TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.

The First Case of a Child Infected with SARS-CoV-2 Omicron Variant in Japan, December 2021.

We report the first pediatric patient infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japan. The patient was a one-year-old boy who resided in Japan. He went abroad with his parents from November 12, 2021 to November 28, 2021 and had no known contact with coronavirus disease (COVID-19) patients there. Upon arrival at the Narita International Airport on November 28, 2021, his father tested positive for SARS-CoV-2 via a quantitative antigen test. Because the boy and his mother tested negative for SARS-CoV-2, they quarantined together at a hotel separately from his father. On December 4, 2021, the boy tested positive by reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2, without symptoms, and was hospitalized with his mother; he and his father were both found to be infected with the SARS-CoV-2 Omicron variant. The boy was not vaccinated against COVID-19. RT-PCR results were negative starting on December 20, 2021. The incubation period and required period for negative conversion of SARS-CoV-2 RNA of the Omicron variant case were similar to those of the cases of conventional strains. We should carefully consider the potential of the SARS-CoV-2 Omicron variant to spread widely among unvaccinated children.

Drug-induced crystalluria attributable to tosufloxacin in children.

BACKGROUND: Drug-induced crystalluria is reportedly caused by a large number of drugs. Tosufloxacin (TFLX), a second-generation fluoroquinolone antibiotic, is reported to cause kidney injury and crystalluria. We retrospectively analyzed patients with crystalluria caused by TFLX to clarify the clinical course of TFLX-induced crystalluria in children. METHODS: This study was designed as a retrospective case series using the database of the National Center for Global Medicine covering the period from January 1, 2020 to March 31, 2021. We enrolled pediatric patients aged 15 years or younger with crystalluria attributable to TFLX treated in our pediatric department and collected clinical data. RESULTS: Thirteen patients were diagnosed with crystalluria attributable to TFLX. The median age of the patients at diagnosis was 4.0 years (range, 0.8-15 years; interquartile range = 1.2-8.8 years), and five patients (38%) were male. Six patients (46%) had gastrointestinal symptoms such as vomiting and abdominal pain, and 12 patients (92%) had decreased oral intake. The median time to diagnosis after TFLX administration was 4 days (range, 2-7 days; interquartile range = 3-6 days). All patients received TFLX at the appropriate dose. Two patients (17%) were diagnosed with acute kidney injury, and both had gastrointestinal symptoms such as vomiting and abdominal pain. CONCLUSIONS: Crystalluria induced by TFLX occurred despite administration of the appropriate dose of TFLX. Physicians should recognize crystalluria and renal injury attributable to TFLX. It may be possible to prevent renal injury by discontinuing drug therapy.

Adapting pediatric health care responses to the COVID-19 pandemic in Japan: A clinical perspective.

The COVID-19 pandemic required our pediatric health care staff to adjust to many irregularities and solve serious issues in our routine clinical practice. In outpatient clinics, many children exhibited common cold symptoms that mimic COVID-19, thus we initially screened patients via an interview form, then later via SARS-CoV-2 antigen test. Cluster infections were entirely avoided by following systematic, everyday precautions. Patientsquality of life has been difficult to maintain during the pandemic, due to social and staffing restrictions. Other unexpected repercussions - such as an unexpected lack of seasonal virus infections, then a respiratory syncytial (RS) virus outbreak - required agile management of hospital resources. While we must continue to adapt our treatment programs in response to the evolving COVID-19 crisis, it remains essential to support the well-being of children through regular health check-ups, mental health support, educational opportunities, proper socialization, and close communication with parents and families.

Successful Treatment with Antibiotics Alone for Infant Rib Osteomyelitis.

Pediatric rib osteomyelitis is a rare disease occurring predominantly in the neonatal period and early childhood and accounting for about 1% of all pediatric osteomyelitis. Compared to osteomyelitis in other parts of the body, pediatric rib osteomyelitis shows few localized findings (such as redness and swelling) and often an indolent lesion as well either of which may delay diagnosis and thus make treatment more difficult. A previously healthy one-year-old girl came to our department with a chief complaint of fever lasting for three days. She was admitted to our department to investigate her fever. At the time of admission, radiographs showed decreased permeability in the left lung field; so, we started antimicrobial therapy on the assumption of pneumonia. On the second day of admission, methicillin-susceptible Staphylococcus aureus was detected in the blood culture. A further, more detailed physical examination revealed some slight left anterior chest swelling. We performed a contrast-enhanced CT scan and an MRI and diagnosed her with rib osteomyelitis complicated with a chest wall abscess. She was given intravenous cefazolin for two weeks, switched to oral cephalexin for four weeks, and then recovered completely. She was treated without surgical intervention, having showed a good response to antimicrobial therapy. Osteomyelitis of the ribs in children is reported to be more common in the lower ribs and to occur more frequently in infants. In many cases, the earliest symptoms are nonspecific, so careful examination to detect any subtle abnormalities-such as swelling or mass-is of key importance for early diagnosis in infants. Regarding treatment, most cases of hematogenous osteomyelitis resolve with antimicrobial therapy alone-although surgical intervention may be required in cases of poor response to antimicrobial therapy. Therefore, early diagnosis of rib osteomyelitis through careful physical examination may reduce the chances of requiring surgical intervention.

