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Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

To clarify predictors of outcomes that can indicate the appropriateness of discharging patients to their own homes following acute ischemic stroke and percutaneous mechanical thrombectomy （PMT）. This study included 99 patients with acute ischemic stroke who were hospitalized in the Department of Neurology at Hospital A and underwent PMT between April 2014 and December 2018. Of these, 32 and 67 patients were discharged to their own homes or to other hospitals, respectively. The following items were retrospectively collected from medical records within 3 days of PMT: age; sex; familial cohabitation and employment status; serum albumin level; consciousness disorders; National Institutes of Health Stroke Scale （NIHSS）, at the most severe time and at 24 hours postoperatively; Brunnstrom recovery stage （BRS） in upper limbs, fingers, and lower limbs; oral intake; independence in activities of daily living such as eating, grooming, toileting, and walking; and higher brain dysfunction. We identified significant differences between the groups in terms of consciousness disorders, both NIHSS scores, BRS, oral intake, independence in eating and grooming, and higher brain dysfunction （p＜0.05）. Multiple logistic regression analysis revealed the following significant predictors of outcomes: NIHSS score at 24 hours postoperatively （odds ratio ［OR］: 1.35; 95％ confidence interval ［CI］: 0.152-0.448） and oral intake （OR: 10.46, 95％ CI: －2.252 to −0.095）. NIHSS score at 24 hours postoperatively and oral intake are useful predictors of patient outcomes following PMT for acute ischemic stroke. These can be assessed even when bed rest levels are low.

A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.

A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02.

We report an 18-year-old female individual with septic arthritis due to Mycobacterium kansasii. Three years and 6 months before arthritis, the patient underwent bone marrow transplantation and developed severe chronic graft-versus-host disease. The arthritis was refractory to medication, and she underwent joint lavage of the right foot, hip joint, and elbow joint. After surgery, her joint symptoms were relieved, and chronic graft-versus-host disease remitted more easily. It is important that we maintain a high index of suspicion for mycobacterial arthritis and diagnose it early when immunosuppressed patients experience chronic pain and joint swelling.

We report an 18-year-old female individual with septic arthritis due to Mycobacterium kansasii. Three years and 6 months before arthritis, the patient underwent bone marrow transplantation and developed severe chronic graft-versus-host disease. The arthritis was refractory to medication, and she underwent joint lavage of the right foot, hip joint, and elbow joint. After surgery, her joint symptoms were relieved, and chronic graft-versus-host disease remitted more easily. It is important that we maintain a high index of suspicion for mycobacterial arthritis and diagnose it early when immunosuppressed patients experience chronic pain and joint swelling.

Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30‑40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next‑generation sequencing (NGS) of >150 cancer‑related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3‑ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel‑based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel‑based NGS approach into the clinical setting may allow for a patient‑oriented strategy of precision treatment for childhood AML.

We report an 18-year-old female individual with septic arthritis due to Mycobacterium kansasii. Three years and 6 months before arthritis, the patient underwent bone marrow transplantation and developed severe chronic graft-versus-host disease. The arthritis was refractory to medication, and she underwent joint lavage of the right foot, hip joint, and elbow joint. After surgery, her joint symptoms were relieved, and chronic graft-versus-host disease remitted more easily. It is important that we maintain a high index of suspicion for mycobacterial arthritis and diagnose it early when immunosuppressed patients experience chronic pain and joint swelling.

We report an 18-year-old female individual with septic arthritis due to Mycobacterium kansasii. Three years and 6 months before arthritis, the patient underwent bone marrow transplantation and developed severe chronic graft-versus-host disease. The arthritis was refractory to medication, and she underwent joint lavage of the right foot, hip joint, and elbow joint. After surgery, her joint symptoms were relieved, and chronic graft-versus-host disease remitted more easily. It is important that we maintain a high index of suspicion for mycobacterial arthritis and diagnose it early when immunosuppressed patients experience chronic pain and joint swelling.

Background Corticosteroids, especially dexamethasone, play a critical role in chemotherapy for pediatric hematological malignancies. We previously observed that patients with complaints of headache or photophobia during corticosteroid administration had high intraocular pressure (IOP). Procedure We measured IOP during corticosteroid administration in 15 patients with acute leukemia or lymphoma undergoing treatment at our institution from January 2016 to December 2018. IOP was measured by an ophthalmologist within seven days of the initiation of standard dose of corticosteroid, which was defined as 60 mg/m(2)/day for prednisolone and 10 mg/m(2)/day for dexamethasone. Results Fifteen patients received 52 courses of chemotherapy containing corticosteroids. IOP exceeded 21 mmHg among 13 patients in 28 courses. Twelve of the 13 patients were administered topical treatment, and six of the 12 patients needed additional diuretic agents. IOP during the chemotherapy courses containing dexamethasone was significantly higher compared with IOP during the chemotherapy courses containing prednisolone. Only two patients complained of symptoms, such as headache and photophobia, and one of the two patients underwent trabeculotomy. Funduscopic findings were normal in all patients. There was a dose-associated decrease in IOP with reduction of dexamethasone dose. Conclusions IOP should be measured during administration of substantial corticosteroid doses even in patients with no symptoms. Further investigations regarding the level of IOP for intervention need to be conducted.

