Long-term efficacy and safety profile of splenectomy for pediatric chronic immune thrombocytopenia.

There are few reports of the long-term efficacy of splenectomy in children with immune thrombocytopenia (ITP). In a 33-year period, we performed splenectomies in 23 pediatric patients with ITP at a single institution in Japan. The age at surgery was 5-22 years with a median of 10 years. The follow-up period was 1-141 months with a median of 48 months. Before surgery, we confirmed the presence or absence of the accessory spleen by contrast-enhanced CT scan and we recommended vaccination with pneumococcal vaccine. Four patients underwent laparotomy before 1998, and 19 patients underwent laparoscopic surgery after 1999. Splenectomy showed high efficacy with a partial response rate of 83% and a complete response rate of 74%. Complete response was maintained in 70% of patients until the end of the observation period, and 91% were able to discontinue long-term management drugs such as steroids. No serious complications such as infectious diseases were observed. Although the number of cases here was small, the long-term efficacy and safety of splenectomy makes it a viable option in pediatric ITP despite the existence of newer therapeutic agents. Further research is necessary to compare the long-term efficacy and safety of splenectomy with new therapeutic agents.

Vedolizumab therapy for pediatric steroid-refractory gastrointestinal acute graft-versus-host disease.

Vedolizumab, an immunosuppressive drug that acts locally on the gastrointestinal tract, is mainly used for the treatment of inflammatory bowel disease, and has been reported to be effective against gastrointestinal acute graft-versus-host disease (GI-aGVHD) in adults. However, there is insufficient evidence for pediatric GI-aGVHD. We used vedolizumab to treat three cases of GI-aGVHD in patients aged 1.5-4.4 years. It was significantly effective in two patients and did not cause serious side effects in any patient. Vedolizumab might be effective and safe for pediatric GI-aGVHD refractory to other treatments, but this must be confirmed in future studies.

Successful hematopoietic stem cell transplantation with reduced dose of busulfan for Omenn syndrome.

Omenn syndrome (OS) is typically observed in the autosomal recessive form of severe combined immunodeficiency (SCID) with autoreactive manifestations, and it requires allogeneic hematopoietic stem cell transplantation. Unlike non-OS SCID, a conditioning regimen is usually required to eradicate T-cells; however, optimal conditioning regimens are not established mainly because of the rarity of OS. Here, we report a case of hematopoietic stem cell transplantation with a reduced dose of busulfan, as a conditioning regimen and successful engraftment with complete chimerism. OS was diagnosed in a one-month-old boy based on a diffuse erythematous rash, absent B-cells, and activated T-cells. Genetic analysis failed to identify causative mutations for OS/SCID, such as RAG1/2. Bone marrow transplantation was performed from his HLA-matched sister with a conditioning regimen consisting of targeted busulfan, fludarabine, and anti-thymocyte globulin. Cyclosporine had been administered before transplantation to control abnormal T-cell activation and continued for graft-versus-host disease (GVHD) prophylaxis. Engraftment was achieved on day 12, and no GVHD symptoms were observed. For stem cell transplantation for OS, prior control of autoreactive symptoms with immunosuppressants is important for safe transplantation and reduced intensity conditioning (RIC) can be an option to achieve sustained engraftment.

Central nervous system ganglioneuroblastoma harboring MYO5A-NTRK3 fusion.

Central nervous system (CNS) ganglioneuroblastoma is a rare neuroectodermal neoplasm and little is known about its clinical and biological features. Herein, we report a pediatric case of CNS ganglioneuroblastoma harboring MYO5A-NTRK3 fusion. The patient, a 4-year-old boy, underwent a partial resection of a supratentorial tumor that was histopathologically diagnosed as a CNS ganglioneuroblastoma. Treatment with radiotherapy was started per the St Jude Medulloblastoma 03 (SJMB03) protocol; however, the tumor progressed rapidly and radiotherapy was temporally discontinued. Meanwhile, the patient underwent a second surgery, in which a gross total resection was successfully performed, following which he completed the remaining protocol-based therapy. Although an early focal recurrence was detected for which he received additional radiotherapy and oral temozolomide, the patient remained in complete remission for 14 months after the completion of the treatment. A central pathological review and molecular analysis were performed that revealed a MYO5A-NTRK3 fusion. Interestingly, the MYO5A-NTRK3 fusion has been recurrently detected in melanocytic tumors but not in other types of tumors. Therefore, it can be speculated that our case might partly share tumorigenesis mechanisms with MYO5A-NTRK3-positive melanocytic tumors. In addition, our case may enable an improved understanding of the pathogenesis and clinical features of CNS ganglioneuroblastomas.

A Case of Pulmonary Veno-occlusive Disease Following Hepatic Veno-occlusive Disease After Autologous Hematopoietic Stem Cell Transplantation for Neuroblastoma.

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension that is usually difficult to diagnose and is refractory to conservative treatment. PVOD can occur in connection with high-dose chemotherapy or hematopoietic stem cell transplantation, similar to hepatic veno-occlusive disease (HVOD). Here, we present a case of neuroblastoma with PVOD following HVOD after high-dose chemotherapy that was resolved with conservative treatment. Respiratory symptoms or edema after HVOD may suggest PVOD, and prompt diagnosis on high-resolution computed tomography will result in a favorable prognosis.

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013-18.

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses. METHODS: VE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed. RESULTS: In the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505-0.621], 0.550 [95% CI, 0.516-0.586]), 0.549 [95% CI, 0.517-0.583], and 1.014 [95% CI, 0.907-1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1-12 years, especially among those aged 1-5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A. CONCLUSIONS: Both one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.

Living Donor Liver Re-Transplantation for Recurrent Hepatoblastoma in the Liver Graft following Complete Eradication of Peritoneal Metastases under Indocyanine Green Fluorescence Imaging.

The curability of chemotherapy-resistant hepatoblastoma (HB) largely depends on the achievement of radical surgical resection. Navigation techniques utilizing indocyanine green (ICG) are a powerful tool for detecting small metastatic lesions. We herein report a patient who underwent a second living donor liver transplantation (LDLTx) for multiple recurrent HBs in the liver graft following metastasectomy for peritoneal dissemination with ICG navigation. The patient initially presented with ruptured HB at 6 years of age and underwent 3 liver resections followed by the first LDLTx with multiple sessions of chemotherapy at 11 years of age. His alpha-fetoprotein (AFP) level increased above the normal limit, and metastases were noted in the transplanted liver and peritoneum four years after the first LDLTx. The patient underwent metastasectomy of the peritoneally disseminated HBs with ICG navigation followed by the second LDLTx for multiple metastases in the transplanted liver. The patient has been recurrence-free with a normal AFP for 30 months since the second LDLTx. To our knowledge, this report is the first successful case of re-LDLTx for recurrent HBs. Re-LDLTx for recurrent HB can be performed in highly select patients, and ICG navigation is a powerful surgical tool for achieving tumor clearance.