-versus-host disease (GVHD) and nonrelapse mortality. If an HLA-matched donor is not available, GVHD prophylaxis with PTCy can also be used for HLA-mismatched HCT in patients with pediatric aplastic anemia (AA). We report two cases of pediatric AA that were treated with HLA-mismatched HCT with reduced-intensity conditioning and PTCy.

Reliability and Validity of the Japanese Pediatric Version of Memorial Symptom Assessment Scale.

Context: Few instruments in Japanese assess health-related quality of life in pediatric cancer patients.

Objectives: To translate the Memorial Symptom Assessment Scale (MSAS) into Japanese pediatric and proxy versions (MSAS-J 7-12, MSAS-J 13-18, and MSAS-J-Proxy) and assess validity and reliability.

Methods: Phase I comprised forward-backward translation and pilot testing in 13 children and 16 guardians.

Genetic Study of Fanconi Anemia in Infancy Revealed FANCI Mutations and Defective ALDH2 Variant: A Case Report.

Fanconi anemia (FA) is a rare genetic disorder that manifests as congenital abnormalities and bone marrow failure (BMF). Most patients with FA present with BMF within the first decade of life; however, neonate and early infancy BMF is rare. Recent studies have shown that a defective aldehyde dehydrogenase 2 (ALDH2) variant accelerates BMF development in patients with FA.

Supportive care for hemostatic complications associated with pediatric leukemia: a national survey in Japan.

Optimal supportive care for disseminated intravascular coagulation (DIC) and hemostatic complications by asparaginase is indispensable for the successful treatment of pediatric leukemia. However, the situation regarding this type of care in Japan is unclear. We conducted a questionnaire-based survey at 155 institutions treating childhood leukemia in Japan.

Successful treatment with 2-chlorodeoxyadenosine of refractory pediatric Langerhans cell histiocytosis with initial involvement of the gastrointestinal tract.

Gastrointestinal (GI) tract involvement in Langerhans cell histiocytosis (LCH) is extremely rare. Langerhans cell histiocytosis with GI tract involvement (GI-LCH) is frequently associated with multi-system disease, and usually presents with severe systemic symptoms, such as protein-losing enteropathy (PLE). Although the GI tract is not included among the organs at risk, the prognosis of GI-LCH is poor, and no effective chemotherapeutic regimen has been identified.

[Pure red cell aplasia following the rapid reduction and discontinuation of cyclosporine for mixed chimerism after allogeneic bone marrow transplantation].

A 19-year-old male with therapy-related myelodysplastic syndrome underwent allogeneic bone marrow transplantation with reduced-intensity conditioning from his HLA-identical sibling whose ABO blood type exhibited major incompatibility with the patient. After post-transplantation 1 month, chimerism analysis of the bone marrow revealed mixed chimerism with 30% of recipient cells, and after post-transplantation 3 months, complete remission was maintained; however, recipient granulocytes were elevated up to 50% per the chimerism analysis. Next, pancytopenia developed following the rapid discontinuation of the immunosuppressive agent.

KMT2A-rearranged infantile acute myeloid leukemia masquerading as juvenile myelomonocytic leukemia.

Mixed lineage leukemia [MLL; now known as lysine methyltransferase 2A (KMT2A)] rearrangement-positive acute myeloid leukemia (AML) and juvenile myelomonocytic leukemia (JMML) are distinct diseases, although age of susceptibility (infancy or early childhood) and abnormal monocytosis are common clinical features. Here, we report two cases of KMT2A-rearranged infantile AML masquerading as JMML at initial presentation. Both cases showed leukocytosis accompanied by atypical monocytosis.

[Monitoring of minimal residual disease after HLA-mismatched allogeneic hematopoietic stem cell transplantation using six-color based HLA-Flow method in pediatric acute leukemia].

HLA-Flow is a flow cytometry-based method using anti-HLA antibodies against mismatched HLA alleles combined with the antibodies against antigens expressed on leukemic cells. It is a sensitive assay to determine minimal residual disease (MRD) after HLA mismatched hematopoietic stem cell transplantation (HSCT). In this study, we report the results of our HLA-Flow using six-color based multicolor fluorescence-activated cell sorting for HLA-mismatched HSCT.

Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do mutations contribute to vulnerability to parkinsonism?

Phosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by , which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition.

Allogeneic Hematopoietic Cell Transplantation for Dyskeratosis Congenita: A Report of 3 Cases.

Although bone marrow failure in patients with dyskeratosis congenita (DKC) can be successfully treated with allogeneic hematopoietic cell transplantation (allo-HCT) using a reduced intensity conditioning (RIC) regimen, the outcome of nonhematological disorders in patients with DKC treated with allo-HCT using RIC has not been fully elucidated. Here, we describe the clinical course of nonhematological disorders after allo-HCT with RIC in 3 consecutive patients with DKC. Allo-HCT with RIC was feasible in all cases; however, patient 1 developed lethal pulmonary disease and patient 2 experienced progression of hepatic fibrosis.