Relapse In Pediatric Patients Research Articles

Evaluation of immature granulocyte percentage and count in pediatric nephrotic syndrome

ABSTRACT Objective The importance of immature granulocytes (IGs) in most infectious and inflammatory diseases has been highlighted. This study aimed to determine the clinical usability and importance of changes in the peripheral complete blood count profile, including IG percentage (IG%) and IG count (IG#), during the relapse and remission phases in pediatric nephrotic syndrome (NS) patients. Methods This retrospective observational study was performed at a tertiary care hospital between February 2020 and August 2022. Demographic characteristics and laboratory parameters were recorded. The IG count and IG% were measured using an automated hematological analyzer. Results IG% and IG# were both higher during the relapse phase of NS than during the remission phase (0.29% ± 0.14%, versus 0.23% ± 0.14%, p = 0.037 and 0.027 ± 0.015 × 103/µL, versus 0.018 ± 0.014 × 103/µL, p = 0.005, respectively). The neutrophil to lymphocyte ratio (NLR), platelet (PLT), white blood cell (WBC), and neutrophil counts had a strong positive correlation with IG# (r = 0.397, p < 0.001; r = 0.352, p < 0.001; r = 0.622, p < 0.001; r = 0.660, p < 0.001, respectively). The NLR, PLT, WBC, and neutrophil counts had a strong positive correlation with IG% (r = 0.348, p < 0.001; r = 0.187, p = 0.039; r = 0.303, p = 0.001; r = 0.426, p < 0.001, respectively). Receiver operating characteristic curve analysis showed that IG# had the best AUC value of 0.69 (95% CI: 0.58–0.77; p = 0.001) for the relapse phase of NS with a cutoff value of 0.025 × 103/µL (sensitivity: 81.0%, specificity: 78.1%). Conclusions It is probable that a high level of immature granulocyte count has a positive correlation for NS relapse in pediatric patients. The IG % and IG# can be used together as biomarkers of inflammation in pediatric NS relapse.

Excellent leukemia control after second hematopoietic cell transplants with unrelated cord blood grafts for post-transplant relapse in pediatric patients.

Patients with leukemia relapse after allogeneic hematopoietic cell transplant (HCT) have poor survival due to toxicity and disease progression. A second HCT often offers the only curative treatment. We retrospectively reviewed our bi-institutional experience (MSKCC-USA; Utrecht-NL) with unrelated cord blood transplantation (CBT) for treatment of post-transplant relapse. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan-Meier method, treatment-related mortality (TRM) and relapse were evaluated using the competing risk method by Fine-Gray. Twenty-six patients age < 21 years received a second (n=24) or third (n=2) HCT with CB grafts during the period 2009-2021. Median age at first HCT (HCT1) was 11.5 (range: 0.9-17.7) years and all patients received myeloablative cytoreduction. Median time from HCT1 to relapse was 12.8 (range 5.5-189) months. At CBT, median patient age was 13.5 (range 1.4-19.1) years. Diagnoses were AML: 13; ALL: 4, MDS: 5, JMML: 2; CML: 1; mixed phenotype acute leukemia: 1. Sixteen patients (62%) were in advanced stage, either CR>2 or with active disease. Median time from HCT1 to CBT was 22.2 (range 7-63.2) months. All patients engrafted after CBT. Thirteen patients developed acute GvHD; 7 had grade III or IV. With a median survivor follow-up of 46.6 (range 17.4-155) months, 3-year OS was 69.2% (95% CI 53.6-89.5%) and 3-year EFS was 64.9% (95% CI 48.8-86.4%). Eight patients died, 3 of AML relapse and 5 due to toxicity (respiratory failure [n=4], GvHD [n=1]) at a median time of 7.7 (range 5.9-14.4) months after CBT. Cumulative incidence of TRM at 3 years was 19.2% (95% CI 4.1-34.4%). Notably, all TRM events occurred in patients transplanted up to 2015; no toxicity-related deaths were seen in the 16 patients who received CBT after 2015. Cumulative incidence of relapse was 15.9% (95% CI 1.6-30.2%) at 3 years, remarkably low for these very high-risk patients. Survival was very encouraging following CB transplants in pediatric patients with recurrent leukemia after first HCT, and TRM has been low over the last decade. CBT needs to be strongly considered as a relatively safe salvage therapy option for post-transplant relapse.

