Perspectives on Patient-Reported Outcome Data After Treatment Discontinuation in Cancer Clinical Trials.

OBJECTIVES: Patient-reported outcome (PRO) data are critical in understanding treatments from the patient perspective in cancer clinical trials. The potential benefits and methodological approaches to the collection of PRO data after treatment discontinuation (eg, because of progressive disease or unacceptable drug toxicity) are less clear. The purpose of this article is to describe the Food and Drug Administration's Oncology Center of Excellence and the Critical Path Institute cosponsored 2-hour virtual roundtable, held in 2020, to discuss this specific issue. METHODS: We summarize key points from this discussion with 16 stakeholders representing academia, clinical practice, patients, international regulatory agencies, health technology assessment bodies/payers, industry, and PRO instrument development. RESULTS: Stakeholders recognized that any PRO data collection after treatment discontinuation should have clearly defined objectives to ensure that data can be analyzed and reported. CONCLUSIONS: Data collection after discontinuation without a justification for its use wastes patients' time and effort and is unethical.

Emotional Well-Being of Pediatric Brain Tumor Survivors and Comparison Peers: Perspectives From Children and Their Parents.

OBJECTIVE: The aim of this study was to examine the emotional well-being of pediatric brain tumor survivors (PBTS) from the perspective of children's self-reports and parents' reports relative to matched comparison peers (COMP) and their parents. It was hypothesized that PBTS would self-report more depression symptoms, loneliness, and lower self-concept than COMP. We also hypothesized that mothers and fathers of PBTS would report more internalizing symptoms and lower total competence for their children. Age and sex effects were examined in exploratory analyses. METHODS: Families of 187 PBTS and 186 COMP participated across 5 sites. Eligible children in the PBTS group were 8-15 years of age and 1-5 years post-treatment for a primary intracranial tumor without progressive disease. COMP were classmates matched for sex, race, and age. RESULTS: PBTS self-reported lower scholastic, athletic, and social competence, but not more depression, loneliness, or lower global self-worth than COMP. Parents of PBTS reported more internalizing symptoms and lower total competence than parents of COMP. With few exceptions, group differences did not vary as a function of child age and sex. CONCLUSION: PBTS reported diminished self-concept in scholastic, athletic, and social domains, while their parents reported broader challenges with internalizing symptoms and total competence. Discrepancies between self-report and parent report require further study to inform targeted interventions for PBTS. Screening survivors for emotional challenges in follow-up clinic or in school setting may help with the allocation of psychosocial support and services for PBTS and their families.

Factors associated with mental health service use among families bereaved by pediatric cancer.

OBJECTIVES: We identified types of interventions used by bereaved family members and examined associations with demographic and medical factors. Furthermore, we examined associations between distress and intervention use among bereaved families. METHODS: Bereaved families (n = 85) were recruited from three children's hospitals 3-12 months after their child died of cancer. One eligible sibling (ages 8-17) per family was randomly selected for participation. During home visits 1-year post-death, parents reported on their own and the sibling's intervention use, helpfulness, and dose (self-help books, support groups, therapy, medication), and distress, defined as internalizing, externalizing, and total problems (Adult Self Report, Child Behavior Checklist). RESULTS: Fifty percent of mothers used medications (n = 43); utilization was low among fathers (17%, n = 9) and siblings (5%, n = 4). Individuals with more total problems were more likely to use medications (mothers: rpb = 0.27; p = 0.02; fathers: rpb = 0.32; p = 0.02; siblings: rpb = 0.26; p = 0.02). Mothers and siblings with more total problems used more services (r = 0.24; p = 0.03 and r = 0.29; p = 0.01, respectively). Among mothers, the overall regression was significant, R2 = 0.11, F(2, 80) = 4.954, p = 0.01; the deceased child's age at death was significantly associated with total services used (b = 0.052, p = 0.022). Among fathers, the overall regression was significant, R2 = 0.216, F(3, 49) = 4.492, p = 0.007; race and years of education were significantly associated with total services used (b = 0.750, p = 0.030 and b = 0.154, p = 0.010). Among siblings, the overall regression was significant R2 = 0.088, F(2, 80) = 3.867, p = 0.025; greater total problems were significantly associated with total services used (b = 0.012, p = 0.007). SIGNIFICANCE OF RESULTS: Although few background factors were related to intervention use, bereaved mothers and siblings may seek services if they have more distress. Healthcare providers should be aware of the types of services that are most often utilized and helpful to bereaved families to connect them with appropriate resources. Future research should investigate other predictors of intervention use and outcomes after the death of a child.

