Pediatric Hematology and Oncology最新文献

Idiopathic pneumonia syndrome (IPS) is a serious complication following allogeneic hematopoietic cell transplantation (HCT), often treated with methylprednisolone (mPSL) pulse therapy. However, treatment responses vary. This study aimed to identify predictors of poor response to mPSL monotherapy. Among 289 patients who underwent allogeneic HCT, 25 developed IPS and received mPSL pulse therapy. Clinical responses were categorized as complete (CCR), partial (PCR), or no response (NR), based on oxygen requirements within 28 days. We compared baseline characteristics of responders (CCR: n = 5; PCR: n = 6) and non-responders (NR: n = 14). Univariate analysis revealed that IPS onset on day +73 or later (p = 0.033), reduced intensity conditioning (p = 0.033), use of total body irradiation (p = 0.049) or fludarabine (p = 0.042), and nonuse of busulfan (p = 0.049) in preparative regimens were associated with poor response. Multivariate analysis identified a longer time from transplantation to IPS onset as a significant predictor of poor response (Odds Ratio 1.017 per 1-day increase; 95% CI 1.007-1.036; p = 0.045). The present study may provide valuable insights into how the responsiveness to mPSL varies depending on the time of IPS onset. Alternative therapeutic strategies may be needed for patients with late-onset IPS.

Sickle cell anemia (SCA) is associated with a high prevalence of cerebrovascular complications, such as ischemic stroke, particularly at young ages. Among various molecules, vitamin D has been implicated in stroke occurrence. By binding to the vitamin D receptor (VDR), vitamin D regulates several mechanisms, potentially influencing pathways involved in the pathophysiology of cerebral vasculopathy. Here, we evaluated the association between VDR gene polymorphisms and 25-hydroxyvitamin D (25(OH)D) levels with CVD in a cohort of patients with SCA. The frequency of CVD and laboratory data were retrospectively obtained from the medical records. Genotyping for the functional FokI (rs2228570) and Cdx-2 (rs11568820) VDR polymorphisms was performed in 459 unrelated SCA patients. 25(OH)D levels were measured in a subset of 45 patients. The TT genotype of the FokI VDR polymorphism was associated with a higher frequency (OR: 2.82; 95% CI: 1.38-5.76, p = 0.006) and higher cumulative incidence (34% vs 16%, p = 0.001) of CVD compared to the other genotypes. Among patients under hydroxyurea (HU) therapy, individuals with the TT-FokI genotype (median: 13.9 ng/mL) had lower 25(OH)D levels compared to those with CC/CT genotypes (median: 20.2 ng/mL; p = 0.033). Similarly, patients with CVD and the TT-FokI genotype (median: 12.3 ng/mL) had reduced 25(OH)D levels compared to CC/CT carriers (median: 20.8 ng/mL; p = 0.034). These findings suggest that the FokI VDR polymorphism may serve as a potential genetic modulator of cerebrovascular complications in individuals with SCA.

Hypoalbuminemia and cancer cachexia predict poor survival in adult cancers, with limited studies in pediatrics. Also, the serial recovery kinetics of serum albumin and its effect on cancer outcomes are unknown. This study investigated trends and determinants of serum-albumin at various time points of therapy and their influence on 3-year survival of pediatric cancers. It included cancer patients below 18yrs. Baseline systemic symptoms, stage/risk-group, nutritional status and serum-albumin at baseline, 3-months, 6-months and 12-months were recorded from hospital database along with outcomes like relapse/death and toxicity. Among 402 patients, hemato-lymphoid cancers (57.71%)were more common. Prevalence of hypoalbuminemia at baseline, 3 m, and 6 m was 46.52%, 26.45% and 22.0%, respectively. Patients with hypoalbuminemia at baseline (HR = 2.1; p = 0.000), 3 m (HR = 2.28; p = 0.000), or 6 m (HR = 2.02; p = 0.001) had lower overall-survival (OS) in univariate analysis, while on multivariate analysis, only risk group (HR = 1.74; p = 0.009) and 6 m albumin (HR = 3.33; p = 0.001) independently predicted OS. For event-free-survival (EFS) risk-group (HR = 1.59; p = 0.018) and 6 m-albumin (HR = 2.91; p = 0.001) were the only independent predictors. Out of various predictors of serum albumin, systemic-symptoms (OR = 8.01, p = 0.008) and baseline-malnutrition (OR = 2.08; p = 0.004) independently predicted baseline-hypoalbuminemia. Organomegaly measured as liver/spleen size(r=-0.39) and systemic inflammation measured as serum-globulin (r=-0.37) had negative correlation with baseline-albumin. In contrast, 6-month albumin was dependent only on baseline systemic symptoms (OR = 5.28; p = 0.007) and independent of baseline malnutrition (OR = 1.72; p = 0.091). We conclude that while baseline albumin is influenced by multiple factors, such as malnutrition, systemic symptoms, inflammatory state (hypergammaglobulinemia), and disease bulk (organomegaly), 6-month albumin is independent of baseline malnutrition and serves as a better predictor of the cancer-inflammation-cachexia-cascade and ultimate survival.

