Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases.

PURPOSE: The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID). METHODS: We retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID. RESULTS: The 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival. CONCLUSIONS: RIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID.

Early detection of the PAX3-FOXO1 fusion gene in circulating tumor-derived DNA in a case of alveolar rhabdomyosarcoma.

Cell-free DNA (cfDNA), which are small DNA fragments in blood derived from dead cells including tumor cells, could serve as useful biomarkers and provide valuable genetic information about the tumors. cfDNA is now used for the genetic analysis of several types of cancers, as a surrogate for tumor biopsy, designated as "liquid biopsy." Rhabdomyosarcoma (RMS), the most frequent soft tissue tumor in childhood, can arise in any part of the body, and radiological imaging is the only available method for estimating the tumor burden, because no useful specific biological markers are present in the blood. Because tumor volume is one of the determinants of treatment response and outcome, early detection at diagnosis as well as relapse is essential for improving the treatment outcome. A 15-year-old male patient was diagnosed with alveolar RMS of prostate origin with bone marrow invasion. The PAX3-FOXO1 fusion was identified in the tumor cells in the bone marrow. After the diagnosis, cfDNA was serially collected to detect the PAX3-FOXO1 fusion sequence as a tumor marker. cfDNA could be an appropriate source for detecting the fusion gene; assays using cfDNA have proved to be useful for the early detection of tumor progression/recurrence. Additionally, the fusion gene dosage estimated by quantitative polymerase chain reaction reflected the tumor volume during the course of the treatment. We suggest that for fusion gene-positive RMSs, and other soft tissue tumors, the fusion sequence should be used for monitoring the tumor burden in the body to determine the diagnosis and treatment options for the patients.

Japanese childhood cancer survivors' readiness for care as adults: a cross-sectional survey using the Transition Scales.

BACKGROUND: Childhood cancer survivors' (CCSs') readiness for adult care has not been evaluated in Japan. We conducted a survey to examine transition barriers and facilitators in CCSs and compared the results with those of CCSs in Canada. METHODS: Participants were selected from the Heart Link mutual-aid health insurance membership directory and the Millefeuille Childhood Cancer Frontiers. We conducted a cross-sectional survey (self-report questionnaire) via mail, using the Transition Scales. RESULTS: In total, 268 questionnaires were collected by January 2016 (response rate, 42.5%). After confirming the reliability and validity of the Transition Scales, we analyzed 242 questionnaires. After excluding questionnaires for CCSs younger than 15 or older than 26 years, we compared scales scores between Japanese and Canadian CCSs. Relative to that of Japanese CCSs, Canadian CCSs showed greater cancer-related worry for 4 items (P < .001) and preference for self-management in 3 items (P < .001). Japanese CCSs showed greater preference for self-management, relative to that of Canadian CCSs, in 5 items (P < .001). In the expectation scale, Japanese CCSs showed lower levels of expectation concerning adult care in 6 of 12 items (P < .001). Relative to that of Canadian CCSs, a significantly higher number of Japanese CCSs preferred to visit the same doctor for long-term care as adults (P < .001). CONCLUSIONS: The results confirmed the reliability and validity of the Transition Scales and showed that Japanese CCSs expressed fewer cancer concerns, but a higher number of Japanese CCSs preferred to visit the same doctor for long-term care as adults.

Successful treatment by coil embolization for infantile hemangioma with Kasabach-Meritt syndrome of newborn.

Infantile hemangioma (IH) is the most common tumor of infancy, and it sometimes associated with Kasabach-Meritt syndrome (KMS) characterized by anemia, intraperitoneal hemorrhage secondary to rupture, coagulopathy, jaundice, and vascular malformations involving the brain, skin, gut, and other organs. Here, we report two newborn patients having IH with KMS at birth. The first patient had a giant hemangioma in the liver, which was successfully treated with i.v. corticosteroid and coil embolization. The second patient had a large hemangioma of the right axillary region, which was also successfully treated with i.v. corticosteroid, beta-blocker, coil embolization and local irradiation. All symptoms were controlled without any side-effects in both patients. According to these findings, combination therapy including coil embolization and corticosteroid is effective for IH patients with KMS. The indications for and timing of coil embolization should be determined further cases have been accumulated.

Procalcitonin as a marker of respiratory disorder in neonates.

