Pre-engraftment syndrome (PES) is poorly characterized, and its clinical significance and the prognostic impact after unrelated cord blood transplantation (CBT) are unclear. To address these issues, we retrospectively analyzed the incidence, risk factors, and clinical outcomes of PES in unrelated CBT recipients. Data of 381 patients who received unrelated CBT from 18 medical centers in Korea were reviewed. PES was defined as unexplained fever >38.3°C not associated with infection, and/or unexplained skin rash with or without evidence of fluid retention before neutrophil recovery. PES developed in 102 patients (26.8%) at a median of 7 days after CBT. Of these patients, 74 patients (72.5%) received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 95% showed clinical improvement. Risk factors for developing PES included low risk disease, myeloablative conditioning, graft-versus-host disease (GVHD) prophylaxis without methotrexate or corticosteroid, and >5.43 x 10(7)/kg infused nucleated cells. Absence of PES was one of the risk factors for graft failure in multivariate analysis. The cumulative incidence of grade II to grade IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% versus 34.4%, P < .01). PES was not associated with chronic GVHD, treatment-related mortality, relapse, or overall survival. PES seems to be common after CBT and may be associated with enhanced engraftment without significant morbidity.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB ( n = 28), and followed by ANK1 ( n = 19), SLC4A1 ( n = 3), SPTA1 ( n = 2), EPB41 ( n = 1), and EPB42 ( n = 1). Concurrent mutations of genes encoding RBC enzymes ( ALDOB, GAPDH, and GSR ) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS. Electronic supplementary material The online version of this article (10.1186/s13023-019-1070-0) contains supplementary material, which is available to authorized users.

PurposeInfantile hepatic hemangioendothelioma (IHHE) is the most common type of hepatic vascular tumor in infancy. We conducted this study to review our clinical experience of patients with IHHE and to suggest management strategies.MethodsWe retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13 females) treated at the Asan Medical Center between 1996 and 2009.ResultsMedian age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%) were diagnosed with IHHE based on sonographically detected fetal liver masses, 5 (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging results, and were confirmed in three patients by histopathology analysis. Six patients were observed without receiving any treatment, whereas 12 received corticosteroids and/or interferon-alpha. One patient with congestive heart failure and a resectable unilobar tumor underwent surgical resection. Three patients with congestive heart failure and unresectable tumors were managed by hepatic artery embolization with/without medical treatment. At a median follow-up of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor disappearance or >50% decrease in tumor size. One patient died due to tumor-related causes.ConclusionIHHE generally has a benign clinical course with low morbidity and mortality rates. Clinical course and treatment outcome did not differ significantly between medically treated and non-treated groups. Surgically unresectable patients with significant symptoms may be treated medically or with hepatic artery embolization.

Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. The exact causes and mechanisms involved in aplastic anemia (AA) are not known. For better understanding of the pathophysiology of AA, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment in patients with AA by immunohistochemical analysis. A total of 10 AA patients and 10 controls were enrolled. Using BM biopsy specimen, we performed immunohistochemistry for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1), lymphocytes, macrophage, and HSCs. Numbers of HSCs and T/B lymphocytes were significantly lower in the AA specimens than the controls, and the AA specimens contained more natural killer cells (CD56(+) cells) (P < 0.01). The 2 groups had similar levels of expression of osteopontin, osteocalcin, nestin, and SDF-1. However, the number of osteonectin(+) cells in the AA specimens was significantly lower than in the control specimens (P<0.01). Our findings support the hypothesis that defects in the stromal cells contribute to the pathogenesis of AA by damaging HSC niche. Immune-mediated natural killer cells may also play a role in the pathogenesis of AA.

To investigate reconstitution of T and NK cells after αβ T lymphocyte-depleted hap- 6,7

BackgroundCentral nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (HSCT) have not been well characterized in the pediatric population.MethodsWe retrospectively analyzed data of 202 consecutive children who underwent allogeneic HSCT (60 from matched related donors, 9 from mismatched related donors, and 133 from unrelated donors) at Asan Medical Center between 1998 and 2009.ResultsTwenty-seven children (13.5%) developed CNS complications within 6 months after HSCT. Calcineurin inhibitor (CNI)-associated neurotoxicity was the most common CNS complication (n=16), followed by CNS infection (n=2), cerebrovascular events (n=2), thrombotic microangiopathy-associated events (n=2), metabolic encephalopathy (n=2), irradiation/chemotherapy injury (n=1), and encephalopathy/myelopathy of unknown causes (n=2). Univariate analysis showed that a transplant from an alternative donor and the occurrence of acute graft-versus-host disease (GVHD) (>grade 2) were associated with a significantly increased risk of CNS complications. In the multivariate analysis, acute GVHD >grade 2 was identified as an independent risk factor for early CNS complications. The 5-year overall survival rate was significantly lower in patients with CNS complications (52.1% vs. 64.9%, P=0.014), whereas CNI-associated neurotoxicity did not affect the survival outcome.ConclusionCNS complications are frequent among children undergoing HSCT, contributing to early death after transplant. More attention should be paid to the development of CNS complications for recipients of alternative donor transplants and patients with severe acute GVHD who are at increased risk for CNS complications.

PurposeTo determine the efficacy and safety of oral propranolol as a first-line treatment for superficially located infantile hemangioma (IH) and propose an assessment tool to measure treatment response.MethodsPatients with superficial IH under 1 year of age were prospectively recruited between May 2012 and December 2013 at the Department of Pediatrics of Chungbuk National University Hospital. Propranolol was administered to 12 infants (median age, 3.8 months) while monitoring cardiovascular and adverse metabolic effects. If a patient showed no adverse events, the dosage was gradually increased up to 3 mg/kg/day and maintained for 1 year. We used our own scoring system to assess treatment response using parameters like change in color, and longest diameter, and thickness of the IH.ResultsEleven out of 12 patients completed the protocol with consistent improvement of hemangiomas during therapy. Patients on propranolol showed a more than 50% involution in the first 3 months, with additional steady involution until 1 year. Patients with the highest scores at 1 month maintained their score and showed better responses until treatment termination. The patient with the lowest score at 1 month did not show any further regression and stopped propranolol treatment 4 months after initiation. In two children with recurrences after successful therapeutic regression, propranolol was effective after being reintroduced. Propranolol treatment was not interrupted in any patient due to adverse events.ConclusionOral propranolol at 3 mg/kg/day showed a consistent, rapid, and therapeutic effect on superficial IHs without significant adverse events.