Serologic status and vaccine response against hepatitis B virus after allogeneic hematopoietic cell transplantation in pediatric patients.

BACKGROUND: Although vaccination against hepatitis B virus (HBV) is recommended for hematopoietic cell transplantation (HCT) recipients, previous studies evaluating serologic status and immunologic response to HBV vaccination in pediatric allogeneic HCT recipients are not enough. OBJECTIVE: This study aimed to evaluate serologic status against HBV and immunologic responses to HBV vaccination in children and adolescents receiving allogeneic HCTs. METHODS: Medical records of the enrolled 61 pediatric patients < 19 years of age who received their first allogeneic HCTs were retrospectively reviewed. RESULTS: Twenty-two (36.1%) of the enrolled patients were positive for hepatitis B surface antibody (HBsAb) after HCT. Chronic graft-versus-host disease was significantly associated with negative HBsAb status after HCT (p = 0.01). With one dose of HBV vaccination after HCT, 40.5% of the vaccinated patients became positive for HBsAb. No clinical factor was associated with the positive conversion of HBsAb after vaccination. CONCLUSIONS: Considering the unsatisfactory seropositive rate and vaccine response against HBV and the lack of significant clinical and laboratory factors predicting serostatus in HCT recipients, universal three doses of HBV vaccination should be necessary after allogeneic HCT.

Ultrasound in Hepatic Veno-occlusive Disease (HVOD) after Pediatric Hematopoietic Stem Cell Transplantation (HSCT): Comparison of Diagnostic Criteria Including the Pediatric Criteria of European Society for Blood and Marrow Transplantation (EBMT).

The European Society for Blood and Marrow Transplantation (EBMT) has recently announced new diagnostic criteria for pediatric hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). We retrospectively inspected 97 ultrasound exams of 60 pediatric HSCT patients, and compared its diagnostic value using the Baltimore, Seattle and pediatric EBMT criteria. Nine of the ten patients who were diagnosed as HVOD only in the EBMT criteria had severe or very severe HVOD. In the Seattle and EBMT criteria, portal vein velocity, peak systolic velocity and resistance index of hepatic artery, gallbladder wall thickening and ascites were statistically significant. No ultrasound variable showed significant association in the Baltimore criteria. All patients with portal vein velocity below 10 cm/s were in higher EBMT grade. A scoring system was developed, to evaluate the overall relationship of the ultrasound findings with the diagnosis of HVOD, showing fair (0.768 and 0.733) AUC in the ROC curve of EBMT and Seattle criteria.

Distinct Clinical Manifestations of Thyroid Cancer After Hematopoietic Stem Cell Transplantation.

BACKGROUND: The incidence of a secondary solid malignancy after hematopoietic cell transplantation (HCT) is increasing in long-term survivors. OBJECTIVE: The aim of this study was to compare the clinicopathological characteristics of HCT recipients with secondary thyroid cancer (STC), with those of non-HCT thyroid cancer patients. METHODS: We retrospectively investigated 5184 patients who received HCT between 1983 and 2016. Of these, 18 patients developed STC and underwent thyroidectomy due to differentiated thyroid cancer. We compared the clinicopathological characteristics of post-HCT thyroid cancer patients (post-HCT group) with those of a primary differentiated thyroid carcinoma cohort (cohort group) from Seoul St. Mary's Hospital. RESULTS: The mean ages at HCT and thyroidectomy after HCT were 22.0 and 31.8 years, respectively, and the median time interval between HCT and thyroidectomy was 5 years (range 1-16). Compared with the cohort group, the post-HCT group was younger at cancer onset and frequently had a palpable mass at initial diagnosis. The post-HCT group had more aggressive features, including larger tumor size, frequent extrathyroidal extension, lymphatic invasion, perineural invasion, and frequent lateral neck node metastasis and distant metastasis, relative to the cohort group; however, most patients (83.2%) in the post-HCT group were stage I or II. Additionally, BRAF V600E mutation was less frequent in the post-HCT group. CONCLUSIONS: We found that STC after HCT showed younger presentation and more aggressive clinical presentation. Therefore, a policy of regular screening, including neck ultrasound examination, may promote early detection and treatment in HCT recipients.