Health Literacy in Patients Considering a Left Ventricular Assist Device: Findings From the DECIDE-LVAD Trial.

OBJECTIVE: To assess the interaction of health literacy and a shared intervention concerning decision quality in patients considering the destination therapy of left ventricular assist device (DT LVAD) implantation. BACKGROUND: Evidence is limited for the use of decision aids by patients with low health literacy and with life-threatening illnesses. METHODS: We performed a secondary analysis of the DECIDE-LVAD Trial, a randomized, stepped-wedge trial conducted from 2015-2017 in the United States. The intervention was the integration of a formal shared decision-making intervention. The main outcome was decision quality as measured by LVAD knowledge and values-treatment concordance. Two components of health literacy were measured by the Rapid Estimate of Adult Literacy in Medicine and Subjective Numeracy Scale instruments. RESULTS: Of the 228 patients studied, 44% (n = 101) received the formal shared decision-making intervention, and half had low health literacy. Knowledge of LVAD improved for patients with low literacy in the intervention group compared to the control group: the difference in increased knowledge score was 10.6%; P = 0.04. Values-treatment concordance improved significantly for patients with low literacy in the intervention group compared to the control group: the median improvement in values-treatment correlation coefficient was 0.43; P = 0.03. These benefits were not significant in those with adequate literacy (n = 171). Patients with low numeracy (n = 94) did not show significant improvements in either measure of decision quality, and patients with adequate numeracy (n = 134) showed improvement in LVAD knowledge but not in values-treatment concordance. CONCLUSIONS: Patients considering DT LVAD implantation with low literacy showed improvement in decision quality after the integration of a shared decision-making intervention.

Dissemination of an evidence-based behavioral intervention to alleviate distress in caregivers of children recently diagnosed with cancer: Bright IDEAS.

BACKGROUND: Four multisite randomized clinical trials of > 1400 caregivers of children newly diagnosed with cancer showed that the Bright IDEAS (BI) paradigm of problem-solving skills training is an acceptable and efficacious approach to alleviating the high levels of distress they experience. To facilitate providing evidence-based caregiver support as recommended in the pediatric oncology standards of care, the project described here was designed to disseminate BI to 200 psychosocial professionals. PROCEDURE: We partnered with the Children's Oncology Group (COG), Association of Pediatric Oncology Social Workers (APOSW), Association of Pediatric Hematology/Oncology Nurses (APHON), and special interest group in pediatric hematology/oncology of the Society for Pediatric Psychology (SPP). Membership surveys revealed substantial enthusiasm for training in BI. We structured training to include review of the evidence base for BI, role plays, and strategies for implementation at individual sites. Four conference calls designed to enhance implementation were held one, two, three, and five months after training. RESULTS: Ten 1.5-day workshops were held in conjunction with annual meetings of COG, APOSW, APHON, and SPP. A total of 209 psychosocial clinicians from 134 sites were trained. Evaluations were highly favorable. Trainees had provided BI to 545 individuals as of the last conference call. CONCLUSIONS: Initial dissemination goals were met. BI is now available at numerous pediatric oncology centers, but it has not become part of routine care. Future work focused on implementation might consider top-down approaches that include direct communication with pediatric oncologists and hospital leaders about the benefits of incorporating this evidence-based intervention systemically.

Psychosocial functioning of caregivers of pediatric brain tumor survivors.

