Pediatric Hematology Oncology Journal最新文献

Thrombotic microangiopathy (TMA) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischaemic damage. The primary mechanism involved is the occurrence of microthrombi due to deficient activity of ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, member 13). The most common types of TMA in children are Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) followed by complement-mediated (CM) TMA, Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) and hereditary thrombotic thrombocytopenic purpura (hTTP) and other rare causes. Since the outcomes are dismal if appropriate treatment is not promptly initiated, there is a need to have a high clinical suspicion. Additionally, urgently performing ADAMTS13 functional activity and autoantibody levels can help differentiate hTTP, immune thrombotic thrombocytopenic purpura (iTTP), and CM-TMA. The etiological differentiation is crucial as eculizumab is a specific therapy with exceedingly good results in CM-TMA. While plasma exchanges are required for iTTP, besides corticosteroids and/or rituximab, plasma infusions suffice for hTTP. This review focuses on the commonly encountered congenital and acquired types of TMA in children and their varied presentations while briefly touching upon the rarer disorders causing TMA.

Implementation science is a relatively young field of study and is the science of delivering evidence-based interventions into routine health care. RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) is an evaluation-type implementation science framework. CANCaRe Africa is preparing a project to assess the implementation and effectiveness of a cash incentive intervention to support families with out-of-pocket costs to prevent treatment abandonment and increase childhood cancer survival in sub-Saharan Africa. Our strategy is to enhance the dissemination of our research findings to local policymakers who can support the scale-up of evidence-based clinical interventions and locally effective implementation strategies. It can be done best by embedding implementation science into our clinical research approaches.

Gilbert syndrome is a benign condition due to UGT1A1 mutations frequently resulting in mild, indirect hyperbilirubinemia. Inherited hemolytic anemias often present with hyperbilirubinemia and hepatosplenomegaly. Over the years, there have been multiple case reports/series in which the extent of unconjugated hyperbilirubinemia exceeds the extent of anemia. When worked up for the unexplained hyperbilirubinemia, these patients were found to carry mutations corresponding to both immune hemolytic anemia as well as Gilbert syndrome. This article aims to emphasise when to suspect this coexistence and how to approach a patient with inherited hemolytic anemia with unexplained jaundice.

Inherited disorders affecting the red blood cell (RBC) membrane result from mutations in membrane or skeletal proteins. Such mutations can impede red cell deformability, leading to a shortened lifespan and early removal of erythrocytes from circulation. This, in turn, results in anemia and jaundice. Hereditary spherocytosis (HS), hereditary elliptocytosis, hereditary ovalocytosis, and hereditary stomatocytosis are examples of these disorders, with HS being the most prevalent form of inherited hemolytic anemia. Disorders of the RBC membrane may stem from structural or transport functional changes, but they inevitably lead to clinical symptoms of hemolytic anemia. Accurate diagnosis is crucial to avoid complications or inappropriate treatment as management varies depending on pathophysiology. In this review, we describe few cases of different types of RBC membrane disorders with variable age of presentation, emphasizing the significance of correct approach, limitations of certain investigations and the need for genetic test to reach a precise diagnosis.

Objectives

To provide a consensus statement describing best practices and evidence regarding the setting up Childhood Cancer Survivor Clinics in India.

Methods

Key topics regarding childhood cancer survivorship clinics were identified during a workshop conducted during the annual Pediatric Hematology Oncology conference (PHOCON) in New Delhi in November 2022. Workshop participants included oncologists, hematologists, medical social workers, representatives of non-government organizations, and childhood cancer survivors. Consensus was generated by combining expert opinion and a review of the literature.

Results

Several components regarding survivorship clinics, including the setting up of survivor clinics separate from the oncology clinic, the leading role of the treating oncologist in survivor clinics, the composition of survivor clinics and the patient pathways in the clinic, the frequency of follow-up for different survivors based on risk stratification, plans in adult survivors and the role of allied specialties like cardiologists, neurologists etc. were discussed.

Conclusion

Care of childhood cancer survivors is complex and requires a multidisciplinary approach centred around patients and their caregivers. Addressing post-treatment concerns is critical to our patient's quality of life as survival improves. There continues to be a need to define effective and efficient programs that can coordinate this multidisciplinary effort toward survivorship.