Adherence to mercaptopurine (6-MP) and habit strength in pediatric acute lymphoblastic leukemia (ALL).

10030 Background: Rates of adherence to mercaptopurine (6-MP) below 90% have been associated with increased relapse in pediatric patients with acute lymphoblastic leukemia (ALL). Habit strength has been associated with medication adherence through multiple mechanisms, including self-efficacy and social norms. The goal of this study was to investigate the relationship between habit strength, adherence to 6-MP, and health-related quality of life domains. Methods: This was a single center, cross-sectional study. A total of 52 participants, including 11 patients (ages 12-23, mean age 16 ± 4, 45% Female) and 41 parents/caregivers (ages 25-43, mean age 37 ± 5, 80% Female) of patients with ALL under the age of 18. Participants completed the Visual Analogue Scale (VASdose), PROMIS Medication Adherence Scale (PMAS), Self-Regulated Habit Index (SRHI), and PROMIS quality of life measures (PROMIS-CAT). Spearman’s rho correlations were used to assess relationships between variables. Eleven semi-structured interviews of patients and caregivers were conducted and analyzed using Grounded Theory coding and thematic analysis. Results: Overall, 81% (n = 42/52) of participants surveyed had high adherence to 6-MP (VASdose ≥95%); 91% (n = 10/11) of patients and 78% (n = 32/41 of parents/caregivers reported high adherence. The median VASdose and PMAS score were 100% (IQR 97-100) and 39.5 (IQR 38-40) across all participants, respectively. Participants with higher adherence, VASdose ≥ 95% and PMAS ≥ 39.5, reported less physiological stress (p = 0.02), and better cognitive function (p = 0.09) and peer relations (p = 0.08), compared to those with lower adherence. No significant correlation was found between medication adherence rate and habit strength. Emerging themes from qualitative coding included the influence of routine and automaticity on 6-MP as well as adherence strategies. Strategies such as reminders, care team communication, and developing personalized tools were cited by participants as potentially improving adherence in taking or administering 6-MP. Other facilitating participant characteristics included experience with medication administration, self-efficacy, and access to social support. Financial burden, scheduling conflicts, and medication access were common barriers cited by participants. Conclusions: Nearly one-fifth of our participants reported lower adherence to 6-MP (VASdose &lt; 95%), which increases risk of relapse. Medication adherence to 6-MP was not associated with habit strength, but our results show preliminary associations between adherence rates and quality of life outcomes, such as physiological stress. Behavioral interventions are needed to better optimize adherence to 6-MP and improve health outcomes in pediatric ALL.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. Thirty-eight patients developed a recurrence at a median of 1.6years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p<.05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4Gy. Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Effectiveness of immediate fixation after cranial distraction osteogenesis

Distraction osteogenesis (DO) is an established safe and effective treatment of craniosynostosis (CS) deformities. However, conventional methods demonstrate some complications, such as long-term maintenance of the distractor and relapse after distractor removal. Only a few studies have overcome these limitations. Therefore, we hypothesized that placing a resorbable plate after removing the distractor will provide additional stability to the newly formed bone, shortening the consolidation period and minimizing relapse. Twenty-six children diagnosed with CS who underwent DO between 2000 and 2019 were retrospectively analyzed. A resorbable plate was fixed across the regenerated bone when distractors were removed. The consolidation period and complication rate were obtained from medical records, and both two- and three-dimensional analyses were performed to obtain relapse rate and brain volume changes using three-dimensional computed tomography. Among 26 patients, the average consolidation period was 90.75±23.75 days in the conventional group (n=11) and 22.77±8.69 days in the intervention group (n=15). In the two-dimensional analysis, the relapse rate was lower in the intervention group. Moreover, in the three-dimensional analysis, the relapse rate of unilateral CS between the affected and unaffected sides was lower in the intervention group. The conventional group had more complications (skin defect and distractor exposure). Resorbable plate placement after distractor removal helps shorten the consolidation period and prevent relapse in pediatric patients with cranial DO. It reduces complications and shows stable results in terms of cranial morphology and symmetric brain growth in patients with CS.