Pediatric Hodgkin lymphoma (HL) treatment has increasingly shifted toward response-adapted protocols, aiming to minimize radiotherapy and employ intensive chemotherapy such as OEPA/COPDAC. We retrospectively reviewed treatment outcomes and toxicities in pediatric HL patients treated with OEPA/COPDAC between 2015 and 2019 at a tertiary care center in Pakistan, a resource limited country, following the Euronet PHL-C1 protocol with radiotherapy reserved for inadequate interim responses. Clinical features, treatment-related toxicities, and hospital admissions were documented. The cohort included 20 patients with a median age of 12 years; 13 (65%) achieved complete remission after OEPA induction and avoided radiotherapy. Toxicities were frequent-15 (75%) after OEPA-1 and 13 (68%) after OEPA-2-most commonly gastrointestinal symptoms and febrile neutropenia. Hospitalization was required in 9 (45%) after the first cycle and 11 (58%) after the second, with one treatment-related death from febrile neutropenia. At median follow-up, overall survival was 95% (95% CI: 69.47-99.28%) and event-free survival was 85% (95% CI: 60.38-94.90%). These findings highlight that OEPA/COPDAC achieves high survival rates even in advanced-stage pediatric HL within low-resource settings. However, the substantial toxicity burden and frequent hospitalizations underscore the need for enhanced supportive care and further evaluation in larger, long-term studies.

The overall incidence of core binding factor acute myeloid leukemia (CBF-AML) in pediatric patients has been reported to be 19%-44.3%. However, the prognostic role of KIT mutations in pediatric CBF-AML remains controversial. This study aimed to investigate whether incorporating KIT mutation status into risk stratification improves long-term outcomes. A total of 114 pediatric CBF-AML patients treated under BCH-AML 2005 protocol and CCLG-AML 2015 protocol were enrolled. KIT mutations were identified using Sanger sequencing, classified as high-risk in CCLG-AML 2015. Relationships between clinical and biological features, outcomes and KIT mutations were evaluated across genetic subgroups. KIT mutations were identified in 25.4% pediatric CBF-AML, with comparable mutation rates in RUNX1::RUNX1T1 and CBFβ::MYH11 subgroups. Patients with KIT mutations showed higher leukemia burdens, including increased bone marrow blasts and white blood cell (WBC) indices. RUNX1::RUNX1T1 subgroup showed poorer 5-year OS than CBFβ::MYH11. Patients with KIT^mut17+ exhibited significantly lower OS, EFS compared to those with KIT^mut8+ and KIT^wt. Notably, RUNX1::RUNX1T1⁺KIT^mut17+ patients exhibited significantly worse OS among genetic subgroups but achieved improved OS under CCLG-AML 2015. KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.

Late effects are a major concern after pediatric hematopoietic stem cell transplantation (HSCT), but data on health outcomes beyond early adulthood remain scarce. This study assessed long-term morbidity and mortality in one of the earliest childhood cancer cohorts treated with HSCT. The study comprised 52 male childhood cancer survivors (survival ≥5 years), treated with HSCT in 1983-2001 at a median age of 6.1 years, and 257 matched population controls. Finnish national healthcare registries provided data on prescription drug purchases, reimbursements for chronic diseases, hospitalizations, and late mortality. Median follow-up was 24.9 years. Compared to population controls, survivors had increased risk for diabetes (HR 16.4, 95% CI 4.33-61.8), severe hypertension (HR 11.4, 95% CI 3.42-37.8), purchases of lipid-lowering drugs (OR 13.5, 95% CI 4.87-41.3), and purchases of antihypertensives (OR 2.58, 95% CI 1.28-5.12). HSCT survivors had also higher risk for hospitalizations due to cardiovascular diseases (HR 6.13, 95% CI 1.52-24.7) and neurological conditions (HR 4.79, 95% CI 1.73-13.2). New diagnoses of epilepsy and secondary neoplasms emerged beyond 20 years post-transplantation. Chronic graft-versus-host disease was associated with increased purchases of thyroxine, growth hormone, and lipid-lowering drugs. Given the high risk for diabetes, hypertension, and dyslipidemia, proactive cardiovascular risk assessment is essential in long-term care after pediatric HSCT. The occurrence of late-onset complications underscores the importance of structured lifelong follow-up.

