Amphiregulin, ST2,and REG3α Biomarker Risk Algorithms as Predictors of Non-Relapse Mortality in Patients with Acute GVHD.

Graft-vs-host disease (GVHD) is a major cause of non-relapse mortality (NRM) following allogeneic hematopoietic cell transplant (HCT). Algorithms containing either the GI GVHD biomarker amphiregulin (AREG) or a combination of two GI GVHD biomarkers, (ST2+REG3α) when measured at GVHD diagnosis are validated predictors of NRM risk, but have never been assessed in the same patients using identical statistical methods. We measured serum concentrations of ST2, REG3, and AREG by ELISA at the time of GVHD diagnosis in 715 patients divided by date of transplant into training (2004-2015) and validation (2015-2017) cohorts. The training cohort (n=341) was used to develop algorithms for predicting probability of 12 month NRM that contained all possible combinations of 1-3 biomarkers and a threshold corresponding to the concordance probability was used to stratify patients for risk of NRM. Algorithms were compared to each other based on several metrics including the area under the receiver operating characteristics curve (AUC), proportion of patients correctly classified, sensitivity, and specificity using only the validation cohort (n=374). All algorithms were strong discriminators of 12 month NRM, whether or not patients were systemically treated (n=321). An algorithm containing only ST2+REG3α had the highest AUC (0.757), correctly classified the most patients (75%), and more accurately risk stratified those who developed Minnesota standard risk GVHD and for patients who received post-transplant cyclophosphamide-based prophylaxis. An algorithm containing only AREG more accurately risk stratified patients with Minnesota high risk GVHD. Combining ST2, REG3α, and AREG into a single algorithm did not improve performance.

Pediatric hematology/oncology healthcare professional emotional health during COVID-19.

OBJECTIVES: Little is known about the impact of coronavirus disease 2019 (COVID-19) on healthcare professional emotional health in pediatric hematology/oncology. Primary objective was to describe anxiety, depression, positive affect, and perceived stress among pediatric hematology/oncology healthcare professionals following a COVID-19 outbreak. Secondary objectives were to compare these outcomes based on contact with a positive person, and to identify risk factors for worse outcomes. MATERIALS AND METHODS: We included 272 healthcare professionals working with pediatric hematology/oncology patients. We determined whether respondents had direct or indirect contact with a COVID-19-positive individual and then measured outcomes using the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, and positive affect measures, and the Perceived Stress Scale. RESULTS: Among eligible respondents, 205 agreed to participate (response rate 75%). Sixty-nine (33.7%) had contact with a COVID-19-positive person. PROMIS anxiety, depression, and positive affect scores were similar to the general United States population. Those who had contact with a COVID-19-positive individual did not have significantly different outcomes. In multiple regression, non-physicians had significantly increased anxiety (nurses: p = 0.013), depression (nurses: p = 0.002, pharmacists: p = 0.038, and other profession: p = 0.021), and perceived stress (nurses: p = 0.002 and other profession: p = 0.011) when compared to physicians. CONCLUSIONS: Pediatric hematology/oncology healthcare professionals had similar levels of anxiety, depression, and positive affect as the general population. Contact with a COVID-19-positive individual was not significantly associated with outcomes. Non-physician healthcare professionals had more anxiety, depression, and perceived stress when compared to physicians. These findings may help to develop programs to support healthcare professional resilience.

Return to Work Among Young Adult Survivors of Allogeneic Hematopoietic Cell Transplantation in the United States.

Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.

A feasibility study examining the impact of yoga on psychosocial health and symptoms in pediatric outpatients receiving chemotherapy.

PURPOSE: Pediatric cancer patients experience symptoms that negatively impact quality of life; yoga may be an effective intervention. The primary objective was to determine the feasibility of a 10-week, weekly individualized yoga intervention for children and adolescents receiving outpatient cancer therapy primarily delivered remotely using Skype. Secondary objectives were to describe depression, anxiety, anger, fatigue, quality of life, and symptoms at 5 and 10 weeks after enrollment. METHODS: We included English-speaking patients aged 10 to 18 years receiving outpatient chemotherapy for cancer. Weekly individualized yoga sessions were offered for 10 weeks. Weeks 1, 5, and 10 were in-hospital while the remaining sessions were delivered remotely using Skype. Twice weekly, homework was assigned between each session. The primary outcome was feasibility, defined as 80% of participants completing at least 60% of planned in-hospital or remote yoga sessions. RESULTS: Between March and November 2017, 10 patients were enrolled. Two patients discontinued the study after one and two sessions. Only six participants achieved at least 60% of planned yoga sessions and thus, the study did not meet the a priori defined feasibility threshold. Among all participants, only one homework session was performed. CONCLUSIONS: A 10-week individualized in-person and remotely conducted yoga intervention was not feasible in children receiving cancer treatments because of failure to achieve the desired frequency of yoga sessions in a sufficient number of participants. Future research should identify approaches to improve compliance with remote yoga sessions and home practice. TRIAL REGISTRATION: NCT03318068.

Successful Myeloablative Matched Unrelated Donor Hematopoietic Stem Cell Transplantation in a Young Girl With GATA2 Deficiency and Emberger Syndrome.

Patients with GATA2 (Emberger syndrome) deficiency needs early hematopoietic stem cell transplant (HSCT) before evolving in to myelodysplastic syndrome or acute myeloid leukemia and with time given compromised organ dysfunction leads to increase regimen-related toxicities. Most published cases have used nonmyeloablative conditioning regimens, show higher incidences of rejection and relapse rates and umbilical cord blood transplant has been reported to be suboptimal in patients with GATA2 deficiency because of longer period of engraftment leads to more infections and mortality. We report a 4.5-year-old girl with GATA2 deficiency who underwent matched unrelated donor HSCT utilizing a myeloablative conditioning regimen including intravenous busulfan (total dose of 12.8 mg/kg) and fludarabine (total dose of 160 mg/m) She tolerated the conditioning regimen and bone marrow infusion well. Her initial chimerism was mixed (90% donor), cyclosporine was gradually weaned and discontinued at day+85 and this resulted in conversion to full-donor chimerism. Bone marrow assessment 3 months post-HSCT revealed normal hematopoiesis and absence of monosomy 7. At 20 months of follow-up she had full-donor chimerism with complete reconstitution of the all hematopoietic stem cells. Myeloablative matched unrelated donor HSCT represents an effective option for cure in patients with GATA2 deficiency and Emberger syndrome.