559 - Encouraging Outcomes after Unrelated Cord Blood Grafts for Post-Transplant Relapse in Pediatric Patients

559 - Encouraging Outcomes after Unrelated Cord Blood Grafts for Post-Transplant Relapse in Pediatric Patients

Predicting Relapse in Pediatric Patients with Acute Lymphoblastic Leukemia Undergoing Stem Cell Transplant Using Interpretable Machine Learning—Applying Machine Learning Beyond 'Big Data'

Predicting Relapse in Pediatric Patients with Acute Lymphoblastic Leukemia Undergoing Stem Cell Transplant Using Interpretable Machine Learning—Applying Machine Learning Beyond 'Big Data'

Reduced-toxicity conditioning regimen with busulfan, fludarabine, rATG, and 400 cGy TBI in pediatric patients undergoing hematopoietic stem cell transplant for high-risk hematologic malignancies.

Myeloablative conditioning regimens decrease the risk of relapse in pediatric patients undergoing allogeneic hematopoietic stem cell transplant (HCT) for hematologic malignancies, but cause significant toxicities PROCEDURE: This prospective study evaluated the use of a reduced-toxicity, myeloablative regimen with dose-adjusted busulfan, fludarabine, antithymocyte globulin and 400 cGy of total body irradiation in 40 patients<21 years of age undergoing HCT for high-risk leukemias. Busulfan pharmacokinetics were measured to target 4000 μmol*min/day in the first 30 patients; this was increased to 5000 μmol*min/day in the subsequent 10 in efforts to further decrease relapse risk RESULTS: Overall survival at two- and five-years post-HCT was 67% and 51%, respectively. Relapse occurred in 11 patients (28%) at a median of seven months and was the leading cause of death. Transplant-related mortality was 8% and 13% at 100 days and one-year post-HCT, respectively. Trends toward improved survival were seen in patients transplanted for myeloid disease using bone marrow as stem cell source who achieved a busulfan AUC>4000 μmol*min/day with two-year relapse-free survival approaching 80% CONCLUSIONS: This conditioning regimen is safe and effective in patients with high-risk leukemias, particularly myeloid disease. Larger studies are needed to compare its safety and efficacy to other myeloablative regimens in this population.

Machine Learning Methods to Better Predict Post-Hematopoietic Stem Cell Transplant (HSCT) Leukemic Relapse in Pediatric Patients with Acute Lymphoblastic Leukemia: Random Forest (RF) Classification Featuring Serial Post-Transplant Lineage-Specific Chimerism

The ability to accurately predict leukemic relapse post-HSCT would improve outcomes by allowing pre-emptive therapeutic strategies. Recent studies have identified post-transplant T- and CD34 cell chimerism as predictors of relapse in patients, who had undergone HSCT for hematologic malignancies (Preuner et al, 2016; Lee et al, 2015). However, these studies assess relapse risk looking at only a single threshold of chimerism using standard regression analysis, which permits only limited consideration of other patient variables. As the result, the findings of these analysis are frequently not applicable to patients generally. Machine learning methods offer the possibility to capture nonlinear relationships and simultaneous interactions between multiple variables, thus better recapitulate the dynamics and nuances of the relapse process in different patients. We use machine learning methods, specifically random forest classification (RF), to build a predictive model of post-transplant relapse and to analyze the data from a cohort of 46 pediatric patients, who received HSCT for acute lymphoblastic leukemia (ALL) and had serial lineage-specific chimerism testing post-transplant. Our model achieved 58 % sensitivity and 98% specificity at predicting relapses in cross validation compared to a baseline model (24% sensitivity, 76% specificity). Consistent with previous reports, our model implicates both peripheral blood (PB) donor CD34 and CD3 chimerism as important variables for relapse. More importantly, the RF showed how different variables interacted with each other, providing additional insights into how to best interpret post-transplant chimerism results. To our knowledge, this is the first study featuring RF machine learning methods in the clinical setting of relapse after HSCT. We use a dataset of patients with ALL undergoing HSCT at Lucile Packard Children's Hospital from 2012 to 2018. Variables collected are summarized in Table 1. The analytical sensitivity of STR-based chimerism testing is 1%. Chimerism results on the same day of relapse were excluded from the analysis. The RF model is based on a set of 500 individual decision trees, each based on a bootstrapped sample of the patient data. A 5-fold cross-validation was used to test predictive skill, with 20% of patients excluded from each fold. We compared results with a Monte Carlo baseline model in which relapse status was repeatedly assigned randomly to each patient with a probability based on the prevalence of relapse in our cohort. Patients, transplantation, and relapse characteristics are summarized in Table 2. Chimerism data are summarized in Table 3. The cross-validation results show a robust predictive skill of relapse within 2 years post-transplant. Our RF achieved 58% sensitivity and 98% specificity, greatly improving the predictive values from the base model (Table 4). Variable importance, the ability of a variable to decrease the error of the prediction model, was calculated for all variables used in our RF (Figure 1). Our analysis shows that the age at the time of transplant has the highest importance, followed by PB donor CD34 chimerism. Bone marrow chimerism generally has lower importance suggesting PB monitoring only is adequate in the clinical setting. We showcase the relationships of 1) age at transplant, 2) donor PB CD34, and 3) donor PB CD3 chimerism to the odds of relapse using a partial dependence plot. Younger patients relapse less often. Donor PB CD34 chimerism exhibits a threshold effect, in which the odds of relapse dramatically decreases when it is above 95% while donor PB CD3 chimerism has a more gradual linear profile (Figure 2). 2D dependence plot of donor PB CD34 and PB CD3 chimerism shows the interaction of the two variables (Figure 3) as continuous variables; relapse risk remaining low with even if donor PB CD3 chimerism is as low as 50% as long as donor PB CD34 chimerism is &amp;gt; 95%. Our study shows that machine learning methods such as RF can be very useful at making accurate predictive model of post-HSCT complications that incorporates multiple variables, allowing for more granular differentiation between different patients. Such analyses can enable more effective deployment of risk-adapted, personalized treatment. By building hundreds of independent decision trees, the RF is also able provide useful insights to the interaction between different variables in a clinically relevant manner. Disclosures No relevant conflicts of interest to declare.