Neuroblastoma (NBL) is a tumor that develops from sympathetic ganglia and most frequently occurs in young children. In mediastinal and cervical cases, Horner syndrome (HS) may occur as a symptom or a surgical complication. The study aimed to evaluate the factors that influence the occurrence of postsurgical HS. The data concerning the clinical presentation, imaging examinations, performed therapies and treatment outcomes of 454 children with NBL were collected, including 117 cases of thoracic and cervical tumors. The statistical analyses of correlations between postsurgical HS occurrence and different features was performed. HS appeared in 57.89% of patients with tumors adjacent to oculosympathetic pathway. Statistical analyses demonstrated a significant impact of tumor location, patients' age and the duration between the onset of symptoms and the diagnosis on HS incidence as a complication of NBL resection. Neoadjuvant chemotherapy was also associated with a lower incidence of postsurgical HS. The radicality of surgery, the time from diagnosis to the procedure and the used technique did not present any statistically significant association with the occurrence of HS. In conclusion, parents of patients should be informed about the risk of HS in every case of a tumor localized near the oculosympathetic tract. Neoadjuvant chemotherapy might help reduce the risk of postsurgical complications.

Hematopoietic stem cell transplantation (HSCT) is a therapeutic modality for pediatric malignancies and inherited and acquired hematological, immunological, and metabolic disorders. The efficacy of HSCT depends on many factors, including conditioning regimens, which are critical for eradicating malignant cells, suppressing the immune system to prevent graft rejection, and establishing an optimal microenvironment for engraftment.Conditioning methodologies have evolved from high-dose chemotherapy and total body irradiation to refined approaches that mitigate toxicity while maintaining their efficacy.The relationship between the conditioning regimen and donor selection influences short- and long-term transplant outcomes and minimizes adverse sequelae.With advances in molecular medicine, there is growing interest in chemotherapy-free conditioning protocols that leverage biological mechanisms to facilitate stem cell acceptance and minimize risks.The concept of "the art in the science" captures the intricate balance and decision-making essential for applying scientific principles to pediatric HSCT conditioning.Personalized medicine, expertise in regimen selection, and ethical considerations are key aspects of this approach.Examples include the customization of conditioning protocols, reduced-intensity conditioning, pharmacogenomics in personalized treatment, precision in drug sequencing and dosing, and innovations in serotherapy and chemo-free conditioning.We discuss historical perspectives, scientific foundations of conditioning, the role of radiation and serotherapy, and the potential shift toward chemo-light and chemo-free approaches.This review explores HSCT conditioning in pediatric patients, examining the scientific underpinnings and expertise required for protocol adaptation, challenges in resource-constrained environments, and evolving clinical demands.

This study aims to investigate sexual activity, focusing on partner sex, in young adult survivors of childhood cancer in comparison to the general population. Furthermore, the study seeks to identify factors among the survivors associated with never having had partner sex. A population-based observational survey study was conducted with adult (aged 19-40) survivors of childhood cancer (n = 2545) and a comparison group from the general population (n = 819). Multivariable logistic regression analyses, stratified by gender, were performed to examine sociodemographic, clinical and psychological factors associated with never having had sex with another person. In comparison to the general population, survivors exhibited lower levels of sexual activity with a partner during the past month (women: 78% vs. 65%, p < 0.001; men: 62% vs. 56%, p = 0.031). A small proportion of survivors reported never having engaged in partner sex, with men reporting this to a greater extent than women (14% vs. 7%, p < 0.001). Factors associated with never having had partner sex included younger age at study, no current occupation and prior cranial irradiation. Additionally, men who self-reported depressive symptoms and women who had undergone hematopoietic stem cell transplantation were more likely to have never engaged in sexual activity with a partner. In conclusion, young adult survivors of childhood cancer have partner sex to a lesser extent than peers. Intensive cancer treatment was related to never having engaged in partner sex. These findings highlight the need for health care professionals to actively address sexuality during surveillance to support sexual health and well-being.

Febrile neutropenia (FN) is a common complication in pediatric oncology patients that typically necessitates hospitalization for intravenous antibiotics, resulting in significant use of hospital resources and decreased patient and family quality of life. Recently several centers have published early discharge guidelines for patients with low-risk FN, but this has not yet been reported at large tertiary centers with high acuity. Here we describe implementation of a low-risk early discharge FN guideline at our tertiary cancer center with resulting decrease in median length of stay (2.39 days saved per early discharge encounter) and no adverse events, including sepsis or infection-related mortality.