Pediatric Blood & Cancer最新文献

Background: Sickle cell disease (SCD) is one of the most common inherited blood disorders worldwide, disproportionately affecting populations in sub-Saharan Africa, India, the Middle East, and the Caribbean. Despite scientific advances in diagnostics, treatment, and emerging curative options, progress toward reducing the global burden of SCD remains hindered by fragmented efforts, inequities in access, and limited health system integration. Global partnerships are increasingly recognized as essential for fostering collaboration, aligning priorities, and ensuring that resources are deployed efficiently.

Methods: This narrative review synthesizes evidence from peer-reviewed literature, global health reports, and case studies of international and regional initiatives to examine the role of partnerships in advancing public health responses to SCD. Particular attention is given to screening, treatment access, advocacy, community engagement, and policy integration, with examples drawn from Africa, the Americas, India, and the Caribbean.

Results: Global partnerships have demonstrated significant contributions to SCD control, including the expansion of newborn screening programs, improved access to hydroxyurea, enhanced blood transfusion safety, and advocacy-driven policy reforms. Collaborative platforms such as the World Coalition on Sickle Cell Disease, the Consortium on Newborn Screening in Africa (CONSA), and regional networks in the Caribbean and India illustrate how coordinated efforts can reduce redundancy and improve outcomes. However, gaps remain in global coordination, data-sharing, sustainable financing, and integration with broader maternal and child health programs. Practical strategies identified include the establishment of a Global Coordinating Council on SCD, development of a global data-sharing framework, creation of regional hubs, and funding alignment mechanisms.

Conclusion: Global partnerships are pivotal in moving toward a generation free from the burden of SCD. By fostering unity, reducing duplication, and ensuring equitable access to innovations, these collaborations provide a pathway for sustainable public health advancement. Achieving this vision requires a coordinated global framework that combines leadership, policy commitment, community engagement, and shared responsibility across all sectors.

Background: Children with transfusion-dependent thalassemia (TDT), also known as thalassemia major, require monthly blood transfusions and regular iron chelation therapy for long-term survival. While the burden of caring for these children is recognized, little has been done to address the parents' experience.

Procedure: A 38-item parent self-report was included in the previously designed disease-specific tool, the transfusion-dependent quality-of-life questionnaire (TranQol), to identify the issues they may be facing. We wanted to ensure that the self-report was reliable and valid. Questionnaires were given to parents during their children's routine clinic visits as part of a multi-center North American study of the TranQol. Construct validity was assessed using Pearson's correlation with the Pediatric Quality of Life (PedsQL) Family Impact Module (FIM) (hypothesis: correlation of 0.4-0.6).

Results: Sixty-seven parents completed both the TranQol and PedsQL Family Impact Module questionnaires at baseline. There was substantial correlation (r = 0.76) between TranQol parent self-report scores (median 63, interquartile range [IQR]: 53-76) and PedsQL Family Impact Module scores (median 77, IQR: 59-89).

Conclusions: The median PedsQL FIM score was similar to previously reported scores for parents of children with sickle cell disease. The TranQol parental burden tool demonstrated construct validity was internally reliable (Cronbach's α = 0.94) and had acceptable test-retest reliability (intraclass correlation coefficient [ICC] = 0.81), for future research into TDT. In addition, this tool could also be used to help clinicians assess the impact of the disease on parents to potentially target appropriate support and care that is required.

Background: Uveal melanoma is the most common malignant primary intraocular tumor in adults, associated with high mortality. Pediatric uveal melanoma generally has a more favorable course. However, when metastasis occurs, therapeutic options are limited.

Design: Clinical presentation, treatment, and outcome of children with uveal melanoma diagnosed in Germany and Austria between 2013 and 2024 were analyzed.

Results: Since 2013, 12 children were diagnosed with uveal melanoma in Germany and Austria-nine in the choroid, three in the ciliary body, and iris. Treatment comprised enucleation (five patients), external beam radiation with protons (two patients), ocular brachytherapy (four patients), and endoresection (one patient). Two patients developed metastasis. A 17-year-old male with liver metastasis died 30 months after diagnosis. A 3-year-old male with metastatic choroidal melanoma presented with metastasis 6 months after enucleation. Chemotherapy followed by nivolumab and ipilimumab led to a complete response. However, immunotherapy caused insulin-dependent diabetes mellitus. Genetic testing revealed a pathogenic constitutional TP53 variant, confirming Li-Fraumeni syndrome (LFS). At 24 months after diagnosis of metastatic disease, he remains in complete response.

Conclusions: This report underscores the rarity and diverse presentation of pediatric choroidal melanoma. Diagnosis of LFS in one patient highlights the importance of genetic testing for tumor predisposition and personalized approaches in managing rare pediatric tumors.

Background: Patient and caregiver perspectives are becoming more commonly represented in medical literature, though they are not always present for rare conditions, such as Langerhans cell histiocytosis (LCH). This study was performed to explore patient and parental perspectives regarding treatment, psychosocial support, and unaddressed healthcare needs in children diagnosed with LCH.

Methods: Four focus group discussions (FGDs) were held with six adolescents with LCH, as well as eight caregivers. Participants were recruited from a single tertiary pediatric academic medical center. Native English speakers representing recurrent and non-recurrent disease were included using consecutive sampling recruitment. FGDs were designed to elicit thematic factors experienced at diagnosis, during treatment, and during surveillance for LCH. Key themes and concepts were identified and classified using the methodological orientation of grounded theory. The cross-platform application Dedoose was used to analyze the qualitative data.