Congenital dyserythropoietic anemia (CDA) are a diverse category of heritable anemia. The causative genetic abnormalities interfere with the normal developmental process of erythrocyte maturation inside the bone marrow. As a consequence, red blood cell precursors die prematurely in the marrow (ineffective erythropoiesis) and the altered mature RBCs that reach peripheral blood have reduced survival. Due to relative rarity and resemblance to other common disorders, the diagnosis is often delayed. Apart from having symptoms related to anemia and chronic hemolysis, most of these patients suffer from complications of iron overload even if not transfusion dependent. Classically, 3 major categories of CDAs have been described (I, II, III). Other described CDA variants are rare. With easier accessibility and widespread availability of genetic testing, it is possible to make molecular diagnoses for most cases. The diagnosis can be accelerated by targeted next-generation sequencing. There's no unifying theory explaining the pathogenesis behind the disease causation. In-depth understanding at the cellular level has clarified the multifactorial pathologic process. In this review, we describe the epidemiology, pathophysiology, clinical features, and management options available for CDA. We also summarize a brief report of 17 patients with CDA diagnosed and treated at our center in the last 5 years.

This retrospective cohort study investigated racial disparities in time to treatment initiation and overall survival (OS) among 23,397 pediatric acute lymphoblastic leukemia (ALL) patients in the United States. Analyzing data from the National Cancer Database, the study revealed significant disparities among racial groups. Black patients had notably lower OS compared to White and Asian and Pacific Islander patients, with a higher hazard ratio (HR = 1.309). Spanish/Hispanic patients also exhibited lower OS and a higher HR compared to non-Spanish/Hispanic patients. These findings underscore the pressing need to address these disparities through comprehensive healthcare policy reforms, environmental regulations, and improved cultural competence within the healthcare system. Eliminating disparities in pediatric ALL incidence is essential to achieving health equity and ensuring the well-being of all children.

Background

Hypotransferrinemia is a rare cause of anemia presenting in early childhood. The clinical scenario may mimic iron deficiency anemia at onset with no response to multiple courses of hematinics. Secondary complications may be due to iron overload in the liver and other organs.

Case report

We report a rare case of congenital hypotransferrinemia in an adolescent girl who presented with microcytic hypochromic anemia refractory to iron therapy in infancy. During long-term follow-up, she developed cardiac failure due to secondary hemochromatosis, which was managed successfully with chelation therapy.

Conclusion

Hypotransferrinemia should be considered as a differential diagnosis of microcytic hypochromic anemia refractory to iron therapy in infancy. Regular follow-up and monitoring are essential to look for evidence of iron overload and optimize chelation therapy to prevent complications.

Background

The gonadotoxic effects of chemotherapy are critical concerns in Pediatric Oncology, given most patients survive their cancer. Future fertility is an important concern in this population, supporting the need for additional research on chemotherapy gonadotoxicity. This study's purpose was to identify associations with premature ovarian insufficiency (POI) in pediatric and young adult female cancer survivors with age at cancer diagnosis, cancer type, and cyclophosphamide equivalent dose (CED).

Methods

We retrospectively collected data on pediatric patients with cancer treated between 2008 and 2017. Inclusion criteria included female gender, age 0–25 y at the time of cancer diagnosis, prior treatment with chemotherapy, and documented ovarian hormone levels following chemotherapy completion.

Results

Two-hundred and forty-five female patients were identified, of whom 57 had documented ovarian hormone levels following chemotherapy. Five patients (9 %) met the criteria for POI. All of the 5 patients were ≥13-years-old at cancer diagnosis and had lymphoma or solid tumor. While there was statistical significance with older age and presene of POI, there was not when comparing tumor type and POI. The 5 patients with POI received a CED between 0 and 28.4 gm/m² demomstrating against a dose-dependent relationship.

Conclusion

Age ≥13 years at cancer diagnosis and a diagnosis of lymphoma/solid malignancy are predictors of POI in children, adolescents, and young adults., A wide range of CED amongst patients with POI suggests the presence of other factors contributing to ovarian dysfunction.