Successful Unmanipulated Haploidentical Hematopoietic Stem Cell Transplant With Post-transplant Cyclophosphamide in a Child With Down Syndrome and Myelodysplastic Syndrome.

Allogeneic hematopoietic stem cell transplant (HSCT) in children with Down syndrome and hematologic malignancies is challenging and is reserved for those who develop relapsed/refractory disease due to concerns regarding transplant-related mortality. Haploidentical HSCT, although performed in limited cases using graft manipulation methods to prevent graft-versus-host disease (GVHD), often results in dismal outcomes. Herein, we report a case of a 12-year-old boy with Down syndrome and myelodysplastic syndrome who underwent unmanipulated haploidentical HSCT using a reduced toxicity treosulfan-based conditioning and in vivo T-cell depletion with post-transplant cyclophosphamide.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part I. Phases of Chronic GVHD, Supportive Care, and Systemic Therapy Discontinuation.

Current literature lacks details on the impact of pediatric chronic graft-versus-host disease (cGVHD) on long-term survivorship after allogeneic hematopoietic cell transplantation (HCT). Nonetheless, cGVHD remains a leading cause of post-transplant morbidity and mortality in children and adolescents, which is particularly relevant given the longer life-expectancy after HCT (measured in decades) compared to older adults. To address this knowledge gap, leaders of the Pediatric Transplant and Cellular Therapy Consortium convened a multidisciplinary taskforce of experts in pediatric cGVHD and HCT late effects known as RESILIENT after Chronic GVHD (Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD).

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100.

Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD.

Acute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model's prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts.

Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD.

Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [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 the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts.

Brochure intervention to manage bothersome taste changes in pediatric patients receiving cancer therapy.

Background: Primary objective was to determine if a patient informational brochure describing potentially useful strategies could help manage specific taste changes. Secondary objective was to describe the specific strategies used and whether the strategies were perceived as being helpful.

Procedure: This single-center study included pediatric patients with cancer or hematopoietic cell transplant recipients receiving active treatment who experienced bothersome taste changes in the last month.

Gut Immunomodulation with Vedolizumab prior to Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients with Inflammatory Bowel Disease.

Inborn errors of immunity (IEI) are often associated with inflammatory bowel disease (IBD). IEI can be corrected by allogeneic hematopoietic stem cell transplantation (HSCT); however, peritransplantation intestinal inflammation may increase the risk of gut graft-versus-host disease (GVHD). Vedolizumab inhibits the homing of lymphocytes to the intestine and may attenuate gut GVHD, yet its role in preventing GVHD in pediatric patients with IEI-associated IBD has not been studied.

Flares of acute graft-versus-host disease: a Mount Sinai Acute GVHD International Consortium analysis.

The absence of a standardized definition for graft-versus-host disease (GVHD) flares and data on its clinical course are significant concerns. We retrospectively evaluated 968 patients across 23 Mount Sinai Acute GVHD International Consortium (MAGIC) transplant centers who achieved complete response (CR) or very good partial response (VGPR) within 4 weeks of treatment. The cumulative incidence of flares within 6 months was 22%, and flares were associated with a higher risk of nonrelapse mortality (NRM; adjusted hazard ratio [aHR], 4.

A Day 14 Endpoint for Acute GVHD Clinical Trials.

The overall response rate (ORR) 28 days after treatment has been adopted as the primary endpoint for clinical trials of acute graft versus host disease (GVHD). However, physicians often need to modify immunosuppression earlier than day (D) 28, and non-relapse mortality (NRM) does not always correlate with ORR at D28. We studied 1144 patients that received systemic treatment for GVHD in the Mount Sinai Acute GVHD International Consortium (MAGIC) and divided them into a training set (n=764) and a validation set (n=380).

Yoga versus iPad active control for fatigue in paediatric cancer therapy: a randomised controlled trial.

Objectives: The primary objective was to determine if individualised yoga for hospitalised children receiving intensive chemotherapy was associated with less fatigue using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS) compared with iPad control.

Methods: This was a multicentre randomised controlled trial of individualised yoga in paediatric patients aged 8-18 years who were inpatients receiving intensive chemotherapy for leukaemia, lymphoma or haematopoietic cell transplantation. Participants were randomised to yoga or iPad groups; allocated programme was delivered individually by trained yoga instructors 5 days/week for 21 days.

Randomized trial of dyadic-report vs proxy-report and self-report symptom assessment for pediatric patients receiving cancer treatments.

Background: We validated different approaches to symptom assessment for pediatric cancer patients based on the Symptom Screening in Pediatrics Tool (SSPedi) for self-report (SSPedi and mini-SSPedi), proxy-report (proxy-SSPedi), and structured dyadic-report (co-SSPedi). The objective was to compare co-SSPedi scores vs proxy-report (proxy-SSPedi) and self-report (SSPedi or mini-SSPedi) scores for pediatric patients receiving cancer treatments.