Results: Seven major themes were identified: (1) the impact of LCH diagnosis and treatment on one's education and school experience; (2) the impact of the medical and healthcare system on one's experience; (3) the need for support and information for families; (4) the impact of LCH on family dynamics; (5) lack of knowledge and understanding before and after diagnosis; (6) emotional responses and coping strategies; and (7) communication challenges related to its lack of classification as a cancer.

Conclusions: These patient and caregiver perspectives provide opportunities to improve the experience of individuals with LCH throughout diagnosis, treatment, and surveillance. These accounts should be heavily considered when developing, altering, or customizing treatment plans for patients with LCH moving forward.

Whether children with acute lymphoblastic leukemia (ALL) living in household poverty are at an increased risk of obesity remains unknown. We address this gap using data from Children's Oncology Group study AALL03N1. Study participants reported annual household income, which was used to categorize poverty from year-specific US Census Bureau thresholds. Obesity was determined using height and weight at study enrollment. Multivariable logistic regression demonstrated 1.5-fold greater odds of obesity (95% confidence interval = 1.0-2.3, p = 0.04) among children with ALL living in poverty. These findings identify a vulnerable group at risk of obesity.

Background: Anthracyclines are among the most effective chemotherapeutic agents used to treat pediatric malignancies. However, their clinical use is limited by dose-dependent toxicities, particularly cardiotoxicity and secondary malignancies. Aclarubicin (Acla) is an anthracycline derivative that induces chromatin damage while sparing DNA damage, offering potential therapeutic benefit with reduced long-term toxicity.

Methods: We evaluated the anti-tumor efficacy and safety profile of Acla in multiple in vitro pediatric cancer models and in vivo mouse models designed to mimic anthracycline re-treatment following prior doxorubicin (Doxo) exposure. Tumor growth, genotoxic stress, survival, and organ toxicity were assessed.

Results: Acla demonstrated robust anti-tumor activity comparable to Doxo across diverse pediatric in vitro models. Unlike Doxo, Acla treatment did not induce significant genotoxic stress. In vivo, mice receiving Acla after Doxo exposure showed no evidence of cumulative cardiotoxicity or end-organ damage. In contrast, a second course of Doxo led to significant toxic mortality but was surprisingly not attributable to classic cardiac injury.

Conclusion: Our study highlights Acla as a promising anthracycline derivative for pediatric cancers, with potent anti-tumor efficacy and a superior safety profile, even following prior anthracycline exposure. These results support continued investigation of chromatin-damaging anthracyclines that can kill pediatric cancer cells without inducing genotoxic stress. In addition, our studies underscore the need to refine preclinical models to better understand both acute and chronic anthracycline toxicities in pediatric and adolescent populations.

Communicating with primary care providers (PCPs) could improve rates of childhood cancer survivors who receive guideline-recommended survivorship care. We aimed to assess the feasibility and acceptability of an interactive, structured telephone handoff between a nurse coordinator and PCP clinics about survivorship care needs of shared patients who were ≥2 years post-treatment and had attended the survivorship clinic. A nurse coordinator successfully contacted 40 (87%) of 46 PCP clinics for a brief (median 5 min, range, 4-11) handoff, all of whom rated the call helpful. Research is needed to better assess the impact of this handoff on the receipt of survivorship care.

Background: Adverse childhood experiences (ACEs) are stressful or traumatic events prior to age 18 that are known to have a lasting impact on individuals' health and well-being. There is a gap in understanding the relationship between ACEs and Other Life Stressors and health status for adults with sickle cell disease (SCD). We examined the impact of adversities within clinical and behavioral health domains that have been associated with ACEs for other populations.

Procedure: Sociodemographics; medical history; patient-reported outcomes, including pain and emotional distress; and reports of de-identified ACEs and Other Life Stressors, were collected from n = 553 participants enrolled in the Sickle Cell Disease Implementation Consortium Registry.

Results: Participants were a median age of 28 years; 57% female; 95% Black/African American; 55% annual household income ≤$25,000; primarily diagnosed with sickle cell anemia (SS or Sβ⁰ thalassemia: 69.6%). Adults with SCD evidenced a high prevalence of exposure to adversity (28.3% reporting four or more ACEs), significantly higher than general or Black/African American populations (p < 0.001). Adjusting for age, gender, SCD genotype, annual household income, and disease-modifying therapy, we found a graded effect for categories of original ACEs (one to three, and four or more), with progressively greater odds of being diagnosed with asthma with increasing ACEs (p <0.0001), as well as for "ever been treated for depression" (p < 0.05).

Conclusions: Our findings support the need for consistent screening for ACEs in adults with SCD and highlight the importance of trauma-informed care approaches to improve clinical and behavioral outcomes and quality of life.

Myeloid/NK cell precursor leukemia (MNKPL) is a rare, aggressive entity often misdiagnosed as acute myeloid leukemia (AML) or aggressive NK cell leukemia (ANKL) because of overlapping markers (CD7⁺, CD13/CD33⁺, CD56⁺, myeloperoxidase [MPO]-). We report a patient initially diagnosed with ANKL; subsequent flow-cytometric reevaluation (CD7⁺, CD13⁺, CD33⁺, CD34⁺, CD56⁺, CD117⁺, MPO^-) supported a diagnosis of MNKPL. RNA sequencing and nested PCR identified an in-frame ZMYND11::MBTD1 fusion. A review of published ZMYND11::MBTD1 leukemias (n = 5) found immunophenotypes highly consistent with MNKPL, suggesting prior misclassification. These findings support ZMYND11::MBTD1 as a recurrent lesion in MNKPL and a practical aid to diagnosis and treatment selection.