BACKGROUND: Assessment of caregiver needs is a recommended standard of care in pediatric oncology. Caregivers of pediatric brain tumor survivors (PBTS) are a subgroup that may be at highest psychosocial risk. This study examined psychosocial functioning of caregivers of PBTS in comparison to caregivers of youth without cancer history. We hypothesized that caregivers of PBTS would exhibit more psychological symptoms, higher caregiver burden, and lower perceptions of social support than caregivers of comparison youth. PROCEDURE: As part of a five-site study, we utilized a matched sample design to evaluate psychosocial functioning of 301 caregivers of 189 PBTS (ages 8-15) who were 1-5 years post treatment, and 286 caregivers of 187 comparison youth matched for sex, race, and age. Caregivers completed measures of psychological symptoms, caregiver burden, and perceptions of social support. Repeated measures mixed models compared outcomes between groups and examined differences based on caregiver sex. Socioeconomic status (SES) was examined as a moderator of significant main effects. RESULTS: Caregivers of PBTS reported similar levels of psychological symptoms to caregivers of comparison youth. Mothers of PBTS mothers reported higher caregiver burden and lower perceptions of social support than mothers of comparison youth. Low SES exacerbated group differences in caregiver burden. CONCLUSIONS: Mothers of PBTS may have more caregiving responsibilities and perceive less social support, but reported similar levels of psychological symptoms to comparison mothers; fathers of PBTS were similar to comparison fathers. The mechanisms involved in this complex psychosocial dynamic require further investigation.

Impact of End-of-Life Circumstances on the Adjustment of Bereaved Siblings of Children Who Died from Cancer.

The aim of this study was to examine the impact of end-of-life (EoL) circumstances on grief and internalizing symptoms among bereaved siblings. Bereaved families (N = 88) were recruited from three sites 3-12 months (M = 11.57, SD = 3.48) after their child's death from cancer. One sibling per family aged 8-17 years (M = 12.41, SD = 2.64) was randomly selected to participate. Families completed measures of siblings' grief and internalizing symptoms, as well as a structured interview about circumstances surrounding the death. Mother and sibling reports of EoL circumstances were generally concordant, except there was a discrepancy between mothers and children about whether or not children expected their sibling's death (t(75) = 1.52, p = .018). Mother reports of sibling internalizing symptoms were above the normative mean (t(83) = 4.44, p ≤ .001 (M = 56.01 ± 12.48), with 39% (n = 33) in the borderline/clinical range. Sibling opportunity to say goodbye was associated with greater grief-related growth (t(79) = - 1.95, p = .05). Presence at the death and wishing they had done something differently were both associated with greater grief (t(80) = - 2.08, p = .04 and t(80) = - 2.24, p = .028, respectively) and grief-related growth (t(80) = - 2.01, p = .048 and t(80) = - 2.31, p = .024, respectively). However, findings were primarily unique to sibling report, with few mother-reported effects. The adjustment of bereaved siblings may be affected by certain modifiable circumstances surrounding the death of their brother or sister. A proportion of bereaved siblings had elevated internalizing symptoms irrespective of circumstances at EoL. Further work is needed to understand predictors of adjustment among bereaved siblings to provide better support and optimize their outcomes.

Bright IDEAS problem-solving skills training for caregivers of children with sickle cell disease: A two-site pilot feasibility trial.

BACKGROUND: Bright IDEAS problem-solving skills training (BI) is an evidence-based behavioral intervention that has been utilized extensively with caregivers of children recently diagnosed with cancer. Considerable evidence has shown that BI is acceptable to caregivers of children recently diagnosed with cancer, and improvements in problem-solving skills mediate reduced symptoms of distress. PROCEDURES: A slightly modified version of BI was offered to caregivers of children with sickle cell disease (SCD) in a two-site pilot feasibility trial. BI was modified to reduce barriers to care, logistical challenges, and stigma associated with receiving behavioral health services. Our goal was to establish high rates of recruitment and retention among caregivers of children with SCD. Recruitment was acceptable (94%; N = 72) and retention reasonable (49%) across both sites with 35 caregivers successfully completing the BI program. RESULTS: Results showed that caregivers of children with SCD, who successfully completed the BI program reported, significant improvements in problem-solving skills immediately and three months after intervention completion. Interestingly, initial levels of distress were low with few caregivers reporting clinically significant levels of distress; distress remained low over time. CONCLUSIONS: Findings are discussed in the context of psychosocial screening and resilience of caregivers of children with SCD.