Long-term Survivors Receive Multimodality Treatment of Second Central Nervous System Relapse in Pediatric Patients with Neuroblastoma

Long-term Survivors Receive Multimodality Treatment of Second Central Nervous System Relapse in Pediatric Patients with Neuroblastoma

Reduced Toxicity, Myeloablative Conditioning Regimen with Busulfan, Fludarabine, Anti-Thymocyte Globulin and 400 Cgy TBI in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant for High-Risk Hematologic Malignancies

<h3>Introduction</h3> Myeloablative conditioning (MAC) regimens decrease the risk of relapse in pediatric patients undergoing hematopoietic stem cell transplant (HCT) but cause significant toxicities: transplant-related mortality (TRM) and late effects. Therefore, a MAC regimen that decreases toxicity has the potential to improve overall survival (OS). Busulfan (Bu), fludarabine (Flu), anti-thymocyte globulin (ATG) and 400 cGy of total body irradiation (TBI), a reduced toxicity, MAC regimen was used in pediatric patients. <h3>Objectives</h3> To evaluate the safety and toxicity of this regimen. Secondary objectives included determining OS at 2 and 5 years, and incidence of relapse and GVHD. <h3>Methods</h3> We prospectively evaluated 40 patients ≤21 years of age undergoing HCT for high-risk leukemias who received dose-adjusted Bu, Flu, ATG and TBI. Bu pharmacokinetics were measured after a test dose and regimen dose 1 to target AUC of 4000-5000 uMol*min/day. <h3>Results</h3> Patients were treated between October 2008 and June 2018 (Table 1). OS was 67% and 51% at 2 and 5 years post-HCT, respectively. OS at 2 and 5 years was 70% and 55% for patients with myeloid disease versus 56% and 37% for patients with lymphoid disease, respectively (p=0.18) (Figure 1). Relapse occurred in 11 (28%) at a median of 7 months. TRM was 8% and 13% at 100 days and 1 year post-HCT, respectively. All patients engrafted. >Grade II acute GVHD was seen in 9 (23%); chronic GVHD was seen in 16 (40%). There was no significant impact of age, disease type, donor source or type on HCT outcomes. Long-term toxicities noted were ovarian insufficiency in 8, and short stature, hypothyroidism and learning disabilities in 2 each. Evaluation of Bu AUCs and multivariate analyses are still ongoing. <h3>Conclusions</h3> Reduced toxicity, MAC regimen was well tolerated with a low incidence of TRM. This regimen shows a trend toward better efficacy in patients with myeloid disease, however larger studies are needed.

