Distinct Expression Profiles of Neuroblastoma-Associated mRNAs in Peripheral Blood and Bone Marrow of Non-High-Risk and High-Risk Neuroblastoma Patients.

Non-high-risk (non-HR) neuroblastoma (NB) patients have excellent outcomes, with more than a 90% survival rate, whereas HR NB patients expect less than a 50% survival rate. Metastatic disease is the principal cause of death among both non-HR and HR NB patients. Previous studies have reported the significant but limited prognostic value of quantitative PCR (qPCR)-based assays, measuring overlapping but different sets of neuroblastoma-associated mRNAs (NB-mRNAs), to detect metastatic disease in both non-HR and HR patient samples. A droplet digital PCR (ddPCR)-based assay measuring seven NB-mRNAs (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was recently developed and exhibited a better prognostic value for HR patient samples than qPCR-based assays. However, it remained to be tested on non-HR patient samples. In the present study, we employed the ddPCR-based assay to study peripheral blood (PB) and bone marrow (BM) samples collected at diagnosis from eight non-HR and eleven HR cases and characterized the expression profiles of NB-mRNAs. The most highly expressed NB-mRNAs in PB and BM differed between non-HR and HR cases, with the CRMP1 mRNA being predominant in non-HR cases and the GAP43 mRNA in HR cases. The levels of NB-mRNAs in PB and BM were 5 to 1000 times lower in non-HR cases than in HR cases. The PB to BM ratio of NB-mRNAs was 10 to 100 times higher in non-HR cases compared to HR cases. The present case series suggests that non-HR and HR NB patients have the distinct expression profiles of NB-mRNAs in their PB and BM.

Impact of prophylactic echinocandin on the development of neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation: A single-center retrospective study.

BACKGROUND: Although neurotoxicity is a major adverse event associated with busulfan, little information is available regarding the association between drug interactions and neurological symptoms during busulfan-based regimens. This study evaluated the association between prophylactic echinocandins and neurological complications in patients receiving busulfan-containing conditioning regimens for stem cell transplantation. METHODS: We retrospectively included consecutive patients who administered intravenous busulfan as a conditioning regimen at our facility between 2007 and 2022. Prophylactic echinocandin use was defined as the use of an echinocandin antifungal drug to prevent invasive fungal disease in SCT recipients. The primary outcome was the incidence of neurological complications within 7 days of busulfan initiation and was compared between the echinocandin group (patients received prophylactic echinocandin) and nonechinocandin group (patients received prophylactic antifungal drugs other than echinocandin and those without antifungal prophylaxis). RESULTS: Among the 59 patients included in this study, the incidence of neurological complications in the echinocandin (n = 26) and nonechinocandin groups (n = 33) was 30.8% and 63.6%, respectively. We observed a negative association between prophylactic echinocandin use and the development of neurological complications after adjusting for the propensity score for receiving prophylactic echinocandins (adjusted odds ratio 0.294, 95% confidence interval 0.090 to 0.959). We observed a lower incidence of neurological complications in the echinocandin group than in the nonechinocandin group. CONCLUSION: Our results suggested that the choice of antifungal prophylaxis is associated with busulfan neurotoxicity.

A novel NFKB1 variant in a Japanese pedigree with common variable immunodeficiency.

Recently, heterozygous loss-of-function NFKB1 variants were identified as the primary cause of common variable immunodeficiency (CVID) in the European population. However, pathogenic NFKB1 variants have never been reported in the Japanese population. We present a 29-year-old Japanese woman with CVID. A novel variant, c.136 C > T, p.(Gln46*), was identified in NFKB1. Her mother and daughter carried the same variant, demonstrating the first Japanese pedigree with an NFKB1 pathogenic variant.

Comparison of passive-scattered and intensity-modulated proton beam therapy of craniospinal irradiation with proton beams for pediatric and young adult patients with brain tumors.

PURPOSE: To investigate the dose stability of craniospinal irradiation based on irradiation method of proton beam therapy (PBT). METHODS AND MATERIALS: Twenty-four pediatric and young adult brain tumor patients (age: 1-24 years) were examined. Treatment method was passive-scattered PBT (PSPT) in 8 patients and intensity-modulated PBT (IMPT) in 16 patients. The whole vertebral body (WVB) technique was used in 13 patients whose ages were younger than 10, and vertebral body sparing (VBS) technique was used for the remaining 11 patients aged 10 and above. Dose stability of planning target volume (PTV) against set-up error was investigated. RESULTS: The minimum dose (Dmin) of IMPT was higher than that of PSPT (p = 0.01). Inhomogeneity index (INH) of IMPT was lower than that of PSPT (p = 0.004). When the irradiation field of the cervical spinal cord level (C level) was shifted, the maximum dose (Dmax) was lower in IMPT, and mean dose (Dmean) was higher than PSPT as movement became greater to the cranial-caudal direction (p = 0.000-0.043). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.034). When the irradiation field of the lumber spinal cord level (L level) was shifted, Dmax was lower in IMPT as movement became greater to the cranial direction (p = 0.000-0.028). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.022). CONCLUSIONS: The PTV doses of IMPT and PSPT are robust and stable in both anterior-posterior and lateral directions at both C level and L level, but IMPT is more robust and stable than PSPT for cranial-caudal movements. TRIAL REGISTRY: Clinical Trial Registration number: No. 04-03.