Responsivity to Problem-Solving Skills Training in Mothers of Children With Cancer.

OBJECTIVE: Bright IDEAS (BI) is a problem-solving skills training (PSST) program that has been demonstrated in earlier randomized controlled trials (RCTs) to be an effective and specific intervention for improving problem-solving skills and reducing negative affect in caregivers of children with cancer. The objectives of this study were to (a) offer an approach to defining meaningful treatment response and to determine the rates of responsivity to PSST; and (b) identify characteristics of PSST responders and nonresponders. METHODS: Data from 154 mothers receiving the BI intervention were analyzed. Drawing on the literature on minimal clinically important differences, two criteria for determining responsivity were calculated for the primary outcome of problem-solving skills: (a) The reliable change index (RCI) based on group data, and; (b) The effect size (ES) of each participant's pre/postintervention change score as a function of the group's baseline SD. RESULTS: Thirty-three percent of the sample met both responsivity criteria immediately posttreatment (39% at follow-up) and 38% (39% at follow-up) met neither. An additional 29% demonstrated a small or greater ES (≥ 0.2) but did not meet the RCI criteria, suggesting possible benefit. The single consistent predictor of responsivity was participants' pretreatment problem-solving skills, with lower skills at baseline predicting greater improvement (p < .001). CONCLUSIONS: These findings highlight the need to go beyond group data in interpreting RCTs and to incorporate measures of meaningful treatment response. Our ability to predict and screen for meaningful treatment response is critical to more precise targeting, enhanced outcomes, and better resource allocation.

Caregiver-guided pain coping skills training for patients with advanced cancer: Results from a randomized clinical trial.

BACKGROUND: Pain is a major concern among patients with advanced cancer and their family caregivers. Evidence suggests that pain coping skills training interventions can improve outcomes, however they have rarely been tested in this population. AIM: To test the efficacy of a caregiver-guided pain coping skills training intervention. The primary outcome was caregiver self-efficacy for helping the patient manage pain. DESIGN: A randomized controlled trial compared the intervention to an enhanced treatment-as-usual control. Dyads in both conditions received pain education, and those in the intervention received three sessions of pain coping skills training. Caregiver outcomes (self-efficacy; caregiver strain, caregiving satisfaction, psychological distress) and patient outcomes (self-efficacy, pain intensity and interference, psychological distress) were collected at baseline and post-intervention. SETTING/PARTICIPANTS: Two hundred two patients with stage III-IV cancer and pain and their family caregivers were enrolled from four outpatient oncology clinics and a free-standing hospice/palliative care organization. RESULTS: Compared to those in the control arm, caregivers in the intervention reported significant increases in caregiving satisfaction (p < 0.01) and decreased anxiety (p = 0.04). In both conditions, caregivers reported improvements in self-efficacy, and patients reported improvements in self-efficacy, pain severity and interference, and psychological distress. CONCLUSIONS: This is the first study to test a pain coping skills intervention targeted to patients and caregivers facing advanced cancer. Findings suggest that pain education provides benefits for patients and caregivers, and coping skills training may be beneficial for caregivers. Further research is needed to optimize the benefits of education and pain coping skills training for improving cancer pain outcomes.Trial registration: ClinicalTrials.gov NCT02430467, Caregiver-Guided Pain Management Training in Palliative Care.

Development and testing of the Hogan Inventory of Bereavement short form for children and adolescents.

To reduce response burden for bereaved children and adolescents, we provide data on the development and psychometric testing of a short form of the Hogan Sibling Inventory of Bereavement (HSIB). The resulting measure of grief symptoms and personal growth was renamed the Hogan Inventory of Bereavement - Short Form (Children and Adolescents; HIB-SF-CA). Psychometric properties were evaluated in a sample of 86 bereaved siblings. Instrument development and validation research design methods were used. Evidence of strong reliability and convergent validity indicates that the 21-item HIB-SF-CA is comparable to the original 46-item HSIB in measuring grief and personal growth in this population.

