The impact of levofloxacin prophylaxis on empiric intravenous antibiotic use in pediatric hematopoietic stem cell transplant recipients.

Levofloxacin prophylaxis during periods of neutropenia in pediatric hematopoietic stem cell transplant (HSCT) may reduce the number of febrile episodes and use of empiric intravenous antibiotics (EIA); however, the literature is conflicting. This retrospective review compared EIA use before and after implementation of levofloxacin prophylaxis at a children's hospital. Levofloxacin prophylaxis was associated with reduced use of certain EIA; however, did not reduce the number of positive blood cultures or clinical deteriorations. Therefore, levofloxacin prophylaxis may have implications for the stewardship of broad-spectrum intravenous antibiotics used in pediatric HSCT.

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. Here we describe a cohort of pediatric patients with IEI-associated IBD treated with vedolizumab before and during allogeneic HSCT. The study involved a retrospective chart review of pediatric patients with IEI-associated IBD treated with vedolizumab at 6 weeks, 4 weeks, and 1 week before undergoing HSCT. The conditioning regimen consisted of treosulfan, fludarabine, and cyclophosphamide with rabbit antithymocyte globulin, and GVHD prophylaxis included tacrolimus and steroids. Eleven patients (6 females) with a median age of 5 years (range, 0.4 to 14 years) with diverse IEI were included. IBD symptoms were characterized by abdominal pain, loose stools, and blood in stools. Four patients had developed a perianal fistula, and 1 patient had a rectal prolapse. One patient had both a gastrostomy tube and a jejunal tube in situ. Treatment of IBD before HSCT included steroids in 11 patients, anakinra in 2, infliximab in 4, sulfasalazine in 2, mesalazine in 2, and vedolizumab. IBD symptoms were considered controlled in the absence of abdominal pain, loose stools, or blood in stools. Graft sources for HSCT were unrelated donor cord in 5 patients (2 with a 5/8 HLA match, 2 with a 7/8 match, and 1 with a 6/8 match), peripheral blood stem cells in 5 patients (2 haploidentical, 1 with a 9/10 HLA match, and 2 with a 10/10 match), and bone marrow in 1 patient (10/10 matched sibling donor). The median number of vedolizumab infusions was 4 (range, 3 to 12) before HSCT and 1 (range, 1 to 3) after HSCT, and all were reported to be uneventful. All patients had engrafted. Acute GVHD occurred in 4 patients and was limited to grade I skin GVHD only. Chronic GVHD occurred in 1 patient and again was limited to the skin. There was no gut GVHD. Three patients experienced cytomegalovirus viremia, and 2 patients had Epstein-Barr virus viremia. At the time of this report, all patients were alive with no evidence of IBD at a median follow-up of 15 months (range, 3 to 39 months). Administration of vedolizumab pre- and post-HSCT in pediatric patients with IEI-associated IBD is well tolerated and associated with a low rate of gut GVHD. These findings provide a platform for the prospective study and use of vedolizumab for GVHD prophylaxis in pediatric patients with known intestinal inflammation as a pre-HSCT comorbidity.

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. SETTING: Academic children's hospital (2000-2015). SUBJECTS: Children (< 18 yr) with PH and requiring PICU care post-HSCT. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The historical prevalence of PH in our center was 2.7% (31/1,148). Twenty patients had a concomitant infection, 15 had bacterial infection, 8 had viral infection, and 3 patients had a fungal infection. With a median follow-up time of 60 months, 7 of 31 patients were alive. Early PH (< 40 d post-HSCT) was associated with improved survival (6/15 vs 1/16, p = 0.035). Patients who received high-dose pulsed corticosteroid had improved survival when compared with those who did not (7/22 vs 0/9, p = 0.0012); this also applied to the subgroup of patients with a concomitant infection (5/15 vs 0, p = 0.001). None of the patients who survived had measurable respiratory sequelae. CONCLUSIONS: PH is a rare but serious complication after HSCT. Corticosteroids were associated with improved survival even in patients with a concomitant infection.

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. Cutaneous lesions appeared only 10 days later resulting in delayed diagnosis and treatment. He was successfully treated with intravenous acyclovir and recovered after a prolonged hospital stay with post-herpetic neuralgia. Abdominal pain in children post HSCT has a broad differential and VZV reactivation should be considered even in absence of cutaneous lesions. Early diagnosis and treatment are essential to reduce VZV-related morbidity and mortality. In this article we present a case report and review clinical presentation and outcome of similar cases in the literature.

Outcome of Haploidentical Peripheral Blood Allografts Using Post-Transplantation Cyclophosphamide Compared to Matched Sibling and Unrelated Donor Bone Marrow Allografts in Pediatric Patients with Hematologic Malignancies: A Single-Center Analysis.

