High Plasma Presepsin Levels in Children With Hemophagocytic Lymphohistiocytosis.

Presepsin is reported as a novel diagnostic and prognostic biomarker for sepsis, and its optimal cutoff value is reported to be 600 to 650 pg/mL. Three children were diagnosed with hemophagocytic lymphohistiocytosis (HLH). The cause of HLH was unknown in cases 1 and 2, while Epstein-Barr virus infection was the cause in case 3. The plasma presepsin levels at the diagnosis were 1020, 1080, and 3160 pg/mL in cases 1, 2, and 3, respectively. In case 1, the plasma level of presepsin decreased to 164 pg/mL on day 19 of her sickness, when symptoms improved. Follow-up plasma presepsin levels were missing for cases 2 and 3. No microbiological pathogens were detected in the blood cultures of any of the patients. Our cases suggest that plasma presepsin levels can be elevated in childhood HLH.

Successful living donor liver transplantation for liver failure due to maternal T cell engraftment following cord blood transplantation in X-linked severe combined immunodeficiency disease: Case report.

Maternal T cells from perinatal transplacental passage have been identified in up to 40% of patients with severe combined immunodeficiency (SCID). Although engrafted maternal T cells sometimes injure newborn tissue, liver failure due to maternal T cells has not been reported. We rescued a boy with X-linked SCID who developed liver failure due to engrafted maternal T cell invasion following living donor liver transplantation (LDLT) following unrelated umbilical cord blood transplantation (UCBT). After developing respiratory failure 3 weeks postpartum, he was diagnosed with X-linked SCID. Pathological findings showed maternal T cells engrafted in his liver and hepatic fibrosis gradually progressed. He underwent UCBT at 6 months, but hepatic function did not recover and liver failure progressed. Therefore, he underwent LDLT using an S2 monosegment graft at age 1.3 years. The patient had a leak at the Roux-en-Y anastomosis, which was repaired. Despite occasional episodes of pneumonia and otitis media, he is generally doing well 6 years after LDLT with continued immunosuppression agents. In conclusion, the combination of hematopoietic stem cell transplantation (HSCT) and liver transplantation may be efficacious, and HSCT should precede liver transplantation for children with X-linked SCID and liver failure.

Successful allogeneic bone marrow transplantation with reduced intensity conditioning regimen for a pediatric relapsed ALK positive anaplastic large cell lymphoma.

Pediatric anaplastic large cell lymphoma (ALCL) is a chemosensitive malignancy, but about 30% of patients experience relapse. In most of these patients, a second complete remission is obtainable with salvage chemotherapy, though relapse free survival rates are as low as 30-60%. Herein, we report a 6-year-old boy with relapsed anaplastic lymphoma kinase (ALK) positive ALCL successfully treated with vinblastine monotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reduced intensity conditioning (RIC) regimen, from his father. One HLA locus from the father was mismatched. The boy had neither severe graft-versus-host disease nor transplantation related complications. He is currently well and has remained disease free for 10 months, to date, since transplantation. Allo-HSCT with a RIC regimen may be a promising treatment strategy for relapsed ALK positive ALCL based on obtaining graft-versus lymphoma effects as well as reducing transplantation-related mortality.

Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is a peroxisomal disorder characterized by white matter degeneration caused by adenosine triphosphate-binding cassette subfamily D member 1 (ABCD1) gene mutations, which lead to an accumulation of very-long-chain fatty acids (VLCFA). Hematopoietic stem cell transplantation (HSCT) is the most effective treatment; however, the ratio of donor-to-recipient cells required to prevent the progression of demyelination is unclear. The proband was diagnosed with the childhood cerebral form of ALD at 5 years of age based on the clinical phenotype, elevated plasma VLCFA levels, and pathogenic ABCD1 mutation c.293C>T (p.Ser98Leu). Soon after the diagnosis, he became bedridden. At 1 year of age, his younger brother was found to carry the same ABCD1 mutation; despite being asymptomatic, at 1 year and 9 months, head magnetic resonance imaging (MRI) showed high-signal-intensity lesions in the cerebral white matter. The patient underwent unrelated cord blood transplantation (UCBT) with a reduced conditioning regimen, which resulted in mixed chimerism. For 7 years after UCBT, the donor chimerism remained low (<10%) in peripheral blood and cerebrospinal fluid. However, even though a second HSCT was not performed, his neurological symptoms and brain MRI findings did not deteriorate. Our case suggests that even a small number of donor cells may prevent demyelination in ALD. This is an important case when considering the timing of a second HSCT.

Rapid blood cell recovery with immunosuppressive therapy combined with romiplostim in a patient with very severe hepatitis-associated aplastic anemia who underwent liver transplantation.

Patients with hepatitis-associated aplastic anemia (HAA) who undergo living-donor liver transplantation (LDLT) have a poor prognosis with infections and bleeding complications. Rapid recovery of blood cells is critical for preventing these complications and improving the outcome. Immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists is considered effective for aplastic anemia. However, there are no data on the benefits of adding thrombopoietin receptor agonists to IST for HAA. We present the case of a child with severe HAA who underwent LDLT, and who achieved rapid blood cell recovery with IST combined with romiplostim, a thrombopoietin receptor agonist. In addition, despite having undergone LDLT, the patient had no adverse events such as serious liver dysfunction or thrombosis. This case suggests that IST combined with thrombopoietin receptor agonists may be a promising treatment option for HAA patients undergoing LDLT.

Analysis of the BRAF and MAP2K1 mutations in patients with Langerhans cell histiocytosis in Japan.

In Langerhans cell histiocytosis (LCH), somatic gene mutations in the mitogen-activated protein kinase pathway have been identified in more than 80% of cases in Western countries, in which mutually exclusive BRAF and MAP2K1 mutations are involved. Among them, BRAF V600E mutation is the major contributor (50-60%). In 59 patients (50 children and nine adults) with LCH (not including pulmonary LCH) in Japan, we first screened for BRAF V600E in all patients followed by target sequencing for other gene mutations in 17 of BRAF V600E-negative patients. As a result, BRAF V600E mutation was detected in 27/59 (46%) patients. We also identified BRAF mutations other than V600E in five and MAP2K1 mutations in nine patients. Thus, gene mutations in BRAF or MAP2K1 were identified in 41/44 (93%) of the fully tested patients. Regarding the correlation of clinical features and genotype in pediatric patients, we found that BRAF V600E mutation status was not correlated with sex, age at diagnosis, disease extent, response to first-line therapy, relapse, or CNS-related sequelae. Interestingly, MAP2K1 exon 2 in-frame deletion was related to the risk organ involvement; however, further studies are required to clarify the impact of these gene mutations on the clinical features of patients with LCH.