Methods: This was a single-center, randomized crossover study enrolling English-speaking dyads of pediatric patients with cancer or hematopoietic cell transplant recipients 4-18 years old and their guardians.

Taste changes in paediatric oncology: longitudinal evaluation.

Objectives: Changes in taste is a common symptom in paediatric patients receiving cancer therapies. The primary objective was to describe the prevalence of taste changes longitudinally over a 6-month time frame among paediatric patients with newly diagnosed cancer. Secondary objective was to identify factors associated with taste changes over time.

Intractable abdominal pain as the sole symptom of Varicella Zoster reactivation after allogeneic stem cell transplantation: brief case report and review of the literature.

After primary infection, Varicella Zoster (VZV) persists in sensory dorsal root ganglia and may be reactivated in periods of diminished T-cell immunity. Varicella Zoster reactivation post allogenic stem cell transplantation (HSCT) can be challenging to diagnose as it does not always present with characteristic skin lesions. We describe a pediatric patient who presented with isolated severe abdominal pain with no other symptoms.

Characterizing the cutaneous late effects of allogeneic hematopoietic stem cell transplantation: A systematic review.

Background: There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients.

Methods: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139).

Validation of co-Symptom Screening in Pediatrics Tool: a novel dyadic approach to symptom screening in pediatric patients receiving cancer treatment.

Background: Co-Symptom Screening in Pediatrics Tool (co-SSPedi) is a dyadic (child-guardian) approach to symptom assessment. Objectives were to evaluate the reliability and validity of co-SSPedi for pediatric patients receiving cancer treatments.

Methods: This multicenter study included dyads of patients aged 4-18 years of age with cancer or undergoing hematopoietic cell transplant and their guardians.

Pulmonary Hemorrhage in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Single-Center Retrospective Study.

Objectives: Pulmonary hemorrhage (PH) is a serious complication posthematopoietic stem cell transplant (HSCT). In view of limited available pediatric data, we performed a retrospective study to describe epidemiology, management, and outcomes of PH post-HSCT in children in our national center.

Design: Retrospective study.

Incidence, clinical presentation, risk factors, outcomes, and biomarkers in de novo late acute GVHD.

Late acute graft-versus-host disease (GVHD) is defined as de novo acute GVHD presenting beyond 100 days after allogeneic hematopoietic cell transplantation (HCT) without manifestations of chronic GVHD. Data are limited regarding its characteristics, clinical course, and risk factors because of underrecognition and changes in classification. We evaluated 3542 consecutive adult recipients of first HCTs at 24 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2014 and August 2021 to better describe the clinical evolution and outcomes of late acute GVHD.

Symptom documentation and intervention in paediatric cancer care-association with severity: observational study.

Objectives: Primary objectives were to determine the relationship between prevalence of symptom documentation and intervention provision, and increasing severity of bothersome symptoms, as identified by guardians using guardian-reported Symptom Screening in Pediatrics Tool (proxy-SSPedi), which is validated and measures the extent of bothersome symptoms in paediatric patients with cancer.

Methods: We included guardians of children 2-7 years of age receiving cancer treatments and seen in hospital daily for 4 consecutive days. Guardians reported proxy-SSPedi at study enrolment and 3 days later.

Feasibility of three times weekly symptom screening in pediatric cancer patients.

Objective: Primary objective was to determine the feasibility of three times weekly symptom reporting by pediatric cancer patients for eight weeks.

Methods: We included English-speaking patients 8-18 years of age with cancer. Patients were sent reminders by text or email to complete Symptom Screening in Pediatrics Tool (SSPedi) three times weekly for eight weeks.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored.

A Prolonged Outbreak of Human Adenovirus A31 (HAdV-A31) Infection on a Pediatric Hematopoietic Stem Cell Transplantation Ward with Whole Genome Sequencing Evidence of International Linkages.

A surge in hematopoietic stem cell transplantation (HSCT) human adenovirus A31 (HAdV-A31) infections was initially observed in late 2014/2015 at SickKids (SK) Hospital, Toronto, Canada. In response, enhanced laboratory monitoring for all adenovirus infections was conducted. Positive samples underwent genotyping, viral culture, and, in selected cases, whole-genome sequencing (WGS).

A diagnostic classifier for pediatric chronic graft-versus-host disease: results of the ABLE/PBMTC 1202 study.

The National Institutes of Health Consensus criteria for chronic graft-versus-host disease (cGVHD) diagnosis can be challenging to apply in children, making pediatric cGVHD diagnosis difficult. We aimed to identify diagnostic pediatric cGVHD biomarkers that would complement the current clinical criteria and help differentiate cGVHD from non-cGVHD. The Applied Biomarkers of Late Effects of Childhood Cancer (ABLE) study, open at 27 transplant centers, prospectively evaluated 302 pediatric patients after hematopoietic cell transplant (234 evaluable).