The introduction of post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis has made haploidentical (haplo) hematopoietic stem cell transplantation (HSCT) a common approach in adults, but pediatric experience is limited. Based on the encouraging adult data and with the aim of decreasing the risk of graft failure, our center is increasingly using peripheral blood stem cells (PBSCs) from haplo donors with PTCy. Here we compare outcomes of bone marrow (BM) transplantation with traditional donor choices, including matched sibling donors (MSDs) and 10/10 HLA matched unrelated donors (MUDs), with those of haplo PBSC grafts in pediatric patients with hematologic malignancies. In this retrospective single-center study, the primary endpoint was the comparison of GVHD-free relapse-free survival (GRFS; defined as absence of acute GVHD [aGVHD] grade III-IV, relapse, death, or chronic GVHD [cGVHD] requiring systemic therapy) for the 3 cohorts. Secondary endpoints included overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), and incidence of aGVHD and cGVHD). A total of 104 consecutive patients underwent first allogeneic (allo)-HSCT for a hematologic malignancy or myelodysplastic syndrome between January 2014 and December 2020 using a haplo family donor (PBSCs; n = 26), an MSD (BM; n = 31), or an MUD (BM; n = 47). Patient demographic and transplantation characteristics were not significantly different across the cohorts, apart from remission status, with the haplo cohort having more patients in third or later complete remission before HSCT (P < .01). The median duration of follow-up for the entire cohort was 573 days. The cumulative incidence of aGVHD (grade II-IV or grade III-IV) was not significantly different among the cohorts; however, the cumulative incidence of cGVHD at 18 months was highest in the MUD cohort (31.7%, versus 10.0% in the MSD cohort and 9.2% in the haplo cohort; P = .02). There were no differences in the 18-month cumulative incidence of relapse or NRM. OS and RFS at 18 months were 80.7% (95% confidence interval [CI], 61.7% to 100%) and 73.8% (95% CI, 55.5% to 98.1%) for the haplo cohort, 83.4% (95% CI, 72.8% to 95.5%) and 70.3% (95% CI, 57.9% to 85.3%) for the MUD cohort, and 80.9% (95% CI, 66.9% to 97.7%) and 66.5% (95% CI, 50.5% to 87.5%) for the MSD cohort, with no statistically significant differences among the cohorts. GRFS at 18 months was 61% (95% CI, 43.3% to 85.9%) for the haplo cohort, 44.6% (95% CI, 31.8% to 62.5%) for the MUD cohort, and 62.1% (95% CI, 45.7% to 84.3%) for the MSD cohort (P = .26). Haploidentical PBSC HSCT with PTCy had comparable outcomes to MSD and MUD BM HSCT and less cGVHD compared with MUD BM HSCT in children. The logistical advantages and lower resource burden of haplo HSCT with PBSCs make it a feasible alternative to MUD HSCT in children with hematologic malignancies. Given that this is a retrospective comparison of transplantation platforms rather than donor types, further prospective studies are warranted. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Peripheral venous catheter collection of immune effector cells and hematopoietic stem cells is feasible and safe in older pediatric patients.

BACKGROUND: The Collection of hematopoietic stem cells (HSC) and immune effector cells (IEC) has unique challenges in children. To maintain adequate blood flow, central venous catheters (CVCs) remain the standard of care in many centers, but are associated with procedural risks and increased resource utilization. The goal of this study was to determine feasibility and safety of peripheral venous catheter (PVC) cell collection in older children. METHODS: Patients and donors requiring venous access with weight >25 kg, age >8 years were screened for PVC collection via 18G PVCs. Those with poor venous access (on history/exam/pre-screening ultrasound) or unable to maintain suitable procedural position were excluded. Comparison was made to CVC collections in a matched patient cohort. RESULTS: Thirty-eight individuals were screened and met age/weight criteria for PVC collection. Five did not have PVC collection attempted due to poor access (n = 4) or behavioral concerns (n = 1). Thirty-three had PVC collection attempt (HSC = 22; IEC = 11) with median age 15.3 year (range 9.7-18.0) and weight 58.5 kg (range 27.9-115.4). Thirty-two of 33 (97%) patients were collected successfully by PVC without adverse events. Comparing PVC to matched CVC collection cohort (n = 18), there was no significant difference in flow rate (48.2 mL/h vs 53.9 mL/h, p = 0.12), collection time (266 min vs 262 min, p = 0.85) or collection efficiency (IEC/CD3 60.9% vs 60.8% p = 0.99; HSC/CD34 53.6% vs 41.3% p = 0.05). CONCLUSION: PVC collection of HSC and IEC is feasible and safe in older children with comparable collection efficiency to CVC collections. Ultrasound screening may reduce failure rates. PVC collections can reduce the risk of CVC insertions and associated healthcare costs.

Delirium in Children Undergoing Hematopoietic Cell Transplantation: A Multi-Institutional Point Prevalence Study.

Introduction: Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant. Methods: This is a multi-institutional point prevalence study. All subjects were prospectively screened for delirium twice daily using the Cornell Assessment of Pediatric Delirium over a 10-day period. De-identified data, including basic demographics and daily characteristics, were extracted from the electronic medical record. Results: Eleven North American institutions were included, 106 children were enrolled, and 883 hospital days were captured. Delirium screening was successfully completed on more than 98% of the study days. Forty-eight children (45%) developed delirium over the course of the 10-day study. Children were diagnosed with delirium on 161/883 study days, for an overall delirium rate of 18% per day. Higher delirium rates were noted in children <5 years old (aOR 0.41 for children over 5 years), and in association with specific medications (melatonin, steroids, and tacrolimus). Conclusion: Delirium was a frequent occurrence in our study cohort, with identifiable risk factors. Delirium screening is highly feasible in the pediatric hematopoietic cell transplant patient population. A large-scale prospective longitudinal study following children throughout their transplant course is urgently needed to fully describe the epidemiology of pediatric delirium, explore the effects of delirium on patient outcomes, and establish guidelines to prevent and treat delirium in the peri-transplant period.

Treatment of acute myeloid leukemia in children: A practical perspective.

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease that requires a multifaceted treatment approach. Although outcomes for low-risk AML have improved significantly over recent decades, high-risk AML continues to be associated with an adverse prognosis. Recent advances in molecular diagnostics, risk stratification, and supportive care have contributed to improvements in outcomes in pediatric AML. Targeted approaches, for example, the use of tyrosine kinase inhibitors to treat FLT3-ITD AML, offer promise and are currently undergoing clinical investigation in pediatric patients. New approaches to hematopoietic stem cell transplantation, including the use of haploidentical donors, are significantly expanding donor options for patients with high-risk AML. This review provides an overview of recent advances in the treatment of pediatric AML that are likely to have clinical impact and reshape the standard of care.