Infantile Stage M Neuroblastoma With 11q Deletion, Mimicking Stage MS.

A 4-month-old boy with abdominal distension was diagnosed with adrenal neuroblastoma with numerous metastases to the liver and nodules in the skin and muscles. Marked hepatomegaly spontaneously regressed with decreasing tumor marker levels, and the final diagnosis was stage M based on radiologic findings confirming metastasis to the pancreas. The neuroblastoma did not have the MYCN amplification but had an 11q aberration. Chemotherapy was initiated at age 6 months with a successful response. Our case reflects the heterogenous clinical behavior of neuroblastoma and highlights the challenging issue of the difference between stage M and stage MS neuroblastoma in infants.

[Hematological neoplasia associated with primary mediastinal germ-cell tumor treated with hematopoietic stem cell transplantation].

The occurrence of a primary mediastinal germ cell tumor and hematological neoplasia provides a poor prognosis that is known to be fatal at a median of 6 months after onset. We report the case of a 15-year-old male who was treated with chemotherapy and hematopoietic cell transplantation based on a report of a surviving case. At diagnosis, the patient had an unresectable mediastinal tumor with elevated alpha-fetoprotein and human chorionic gonadotropin levels and acute megakaryoblastic leukemia. We prioritized treatment with chemotherapy for the tumor owing to the oncological emergency. We then performed leukemia induction therapy and achieved complete remission. Although we used CDDP in combination with intensive therapy, the mediastinal tumor grew too large for it to be safely resected. We transplanted bone marrow from the patient's human leukocyte antigen-haploidentical sibling upon conditioning with busulfan-melphalan. After 44 days, the leukemia recurred in the patient's central nervous system. This was followed by various post-transplant complications, and the patient died of organ failure that was associated with infectious diseases. At necropsy, a poorly engrafted bone marrow was observed. The mediastinal tumor was primarily necrotic, although some immature teratoma components were observed. No leukemic precursor cells were detected. Residual mediastinal tumors may be associated with the recurrence of leukemias. We seek a treatment strategy that enables early tumor resection and high-dose chemotherapy. Further case studies are warranted along with the development of effective treatment methods.

SARS-CoV-2 infection among returnees on charter flights to Japan from Hubei, China: a report from National Center for Global Health and Medicine.

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] vs. 9/745 [1.2%]: p = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.

A Case of Childhood Blastic Phase Chronic Myeloid Leukemia With Minor BCR-ABL.

Chronic myeloid leukemia (CML) is commonly associated with major BCR-ABL transcript. We present a child with blastic phase CML associated with minor BCR-ABL transcript without prior CML diagnosis. Diagnosis was achieved by fluorescence in situ hybridization of peripheral blood neutrophils, which identified 90% as BCR-ABL positive. The patient received chemotherapy with imatinib followed by dasatinib and underwent reduced-intensity hematopoietic allogeneic stem cell transplantation with prophylactic posttransplant dasatinib for 2 years and has remained in complete molecular remission. Our intensified treatment regimen was effective compared with previous studies on minor BCR-ABL CML describing inferior outcomes with tyrosine kinase inhibitor therapy.

Moyamoya syndrome in a pediatric patient with congenital human immunodeficiency virus type 1 infection resulting in intracranial hemorrhage.

In the era of Antiretroviral Therapy (ART) in which human immunodeficiency virus type 1 (HIV-1) infection affected children can expect a better prognosis, the importance of careful follow up of pediatric HIV-1 cases for neurological complications has been growing. We present a case of hemorrhagic Moyamoya syndrome in a child with congenital HIV-1 infection. A 10-year-old girl was referred to our hospital for the treatment of Pneumocystis Jirovecii Pneumonia (PCP: Pneumocystis pneumonia). Her HIV-1 control was poor and Moyamoya syndrome was found during the opportunistic infection screening at admission. Despite subsequent successful treatment of PCP and HIV-1 infection, we could not save her life due to the intracranial hemorrhage caused by Moyamoya syndrome. A few reported cases of Moyamoya syndrome associated with HIV-1 infection have shown negative outcomes when the control of HIV-1 infection is unsuccessful. Recently "HIV-associated vasculopathy" has been used to describe the cerebrovascular disorder related to HIV-1 infection that is caused by the endothelial dysfunction induced from chronic inflammation and cytokine imbalances due to HIV-1 infection. We assumed that "HIV-associated vasculopathy" may have contributed to the development of collateral vessels impairment related to the bleeding, although the mechanism of vascular damage with HIV-1 infection is not yet well defined. Therefore proper management of the HIV-1 infection is crucial for Moyamoya syndrome with HIV-1 cases. Furthermore it is better to take into account the risk of intracerebral hemorrhage when considering the indication and timing of the revascularization surgery, although generally hemorrhaging is rare in Moyamoya disease in children.