Reduced-intensity allogenic transplantation for children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Survival rates of patients with Philadelphia chromosome-positive ALL (Ph+ALL) have improved considerably with the introduction of tyrosine kinase inhibitors (TKI); however, hematopoietic stem cell transplantation (HSCT) continues to play an important role. Reduced-intensity conditioning (RIC) regimens have been widely applied particularly for older patients, but their validity for children and adolescents with Ph+ALL has not been investigated. In this study, data from patients receiving HSCT for de novo Ph+ALL in first or second remission at ages younger than 25 years and with a history of pre-HSCT TKI therapy were retrospectively collected through the nationwide registry in Japan. In 265 patients who received myeloablative conditioning (MAC) and 33 patients receiving RIC, 5-year leukemia-free survival (LFS) rates were 67.3% and 79.8%, respectively (p = 0.142). Multivariate analysis of LFS, focusing on patients with good performance status, identified RIC as a significant prognostic factor for LFS (hazard ratio 0.32, p = 0.032), as well as older age, higher leukocyte count at diagnosis, and disease with additional chromosomal abnormalities. These trends were similar when we focused on patients who received prophylactic post-HSCT TKI treatment, as 5-year LFS was 81.0% for MAC and 84.4% for RIC (p = 0.748). In summary, HSCT with RIC regimen showed at least comparable LFS to HSCT with MAC regimen, and RIC was an independent favorable prognostic factor on multivariate analysis adjusting potential prognostic factors. While patient numbers were limited, our data suggest that RIC may be safely applied in this group, particularly combined with prophylactic post-HSCT TKI maintenance therapy.

Development and evaluation of a rapid one-step high sensitivity real-time quantitative PCR system for minor BCR-ABL (e1a2) test in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).

OBJECTIVE: Minimal residual disease assessment of BCR-ABL messenger ribonucleic acid levels is crucial in Philadelphia chromosome-positive acute lymphoblastic leukemia for prognosis and treatment planning. However, accurately quantifying minor BCR-ABL transcripts, which comprise 70% of Philadelphia chromosome-positive acute lymphoblastic leukemia cases, lacks a national-approved method. METHODS: We developed the "Otsuka" minor BCR-ABLmessenger ribonucleic acid assay kit with exceptional precision (0.00151%). Minor BCR-ABL messenger ribonucleic acid levels were analyzed in 175 adults, 36 children with acute lymphoblastic leukemia and 25 healthy individuals to evaluate the kit's performance. RESULTS: The "Otsuka" kit showed high concordance with a commonly used chimeric gene screening method, indicating reliable detection of positive cases. Quantitative results demonstrated a robust correlation with both a laboratory-developed test and a diagnostic research product. The "Otsuka" kit performs comparably or even surpass to conventional products, providing valuable insights into Philadelphia chromosome-positive acute lymphoblastic leukemia pathology. CONCLUSIONS: The 'Otsuka" minor BCR-ABL messenger ribonucleic acid assay kit exhibits excellent performance in quantifying minor BCR-ABL transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Our results align well with established screening methods and show a strong correlation with laboratory-developed tests and diagnostic research products. The "Otsuka" kit holds great promise as a valuable tool for understanding Philadelphia chromosome-positive acute lymphoblastic leukemia pathology and guiding effective treatment strategies.

Catheter-related bloodstream infection caused by Tsukamurella tyrosinosolvens identified by secA1sequencing in an immunocompromised child: a case report.