Enterococcal bacteremia in febrile neutropenic children and adolescents with underlying malignancies, and clinical impact of vancomycin resistance.

PURPOSE: Enterococci are a common cause of bacteremia in immunocompromised patients. Although the increase of vancomycin-resistant enterococci (VRE) makes appropriate antibiotic therapy difficult, clinical characteristics of enterococcal bacteremia and the impact of VRE infection on outcomes have rarely been reported in immunocompromised children. METHODS: We enrolled children and adolescents (< 19 years of age) with underlying malignancies who were diagnosed with enterococcal bacteremia during febrile neutropenia between 2010 and 2017. Medical records of the enrolled children were retrospectively reviewed to evaluate the clinical characteristics of enterococcal bacteremia and impact of VRE infection on outcomes. RESULTS: Thirty-six episodes of enterococcal bacteremia were identified in 30 patients. VRE infection was identified in 11 episodes (30.6%); the 7- and 30-day mortalities were 27.8% and 44.4%, respectively. Acute lymphoblastic leukemia (50.0%) and acute myeloid leukemia (30.6%) were the most common underlying disorders. Three (8.3%) of the patients were in complete remission, and palliative and reinduction chemotherapies were administered in 47.2% and 36.1% of episodes, respectively. Empirical antibiotic therapy was appropriate in 64.0% of patients with vancomycin-susceptible enterococcal infection and in none of the VRE-infected patients (p = 0.001). However, the 30-day mortality was not significantly different between the two patient groups (44.0% vs. 45.5%, p = 1.000). CONCLUSIONS: Most episodes of enterococcal bacteremia occurred in advanced stages of underlying malignancies, and still showed high mortality. The prognosis seemed to be related to the underlying disease condition rather than vancomycin resistance of the isolated enterococci, although the number of enrolled patients was small.

Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study.

BACKGROUND: Although the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients. METHODS: Thirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and ß-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined. RESULTS: Thirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal ß-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%. CONCLUSIONS: Mortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

Treatment of children with acute lymphoblastic leukemia with risk group based intensification and omission of cranial irradiation: A Korean study of 295 patients.

BACKGROUND: Recent studies indicate 70-80% event-free survival (EFS) for pediatric acute lymphoblastic leukemia (ALL). In this study, we report the outcome of 295 children and adolescents treated at our institution, with stratification into four risk groups, and omission of cranial irradiation in all patients. PROCEDURE: Patients were diagnosed from January 2005 to December 2011 and classified and treated as low, standard, high, and very high risk groups. A delayed intensification phase was given twice for high and very high risk groups. None of the patients received cranial irradiation for central nervous system (CNS) prophylaxis. RESULTS: The 10-year EFS and overall survival (OS) were 78.5 ± 2.5% and 81.9 ± 2.7%, respectively. EFS according to risk group was as follows: low risk 91.2 ± 3.7%, standard risk 98.1 ± 1.9%, high risk 81.5 ± 4.3%, very high risk 59.4 ± 5.3%. In a multivariate analysis, high hyperdiploidy and infant ALL were significant predictors of EFS. Cumulative incidence of any relapse, isolated CNS relapse, and any CNS relapse were 17.1 ± 2.3%, 1.5 ± 0.7%, and 2.3 ± 0.9%, respectively. Other events included infection-related deaths during remission induction chemotherapy (3), primary refractory disease (2), and treatment-related deaths in first complete remission (8). CONCLUSIONS: In this single-institution study of Korean pediatric ALL patients, risk group based intensification with omission of cranial irradiation resulted in EFS comparable to previous studies, excellent survival of low- and standard-risk patients, and a low rate of CNS relapse.

Varicella with rapidly progressive hepatitis presenting with multiple hepatic nodules in a child with acute leukemia.

