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1.
Pediatr Blood Cancer ; 71(8): e31059, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38721864

RESUMO

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.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Transplante de Células-Tronco Hematopoéticas , Levofloxacino , Humanos , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Criança , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Masculino , Feminino , Antibioticoprofilaxia/métodos , Pré-Escolar , Adolescente , Lactente , Neutropenia/induzido quimicamente , Neutropenia/prevenção & controle , Administração Intravenosa
2.
Pediatr Crit Care Med ; 25(1): e47-e51, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37539962

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco
3.
Pediatr Hematol Oncol ; 41(3): 224-228, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37898904

RESUMO

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.


Assuntos
Varicela , Transplante de Células-Tronco Hematopoéticas , Herpes Zoster , Humanos , Criança , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/etiologia , Herpesvirus Humano 3/fisiologia , Ativação Viral , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Dor Abdominal/complicações , Transplante de Células-Tronco/efeitos adversos
4.
Transfusion ; 61(12): 3413-3419, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34751944

RESUMO

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.


Assuntos
Cateterismo Venoso Central , Cateteres Venosos Centrais , Adolescente , Idoso , Criança , Humanos , Antígenos CD34 , Cateterismo Venoso Central/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Células-Tronco Hematopoéticas , Ultrassonografia
5.
Pediatr Blood Cancer ; 68(7): e28979, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33844444

RESUMO

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.


Assuntos
Leucemia Mieloide Aguda , Criança , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Tirosina Quinase 3 Semelhante a fms/genética
7.
Transplant Cell Ther ; 30(5): 546.e1-546.e7, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38458476

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças Inflamatórias Intestinais , Transplante Homólogo , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Feminino , Criança , Masculino , Adolescente , Pré-Escolar , Doenças Inflamatórias Intestinais/tratamento farmacológico , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Lactente , Imunomodulação , Condicionamento Pré-Transplante/métodos
8.
Lancet Haematol ; 11(8): e580-e592, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39002551

RESUMO

BACKGROUND: Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD. METHODS: In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m2 twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing. FINDINGS: Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment discontinuation), one due to Aspergillus infection, one due to septic shock, and one due to acute respiratory distress syndrome; none were considered to be related to study drug. INTERPRETATION: Pending final analysis, this study suggests that ruxolitinib is active and well tolerated in both treatment-naive and corticosteroid-refractory patients aged 2 years to younger than 18 years with chronic GVHD, thereby supporting its use in this patient population. The safety profile of ruxolitinib in this patient population is consistent with that of adults. Final analysis of this study will provide further information on the long-term benefits of ruxolitinib in children with chronic GVHD. FUNDING: Novartis.


Assuntos
Corticosteroides , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Nitrilas , Pirazóis , Pirimidinas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Corticosteroides/uso terapêutico , Doença Crônica , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pirazóis/uso terapêutico , Pirazóis/efeitos adversos , Pirimidinas/uso terapêutico , Resultado do Tratamento
9.
Transplant Cell Ther ; 28(3): 158.e1-158.e9, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34838785

RESUMO

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.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Adulto , Aloenxertos , Medula Óssea , Criança , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/terapia , Humanos , Recidiva Local de Neoplasia/complicações , Estudos Retrospectivos , Irmãos , Estados Unidos , Doadores não Relacionados
10.
Front Oncol ; 11: 627726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968727

RESUMO

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.

14.
Indian Pediatr ; 2013 October; 50(10): 974
Artigo em Inglês | IMSEAR | ID: sea-170026
15.
Indian Pediatr ; 2013 September; 50(9): 886
Artigo em Inglês | IMSEAR | ID: sea-169983
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