Abstract Chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (L-aGVHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGVHD and to better classify graft-versus-host disease (GVHD) syndromes but have not been validated in patients <18 years of age. The objectives of this prospective multi-institution study were to determine: (1) whether the NIH-CC could be used to diagnose pediatric cGVHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGVHD and L-aGVHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGVHD and L-aGVHD using the NIH-CC. Twenty-seven transplant centers enrolled 302 patients <18 years of age before conditioning and prospectively followed them for 1 year posttransplant for development of cGVHD. Centers justified their cGVHD diagnosis according to the NIH-CC using central review and a study adjudication committee. A total of 28.2% of reported cGVHD cases was reclassified, usually as L-aGVHD, following study committee review. Similar incidence of cGVHD and L-aGVHD was found (21% and 24.7%, respectively). The most common organs involved with diagnostic or distinctive manifestations of cGVHD in children include the mouth, skin, eyes, and lungs. Importantly, the 2014 NIH-CC for bronchiolitis obliterans syndrome perform poorly in children. Past acute GVHD and peripheral blood grafts are major risk factors for cGVHD and L-aGVHD, with recipients ≥12 years of age being at risk for cGVHD. Applying the NIH-CC in pediatrics is feasible and reliable; however, further refinement of the criteria specifically for children is needed.
Mutations in the CBL gene were first identified in adults with various myeloid malignancies. Some patients with juvenile myelomonocytic leukemia (JMML) were also noted to harbor mutations in CBL, but were found to have generally less aggressive disease courses compared to patients with other forms of Ras pathway-mutant JMML. Importantly, and in contrast to most reports in adults, the majority of CBL mutations in JMML patients are germline with acquired uniparental disomy occurring in affected marrow cells. Here, we systematically studied a large cohort of 33 JMML patients with CBL mutations and found that this disease is highly diverse in presentation and overall outcome. Moreover, we discovered somatically acquired CBL mutations in 15% of pediatric patients who presented with more aggressive disease. Neither clinical features nor methylation profiling were able to distinguish patients with somatic CBL mutations from those with germline CBL mutations, highlighting the need for germline testing. Overall, we demonstrate that disease courses are quite heterogeneous even among patients with germline CBL mutations. Prospective clinical trials are warranted to find ideal treatment strategies for this diverse cohort of patients.
Malnutrition is a significant issue for pediatric patients with cancer. We sought to evaluate the effectiveness and complication rate of percutaneous endoscopic gastrostomy (PEG) placement in pediatric oncology patients.A retrospective chart review was performed on 49 pediatric oncology patients undergoing PEG placement at Johns Hopkins All Children's Hospital between 2000 and 2016. Demographic and clinical characteristics, complications, absolute neutrophil count at time of PEG placement and at time of complications, length of stay, and mortality were identified. Weight-for-age Z-scores were evaluated at time of- and six months post-PEG placement.The overall mean weight-for-age Z-score improved by 0.73 (p<0.0001) from pre- (-1.11) to post- (-0.38) PEG placement. Improvement in Z-score was seen in patients who were malnourished at time of PEG placement (1.14, p<0.0001), but not in those who were not malnourished (0.32, p=0.197). Site infections were seen in 12 (24%), buried bumper syndrome in five (10%), and tube dislodgement in one (2%) patient. One patient (2%) with fever was treated for possible peritonitis. There were no cases of other major complications, including gastric perforation, gastrocolic fistula, clinically significant bleeding, or PEG-related death documented.Consistent with previous studies, our data suggests a relationship between site complications (superficial wound infection, buried bumper syndrome) and neutropenia. Additionally, PEG placement appears to be an effective modality for improving nutritional status in malnourished pediatric oncology patients. However, larger prospective studies with appropriate controls and adjustment for potential confounders are warranted to confirm these findings.
Background Previous studies have explored post-hematopoietic cell transplant (HCT) outcomes by race in adults; however, pediatric data addressing this topic are scarce. Procedure This retrospective registry study included 238 White (W) and 57 Black (B) children with hematologic malignancies (HM) receiving first allogeneic HCT between 2010 and 2019 in one of five Florida pediatric HCT centers. Results We found no differences between W and B children by transplant characteristics, other than donor type. There was a significant difference in use of HLA-mismatched donors (HLA-MMD) (53% W, 71% B, p=0.01). When comparing HLA-MMD use to fully HLA-matched donors, B had RR of 1.47 [95% CI 0.7-3] of receiving a mismatched unrelated donor (MMUD), RR of 2.34 [95% CI 1.2-4.4] of receiving a mismatched related donor (MMRD), and a RR of 1.9 [95% CI 0.99-3.6] of receiving a mismatched cord blood donor (MMCBD) HCT, respectively. There was no significant difference in the incidence of aGVHD (48% W, 35% B), p=0.1 or cGVHD (19% W 28% B, p=0.1), or primary cause of death. Overall 24-month survival was 61% [95% CI 54-68%] for W, and 60% [95% CI 38-68] for B children, log-rank p=0.72. While HLA matching improved survival in W children, the number of B children receiving HLA-matched HCT was too small to identify the impact of HLA matching on survival. Conclusions In this contemporary cohort of children with HM we found that B children were more likely to receive HLA-MMD transplants, but this did not adversely affect survival or GVHD rates.
BK virus (BKV) infection is associated with hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HSCT) recipients and nephropathy after kidney transplantation. We assessed the association between BKV and kidney and bladder complications in children developing HC by retrospectively reviewing 221 consecutive pediatric allogeneic HSCT recipients at the Children's Hospital of Philadelphia from 2005 to 2011. We included all patients with BKV PCR testing performed for clinical indication from day 0 until 1 year post-HSCT (N = 68). We assessed the association of any BKV infection (urine and/or blood) or peak BK viremia ≥ 10,000 copies/mL (high viremia) with severe HC (defined as grade IV—bladder catheterization or surgical intervention); the need for dialysis; serum creatinine–estimated glomerular filtration rate at the time of BKV testing, day 100, and day 365; and death. Children with high viremia more likely developed severe HC compared with those with peak viremia < 10,000 copies/mL (21% versus 2%; P = .02). BKV infection of the blood or urine was not associated with the need for dialysis, change in estimated glomerular filtration rate, or mortality. BKV infection is common after pediatric allogeneic HSCT, and plasma testing in those with HC may predict patients who will develop severe bladder injury.
