Unusual Presentation of Thrombotic Thrombocytopenic Purpura in a Newly Diagnosed Pediatric Patient With Systemic Lupus Erythematosus in the Setting of MIS-C.

The understanding of coronavirus disease 2019 (COVID-19) immune dysregulation is evolving. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with alternations in both innate and adaptive immunity, probably caused by a complex interplay of genetics and environmental exposure with various triggers. A rare hematological complication of SLE as well as recently reported in an adult with COVID-19 is thrombotic thrombocytopenic purpura. We report a pediatric case with features suggestive of the multisystem inflammatory syndrome in children with coronary artery ectasia, thrombotic thrombocytopenic purpura, and new-onset SLE.

Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation: Single-center experience from Jordan.

Bacterial infection is a serious sequela following AHSCT; however, limited data are available regarding pediatric recipients, especially in developing countries. We retrospectively analyzed the incidence and risk factors of bacterial infections during the first 100 days after AHSCT in children at KHCC in Amman, Jordan between January, 2005 and September, 2013. A total of 65 patients were identified, with median age of four yr (1-17). Forty-seven patients (72.3%) had solid tumors and 18 (27.7%) had lymphoma. Bacterial infections were documented in 33 patients (50%), with a total of 63 episodes. Gram-negative infection (57.1%) was more prevalent than Gram-positive infection (38%). The risk of bacterial infections was higher among patients less than five yr of age (p = 0.028) and those who developed hypogammaglobulinemia requiring IVIG replacement (p = 0.001). Patients with solid tumors developed more bacterial infections compared to patients with lymphoma (p = 0.0057). No deaths were attributed to bacterial infection. Bacterial infection rate is high among recipients of AHSCT in Jordan with Gram-negative bacteria being the most common.

Incidence and risk factors for cytomegalovirus (CMV) reactivation following autologous hematopoietic stem cell transplantation in children.

There are limited data on the incidence of CMV reactivation following autologous HSCT (AHSCT) in children. We retrospectively reviewed the incidence and risk factors for CMV reactivation in 72 children who received AHSCT. Twenty-two patients (31%) had positive CMV antigenemia at a median of 23 days (12-31) following transplant. Four patients (6%) required preemptive therapy and all episodes resolved. None of the patients developed CMV disease. Only being CMV seropositivity prior to transplant was significantly associated with CMV reactivation (P < 0.001). The incidence of CMV reactivation following pediatric AHSCT is low, and surveillance beyond 30 days is not needed.

Targeted Therapies in Pediatric Acute Myeloid Leukemia - Evolving Therapeutic Landscape.

Acute myeloid leukemia (AML) accounts for 25% of all leukemia diagnosis and is characterized by distinct cytogenetic and molecular profile. Advances in the understanding of the causative driver mutations, risk-based therapy and better supportive care have led to an overall improvement in survival with frontline therapy. Despite these improvements, a significant number fail either because of primary refractory disease to the conventional 7+3 combination of anthracyclines and cytosine arabinoside (Cytarabine; Ara-C) or experience relapse post remission. Salvage therapy is complicated by the cardiotoxicity driven limitations on the reuse of anthracyclines and development of resistance to cytarabine. In this chapter authors will review the recent studies with targeted agents for refractory AML including targets for immunotherapeutic strategies.

The Impact of COVID-19 on Pediatric Malignancy Diagnosis and Treatment: Never the Same but Lessons Learned.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare providers, hospital systems, and leading oncologic societies to quickly adapt and formulate new guidelines for the effective understanding, management, and treatment of patients with pediatric malignancy.

Curing childhood cancer the "Natural" Way: Nature as the source of chemotherapy agents.

For many centuries, products of natural origin from plants, marine, microbes and soil micro-organisms have been studied by numerous researchers across the world to yield many of the chemotherapeutic agents we use in this modern era. There has been a tremendous gain in knowledge from various screening and separating techniques which led to the discovery of biologically active small molecules from natural products. Preclinical studies testing the antitumor activities of these agents against tumor cell lines and xenograft animal models were the gateway to the clinical trials in humans leading to the approval of these agents that are in clinical use today. This review summarizes how various chemotherapeutic agents were discovered from products of natural origin, their preclinical development, and their indications in both pediatric and adult oncology. Many of these natural products have contributed to the very high cure rates of both pediatric leukemias and solid tumors.

Recurrent vincristine-associated fever in a child with Wilms tumor.