Abdominal pain may precede the characteristic varicella skin lesions in immunocompromised patients with visceral varicella. The absence of skin lesions may delay timely diagnosis and treatment of varicella for those patients. Furthermore, abdominal imaging findings to provide information to diagnose visceral varicella have rarely been reported. Varicella was diagnosed in a 5-year-old boy with acute lymphoblastic leukemia complaining of fever and abdominal pain followed by papulovesicular skin lesions. Later, the patient was found to have rapidly progressive acute hepatitis, and abdominal computed tomography showed multiple hypodense hepatic nodules. The patient was treated with intravenous acyclovir, intravenous immunoglobulin, and empirical antibiotic and antifungal therapy. However, his fever and abdominal pain persisted, and a laparoscopic liver biopsy was performed to differentiate other causes of the persisting symptoms. Eventually, the patient was diagnosed with visceral varicella based on histopathologic findings. In conclusion, visceral varicella should be considered in immunocompromised patients with abdominal pain and multiple hypodense hepatic nodules on abdominal imaging studies. However, bacteria, fungi, and tuberculosis can produce similar imaging findings; therefore, a biopsy may be necessary in patients not responding to antiviral therapy.

Serum galactomannan index for early prediction of mortality in immunocompromised children with invasive pulmonary aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is the most common invasive fungal disease in immunocompromised patients, and it has a 30 % mortality rate despite appropriate antifungal therapy. This retrospective study was performed to determine risk factors for mortality in immunocompromised children with IPA. METHODS: Medical records of 45 probable/proven IPA cases diagnosed in children with hematologic/oncologic diseases were reviewed. Selected cases were divided into the survival (n = 30) and fatality (n = 15) groups based on survival at 12 weeks after antifungal therapy. Clinical characteristics and serum galactomannan indices (GMIs) were compared between the two groups. RESULTS: Significantly more children in the fatality group were male (p = 0.044), not in complete remission of the underlying malignancies (p = 0.016), and had received re-induction/salvage or palliative chemotherapy (p = 0.035) than those in the survival group. However, none of these factors was significantly associated with mortality in a multivariate analysis. Serum GMIs were higher in the fatality group than in the survival group during the entire period of antifungal therapy, and serum GMI at 1 week after antifungal therapy was most significantly associated with mortality. A serum GMI > 1.50 at 1 week after antifungal therapy exhibited a sensitivity and specificity of 61.5 % and 89.3 %, respectively, in predicting mortality within 12 weeks after antifungal therapy. CONCLUSIONS: Higher serum GMI in the early phase of antifungal therapy was associated with mortality in immunocompromised children with IPA. These children should receive more intensive care for IPA than others.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

High-Dose Busulfan-Fludarabine Conditioning and Low Alveolar Volume as Predictors of Pulmonary Complications after Allogeneic Peripheral Blood Stem Cell Transplantation in Children.

This study was conducted to investigate risk factors and predictors of infectious and noninfectious pulmonary complications (PCs) after allogeneic hematopoietic stem cell transplantation in children. We conducted a retrospective analysis of the post-transplantation PCs of 240 patients who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) between 2009 and 2018. Transplantation-related variables, pretransplantation baseline spirometry, body plethysmography, and CO diffusing capacity were analyzed for association with the development of infectious PCs (IPCs) and noninfectious PCs (NIPCs). Compared with the control group, the PC group had statistically significantly lower overall survival (50.6% versus 77.8%; P < .001), higher disease-related mortality (26.6% versus 54.4%; P < .001), and higher nonrelapse mortality (31.6% versus 5.9%; P < .001). A greater number of patients received pretransplantation conditioning with high-dose busulfan (520 mg/m2; Bu 520) and fludarabine (160 mg/m2; Flu 160) in both the IPC and NIPC groups. In the multivariate Cox hazard regression analysis, Bu 520 significantly increased the risk of NIPCs (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.13 to 3.49; P = .016), and Flu 160 was a predictor of IPCs (HR, 1.99; 95% CI, 1.13 to 3.49; P = .016). The Bu 520 + Flu 160 regimen was associated with a statistically significant increase in the risk of NIPC (HR, 1.92; 95% CI, 1.09 to 3.37; P = .023). In a multivariate analysis using pretransplantation baseline lung function, alveolar volume (VA) grades 3 and 4 and lung function score (LFS) VA categories III and IV were associated with increased risk for both IPCs and NIPCs. Our data identify receipt of the high-dose Bu-Flu conditioning regimen as an independent risk factor for NIPCs after allo-PBSCT. Impaired CO diffusing capacity before transplantation, especially VA reduction, contributes to the risk of post-transplantation pulmonary complications, and pretransplantation risk can be estimated by grading the degree of insufficiency of VA and LFS VA.

