Ibrutinib for the treatment of chronic graft-vs-host disease in pediatric hematopoietic stem cell transplant patients: A single-center experience.

cGVHD is a significant cause of morbidity and mortality after transplant. Ibrutinib has been studied as treatment for cGVHD in the adult population. Pediatric dosing and safety of ibrutinib are unknown. We conducted a retrospective review on the use of ibrutinib in 22 children with cGVHD at Cincinnati Children's Hospital Medical Center. All patients received a dose of 250 mg/m2 orally, once daily. Responses were measured at 6 months after drug initiation using the 2014 NIH consensus panel response criteria. Twenty-two patients of median age 13.5 years received ibrutinib. cGVHD grades were severe (n = 15), moderate (n = 6), and mild (n = 1). Eight patients stopped ibrutinib prior to 3 months due to adverse events or death and could not be evaluated for 6-month response. Of the 14 evaluable patients, 12 achieved a partial response at 6 months and two patients had progressive disease. Seven evaluable patients with lung involvement had stable lung function at 6 months. One patient had EBV reactivation, and one patient developed pneumococcal sepsis despite appropriate prophylaxis while on ibrutinib therapy. No fungal infections occurred while on ibrutinib. Adverse events leading to discontinuation included recurrent fevers without a source, extensive bruising, oral bleeding, gastrointestinal distress, lower GI bleeding, dizziness, elevated transaminases, and pneumococcal sepsis. Ibrutinib administration of 250 mg/m2 oral daily shows promising responses in pediatric cGVHD. Pediatric-focused pharmacokinetic-directed studies are needed to establish optimal dosing and define efficacy in children.

Ruxolitinib for the Treatment of Chronic GVHD and Overlap Syndrome in Children and Young Adults.

BACKGROUND: Ruxolitinib, a JAK1/2 inhibitor, is used to treat chronic graft versus host disease (cGVHD) in adult allogeneic hematopoietic stem cell transplant patients, but experience in children is limited, perhaps because of lack of pediatric dosing information. In this report, we describe our pediatric and young adult dosing strategy experience in cGVHD. METHODS: Ruxolitinib was administered orally at 5 mg twice daily for children ≥25 kg or 2.5 mg twice daily if <25 kg. The dose was halved with concurrent azole administration and increased to a maximum of 10 mg twice daily if tolerated. Responses were evaluated using the 2014 NIH consensus criteria. Phosphorylation of lymphocyte STAT5 following dosing, a surrogate of JAK inhibition, was evaluated by flow cytometry. RESULTS: Twenty patients with a median age 14.6 y (range 5-26 y) received ruxolitinib for severe (n = 9) and moderate (n = 11) cGVHD. Median steroid dose was 0.5 mg/kg/d (range 0.08-1.5 mg/kg/d) at ruxolitinib initiation. Two patients with moderate cGVHD achieved a complete response (CR), while 12 patients achieved a partial response (PR) at a median of 48 d (range 17-98 d) from the first ruxolitinib dose, for an overall response rate of 70%. Eleven patients are maintaining their PRs. pSTAT5 on lymphocytes was absent or decreased (0%-6% events) in 5 evaluated patients, suggesting adequate inhibition. Three patients discontinued ruxolitinib because of neutropenia, thrombocytopenia, or elevated alanine aminotransferase. Four patients developed bacterial infections, and 3 experienced symptomatic viral infections. Two patients died from complications related to progressive severe cGVHD. CONCLUSIONS: Ruxolitinib using our dosing strategy demonstrates promise for treating cGVHD in children.

Pneumatosis intestinalis after hematopoietic stem cell transplantation: When not doing anything is good enough.

BACKGROUND/PURPOSE: Pneumatosis intestinalis (PI) has been reported in hematopoietic stem cell transplant recipients (HSCT) since 1980s and at present there is no uniform consensus of the significance and management of this condition. METHODS: We retrospectively reviewed medical records of 990 consecutive pediatric HSCT recipients and examined data for clinical PI presentation, management and outcomes RESULTS: PI was identified in 53 patients (5.4%), mainly allogeneic HSCT recipients receiving systemic steroids. Abdominal X-ray was the main diagnostic modality. Forty-seven patients (89%) were evaluated because of clinical concerns and others were identified as incidental findings. Pneumoperitoneum was reported in 15 patients (28%). None of these patients had signs of acute abdomen. The majority of patients (43/53, 81%) had no targeted clinical intervention for PI and resolved PI in a median of 15 days (IQR 3-61). Surgery consult was only requested for 7/53 (13%) patients, three of whom had evidence of pneumoperitoneum. None of these patients required any surgical interventions. CONCLUSIONS: Pneumatosis intestinalis commonly occurs in HSCT recipient receiving steroids, but unlike with NEC, PI rarely poses clinical risk after transplant. The majority of HSCT recipients with PI require only close monitoring without interventions. Surgical evaluation should be based on clinical symptoms and not PI presence alone.

Evidence-based care of the child with deformational plagiocephaly, Part I: assessment and diagnosis.

Non-synostotic deformational plagiocephaly (DP) is head asymmetry that results from external forces that mold the skull in the first year of life. Primary care providers are most likely to encounter DP when infants present for well-child care, and for this reason it is important that providers be competent in assessing, diagnosing, and participating in the prevention and management of DP. The purpose of this two-part series on DP is to present an overview of assessment, diagnosis, and evidence-based management of DP for health care providers. In Part I we provide a brief background of DP and associated problems with torticollis and infant development, and we present strategies for visual and anthropometric assessment of the infant with suspected DP. We also provide tools for differentiating DP from craniosynostosis and for classifying the type and severity of lateral and posterior DP. Part II (to be published in a future issue of the Journal of Pediatric Health Care) provides a synthesis of current evidence and a clinical decision tool for evidence-based management of DP.

Evidence-based care of the child with deformational plagiocephaly, part II: management.

Non-synostotic deformational plagiocephaly (DP) is a common condition that affects as many as one in five infants in the first 2 months of life. The purpose of this article, the second in a two-part series, is to present a synthesis of the evidence related to management of deformational plagiocephaly and an evidence-based clinical decision tool for multidisciplinary management of DP. We systematically reviewed and graded the literature on management of DP from 2000 to 2011 based on level of evidence and quality. The evidence suggests that although many cases of DP will improve over time, conservative management strategies such as repositioning, physical therapy, and cranial molding devices can safely and effectively minimize the degree of skull asymmetry when implemented in the first year of life. Outcomes are best when the timing of diagnosis and severity of asymmetry guide decision making related to interventions and referrals for DP. Prevention and management of early signs of DP are best achieved in a primary care setting, with multidisciplinary management based on the needs of the child and the goals of the family.