BACKGROUND: Fever is a common complaint among children with an underlying oncologic diagnosis, especially during chemotherapy courses and periods of neutropenia. Chemotherapy-induced fever is well described in relation to specific chemotherapy agents. However, fever induced by vincristine (VCR) has only been rarely reported. CASE: We describe a case of a 5-year-old female with stage III Wilms tumor who had recurrent VCR-associated fever that was controlled with prophylactic dexamethasone and acetaminophen. CONCLUSION: In patients developing recurrent fever following chemotherapy with VCR, febrile allergic reaction and prophylactic treatment should be considered after exhaustion of appropriate investigations.

The paradox of Myeloid Leukemia associated with Down syndrome.

Children with Down syndrome constitute a distinct genetic population who has a greater risk of developing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) compared to their non-Down syndrome counterparts. The risk for developing solid tumors is also distinct from the non-Down syndrome population. In the case of myeloid leukemias, the process of leukemogenesis in Trisomy 21 begins in early fetal life where genetic drivers including GATA1 mutations lead to the development of the preleukemic condition, transient abnormal myelopoiesis (TAM). Various other mutations in genes encoding cohesin, epigenetic regulators and RAS pathway can result in subsequent progression to Myeloid Leukemia associated with Down Syndrome (ML-DS). The striking paradoxical feature in the Down syndrome population is that even though there is a higher predisposition to developing AML, they are also very sensitive to chemotherapy agents, particularly cytarabine, thus accounting for the very high cure rates for ML-DS compared to AML in children without Down syndrome. Current clinical trials for ML-DS attempt to balance effective curative therapies while trying to reduce treatment-associated toxicities including infections by de-intensifying chemotherapy doses, if possible. The small proportion of patients with relapsed ML-DS have an extremely poor prognosis and require the development of new therapies.

Saphenous vein patch for correction of anomalous origin of the right coronary artery from the left main coronary artery.

Anomalous origin of the coronary arteries is a rare congenital heart defect that may lead to disturbed life style, myocardial infarction and sudden death. This report describes a young lady with the right coronary artery arising from the left main coronary artery, which was confirmed by coronary angiography and corrected surgically using saphenous vein patch.

The effect of pomelo mix ethyl acetate extract on CYP3A6 and P-glycoprotein gene transcripts in rabbits.

Pomelo fruit juice and pomelo ethylacetate extract have been shown to increase the bioavailability of some CYP3A substrates. The purpose of this study was to investigate if this effect might be contributed to by changes in CYP3A and p-glycoprotein mRNAs levels in the liver and proximal small intestine. The ethyl acetate extract of pomelo mix was administered for 7 days to 10 rabbits. Nine rabbits were administered tap water for 7 days. The administration was through oral intubation to the stomach. On the 8(th) day, the rabbits were sacrificed, and the liver and the proximal 15 cm of the small intestine were dissected. Total RNA was extracted from the specimens and cDNA was prepared by quantitative real-time-polymerase chain reaction (RT-PCR) using specific primers. The ethyl acetate extract of pomelo mix reduced the mRNA expression of CYP3A6 almost 5-folds in the intestine and 2-folds in the liver. In contrast, a 1-fold increase to the p-glycoprotein mRNA expression was observed under the same experimental conditions. In conclusion, the ethyl acetate extract of pomelo mix reduced the mRNA expression of CYP3A6 in both intestine and liver but to different degrees, while the p-glycoprotein mRNA expression was not reduced.

Chronic total occlusion of left main coronary artery in a young man.

Chronic total occlusion of the left main coronary artery is rarely encountered in coronary angiography. Patients are at high risk of death because of its intimate association with massive anterior myocardial infarction. A 29-year-old man with no cardiac risk factors, presented with myocardial infarction and severe mitral regurgitation. Coronary angiography revealed chronic total occlusion of the left main coronary artery. He underwent coronary artery bypass grafting and mitral valve repair.

Hypercoagulability in a newborn with concomitant homozygous factor V Leiden and severe homozygous protein C deficiency type 1.

This is a case report of a female newborn presented with skin necrotic lesions 1 week after delivery. Laboratory investigations revealed severe homozygous protein C deficiency associated with homozygous factor V Leiden, although her pregnancy and perinatal periods were otherwise uneventful, with negative family history of thrombotic or bleeding disorders. Patient stabilization was established by supportive measures and long-term administration of fresh frozen plasma and warfarin.