BACKGROUND: Tsukamurella spp. are obligate aerobic, gram-positive, non-motile, and slightly acid-fast bacilli belonging to the Actinomycetes family. They share many characteristics with Nocardia, Rhodococcus, Gordonia, and the rapidly growing Mycobacterium species. Therefore, standard testing may misidentify Tsukamurella spp. as another species. Accurate and rapid diagnosis is critical for proper infection management, but identification of this bacterium is difficult in the standard laboratory setting. CASE PRESENTATION: A bloodstream infection caused by a gram-positive bacterium and related to a central venous catheter was identified in an immunocompromised 2-year-old girl. Tsukamurella tyrosinosolvens was identified by modified secA1 sequencing. Antibiotic treatment and removal of the central venous catheter resolved the infection. Inappropriate management of the catheter during an overnight stay outside of the hospital was considered as a possible source of infection. CONCLUSIONS: SecA1 sequencing may be a useful diagnostic tool in the identification of T. tyrosinosolvens. Providing proper central venous catheter care instructions to patients, their families, and medical staff is important for infection prevention.

Higher levels of minimal residual disease in peripheral blood than bone marrow before 1st and 2nd relapse/regrowth in a patient with high­risk neuroblastoma: A case report.

More than half of patients with high-risk neuroblastoma (HR-NB) experience relapse/regrowth due to the activation of chemoresistant minimal residual disease (MRD). MRD in patients with HR-NB can be evaluated by quantitating neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow (BM) and peripheral blood (PB) samples. Although several sets of NB-mRNAs have been shown to possess a prognostic value for MRD in BM samples (BM-MRD), MRD in PB samples (PB-MRD) is considered to be low and difficult to evaluate. The present report describes an HR-NB case presenting higher PB-MRD than BM-MRD before 1st and 2nd relapse/regrowth. A 3-year-old female presented with an abdominal mass, was diagnosed with HR-NB, and treated according to the nationwide standard protocol for HR-NB. Following systemic induction and consolidation therapy with local therapy, the patient achieved complete remission but experienced a 1st relapse/regrowth 6 months after maintenance therapy. The patient partially responded to salvage chemotherapy and anti-GD2 immunotherapy but had a 2nd relapse/regrowth 14 months after the 1st relapse/regrowth. Consecutive PB-MRD and BM-MRD monitoring revealed that PB-MRD was lower than BM-MRD at diagnosis (100 times) and 1st and 2nd relapse/regrowth (1,000 and 3 times) but became higher than BM-MRD before 1st and 2nd relapse/regrowth. The present case highlights that PB-MRD can become higher than BM-MRD before relapse/regrowth of patients with HR-NB.

Association between conditioning intensity and height growth after allogeneic hematopoietic stem cell transplantation in children.

BACKGROUND: The present study aimed to examine the association between the conditioning intensity and height growth in pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We reviewed the clinical records of 89 children with malignant diseases who underwent initial allo-HSCT between 2003 and 2021. Height measurements were standardized using standard height charts prepared by the Japanese Society for Pediatric Endocrinology to calculate standard deviation score (SDS). We defined short stature as a height SDS less than -2.0 in that reference. Myeloablative conditioning (MAC) comprised total-body irradiation at more than 8 Gy and busulfan administration at more than 8 mg/kg (more than 280 mg/m2 ). Other conditioning regimens were defined as reduced intensity conditioning (RIC). RESULTS: A total of 58 patients underwent allo-HSCT with MAC, and 31 patients received allo-HSCT with RIC. There were significant differences in the height SDS at 2 and 3 years after allo-HSCT between MAC and RIC group (-1.33 ± 1.20 vs. -0.76 ± 1.12, p = 0.047, -1.55 ± 1.28 vs. -0.75 ± 1.11, p = 0.022, respectively). Multivariate logistic regression analysis with the adjustments for potential confounding factors of patients less than 10 years of age at allo-HSCT and chronic graft-versus host disease demonstrated that MAC regimen was associated with a markedly increased risk of a short stature at 3 years after allo-HSCT (adjusted odds ratio, 5.61; 95% confidence interval, 1.07-29.4; p = 0.041). CONCLUSION: The intensity of conditioning regimen may be associated with short statures after allo-HSCT.

Comparison of Craniospinal Irradiation Using Proton Beams According to Irradiation Method and Initial Experience Treating Pediatric Patients.

Purpose: This study compared craniospinal irradiation using proton beam therapy (PBT) according to irradiation method and investigated the initial effects. Methods and Materials: Twenty-four pediatric patients (1-24 years old) who received proton craniospinal irradiation were examined. Passive scattered PBT (PSPT) and intensity modulated PBT (IMPT) were used in 8 and 16 patients, respectively. The whole vertebral body technique was used for 13 patients <10 years old, and the vertebral body sparing (VBS) technique was used for the remaining 11 patients aged ≥10 years. The follow-up period was 17 to 44 (median, 27) months. Organ-at-risk and planning target volume (PTV) doses and other clinical data were examined. Results: The maximum lens dose using IMPT was lower than that using PSPT (P = .008). The mean thyroid, lung, esophagus, and kidney doses were lower in patients treated using the VBS technique compared with the whole vertebral body technique (all P < .001). The minimum PTV dose of IMPT was higher than that of PSPT (P = .01). The inhomogeneity index of IMPT was lower than that of PSPT (P = .004). Conclusions: IMPT is better than PSPT at reducing the dose to the lens. The VBS technique can decrease the doses to neck-chest-abdomen organs. The PTV coverage of IMPT is superior to that of PSPT.