A Case of Malignant Melanoma Arising in Mediastinal Malignant Teratoma.

We report about a 14-year-old boy who presented with an anterior mediastinal mass that was diagnosed as malignant teratoma. Surgical resection was performed along with pre- and postoperative chemotherapy. Although elevated alpha-fetoprotein became negative, he experienced pain in his right hip joint 3 months after resection. Systematic evaluation revealed multiple locations of metastasis, and the pathological diagnosis based on bone biopsy was malignant melanoma originating from malignant teratoma, which rapidly progressed. He died 15 months after diagnosis of the original malignant teratoma. Diagnosing and treating malignant transformation of teratoma, including malignant melanoma, is difficult because it is very rare. To our knowledge, this is the second reported case of malignant melanoma arising from a mediastinum malignant teratoma, with both cases having a poor prognosis. In addition to the follow-up of tumor markers, systematic evaluation, including imaging, should be considered even after remission to monitor malignant transformation of teratoma. We expect to establish a successful therapy and improve mortality rate after more such cases are accumulated.

FDG-PET/CT for Detection of Extramedullary Disease in 2 Pediatric Patients With AML.

Positron emission tomography combined with computed tomography (PET/CT) is a promising diagnostic procedure for the detection of extramedullary disease (EMD) in acute myeloid leukemia. We studied 2 children with acute myeloid leukemia who underwent PET to assess for EMD at diagnosis as well as in remission. We detected 5 EMD lesions in 2 cases with PET, only 2 of which were detectable on clinical examination. Our cases show PET's increased sensitivity over physical examination alone in assessing and monitoring the extent of this disease.

Kawasaki disease refractory to standard treatments that responds to a combination of pulsed methylprednisolone and plasma exchange: Cytokine profiling and literature review.

UNLABELLED: We present a case of Kawasaki Disease (KD) that was refractory to plasma exchange (PE), but which finally responded to concurrent intravenous methylprednisolone pulse (IVMP) and PE treatment. To determine direct and indirect evidence for the efficacy of this combination therapy, we analyzed data of patients with refractory KD by review of the literature using medical databases and cytokine profiling. For literature searches, we used the Pubmed™ and Ichushi™ databases. Search terms used included "Kawasaki disease" and "plasma exchange" to extract articles that described KD cases treated with PE. For cytokine profiling, we measured interleukin (IL)-6, soluble tumor necrosis factor-α receptor (sTNF-αR) type 1 and type 2 before and after PE and PE with IVMP. Our search revealed 201 KD patients treated with PE, of which PE treatment was effective in 188 patients (93.5%), but not in 13 cases (6.5%). All 13 cases were treated successfully with additional treatment. Of the 13 cases, only six (2.5%) had recurrence during the PE treatment period. In our case, cytokine profiling showed PE treatment decreased IL6, while sTNF-αR type1 and type2 remained at high levels. PE and IVMP decreased IL-6 and sTNFα-R type 1 and type 2 levels. CONCLUSION: PE concurrent with additional anti-inflammatory treatment such as IVMP might be a very promising treatment option for PE refractory patients.

Salmonella meningitis: a report from National Hue Central Hospital, Vietnam.

Four Vietnamese infants who survived infection with Salmonella meningitis are reported. A female infant who experienced relapse recovered without complications and another had neurological sequellae. The remaining 2 infants survived without complications. The initial treatment was chloramphenicol and ceftriaxone, whereas a change of antibiotics to imipenem and fluoroquinolone was required for 2 infants. Fluoroquinolone may be a treatment option in patients with Salmonella meningitis who experience complications even though the drug is contraindicated for the pediatric age group.

Continuous and high-dose cytarabine combined chemotherapy in children with down syndrome and acute myeloid leukemia: Report from the Japanese children's cancer and leukemia study group (JCCLSG) AML 9805 down study.

BACKGROUND: The aim of the JCCLSG AML 9805 Down study was to evaluate the effect of continuous and high-dose cytarabine combined chemotherapy on the survival outcome of acute myeloid leukemia (AML) with Down syndrome (DS). PROCEDURE: From May 1998 to December 2006, DS patients with newly diagnosed AML were enrolled. Remission induction therapy consisted of two courses of pirarubicin, vincristine, and continuous-dose cytarabine (AVC1). The patients who achieved complete remission (CR) after two courses of AVC1 were subsequently treated with mitoxantrone and continuous-dose cytarabine (MC), etoposide and high-dose cytarabine (EC) and pirarubicin, vincristine, and continuous-dose cytarabine (AVC2). RESULTS: Twenty-four patients were enrolled. All patients were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia. Twenty-one patients achieved CR. Three patients died during remission induction therapy due to serious infection. No toxic deaths were observed during remission. All but one patient maintained CR without serious complications. The 5-year overall and event-free survivals were 87.5% ± 6.8% and 83.1% ± 7.7%, respectively. CONCLUSIONS: Continuous and high-dose cytarabine combined chemotherapy with reduced intensity would be effective in DS children with AML.