Second Allogeneic Hematopoietic Cell Transplant Is a Successful Salvage Modality for Pediatric Patients Who Relapse after First Transplant

<h3>Introduction</h3> Disease relapse remains a major cause of treatment failure in pediatric patients receiving allogeneic hematopoietic cell transplantation (HCT) for high-risk acute leukemias (AL) or myelodysplastic syndrome (MDS). Comprehensive data on prognostic factors and outcomes after post-transplant relapse in pediatric patients is lacking. <h3>Objective</h3> The goal of this study was to identify factors associated with survival following post-transplant relapse. <h3>Methods</h3> We performed a retrospective study of pediatric patients who experienced disease relapse following their 1st HCT for AL or MDS between 1990 – 2018 at our institution. Patient, disease and transplant-related characteristics were extracted from the medical record. Overall survival (OS) was estimated by the Kaplan-Meier (KM) method and compared using the log-rank test. Cox and logistic regression were performed to identify factors statistically associated with outcomes after post-transplant relapse. <h3>Results</h3> During the study period, 703 patients received 1^st HCT, of which 221 (31%) relapsed at a median of 3.9 months after HCT. Of these relapsed patients, 60% (n = 132) received some chemotherapy or supportive care after post-transplant relapse, 13% (n = 28) received donor lymphocyte infusion only and 28% (n = 61) were able to proceed to a 2nd HCT. Patients who received a 2nd HCT were more likely to have been in first remission at the time of 1st HCT (<i>P</i> = 0.02), experienced relapse more than 6 months after 1st HCT (<i>P</i> < 0.001), experienced acute or chronic GVHD (<i>P</i> = 0.05 and 0.01, respectively) and relapsed in the current decade (2011 – 2018) (<i>P</i> = 0.001). Of the 61 patients who received a 2nd HCT, 18 (30%) were alive at last follow-up, compared to 7 (4%) of 160 patients who had received other therapies. In a multivariable model, longer interval from HCT to relapse (<i>P</i> < 0.001), being able to receive a 2nd HCT (<i>P</i> < 0.001) and receiving a HCT in the current decade (<i>P</i> < 0.001) were found to be significantly associated with OS (Fig 1 & 2). Factors that are typically associated with poor outcomes after HCT, such as disease status or type of HCT, donor and graft source were not predictive of survival following post-transplant relapse. <h3>Conclusion</h3> Duration of remission before post-transplant relapse was identified as the strongest independent predictor of a patient's ability to receive a 2nd HCT as well as survival after relapse. The 3-year OS for patients who received a 2nd HCT was 6 times higher than that for patients who did not receive a 2nd HCT. Although the outcomes after 2nd HCT are not commendable, they are improving with time. Our data supports the argument that, when feasible, pediatric patients experiencing post-transplant relapse should be considered for 2nd HCT.

More precisely defining risk peri-HCT in pediatric ALL: pre- vs post-MRD measures, serial positivity, and risk modeling

AbstractDetection of minimal residual disease (MRD) pre– and post–hematopoietic cell transplantation (HCT) for pediatric acute lymphoblastic leukemia (ALL) has been associated with relapse and poor survival. Published studies have had insufficient numbers to: (1) compare the prognostic value of pre-HCT and post-HCT MRD; (2) determine clinical factors post-HCT associated with better outcomes in MRD+ patients; and (3) use MRD and other clinical factors to develop and validate a prognostic model for relapse in pediatric patients with ALL who undergo allogeneic HCT. To address these issues, we assembled an international database including sibling (n = 191), unrelated (n = 259), mismatched (n = 56), and cord blood (n = 110) grafts given after myeloablative conditioning. Although high and very high MRD pre-HCT were significant predictors in univariate analysis, with bivariate analysis using MRD pre-HCT and post-HCT, MRD pre-HCT at any level was less predictive than even low-level MRD post-HCT. Patients with MRD pre-HCT must become MRD low/negative at 1 to 2 months and negative within 3 to 6 months after HCT for successful therapy. Factors associated with improved outcome of patients with detectable MRD post-HCT included acute graft-versus-host disease. We derived a risk score with an MRD cohort from Europe, North America, and Australia using negative predictive characteristics (late disease status, non–total body irradiation regimen, and MRD [high, very high]) defining good, intermediate, and poor risk groups with 2-year cumulative incidences of relapse of 21%, 38%, and 47%, respectively. We validated the score in a second, more contemporaneous cohort and noted 2-year cumulative incidences of relapse of 13%, 26%, and 47% (P < .001) for the defined risk groups.

α-Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium.