Phase 2 study of combination chemotherapy with bortezomib in children with relapsed and refractory acute lymphoblastic leukemia.

Treatment outcomes for children with relapsed and refractory acute lymphoblastic leukemia (R/R-ALL) remain poor, and the optimal induction therapy has not been determined. Bortezomib is a proteasome inhibitor that acts synergistically and additively with standard chemotherapy for ALL. We evaluated the efficacy and safety of combination chemotherapy with bortezomib in children with R/R-ALL. This single-arm, multicenter, phase 2 study was conducted in Japan between 2016 and 2020. Eligible patients were divided into two cohorts: a high-risk first-relapse cohort of untreated patients with high-risk first-relapsed ALL and an expansion cohort of patients with refractory ALL, including multiple relapses, relapse after allogeneic hematopoietic cell transplantation, and induction failure. All patients received a single course of chemotherapy as induction therapy. Sixteen patients (10 in the high-risk first-relapse cohort, six in the expansion cohort) were evaluable. The overall remission rate after induction therapy was 60% in the high-risk first-relapse cohort and 16.7% in the expansion cohort. All patients had minimal residual disease. Adverse events were acceptable except for interstitial lung disease and hypoxia in a patient in the expansion cohort, but addition of bortezomib to conventional chemotherapy did not produce obvious improvement in children with R/R-ALL.

Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group.

BACKGROUND: T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. METHODS: In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group. Patients were stratified into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, CNS status, and end-of-consolidation minimal residual disease. We used the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP)-BFM-ALL 2000-backbone chemotherapy. Nelarabine (650 mg/m2 per day for 5 days) was given to high-risk and very high-risk patients. All patients received, until the measurement of end-of-consolidation minimal residual disease, an identical therapy schedule, which included the prednisolone pre-phase remission induction therapy with dexamethasone (10 mg/m2 per day, for 3 weeks [for patients <10 years] or for 2 weeks including a 7-day off interval [for patients ≥10 years]) instead of prednisolone, and consolidation therapy added with Escherichia coli-derived L-asparaginase. On the basis of the stratification, patients received different intensities of treatment; L-asparaginase-intensified standard BFM-type therapy for standard risk and nelarabine-added high risk BFM-type therapy for high risk. In the very high-risk group, patients were randomly assigned (1:1) to group A (BFM-based block therapy) and group B (another block therapy, including high-dose dexamethasone) stratified by hospital, age (≥18 years or <18 years), and end-of-induction bone marrow blast percentage of M1 (<5%) or M2 (≥5%, <25%)+M3 (≥25%). Cranial radiotherapy was limited to patients with overt CNS disease at diagnosis (CNS3; >5 white blood cells per µL with blasts) and patients with no evidence of CNS disease received protracted triple intrathecal therapy. Only very high-risk patients were scheduled to receive HSCT. The primary endpoint was 3-year event-free survival for the entire cohort and the proportion of patients with disappearance of minimal residual disease between randomly assigned groups A and B in the very high-risk group. Secondary endpoints were overall survival, remission induction rate, and occurrence of adverse events. 3 years after the completion of patient accrual, a primary efficacy analysis was performed in the full analysis set and the per-protocol set. This study is registered with the Japan Registry of Clinical Trials, jRCTs041180145. FINDINGS: Between Dec 1, 2011, and Nov 30, 2017, of 349 eligible patients (median age 9 years [IQR 6-13]), 238 (68%) were male, and 28 (8%) patients had CNS3 status. 168 (48%) patients were stratified as standard risk, 103 (30%) as high risk, 39 (11%) as very high risk, and 39 (11%) as no risk (patients who had off protocol treatment before risk assessment. The composite complete remission (complete remission plus complete remission in suppression) rate after remission induction therapy was 89% (298 of 335 patients). HSCT was performed in 35 (10%) of 333 patients. With a median follow-up of 5·2 years (IQR 3·6-6·7), 3-year event-free survival was 86·4% (95% CI 82·3-89·7%) and 3-year overall survival was 91·3% (87·7-93·8%). The proportion of minimal residual disease disappearance was 0·86 (12 of 14 patients; 95% CI 0·57-0·98) in group A and 0·50 (6 of 12 patients, 0·21-0·79) in group B. Grade 3 peripheral motor neuropathy was seen in 11 (3%) of 349 patients and sensory neuropathy was seen in 6 (2%) patients. The most common grade 3 or worse adverse event was febrile neutropenia (294 [84%] of 349 patients). Treatment-related death occurred in three patients due to sepsis, gastric perforation, or intracranial haemorrhage during remission induction. INTERPRETATION: The ALL-T11 protocol produced encouraging outcomes with acceptable toxicities despite limited cranial radiotherapy and HSCT use. FUNDING: Ministry of Health, Labor and Welfare of Japan, and Japan Agency for Medical Research and Development. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Intensification of treatment with vinca alkaloid does not improve outcomes in pediatric patients with Langerhans cell histiocytosis: results from the JPLSG LCH-12 study.