Background Corticosteroids, especially dexamethasone, play a critical role in chemotherapy for pediatric hematological malignancies. We previously observed that patients with complaints of headache or photophobia during corticosteroid administration had high intraocular pressure (IOP). Procedure We measured IOP during corticosteroid administration in 15 patients with acute leukemia or lymphoma undergoing treatment at our institution from January 2016 to December 2018. IOP was measured by an ophthalmologist within seven days of the initiation of standard dose of corticosteroid, which was defined as 60 mg/m(2)/day for prednisolone and 10 mg/m(2)/day for dexamethasone. Results Fifteen patients received 52 courses of chemotherapy containing corticosteroids. IOP exceeded 21 mmHg among 13 patients in 28 courses. Twelve of the 13 patients were administered topical treatment, and six of the 12 patients needed additional diuretic agents. IOP during the chemotherapy courses containing dexamethasone was significantly higher compared with IOP during the chemotherapy courses containing prednisolone. Only two patients complained of symptoms, such as headache and photophobia, and one of the two patients underwent trabeculotomy. Funduscopic findings were normal in all patients. There was a dose-associated decrease in IOP with reduction of dexamethasone dose. Conclusions IOP should be measured during administration of substantial corticosteroid doses even in patients with no symptoms. Further investigations regarding the level of IOP for intervention need to be conducted.

Background Corticosteroids, especially dexamethasone, play a critical role in chemotherapy for pediatric hematological malignancies. We previously observed that patients with complaints of headache or photophobia during corticosteroid administration had high intraocular pressure (IOP). Procedure We measured IOP during corticosteroid administration in 15 patients with acute leukemia or lymphoma undergoing treatment at our institution from January 2016 to December 2018. IOP was measured by an ophthalmologist within seven days of the initiation of standard dose of corticosteroid, which was defined as 60 mg/m(2)/day for prednisolone and 10 mg/m(2)/day for dexamethasone. Results Fifteen patients received 52 courses of chemotherapy containing corticosteroids. IOP exceeded 21 mmHg among 13 patients in 28 courses. Twelve of the 13 patients were administered topical treatment, and six of the 12 patients needed additional diuretic agents. IOP during the chemotherapy courses containing dexamethasone was significantly higher compared with IOP during the chemotherapy courses containing prednisolone. Only two patients complained of symptoms, such as headache and photophobia, and one of the two patients underwent trabeculotomy. Funduscopic findings were normal in all patients. There was a dose-associated decrease in IOP with reduction of dexamethasone dose. Conclusions IOP should be measured during administration of substantial corticosteroid doses even in patients with no symptoms. Further investigations regarding the level of IOP for intervention need to be conducted.

The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-bodysparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s +/- 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.

The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-bodysparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s +/- 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.

Background Corticosteroids, especially dexamethasone, play a critical role in chemotherapy for pediatric hematological malignancies. We previously observed that patients with complaints of headache or photophobia during corticosteroid administration had high intraocular pressure (IOP). Procedure We measured IOP during corticosteroid administration in 15 patients with acute leukemia or lymphoma undergoing treatment at our institution from January 2016 to December 2018. IOP was measured by an ophthalmologist within seven days of the initiation of standard dose of corticosteroid, which was defined as 60 mg/m(2)/day for prednisolone and 10 mg/m(2)/day for dexamethasone. Results Fifteen patients received 52 courses of chemotherapy containing corticosteroids. IOP exceeded 21 mmHg among 13 patients in 28 courses. Twelve of the 13 patients were administered topical treatment, and six of the 12 patients needed additional diuretic agents. IOP during the chemotherapy courses containing dexamethasone was significantly higher compared with IOP during the chemotherapy courses containing prednisolone. Only two patients complained of symptoms, such as headache and photophobia, and one of the two patients underwent trabeculotomy. Funduscopic findings were normal in all patients. There was a dose-associated decrease in IOP with reduction of dexamethasone dose. Conclusions IOP should be measured during administration of substantial corticosteroid doses even in patients with no symptoms. Further investigations regarding the level of IOP for intervention need to be conducted.