There are several studies describing the correlation between unsatisfactory tumor marker decline and a poor prognosis for adult patients treated for germ cell tumors. In pediatric patients, the data are limited. Therefore, this study retrospectively analyzed data from Children's Oncology Group (COG) protocol AGCT0132 to determine whether a relationship exists between α-fetoprotein (AFP) decline and outcome. One hundred thirty-one patients with germ cell tumors who were enrolled in COG protocol AGCT0132 were eligible for this analysis of AFP decline. The serum AFP half-life was calculated from levels collected postoperatively as a baseline and after the start of chemotherapy. AFP decline was defined as automatically satisfactory (AFP normalized within the first 2 AFP measures after the start of chemotherapy), calculated satisfactory (AFP half-life ≤7days after the start of chemotherapy), and unsatisfactory. The 3-year cumulative incidence of relapse was 11% (95% confidence interval [CI], 6.0%-18%) for patients with a satisfactory decline and 38% (95% CI, 13%-64%) for patients with an unsatisfactory decline (P=.006). In stratified analyses, this effect was limited to patients who were 11years of age or older and had standard risk 2 (SR2) disease (P=.004 and P=.007, respectively). Three-year overall survival (OS) for patients with a satisfactory decline versus an unsatisfactory decline was not statistically significant. This study is the first to show an association between AFP decline and the cumulative incidence of relapse in pediatric patients treated for germ cell tumors. Recognition of patients at high risk for relapse may allow for early intensification of therapy, which could affect future clinical trial design.

Quality Improvement Initiative to Reduce Admissions for Nephrotic Syndrome Relapse in Pediatric Patients.

Introduction: Childhood nephrotic syndrome is frequently seen in pediatric nephrology practice and often requires patient hospitalization for management. Numerous complications of this disease can be managed in an outpatient setting if brought to the attention of the medical team in a timely manner. Outpatient management will reduce healthcare cost and improve patient safety. The goal of this quality improvement initiative was to reduce admissions for nephrotic syndrome relapse from 8 to <5 admissions at a single center in a 3-month period.Methods: Fish-bone analysis was used to determine barriers to early recognition of relapse and successful outpatient care. Patient education about the disease process was identified as the primary barrier. A standardized approach to patient education as well as educational materials were developed. Champions were identified within each stakeholder group to train and disseminate the new process. Admission counts were compared from 3 years prior to implementation to 2 years post-implementation. Clinic visits for nephrotic syndrome were tallied as a balancing measure. Patients were surveyed in the outpatient clinics about whether they had ever received the education as a process measure.Results: Admission counts were reduced and met goal for the first 3 quarters that were examined; however, the number of admissions went above target in the last quarter. Clinic visit numbers did not change over the study period. Process measure showed that 75–80% of families were provided with nephrotic syndrome education.Conclusion: A standardized approach to patient and family education about idiopathic nephrotic syndrome can reduce admissions for management of relapse. This will reduce healthcare expenditure as well as improve patient safety.

Use of granulocyte colony-stimulating factor and risk of relapse in pediatric patients treated for acute myeloid leukemia according to NOPHO-AML 2004 and DB AML-01.

Supportive-care use of granulocyte colony-stimulating factor (G-CSF) in pediatric acute myeloid leukemia (AML) remains controversial due to a theoretical increased risk of relapse and limited impact on neutropenic complications. We describe the use of G-CSF in patients treated according to NOPHO-AML 2004 and DB AML-01 and investigated associations with relapse. Patients diagnosed with de novo AML completing the first week of therapy and not treated with hematopoietic stem cell transplantation in the first complete remission were included (n=367). Information on G-CSF treatment after each course (yes/no) was registered prospectively in the study database and detailed information was gathered retrospectively from each center. Descriptive statistics were used to describe G-CSF use and Cox regression to assess the association between G-CSF and risk of relapse. G-CSF as supportive care was given to 128 (35%) patients after 268 (39%) courses, with a large variation between centers (0-93%). The use decreased with time-the country-adjusted odds ratio was 0.8/diagnostic year (95% confidence interval [CI] 0.7-0.9). The median daily dose was 5 μg/kg (range 3-12 μg/kg) and the median cumulative dose was 75 μg/kg (range 7-1460 μg/kg). Filgrastim was used in 82% of G-CSF administrations and infection was the indication in 44% of G-CSF administrations. G-CSF was associated with increased risk of relapse-the adjusted hazard ratio was 1.5 (95% CI 1.1-2.2). G-CSF as supportive care was used in a third of patients, and use decreased with time. Our results indicate that the use of G-CSF may be associated with an increased risk of relapse.