Allogeneic hematopoietic cell transplantation in patients with juvenile myelomonocytic leukemia in Korea: a report of the Korean Pediatric Hematology-Oncology Group.

Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. This multicenter study evaluated the characteristics, outcomes, and prognostic factors of allogeneic hematopoietic cell transplantation (HCT) in recipients with JMML who were diagnosed between 2000 and 2019 in Korea. Sixty-eight patients were retrospectively enrolled-28 patients (41.2%) received HCT during 2000-2010 and 40 patients (58.8%) during 2011-2020. The proportion of familial mismatched donors increased from 3.6 to 37.5%. The most common conditioning therapy was changed from Busulfan/Cyclophosphamide-based to Busulfan/Fludarabine-based therapy. The 5-year probabilities of event-free survival (EFS) and overall survival (OS) were 52.6% and 62.3%, respectively. The 5-year incidence of transplant-related mortality was 30.1%. Multivariate analysis revealed that the proportion of hemoglobin F ≥ 40%, abnormal cytogenetics, and matched sibling donors were independent risk factors for a higher relapse rate. Patients whose donor chimerism was below 99% had a significantly higher relapse rate. Better OS and lower treatment-related mortality were observed in patients with chronic graft-versus-host disease (GVHD), whereas grade III or IV acute GVHD was associated with worse EFS. In conclusion, the number of transplant increased along with the increase in alternative donor transplants, nevertheless, similar results were maintained. Alternative donor transplantation should be encouraged.

Response to chemotherapy in juvenile myelomonocytic leukemia and its clinical implications for survival: A retrospective registry-based study of the Korean Pediatric Hematology-Oncology Group.

Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. The chemotherapeutic effect on survival remains unclear, and feasible standardized response criteria are yet to be established. We aimed to evaluate the chemotherapeutic response and its effect on survival in patients with JMML. A retrospective registry was reviewed for children diagnosed with JMML between 2000 and 2019. Response was assessed according to the criteria proposed by the International JMML Symposium in 2007 (criteria I) and the updated version in 2013 with its modifications (criteria II). A total of 73 patients were included in this study. Complete response (CR) rates were 46.6% and 28.8% using the criteria I and criteria II, respectively. A platelet count ≥ 40 × 109/L at diagnosis was associated with higher CR rates using the criteria II. Patients with criteria I-based CR had a better overall survival (OS) than those without CR (81.1% vs. 49.1% at 5 years). Patients with criteria II-based CR showed better OS (85.7% vs. 55.5% at 5 years) and event-free survival (EFS) (71.1% vs. 44.7% at 5 years) than those without CR. Additionally, a trend toward better EFS was observed in patients with criteria II-based CR than in those with criteria I-based CR but without criteria II-based CR (71.1% vs. 53.8% at 5 years). Chemotherapeutic response is associated with better survival outcomes. Along with splenomegaly, the addition of platelet count recovery, existence of extramedullary leukemic infiltration, and more stringent leukocyte counts to the response criteria allows for a more sensitive prediction of survival outcomes.

Association between cytokine concentration kinetics and prolonged fever in febrile neutropenic children with bacteremia.

INTRODUCTION: Although prolonged fever in patients with neutropenic fever (NF) during empirical antibiotic therapy could be caused by dysregulated immune responses, its association with cytokine concentrations has rarely been investigated. This study determined the kinetics of cytokine concentrations in pediatric patients with NF and bacteremia and evaluated the impact of cytokine concentration kinetics on prolonged fever. METHODS: Concentrations of 13 cytokines were measured on the initial day of NF (Day 1) and 3 days (Day 4) and 7 days (Day 8) later in 10 patients with NF with bacteremia, and their kinetics was determined. The results for each cytokine concentration on each sampling day were compared for patients with fever that lasted ⩾3 days and those with fever that lasted <3 days. RESULTS: Interleukin (IL)-6 (p < .001) and IL-10 (p = .001) concentrations were significantly higher on Day 1 than on Days 4 and 8. However, the increased IL-6 (p = 1.000) and IL-10 (p = 1.000) concentrations on Day 1 were not associated with prolonged fever (⩾3 days). For other cytokines, the concentrations measured on Days 1, 4, and 8 were similar regardless of fever duration. CONCLUSION: Prolonged fever in patients with NF and bacteremia was not associated with a prolonged increase in a specific cytokine concentration.

