IMPORTANCE Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. OBJECTIVE To describe the use of rituximab and to assess whether its use is associated with shortor long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. EXPOSURE One or more doses of rituximab. MAIN OUTCOMES AND MEASURES Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. RESULTS We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19 + or CD20 + cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-forage B cell counts. Recovery of CD27 + memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM.
The global experience with pediatric Kaposi sarcoma (KS) has evolved immensely since the onset of HIV (human immunodeficiency virus). In this review, current perspectives on childhood KS are discussed in the context of the HIV epidemic in sub-Saharan Africa. Endemic (HIV-unrelated) KS was first described over 50 years ago in central and eastern Africa, regions where human herpesvirus-8, the causative agent of KS, is endemic. With the alarming rise in HIV prevalence over the past few decades, KS has become not only the most common HIV-related malignancy in Africa, but also one of the most common overall childhood cancers throughout the central, eastern, and southern regions of the continent. The unique clinical features of pediatric KS that were described in those early endemic KS reports have been re-affirmed by the contemporary experience with HIV-related KS. These characteristics include a predilection for primary lymph node involvement, significant proportions of patients lacking prototypical cutaneous lesions, and the potential for fulminant disease progression. Other clinical features that distinguish childhood KS from adult disease include disease presentation with severe cytopenias, and the common occurrence of childhood KS without severe CD4 count suppression. Distinct clinical heterogeneity in disease presentation and treatment response have been demonstrated. Long-term complete remission and event-free survival can be achieved—especially in children with lymphadenopathic KS—utilizing treatment with antiretroviral therapy plus mild–moderate chemotherapy regimens that are well tolerated, even in low-income settings. A pediatric-specific staging classification and risk-stratification platform have been retrospectively validated, and may help guide therapeutic strategies. With expansion of the HIV treatment infrastructure throughout Africa, coupled with recent developments in establishing comprehensive pediatric oncology programs, there is great potential for improving outcomes for children with KS. Increased awareness of the unique clinical nuances and collaborative evaluations of pediatric-specific treatment paradigms are required to optimize survival for children with KS.
Abstract. The effectiveness of rotavirus vaccine in the field may set the stage for a changing landscape of diarrheal illness affecting children worldwide. Norovirus and rotavirus are the two major viral enteropathogens of childhood. This study describes the prevalence of norovirus and rotavirus 2 years after widespread rotavirus vaccination in Cochabamba, Bolivia. Stool samples from hospitalized children with acute gastroenteritis (AGE) and outpatients aged 5-24 months without AGE were recruited from an urban hospital serving Bolivia's third largest city. Both viruses were genotyped, and norovirus GII.4 was further sequenced. Norovirus was found much more frequently than rotavirus. Norovirus was detected in 69/201 (34.3%) of specimens from children with AGE and 13/71 (18.3%) of those without diarrhea. Rotavirus was detected in 38/201 (18.9%) of diarrheal specimens and 3/71 (4.2%) of non-diarrheal specimens. Norovirus GII was identified in 97.8% of norovirus-positive samples; GII.4 was the most common genotype (71.4% of typed specimens). Rotavirus G3P [8] was the most prevalent rotavirus genotype (44.0% of typed specimens) and G2P [4] was second most prevalent (16.0% of typed specimens). This community is likely part of a trend toward norovirus predominance over rotavirus in children after widespread vaccination against rotavirus.
SOS following short courses of 6-TG in DI is clinically distinct from SOS following prolonged courses of 6-TG in maintenance, particularly in its early presentation and outcomes.
Black and Hispanic children with acute myeloid leukemia (AML) have worse outcomes compared to White children. AML is a heterogeneous disease with numerous genetic subtypes in which these disparities have not been specifically investigated. In this study, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to examine the association of race-ethnicity with leukemia cytogenetics, clinical features, and survival outcomes within major cytogenetic subgroups of pediatric AML. Compared to White non-Hispanic patients, t(8;21) AML was more prevalent among Black (OR, 2.22; 95% CI, 1.28-3.74) and Hispanic patients (OR, 1.74; 95% CI, 1.05-2.83). The poor prognosis KMT2A rearrangement t(6;11)(q27;q23) was more prevalent among Black patients (OR, 6.12; 95% CI, 1.81-21.59). Among those with KMT2Ar AML, Black race was associated with inferior event-free survival (EFS) (HR, 2.31; 95% CI, 1.41-3.79) and overall survival (OS) (HR, 2.54; 1.43-4.51). Hispanic patients with KMT2Ar AML also had inferior EFS (HR, 2.20; 95% CI, 1.27-3.80) and OS (HR, 2.07; 95% CI, 1.09-3.93). Similarly, among patients with t(8;21) or inv(16) AML (i.e., core binding factor AML), Black patients had inferior outcomes (EFS HR, 1.93; 95% CI, 1.14-3.28 and OS HR, 3.24; 95% CI, 1.60-6.57). This disparity was not detected among patients receiving gemtuzumab ozogamicin. In conclusion, racial-ethnic disparities in survival outcomes among young people with AML are prominent and vary across cytogenetic subclasses. Future studies should explore the socioeconomic and biologic determinants of these disparities.
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