Chemotherapy with cytarabine, vincristine (VCR), and prednisolone has achieved low mortality rates in pediatric patients with Langerhans cell histiocytosis (LCH). However, relapse rates remain high, making event-free survival (EFS) rates unsatisfactory. A nationwide clinical trial, LCH-12, tested a modified protocol in which the early maintenance phase was intensified with increasing dosages of VCR. Patients newly diagnosed with multifocal bone (MFB) or multisystem (MS) LCH and aged < 20 years at diagnosis were enrolled between June 2012 and November 2017. Of the 150 eligible patients, 43 with MFB were treated for 30 weeks and 107 with MS LCH were treated for 54 weeks. One patient with MS LCH died of sepsis during the induction phase. The 3-year EFS rates among patients with MFB LCH, risk organ (RO)-negative MS LCH, and RO-positive MS LCH were 66.7% (95% confidential interval [CI], 56.5-77.0%), 66.1% (95% CI 52.9-76.4%), and 51.1% (95% CI 35.8-64.5%), respectively, similar to previously observed rates. EFS rates were significantly lower in patients with disease activity scores > 6 than in those with scores ≤ 6. The strategy that included more intense treatment with VCR was not effective. Other strategies are required to improve outcomes in patients with pediatric LCH.

Nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia in the absence of intracranial devices: a case report.

BACKGROUND: Coagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices. CASE PRESENTATION: A 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient's symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72. CONCLUSIONS: To the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.

Targeting of SIRPα as a potential therapy for Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare neoplastic disorder characterized by inflammatory lesions arising from the anomalous accumulation of pathogenic CD1a+ CD207+ dendritic cells (DCs). SIRPα is a transmembrane protein highly expressed in myeloid cells such as DCs and macrophages. Here we show that SIRPα is a potential therapeutic target for LCH. We found that SIRPα is expressed in CD1a+ cells of human LCH lesions as well as in CD11c+ DCs in the spleen, liver, and lung of a mouse model of LCH (BRAFV600ECD11c mouse), in which an LCH-associated active form of human BRAF is expressed in a manner dependent on the mouse Cd11c promoter. BRAFV600ECD11c mice manifested markedly increased numbers of CD4+ T cells, regulatory T cells, and macrophages as well as of CD11c+ MHCII+ DCs in the spleen. Monotherapy with a mAb to SIRPα greatly reduced the percentage of CD11c+ MHCII+ DCs in peripheral blood, LCH-like lesion size in the liver, and the number of CD11c+ MHCII+ DCs in the spleen of the mutant mice. Moreover, this mAb promoted macrophage-mediated phagocytosis of CD11c+ DCs from BRAFV600ECD11c mice, whereas it had no effects on the viability or CCL19-dependent migration of such CD11c+ DCs or on their expression of the chemokine genes Ccl5, Ccl20, Cxcl11, and Cxcl12. Our results thus suggest that anti-SIRPα monotherapy is a promising approach to the treatment of LCH that is dependent in part on the promotion of the macrophage-mediated killing of LCH cells.

Epidural Spinal Cord Compression as the Presenting Manifestation of Acute Myeloid Leukemia: A Case Report and Literature Review.

We herein report a rare case of spinal cord compression due to epidural involvement of acute myeloid leukemia (AML). A 14-year-old boy presented with a 7-day history of back pain, paraplegia and hypoesthesia. Contrast-enhanced computed tomography revealed an epidural mass. Emergency laminectomy and resection of the mass were performed. Histopathologically, the resected mass was comparable to an extramedullary mass of AML. Chemotherapy was initiated, and complete remission was achieved. Neurological sequelae remained after the treatment. Based on the present and previous reports, spinal cord compression from epidural AML involvement may progress rapidly.