Quantitative CT lung densitometry as an obstructive marker for the diagnosis of bronchiolitis obliterans in children.

The purpose of this study is to evaluate the quantitative diagnostic performance of computed tomography (CT) densitometry in pediatric patients with bronchiolitis obliterans (BO). We measured the mean lung density (MLD) and represented the difference of MLD in inspiratory and expiratory phases (MLDD), the ratio of the MLD (E/I MLD), and the relative volume percentage of lung density at 50-Hounsfield unit (HU) interval threshold (E600 to E950). We calculated the sensitivity, specificity, and diagnostic accuracy of the lung density indices for the diagnosis of BO. A total of 81 patients, including 51 patients with BO and 30 controls, were included in this study. In the BO patients, expiratory (EXP) MLD and MLDD were significantly lower, and E/I MLD and expiratory low attenuation areas below the threshold of -850 HU to -950 HU (E850, E900, and E950) were statistically significantly higher than controls. Multivariate logistic regression analysis showed that MLDD (odds ratio [OR] = 0.98, p < .001), E/I MLD (OR = 1.39, p < .001), and E850 to E950 were significant densitometry parameters for BO diagnosis. In a receiver-operating characteristic analysis, E900 (cutoff, 1.4%; AUC = 0.920), E/I MLD (cutoff, 0.87; AUC = 0.887), and MLDD (cutoff, 109 HU; AUC = 0.867) showed high accuracy for the diagnosis of BO. In conclusion, the lung CT densitometry can serve as a quantitative marker providing additional indications of expiratory airflow limitation in pediatric patients with BO.

Clinical Characteristics and Treatment Outcomes of Childhood Acute Promyelocytic Leukemia in Korea: A Nationwide Multicenter Retrospective Study by Korean Pediatric Oncology Study Group.

PURPOSE: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. MATERIALS AND METHODS: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. RESULTS: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). CONCLUSION: This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Efficacy of low dose antithymocyte globulin on overall survival, relapse rate, and infectious complications following allogeneic peripheral blood stem cell transplantation for leukemia in children.

Antithymocyte globulin (ATG) and anti-T lymphocyte globulin (ATLG) have been widely used to prevent graft-versus-host disease (GvHD), each with distinct properties and noninterchangeable doses. However, the optimal dose of ATG in children undergoing allo-PBSCT for leukemia has not yet been established. Therefore, the impact of ATG dose on overall survival (OS), relapse, GvHD, and infectious complications was investigated. Patients administered high dose (unrelated: 7.5 mg/kg, haploidentical: 10.0 mg/kg) and low dose (unrelated: 3.75 mg/kg, haploidentical: 5.0 mg/kg) ATG during two consecutive time periods were compared. There were 78 (39.8%) patients in the low dose group and 118 (60.2%) in the high dose group. OS was superior in the low dose group compared to the high dose group (P = 0.017), and relapse incidence was significantly lower in the low dose group (P = 0.022). Cumulative incidences of acute and chronic GvHD were similar between the groups (P = 0.095 and P = 0.672, respectively). Cytomegalovirus reactivation (70.3% vs. 51.3%, P = 0.007), Epstein-Barr virus reactivation (81.4% vs. 39.7%, P < 0.001), and invasive bacterial infections (12.7% vs. 0%, P = 0.001) post transplant were more frequent in the high dose group compared to the low dose group. Therefore, low dose ATG is more optimal in pediatric allo-PBSCT providing better OS while lowering the risk of relapse and infectious complications.

Source Identification of Klebsiella pneumoniae Causing Six Episodes of Recurrent Sepsis in an Adolescent That Underwent Hematopoietic Stem Cell Transplantation.