We described three boys with X-linked severe combined immunodeficiency (X-SCID) who were successfully treated by reduced-intensity stem cell transplantation from unrelated cord blood (CB). Mean age at the transplantation was 5.7 months (range, 3-9 months). Pre-transplantation conditioning for all patients consisted of fludarabine (FLU) (30 mg/m2/day) from day -7 to day -2 (total dose 180 mg/m2) and busulfan (BU) 4mg/kg/day from day -3 to day -2 (total dose 8 mg/kg). All of the CB units were serologically matched HLA-A, B, and DR loci. Although two of them had suffered from fungal or bacterial pneumonia before transplantation, there were no other infectious complications during transplantation. All the patients have engrafted and achieved 100% donor chimerism. We also confirmed full donor chimerism of both T and B cells. Only one patients developed acute GVHD grade III, which resolved by increasing the dose of oral corticosteroid. None of the patients have developed chronic GVHD during the follow up for 21 to 77 months. No patients had received intravenous immunoglobulin replacements after the transplantations, or showed delay in psychomotor development. Reduced-intensity conditioning consisting of FLU and BU and transplantation from unrelated CB was effective and safe treatment for patients with X-SCID.

We described three boys with X-linked severe combined immunodeficiency (X-SCID) who were successfully treated by reduced-intensity stem cell transplantation from unrelated cord blood (CB). Mean age at the transplantation was 5.7 months (range, 3-9 months). Pre-transplantation conditioning for all patients consisted of fludarabine (FLU) (30 mg/m2/day) from day -7 to day -2 (total dose 180 mg/m2) and busulfan (BU) 4mg/kg/day from day -3 to day -2 (total dose 8 mg/kg). All of the CB units were serologically matched HLA-A, B, and DR loci. Although two of them had suffered from fungal or bacterial pneumonia before transplantation, there were no other infectious complications during transplantation. All the patients have engrafted and achieved 100% donor chimerism. We also confirmed full donor chimerism of both T and B cells. Only one patients developed acute GVHD grade III, which resolved by increasing the dose of oral corticosteroid. None of the patients have developed chronic GVHD during the follow up for 21 to 77 months. No patients had received intravenous immunoglobulin replacements after the transplantations, or showed delay in psychomotor development. Reduced-intensity conditioning consisting of FLU and BU and transplantation from unrelated CB was effective and safe treatment for patients with X-SCID.

We described three boys with X-linked severe combined immunodeficiency (X-SCID) who were successfully treated by reduced-intensity stem cell transplantation from unrelated cord blood (CB). Mean age at the transplantation was 5.7 months (range, 3-9 months). Pre-transplantation conditioning for all patients consisted of fludarabine (FLU) (30 mg/m2/day) from day -7 to day -2 (total dose 180 mg/m2) and busulfan (BU) 4mg/kg/day from day -3 to day -2 (total dose 8 mg/kg). All of the CB units were serologically matched HLA-A, B, and DR loci. Although two of them had suffered from fungal or bacterial pneumonia before transplantation, there were no other infectious complications during transplantation. All the patients have engrafted and achieved 100% donor chimerism. We also confirmed full donor chimerism of both T and B cells. Only one patients developed acute GVHD grade III, which resolved by increasing the dose of oral corticosteroid. None of the patients have developed chronic GVHD during the follow up for 21 to 77 months. No patients had received intravenous immunoglobulin replacements after the transplantations, or showed delay in psychomotor development. Reduced-intensity conditioning consisting of FLU and BU and transplantation from unrelated CB was effective and safe treatment for patients with X-SCID.

We described three boys with X-linked severe combined immunodeficiency (X-SCID) who were successfully treated by reduced-intensity stem cell transplantation from unrelated cord blood (CB). Mean age at the transplantation was 5.7 months (range, 3-9 months). Pre-transplantation conditioning for all patients consisted of fludarabine (FLU) (30 mg/m2/day) from day -7 to day -2 (total dose 180 mg/m2) and busulfan (BU) 4mg/kg/day from day -3 to day -2 (total dose 8 mg/kg). All of the CB units were serologically matched HLA-A, B, and DR loci. Although two of them had suffered from fungal or bacterial pneumonia before transplantation, there were no other infectious complications during transplantation. All the patients have engrafted and achieved 100% donor chimerism. We also confirmed full donor chimerism of both T and B cells. Only one patients developed acute GVHD grade III, which resolved by increasing the dose of oral corticosteroid. None of the patients have developed chronic GVHD during the follow up for 21 to 77 months. No patients had received intravenous immunoglobulin replacements after the transplantations, or showed delay in psychomotor development. Reduced-intensity conditioning consisting of FLU and BU and transplantation from unrelated CB was effective and safe treatment for patients with X-SCID.