Relapse in children with clinical stage I testicular yolk sac tumors after initial orchiectomy.

To evaluate risk factors of relapse in pediatric patients with clinical stage I (CS1) testicular yolk sac tumors. With retrospective analysis, the medical records of children with pure testicular yolk sac tumors who were referred to Sun Yat-sen University Cancer Center and The First Affiliated Hospital from January 1995 to December 2015 were selected and recorded. Histopathology and staging were retrieved and multivariate analysis was performed with SPSS 20.0 software. 90 children with CS1 testicular yolk sac tumors were selected, and 21 of them underwent chemotherapy following initial orchiectomy. The median age of them was 17months. With a median follow-up of 61months (range 11-183months), 84 patients were alive and 3 patients died, whereas the status was unknown in 3 patients. 30 patients experienced relapse within a median time of 4 months, including only 1 patient who underwent primary chemotherapy, and 28 of these patients underwent salvage chemotherapy. According to adjusted analysis, lymphovascular invasion (LVI) (P < 0.001), necrosis (P = 0.003) and primary chemotherapy (P = 0.008) were independent predictors of event-free survival. The 4-year event-free survival of high- and low-risk patients was 46.5% and 85.1%, respectively (P < 0.001). LVI and necrosis were independent risk factors for relapse in pediatric patients with CS1 testicular yolk sac tumors, and primary chemotherapy was effective. Thus, individualized management might be feasible for these patients according to risk classification.

A randomized, open-label study to evaluate an intermittent dosing regimen of fluticasone propionate 0.05% cream in combination with regular emollient skin care in reducing the risk of relapse in pediatric patients with stabilized atopic dermatitis

Background: Atopic dermatitis (AD) is a chronic, relapsing disease that requires maintenance treatment. This study examined the efficacy and safety of extended intermittent fluticasone propionate (FP) 0.05% cream, with emollient, vs emollient alone in children with AD.Methods: Eligible patients (aged 1–17 years) received FP 0.05% cream twice daily for 4 weeks (acute phase) then randomized (1:1) to FP 0.05% cream once daily, twice per week plus emollient (Group A) or emollient alone (Group B) for up to 20 weeks (maintenance phase). Primary endpoint was time to first AD relapse. Safety was assessed throughout.Results: This study enrolled 123 patients into the acute phase, of whom 107 entered the maintenance phase (Group A: 54; Group B; 53). Three patients (5.6%) in Group A and 30 (56.6%) in Group B experienced relapse (maintenance phase). Due to a low number of relapses, median time to first relapse could not be calculated for Group A; in Group B, it was 142 d (95% CI: 50, 150; p < .0001 vs Group A). FP and emollient were well tolerated.Conclusions: In pediatric patients with stabilized AD, FP 0.05% cream plus emollient (for AD maintenance treatment) significantly reduced the risk of relapse vs emollient alone.

Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis

Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P = .0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P = .001), and cGVHD (HR, .32; 95% CI, .19 to .54; P < .001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P = .0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P = .0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P = .0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P = .0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.

The Association between Red Cell Distribution Width and Mortality in Pediatric Acute Lymphoblastic Leukemia

Background: Red cell distribution width (RDW) is one of the standard parameters with blood cell counts. Studies have revealed that RDW could be used as a predictor of mortality in different contexts. However, data about the relation of RDW with hematologic malignancies is limited. In this research, we evaluated the relation of RDW with mortality in pediatric acute lymphoblastic leukemia (ALL). Materials and methods: In the oncology department of a tertiary care children hospital, between years of 2010 to 2013, we had 83 registered cases of acute lymphoblastic leukemia (ALL) whose data was collected and analyzed retrospectively. RDW, mean corpuscular volume (MCV), hemoglobin (Hgb) and platelet (Plt) measurements were recorded and their relation with mortality, leukemia relapses and treatment cessation was examined. Results: A total 83 patients were enrolled in the study. The mean age was 5.5 years and 50 (60.2%) were male. The mean baseline RDW level was 16.0%, and it ranged from 11.2% to 23.2%. During the study period, 12(14.5%) cases had died. The rate of mortality did not significantly correlate with RDW level. Conclusions: Although a relationship between elevated RDW and mortality has been reported in several contexts, we did not find any significant correlation between the RDW level and the rate of mortality and relapse in pediatric patients with acute lymphoblastic leukemia (ALL).