Septicemia or bacteremia is one of the leading causes of death worldwide. Long-term tunneled central venous catheters (CVCs) are usually placed in children undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) for underlying hemato-oncologic malignancies. However, catheter-related complications have been reported frequently, and there is high morbidity and mortality related to catheter-line-associated bloodstream infections (CLABSIs). We report a rare case of six episodes of recurrent K. pneumoniae sepsis within a 6-month period in a 12-year-old male adolescent that underwent HSCT for acute lymphoblastic leukemia, despite treatment with susceptible antibiotics. The patient received extensive diagnostic evaluations to find the hidden source; however, failure to discover the primary source led to multiple recurrences. Through enterobacterial repetitive intergenic consensus (ERIC)-PCR, we were able to identify the relationship between the six episodes and recognize the source of bacteremia.

A Case of Disseminated Herpes Zoster Presenting as Vesicles Limited to Skin Lesions with Lymphoma Cutis Involvement.

After primary infection, varicella zoster virus (VZV) causes prolonged latent infections that may reactivate, depending on the immunologic status of the host. We present a case of VZV reactivation in a 10-year-old male patient that underwent unrelated peripheral blood stem cell transplantation (uPBSCT) for T-lymphoblastic lymphoma with lymphoma cutis lesions. This patient had a history of herpes zoster involving the right L2-5 dermatome and trigeminal V1 dermatome prior to uPBSCT. Three months post-uPBSCT, the patient's underlying disease relapsed, and the patient presented with lymphoma cutis lesions. A few days after a skin biopsy was performed to pathologically confirm skin relapse, vesicles appeared only involving the skin areas with lymphoma cutis. This case illustrates how decreased areas of epidermal immune mechanisms may cause atypical presentations of varicella infection.

Hb-adjusted DLCO with GLI reference predicts long-term survival after HSCT in children.

This study aimed to evaluate the pretransplant diffusing capacity as a predictor of outcomes in pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). Retrospective cohort study of 176 children followed outcomes for 5 years after allo-HSCT. We conducted an analysis of PFTs include spirometry, body plethysmography, and diffusing capacity prior to allo-HSCT. We analyzed the probabilities of overall survival (OS), disease-related mortality (DRM), and non-relapse mortality (NRM). Of all carbon monoxide diffusing capacity (DLCO) parameters obtained using the Global Lung Function Initiative (GLI)-2017, univariate analysis showed that the grade 3, 4 of DLCOadj and Category III, IV of LFS significantly increase NRM (p = 0.003 and p = 0.008). Multivariate analysis indicated that a significant increase in the risk of NRM is associated with grades 3, 4 DLCOadj (hazard ratio [HR] = 4.90, p = 0.020). Kaplan-Meier analyses showed that a significant stepwise increase in NRM was observed with both worse pretransplant DLCOadj grades and LFS categories (p < 0.001 and p = 0.003). A compromised pretransplant diffusing capacity and a high LFS significantly increase the risk of NRM. Especially, DLCOadj before transplantation can be used as an important predictor of NRM after allo-HSCT in children with malignancy.

Clinical characteristics and viral load patterns in children with cytomegalovirus gastrointestinal disease after allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) reactivation in allogeneic hematopoietic stem cell transplantation (allo-HSCT) causes significant morbidity and mortality. This study aimed to investigate the clinical characteristics of children diagnosed with CMV GI disease after allo-HSCT. This was a retrospective cohort study of patients <19 years old that underwent allo-HSCT during an 11-year period. Of the 756 patients, 55.5% (n = 420) experienced post-transplant CMV DNAemia, 2.9% (n = 22) were diagnosed with proven CMV GI diseases, and the highest incidence was found in familial mismatched donors (5.6%, P = 0.029). CMV GI disease was diagnosed <100 days of transplant in 68.2% (n = 15/22), and 13.6% (n = 3/22) did not have concurrent CMV DNAemia. Patients were divided into five groups based on the patterns of CMV viremia initiation and duration post-HSCT. At 3 months post-transplant, lower CD4+ (P = 0.006) and CD8+ (P = 0.011) T-cell counts were observed in patients with waxing and waning CMV viral load titers >100 days post-transplant (groups 1-3) compared to those with CMV DNAemia only prior to 100 days post-transplant and those without concurrent CMV DNAemia (groups 4-5). A higher 1-year all-cause mortality was observed in groups 1-3 compared to groups 4-5 (42.8% vs. 0%; P = 0.051). Active surveillance and aggressive management of CMV reactivation is crucial, especially in children with delayed CD4+ and CD8+ T-cell reconstitution after allo-HSCT.