BACKGROUND: Serum procalcitonin (PCT) increases in various respiratory disorders such as acute respiratory distress syndrome. Elevated PCT is also observed in healthy neonates. In this study, we investigated whether PCT is a good marker of respiratory disorder in neonates. METHODS: A total of 155 neonates with or without respiratory disorder, were eligible for the study. PCT was measured on electrochemiluminescence immunoassay. Each neonate was allocated to the non-respiratory disorder (control) group (n = 95), or a respiratory disorder group (n = 60). PCT was compared between the groups, and association with other markers, including C-reactive protein (CRP) and white blood cell (WBC) count, was analyzed. RESULTS: Of the 60 neonates in the respiratory disorder group, 39, 10, five, one, two, two, and one neonates had transient tachypnea of the newborn, respiratory distress syndrome, air leak syndrome, meconium aspiration syndrome, 18-trisomy, neonatal asphyxia, and congenital diaphragmatic hernia, respectively. Mean PCT, CRP and WBC count in the respiratory disorder group were 9.01 ng/mL, 0.26 mg/dL, and 16,100 cells/µL, respectively. The area under the curve obtained for PCT in distinguishing between the respiratory disorder and control groups was 0.85 (sensitivity, 66.7%; specificity, 93.0%; optimum cut-off, 3.73 ng/mL), that for CRP was 0.72 (sensitivity, 75.0%; specificity, 64.6%; optimum cut-off, 0.14 mg/dL), and for WBC it was 0.44 (sensitivity, 60.0%; specificity, 29.6%; optimum cut-off, 15,000 cells/µL). CONCLUSIONS: PCT is more susceptible, as a diagnostic parameter of infection, to the effect of respiratory disturbance than CRP and WBC.

Therapeutic Effect of Linezolid in Children With Health Care-Associated Meningitis or Ventriculitis.

We evaluated the efficacy of linezolid treatment in 6 children with health care-associated meningitis or ventriculitis (HCAMV) caused by gram-positive cocci. All children were diagnosed and treated at the Ehime University Hospital between January 2010 and December 2017. Of these, 5 were treated with linezolid as an empirical therapy. In these 5 patients, vancomycin was initially used but was changed to linezolid because of cerebrospinal fluid (CSF) culture positivity (n = 3) and a high minimum inhibitory concentration of vancomycin (n = 2). The most common HCAMV pathogens were methicillin-resistant coagulase-negative staphylococci (n = 3). In 3 patients, vancomycin concentration was low in CSF but reached the target concentration in serum, while linezolid concentration was high in both CSF and serum. HCAMV treatment using antimicrobial agents with poor CSF penetration may increase the likelihood of therapy failure. Linezolid is more susceptible as the first-line treatment for HCAMV compared with vancomycin.

Hematopoietic cell transplantation for myeloid/NK cell precursor acute leukemia in second remission.

Myeloid/natural killer cell precursor acute leukemia (MNKPL) is a rare leukemia subtype characterized by a high incidence of extramedullary infiltration. No appropriate treatment strategy has so far been developed. Acute myelogenous leukemia-type chemotherapy combined with L-Asparaginase is an effective treatment for MNKPL. Hematopoietic cell transplantation is a second option in refractory cases.

Ocular manifestation in myeloid/NK cell precursor acute leukemia: a case report. Diagnosed by flow cytometry and PCR from aqueous humor.

BACKGROUND: Myeloid/NK cell precursor acute leukemia (MNKL) is a rare type of leukemia, and ocular complications have not previously been reported. We now report a patient with MNKL who developed intraocular infiltrates during follow-up. METHODS AND RESULTS: A 13-year-old boy diagnosed with MNKL developed left eye pain 3 months after starting treatment. Examination of the left eye revealed a visual acuity of counting fingers at 20 cm, ciliary hyperemia, small corneal keratic precipitates, hypopyon, grade 4 vitreous opacities, and an obscured fundus. The differential diagnosis was between an opportunistic infection associated with immunodeficiency and an intraocular leukemic cell infiltrate. Therefore, a sample of aqueous humor was aspirated. Multiplex PCR/broad-range PCR of the aqueous humor was below detection limits for viruses, bacteria, and fungi. Flow cytometry (FCM) detected NK-related CD56-positive cells, thus leading to a diagnosis of ocular infiltrates due to MNKL. With treatment of the ocular infiltrates by consolidation systemic chemotherapy including intrathecal methotrexate (MTX), there was clearing of the vitreous opacities; and optic disc swelling, retinal hemorrhages, exudates, and protuberant lesions were now seen. With the addition of local radiation therapy to the eye, there was a dramatic treatment response, with regression of the optic disc findings and retinal lesions, and an improved visual acuity of 1.5. CONCLUSION: We encountered the first case of MNKL in which ocular infiltrates developed during follow-up. Multiplex PCR and FCM of the aqueous humor were useful in rapidly distinguishing leukemic cell infiltrates from an opportunistic infection. This case highlights the usefulness of intrathecal MTX and local radiotherapy in treating ocular infiltrates in patients with MNKL.