A multicenter trial of a shared DECision Support Intervention for Patients offered implantable Cardioverter-DEfibrillators: DECIDE-ICD rationale, design, Medicare changes, and pilot data.

Shared decision making (SDM) facilitates delivery of medical therapies that are in alignment with patients' goals and values. Medicare national coverage decision for several interventions now includes SDM mandates, but few have been evaluated in nationwide studies. Based upon a detailed needs assessment with diverse stakeholders, we developed pamphlet and video patient decision aids (PtDAs) for implantable cardioverter/defibrillator (ICD) implantation, ICD replacement, and cardiac resynchronization therapy with defibrillation to help patients contemplate, forecast, and deliberate their options. These PtDAs are the foundation of the Multicenter Trial of a Shared Decision Support Intervention for Patients Offered Implantable Cardioverter-Defibrillators (DECIDE-ICD), a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute aimed at understanding the effectiveness and implementation of an SDM support intervention for patients considering ICDs. Finalization of a Medicare coverage decision mandating the inclusion of SDM for new ICD implantation occurred shortly after trial initiation, raising novel practical and statistical considerations for evaluating study end points. METHODS/DESIGN: A stepped-wedge randomized controlled trial was designed, guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) planning and evaluation framework using an effectiveness-implementation hybrid type II design. Six electrophysiology programs from across the United States will participate. The primary effectiveness outcome is decision quality (defined by knowledge and values-treatment concordance). Patients with heart failure who are clinically eligible for an ICD are eligible for the study. Target enrollment is 900 participants. DISCUSSION: Study findings will provide a foundation for implementing decision support interventions, including PtDAs, with patients who have chronic progressive illness and are facing decisions involving invasive, preference-sensitive therapy options.

Are we friends? Best friend nominations in pediatric brain tumor survivors and associated factors.

BACKGROUND: Pediatric brain tumor survivors (PBTSs) are at risk of impairments in social competence. Limited information is available regarding nominations and reciprocated nominations of PBTSs as best friends and factors which may predict these. PROCEDURE: Caregivers of children (n = 32) aged 8-16 (38% low-grade glioma, 34% medulloblastoma, 28% other) completed ratings of child adjustment at baseline (T1) and PBTSs and classmates completed the Three Best Friends measure approximately 12 months later (T2). Sociometric data yielded ratings of best friend nominations and reciprocated best friend nominations. RESULTS: Nominations of PBTSs as best friends were not significantly different than controls, but PBTSs had fewer reciprocated best friend nominations than controls. Approximately half of PBTSs in this study did not have any reciprocated best friend nominations and 25% were not nominated by any peer as a best friend. Greater symptoms of depression and lower social skills in PBTSs were associated with fewer nominations as a best friend by peers and a greater likelihood of no reciprocal best friend nominations. Greater difficulties in emotional control were associated with fewer nominations as a best friend by peers. CONCLUSIONS: The discrepancy between reciprocated best friend nominations and best friend nominations highlights a need to attend to reciprocal friendships in PBTSs and further understand social information processes in this population. Longitudinal analyses illustrate the impact of emotional adjustment on PBTS friendships.

PROMIS measures can be used to assess symptoms and function in long-term hematopoietic cell transplantation survivors.

