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Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality post cord blood transplantation (CBT). It has been suggested that the graft-versus-host disease (GVHD) and immunosuppressants have an impact on CMV infection. This study evaluated the incidence, outcomes, and risk factors of CMV infection, while focusing on GVHD and the use of immunosuppressants, in 103 children who had received CBT. Among the patients, 92.2% were positive for CMV serology, while CMV antigenemia was observed in 68.9% and CMV disease developed in 26.2%. CMV enterocolitis was the most common, followed by retinitis and pneumonia. Patients with positive CMV serology and grade II to IV GVHD were independently associated with CMV antigenemia. Recurrent CMV antigenemia was observed significantly more frequently in patients with extensive chronic GVHD. Patients with CMV disease showed significantly worse overall survival, relapse-free survival, and non-relapse mortality than those without CMV disease. In conclusion, CMV infection is common post-CBT in countries with a high rate of CMV seropositivity in the general population and is related to worse outcomes. GVHD severity is associated with the development and recurrence of CMV infection. Thus, efforts need to be made to prevent CMV infection in children post-CBT. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to report our single-center experience of allogeneic hematopoietic cell transplantation (HCT), which has been the only curative option for certain patients with lethal primary immunodeficiencies (PIDs).Methods: We summarized the results of HCT performed for patients with PIDs for 11 consecutive years from 2006 to 2016 at Samsung Medical Center, Seoul, Korea. Twenty-six patients with PIDs received HCT. Most had chronic granulomatous disease (42.3%), Wiskott Aldrich syndrome (15.4%), or severe combined immunodeficiency (11.5%).Results: Nine patients (34.6%) received HCT during the former half period and 17 patients (65.4%) during the latter half period. Donor types were categorized as: matched sibling donor (n = 5), unrelated donor (n = 17), and familial mismatched donor (FMMD) (n = 4). Unrelated HCT and FMMD transplantation were increasingly performed in the latter half period compared to the first (5 vs. 16, P = 0.034). Five patients experienced initial engraftment failure, but all of them were eventually engrafted after additional HCTs. The 3-year probability of overall survival was 72.0%. Seven patients (26.9%) died, and the causes of death were bacterial sepsis (n = 4), pneumonia (n = 1), chronic graft-versus-host disease (GVHD) (n = 1), and diffuse alveolar hemorrhage (n = 1). Two patients with bacterial sepsis and a patient with pneumonia also had chronic GVHD. Unrelated HCT and use of methotrexate were associated with poor outcome. Complete chimerism was attained in 85.0% at 1 year after HCT.Conclusion: PID candidates have been increasingly identified for allogeneic HCT in Korea, and the majority of them could be cured by HCT. Establishment of a systematic registry of PID patients for HCT is needed. [ABSTRACT FROM AUTHOR]

Background We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis ( HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH. Methods The Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011. Results In the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein-Barr virus infection. Of 238 evaluable patients, central nervous system ( CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118-308C>T and c.754-1G>C). The 5-yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5-yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome. Conclusion Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein-Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments. [ABSTRACT FROM AUTHOR]

This study analyzes the data reported to the Korean Cord Blood Registry between 1994 and 2008, involving children and adolescents with non-malignant diseases. Sixty-five patients were evaluated in this study: SAA (n = 24), iBMFS, (n = 16), and primary immune deficiency/inherited metabolic disorder (n = 25). The CI of neutrophil recovery was 73.3% on day 42. By day 100, the CI of acute grade II-IV graft-versus-host disease was 32.3%. At a median follow-up of 71 months, five-yr OS was 50.7%. The survival rate (37.5%) and CI of neutrophil engraftment (37.5%) were lowest in patients with iBMFS. Deaths were mainly due to infection, pulmonary complications, and hemorrhage. In a multivariate analysis, the presence of >3.91 × 105/kg of infused CD34 + cells was the only factor consistently identified as significantly associated with neutrophil engraftment (p = 0.04) and OS (p = 0.03). UCBT using optimal cell doses appears to be a feasible therapy for non-malignant diseases in children and adolescents for whom there is no appropriate HLA-matched related donor. Strategies to reduce transplant-related toxicities would improve the outcomes of UCBT in non-malignant diseases. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake in the 7th author’s given name. The correct version is presented above. [ABSTRACT FROM AUTHOR]

Abstract: 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 107/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. [Copyright &y& Elsevier]

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective for preventing graft-versus-host disease (GVHD) and the rejection of organ transplants. After the promising results of our preliminary study, we conducted a phase II prospective multicenter clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and thymoglobulin conditioning regimen to allow good engraftment in patients who underwent unrelated transplantation for SAA. Twenty-eight patients underwent bone marrow (N = 15) or mobilized peripheral blood (N = 13) transplantation from HLA-matched unrelated donors with Cy (50 mg/kg once daily intravenously (i.v.) on days −9, −8, −7, and −6), Flu (30 mg/m2 once daily i.v. on days −5, −4, −3, and −2), and thymoglobulin (2.5 mg/kg once daily i.v. on days −3, −2, and −1). Donor-type hematologic recovery was achieved in all patients. The estimated survival rate (SR) was 67.9%, and all the events were treatment-related mortality (TRM), which included thrombotic microangiopathy (N = 2), pneumonia (N = 1), myocardiac infarction (N = 1), posttransplantation lymphoprolifarative disease (N = 3), and chronic GVHD-associated complications (N = 2). The SR of patients who received bone marrow (60.0%) was not different from that of patients who received mobilized peripheral blood (76.9%) (P = .351), but the SR of patients who received more than 15 units of red blood cells before transplantation (45.5%) was significantly lower than that of the other patients (82.4%) (P = .048). The Flu, Cy, and thymoglobulin conditioning regimen achieved promising results for successful engraftment, but the TRM was high. This study was registered at www.clinicaltrials.gov (NCT00737685), and now we are performing a new multicenter study (NCT00882323) to decrease the TRM by reducing the dose of Cy. [Copyright &y& Elsevier]