TITLE PAGETitle: Comment on: evaluating age and sex-specific rates of gall bladder disease in children with sickle cell diseaseArticle type: Letter to the editorCorrespondence : 1. Ifra Eeman Ahmed contact : 03335890003 Email : firstname.lastname@example.orgInstitution : Federal medical & dental college,IslamabadAddress: House#2,Street#15g,Sector A,Bahria Enclave,IslamabadCo-author : 2. Satesh KumarContact: +92-3325252902 Email:Institute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa citi Garden east, KarachiWord count: 391Conflict of interest : NoneDeclaration : NoneAcknowledgment : None
Daratumumab induced Minimal Residual Disease Negative Remission in CD 38 (dim) Positive Pediatric Acute Myeloid LeukemiaPronamee Borah1, Dinah Ng1, Nitin Dayal2, Sangeeta Pathak3, Rahul Naithani11Hematology and Bone Marrow Transplant Division, Max Superspecialty Hospital, Delhi, India2Department of Lab Medicine, Max Superspecialty Hospital, Delhi, India3Department of Transfusion medicine, Max Superspecialty Hospital, Delhi, IndiaConflicts of interest: None to declare.No financial support was obtained in this study.Text word count 815Brief running title: Daratumumab in Pediatric AMLKey Words: Daratumumab, AML, ChildrenTables: 0; Figures: 0
A 19 year-old adolescent girl with Dravet syndrome, characterized by complex seizure disorder and global developmental delay, presented with B-cell acute lymphoblastic leukemia. The genetic basis for her Dravet syndrome was a pathogenic variant in SCN1A, a sodium channel subunit. SCN1A is chiefly expressed in neuronal tissue, but bioinformatic analysis demonstrated its presence in B cell lineage. One estimate suggested that 10% of children with pediatric cancer have a germline predisposition involving proto-oncogenes or tumor suppressors. This number might be even higher should non-classical genetic variants, such as that encoding a sodium channel subunit, be considered.
Severe autoimmune lymphoproliferative syndrome phenotype in a pediatric patient with a germline FAS gene variant Authors: Alexandra Dreyzin MD MS1; Jinjun Cheng MD PhD2, David Leitenberg MD PhD3, and Yaser Diab MBBS1Center for Cancer and Blood Disorders, Children’s National Hospital, Washington, DCDivision of Pathology and Laboratory Medicine, Children’s National Hospital, Washington, DCDepartment of Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Title : Comment on: [Lost at Sea in Search of a Diagnosis: A Case of Unexplained Bleeding]Subtitle : Scurvy from chemotherapy-induced adverse effects in an adolescent oncology patientAuthors : Michelle Toker, BS and Benedict Wu, DO, PhDAffiliation : Division of Dermatology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USACorresponding author :Michelle TokerAlbert Einstein College of Medicine, Montefiore Medical CenterEmail: email@example.comTelephone: 516-946-4726Funding and support : NoneConflicts of Interest : NoneManuscript word count : 452Reference count : 6Figure count : 1Table count : 0Key words : chemotherapy, oncology, pediatrics, nutritional deficiency, vitamin C deficiency, scurvyDear Editor,The brief report published by Amos et al in 2016 shed light on the occurrence of scurvy in pediatric and adolescent patients with dietary restrictions.1 Indeed, patients with neurodevelopmental conditions are most commonly associated with the risk of developing scurvy; other at-risk patients include those with gastrointestinal disorders, alcoholism, and psychiatric conditions.2, 3 We aim to expand upon the situations when scurvy should be considered by presenting a case of an adolescent male diagnosed with scurvy secondary to the adverse effects of his chemotherapy.A 19-year-old male with a 10-month history of high-risk pre-B-cell acute lymphoblastic leukemia was consulted by the dermatology service for a new diffuse rash present for four days. He was recently enrolled in a phase 3 randomized trial of inotuzumab ozogamicin and was receiving methotrexate and vincristine. The chemotherapy regimen induced severe dizziness, nausea, and vomiting refractory to anti-emetic medications. His aversion to chemotherapy was so strong that it caused him to feel nauseated between treatment sessions. He also endorsed painful oral and pharyngeal sores that made it difficult to tolerate a regular diet. In addition to oropharyngeal pain, he experienced marked arthralgia and fatigue, which he also attributed to the chemotherapy. Additionally, the patient reported that vincristine reduced his taste sensation, which led to a poor appetite. These adverse symptoms culminated in a loss of 6.7 kg (9.1%) in less than one month.Physical examination revealed peri-follicular purpura on the back (Fig 1A), face, and bilateral upper and lower extremities. Upon closer inspection, we noted prominent corkscrew (spiral and curly appearance) hairs (Fig 1B). The lower mucosal lip had superficial erosions with scalloped-borders and fine petechiae (Fig 1C). Laboratory evaluation revealed pancytopenia with a platelet count of 42 k/UL and low serum levels of vitamin C (<0.1 mg/dL), potassium (3.4 mEq/L), magnesium (1.1 mg/dL), and albumin (2.8 g/dL). Serum vitamin A (35 mcg/dL) levels were within normal limits. The patient was diagnosed with scurvy due to poor food intake from his chemotherapy-induced nausea, emesis, and mucositis. It was thought that acidic foods, such as citrus, exacerbated the mucosal erosions, which caused him to avoid vitamin C-rich foods.Scurvy, caused by a prolonged L-ascorbic acid (vitamin C) deficiency, may manifest as pathognomonic corkscrew hairs with petechiae, gingival pain and bleeding, vascular fragility, arthralgias, fatigue, and numerous gastrointestinal symptoms.4,5, 6 Although vitamin C deficiency was an indirect result of his chemotherapy, scurvy, by itself, may have aggravated his symptoms, thereby creating a vicious cycle of poor oral intake. Our case highlights the complex relationship between chemotherapy-induced mucocutaneous adverse effects, a limited diet, and vitamin C deficiency. We recommend clinicians to consider scurvy in oncology patients, with or without thrombocytopenia, presenting with peri-follicular purpura and corkscrew hairs.Ethics Statement: Informed patient consent was obtained for publication of the case details and photographs.