BACKGROUND: Patient-reported outcomes for hematopoietic cell transplantation (HCT) survivors are well characterized with established measures; however, there is little experience with the new, freely available Patient-Reported Outcomes Measurement Information System (PROMIS) measures in this population. The aim of this study was to compare the performance of the PROMIS measures in the HCT setting with the performance of the commonly used 36-Item Short Form Health Survey (SF-36). METHODS: Adult HCT survivors from the Fred Hutchinson Cancer Research Center (n = 4446) were mailed a survey that included the following as part of an annual follow-up survey: the Patient-Reported Outcomes Measurement Information System-Global Health (PROMIS-GH; 10 questions), the 29-Item Patient-Reported Outcomes Measurement Information System Profile (PROMIS-29), and the SF-36. RESULTS: Both the SF-36 and PROMIS measures were available for 1634 HCT recipients (503 autologous recipients and 1131 allogeneic recipients). The overall response rate was 46%. The median time after transplantation for allogeneic and autologous recipients was 12.0 years (range, 0.4-44.1 years) and 6.1 years (range, 0.4-30.1 years), respectively. With the SF-36 or PROMIS-GH, overall physical functioning was somewhat lower in comparison with the general population, but mental functioning was similar. Component and domain scores with similar contents were strongly correlated by Pearson correlation coefficients: the Global Health-Physical and SF-36 Physical Component Summary scores for autologous (r = 0.82) and allogeneic recipients (r = 0.83) and the PROMIS-29 and SF-36 physical function, pain, and vitality/fatigue scores for allogeneic (0.87, -0.82, and -0.82, respectively) and autologous recipients (0.84, -0.82, and -0.81, respectively). The correlation between the Global Health-Mental and SF-36 Mental Component Summary scores was lower (0.70 for autologous recipients and 0.72 for allogeneic recipients). CONCLUSIONS: Physical and mental symptoms and function in autologous and allogeneic HCT survivors can be adequately assessed with PROMIS-29 and PROMIS-GH. Cancer 2018;124:841-9. © 2017 American Cancer Society.

A randomized trial of heart failure disease management in skilled nursing facilities (SNF Connect): Lessons learned.

BACKGROUND/AIMS: Conducting clinical trials in skilled nursing facilities is particularly challenging. This manuscript describes facility and patient recruitment challenges and solutions for clinical research in skilled nursing facilities. METHODS: Lessons learned from the SNF Connect Trial, a randomized trial of a heart failure disease management versus usual care for patients with heart failure receiving post-acute care in skilled nursing facilities, are discussed. Description of the trial design and barriers to facility and patient recruitment along with regulatory issues are presented. RESULTS: The recruitment of Denver-metro skilled nursing facilities was facilitated by key stakeholders of the skilled nursing facilities community. However, there were still a number of barriers to facility recruitment including leadership turnover, varying policies regarding research, fear of litigation and of an increased workload. Engagement of facilities was facilitated by their strong interest in reducing hospital readmissions, marketing potential to hospitals, and heart failure management education for their staff. Recruitment of patients proved difficult and there were few facilitators. Identified patient recruitment challenges included patients being unaware of their heart failure diagnosis, patients overwhelmed with their illness and care, and frequently there was no available proxy for cognitively impaired patients. Flexibility in changing the recruitment approach and targeting skilled nursing facilities with higher rates of admissions helped to overcome some barriers. CONCLUSION: Recruitment of skilled nursing facilities and patients in skilled nursing facilities for clinical trials is challenging. Strategies to attract both facilities and patients are warranted. These include aligning study goals with facility incentives and flexible recruitment protocols to work with patients in "transition crisis."

A Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute Respiratory Failure.

RATIONALE: Early physical therapy (PT) interventions may benefit patients with acute respiratory failure by preventing or attenuating neuromuscular weakness. However, the optimal dosage of these interventions is currently unknown. OBJECTIVES: To determine whether an intensive PT program significantly improves long-term physical functional performance compared with a standard-of-care PT program. METHODS: Patients who required mechanical ventilation for at least 4 days were eligible. Enrolled patients were randomized to receive PT for up to 4 weeks delivered in an intensive or standard-of-care manner. Physical functional performance was assessed at 1, 3, and 6 months in survivors who were not currently in an acute or long-term care facility. The primary outcome was the Continuous Scale Physical Functional Performance Test short form (CS-PFP-10) score at 1 month. MEASUREMENTS AND MAIN RESULTS: A total of 120 patients were enrolled from five hospitals. Patients in the intensive PT group received 12.4 ± 6.5 sessions for a total of 408 ± 261 minutes compared with only 6.1 ± 3.8 sessions for 86 ± 63 minutes in the standard-of-care group (P < 0.001 for both analyses). Physical function assessments were available for 86% of patients at 1 month, for 76% at 3 months, and for 60% at 6 months. In both groups, physical function was reduced yet significantly improved over time between 1, 3, and 6 months. When we compared the two interventions, we found no differences in the total CS-PFP-10 scores at all three time points (P = 0.73, 0.29, and 0.43, respectively) or in the total CS-PFP-10 score trajectory (P = 0.71). CONCLUSIONS: An intensive PT program did not improve long-term physical functional performance compared with a standard-of-care program. Clinical trial registered with www.clinicaltrials.gov (NCT01058421).

Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

Lactate Clearance and Normalization and Prolonged Organ Dysfunction in Pediatric Sepsis.

OBJECTIVES: To evaluate whether lactate clearance and normalization during emergency care of pediatric sepsis is associated with lower rates of persistent organ dysfunction. STUDY DESIGN: This was a prospective cohort study of 77 children <18 years of age in the emergency department with infection and acute organ dysfunction per consensus definitions. In consented patients, lactate was measured 2 and/or 4 hours after an initial lactate; persistent organ dysfunction was assessed through laboratory and physician evaluation at 48 hours. A decrease of ≥ 10% from initial to final level was considered lactate clearance; a final level < 2 mmol/L was considered lactate normalization. Relative risk (RR) with 95% CIs, adjusted in a log-binomial model, was used to evaluate associations between lactate clearance/normalization and organ dysfunction. RESULTS: Lactate normalized in 62 (81%) patients and cleared in 70 (91%). The primary outcome, persistent 48-hour organ dysfunction, was present in 32 (42%). Lactate normalization was associated with decreased risk of persistent organ dysfunction (RR 0.46, 0.29-0.73; adjusted RR 0.47, 0.29-0.78); lactate clearance was not (RR 0.70, 0.35-1.41; adjusted RR 0.75, 0.38-1.50). The association between lactate normalization and decreased risk of persistent organ dysfunction was retained in the subgroups with initial lactate ≥ 2 mmol/L and hypotension. CONCLUSIONS: In children with sepsis and organ dysfunction, lactate normalization within 4 hours was associated with decreased persistent organ dysfunction. Serial lactate level measurement may provide a useful prognostic tool during the first hours of resuscitation in pediatric sepsis.

Pathologic Risk Factors in Pediatric and Adolescent Patients With Clinical Stage I Testicular Stromal Tumors.

BACKGROUND: Testicular stromal tumors (TSTs) are rare. In adult men with TSTs, various pathologic risk factors have been identified in patients with clinically localized disease that increase the risk of occult metastatic disease (OMD). We systematically reviewed existing literature to analyze the impact of these risk factors on OMD in prepubertal (0 to 12 y) and postpubertal (13 to 21 y) patients. METHODS: A literature search was conducted using the combination of terms: "testicular stromal tumors," "testicular leydig cell tumors," "testicular sertoli tumors," "testicular interstitial tumors," "testicular granulosa tumor," and "testicular sex cord tumors." Studies of patients 0 to 21 years with clinical stage I TSTs were included. RESULTS: A total of 100 patients from 31 publications were included with a median age at diagnosis of 5.7 years (range, 1.2 mo to 21 y). Seventy-nine patients were 12 years and below (median 7.2 mo) and 21 patients were 13 to 21 years (median 16 y). No patients in either group were identified to have OMD at retroperitoneal lymph node dissection or during follow-up surveillance (median follow-up 45.6 y; range, 4 to 360 mo). 99% of those 12 years and below versus 95% of those above 12 years had 0 to 1 pathologic risk factors, and 1% versus 5% had 2+ pathologic risk factors (P=0.38). CONCLUSIONS: Clinical stage I TSTs in adolescent, postpubertal patients appear to behave in a benign manner with few pathologic risk factors, similar to prepubertal patients. Given the low risk of relapse in this population, low-impact surveillance strategies are paramount. Prospective study of these patients is needed, and entry into a tumor registry such as the International Ovarian and Testicular Stromal Tumor Registry is important to learning more about this rare disease.