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder due to mutations in the TYMP gene. Clinical findings are characterized by neurologic manifestations and severe gastrointestinal dysfunction. The syndrome is usually fatal, the most effective treatment appears to be hematopoietic stem cell transplantation (HSCT). Aim:In this retrospective study, we evaluated HSCT that was performed using a reduced toxicicity myeloablative conditioning regimen in patients with MNGIE at our center. Results: A total of 6 allogeneic transplant procedures were performed in 4 patients. Three patients’ donors had fully matched donors, and one patients’ donor was haploidentical. Treosulfan-based myeloablative conditioning regimen was applied in 5 of 6 transplants. Bone marrow was used as a stem cell source. One patient is being followed up in the 4th year of posttransplant with full chimeric and without Graft versus host disease (GVHD). One patient died of acute stage IV GIS GVHD. Two patients underwent second transplantation due to engraftment failure, one of which was the patient who had a haploidentical transplant. Conclusions: Treosulfan-based regimen is well tolerated. Engraftment failure with this conditioning regimen can be a significant problem. We share our haploidentical transplant experience, which will be the first reported case in the literature.
Background: Pain is the clinical hallmark of sickle cell disease (SCD) leading to hospitalization, psychological sequelae and a decreased health-related quality of life. The aim of this systematic literature review is to evaluate the efficacy of non-pharmacological interventions in reducing sickle cell-related pain in children with SCD. Methods: A comprehensive literature search up until October 2022 was performed to identify studies that investigated the efficacy of non-pharmacological interventions on (1) pain frequency and/or intensity, and (2) analgesic and health service use in children with SCD. Randomized controlled (RCTs) trials and quasi-experimental designed (QED) studies that investigated non-pharmacological interventions for pediatric patients with SCD until the age of 21 years were considered for inclusion. Results: Ten articles (5 RCTs and 5 QED studies) with 422 participants were included. They investigated cognitive behavioral therapy (CBT) (n =5), biofeedback (n=2), massage (n=1), virtual reality (n=1) and yoga (n=1). CBT, biofeedback, massage, virtual reality and yoga significantly reduced frequency and/or intensity of SCD-related pain. Biofeedback also significantly reduced analgesic use. Conclusion: Non-pharmacological interventions may be effective in reducing pain in pediatric SCD patients. However, due to the heterogeneity of the included studies a quantitative analysis could not be performed. Awaiting further supporting evidence, healthcare providers should consider implementing these interventions as valuable part of a comprehensive pain management strategy plan to improve the outcome of sickle cell-related pain.
Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by defective DNA repair, leading to hypersensitivity to ultraviolet (UV) sunlight and predisposes to various cutaneous and non-cutaneous malignancies. Platinum compounds are used against cutaneous cancers as concurrent chemoradiotherapy. But the XP gene polymorphism has a potential role in metabolism of these agents and their susceptibility. Here, we report a case of cutaneous squamous cell carcinoma in a patient with XP who had severe toxicity to chemotherapy. We also discuss other similar cases reported in literature of this entity, to highlight this potentially lethal pharmacogenomic association.
CD19-directed chimeric antigen receptor T lymphocytes (CAR-T) have led to durable remissions in children with refractory and/or multiply relapsed B-lymphoblastic leukemia. For those who relapse or lose B-cell aplasia post-CAR-T, the role of CAR-T reinfusion is unclear. We report a case of durable remission with tisagenlecleucel reinfusion despite failure to achieve B-cell aplasia and compare this case to seven additional children who received multiple tisagenlecleucel infusions at our institution. Our experience suggests that reinfusion is safe and may be a definitive therapy for a small subset of patients. Reinfusion can also reintroduce remission and/or B-cell aplasia, allowing for subsequent therapies.
Hemophagocytic lymphohistiocytosis (HLH) is an uncommon immunologic disorder associated with high rates of morbidity and mortality characterized by systemic inflammation and multiorgan dysfunction. The standard of care for primary treatment of HLH is chemotherapy (i.e. etoposide), but consideration of alternative therapies is warranted to support treatment goals for critically ill pediatric patients. We present the case of a 7-year-old male with trisomy 21, acute multiorgan failure secondary to infection, and subsequent HLH who was successfully treated with ruxolitinib. This represents the first use of ruxolitinib as a first-line agent for secondary HLH in a critically ill child with trisomy 21.