Burden beyond the cure: Iron overload following pediatric stem cell transplantation.

Iron overload (IOL) is an increasingly recognized complication among pediatric and young adult survivors of hematopoietic stem cell transplantation (HSCT) contributing to significant morbidity and mortality. The pathogenesis of IOL post-HSCT is multifactorial, driven by transfusion burden, impaired erythropoiesis, and increased gastrointestinal iron absorption, leading to toxic non-transferrin bound iron accumulation and oxidative tissue injury. Despite its clinical significance, consensus guidelines for the diagnosis, monitoring, and management of IOL in this population remain limited.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part III. Long-Term Impact of Chronic Graft-versus-Host Disease on Endocrinologic, Cardiovascular, and Metabolic Outcomes in Survivors of Pediatric Hematopoietic Cell Transplantation.

Chronic graft-versus-host disease (cGVHD) has a profound impact on the endocrinologic and cardiovascular health of survivors of transplantation performed in childhood. The impact of cGVHD is long-lasting and contributes to morbidity and early mortality through multiple mechanisms. Organs and tissues may be direct targets of alloreactive donor-derived immune cells.

Barriers to Receiving Follow-up Care Among Childhood Cancer Survivors.

Little is known on why adherence to follow-up care in childhood cancer survivors (CCS) is lacking. This study characterized barriers to adherence to follow-up care among CCS, identified sociodemographic correlates of barriers, and examined whether barriers to follow-up care relate to health-related quality of life. Adult CCS (N=84) were anonymously surveyed via REDCap using the Barriers to Care Questionnaire (BCQ) and the Quality of Life Scale-Cancer Survivor (QOL-CS).

Severe Coronavirus Disease 2019 Infection in an Adolescent Patient After Hematopoietic Stem Cell Transplantation.

Infection with the severe acute respiratory syndrome coronavirus 2 causes severe acute lung injury in approximately 5% of infected adults, but few reports have been made of severe pediatric disease. We present an adolescent patient who contracted severe acute respiratory syndrome coronavirus 2 one week after a paternal haplo-identical hematopoietic stem cell transplant, with development of severe hyperferritinemic acute lung injury and macrophage activation-like syndrome. We present her case and a comparison of her laboratory data with those of a cohort of pediatric patients with coronavirus disease 2019 without severe disease.

How I approach peer support in pediatric hematology/oncology.

Peer support has begun to gain traction as a mechanism for improving well-being in medicine. In this paper, we share our experience building, training, and piloting a peer support team based on a "critical incident stress management" model. The HOPES team (Helping Our Peers Endure Stress) is dedicated to, and composed entirely of, members of our division of pediatric hematology/oncology.

Cost of survivorship care and adherence to screening-aligning the priorities of health care systems and survivors.

Childhood cancer survivors (CCS) experience significant morbidity due to treatment- related late effects and benefit from late-effects surveillance. Adherence to screening recommendations is suboptimal. Survivorship care programs often struggle with resource limitations and may benefit from understanding institution-level financial outcomes associated with patient adherence to justify programmatic development and growth.

Congenital Hepatoblastoma and Beckwith-Wiedemann Syndrome.

Following the discovery of a fetal hepatic tumor, labor was induced at 38 weeks, and a phenotypically normal female was delivered vaginally. A serum alpha-fetoprotein level at birth was 373,170 ng/mL. Postnatal magnetic resonance imaging confirmed a mass in the right lobe of the liver, and a percutaneous core biopsy revealed an epithelial type hepatoblastoma with predominantly embryonal histology.

Caring for survivors of childhood cancer: it takes a village.

Purpose Of Review: Over 80% of children diagnosed with cancer are now cured. The burgeoning population of survivors of childhood cancer experiences high rates of morbidity and mortality due to 'late-effects' of treatment. These can be defined as any consequence of treatment that persists beyond or develops after the completion of cancer therapy.

Burnout in pediatric hematology/oncology-time to address the elephant by name.

The last decade has brought increasing recognition that the wellness of health care providers has an impact on the quality of care, patient satisfaction, and health care economics. This review will describe models of burnout, discuss the impact of burnout on medicine with a focus on pediatric hematologists/oncologists, and present interventions that may help ameliorate physician burnout.

Racial and ethnic disparities in treatment and survival of pediatric sarcoma.

Background: Childhood sarcomas are rare and require complex interdisciplinary care including surgery, chemotherapy, and radiation. The goal of this study was to determine if racial or ethnic disparities exist for pediatric sarcoma patients in the United States.

Methods: The United States' National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify patients aged 0-21 diagnosed with primary sarcomas from 1973 to 2012.

Therapeutic plasma exchange for a case of refractory opsoclonus myoclonus ataxia syndrome.

Opsoclonus myoclonus ataxia syndrome (OMAS) can be refractory to standard therapies and devastating. Alternative treatments are imperative. A 14-month-old male diagnosed with neuroblastoma and paraneoplastic OMAS achieved complete cancer remission with chemotherapy.

Looking for trouble: Adherence to late-effects surveillance among childhood cancer survivors.

Background: Childhood cancer survivors (CCSs) are at high risk of morbidity and mortality from long-term complications of their cancer treatment. The Children's Oncology Group developed screening guidelines to enable the early identification of and intervention for late effects of cancer treatment. There is a paucity of data on the adherence of CCSs to screening recommendations.

Arterial stiffness in childhood cancer survivors.

Background: Cardiovascular disease is prevalent among childhood cancer survivors (CCS). Arterial stiffness measured by pulse wave velocity (PWV) may be predictive of cardiovascular morbidity. Increased PWV has been seen in adults following chemotherapy.

Fertility preservation for adolescent women with cancer.

As the cure rate for adolescents with cancer has improved, the focus on future reproductive potential has increased. Despite a concerted effort to reduce the impact of cancer treatment on fertility through the alteration of therapy and the implementation of protective measures, many adolescent women with cancer remain at risk for impaired reproductive potential. Although the only standard-of-care approach to fertility preservation in this population remains embryo cryopreservation, there has been intense development of oocyte and ovarian cryopreservation as viable alternatives.

Noninvasive bioluminescent imaging of primary patient acute lymphoblastic leukemia: a strategy for preclinical modeling.

The efficient engraftment in immune-deficient mice achieved with both acute lymphoblastic leukemia (ALL) cell lines and primary samples has facilitated identification of the antileukemia activity of a wide variety of agents. Despite widespread usage, however, little is known about the early ALL localization and engraftment kinetics in this model, limiting experimental read-outs primarily to survival and endpoint analysis at high disease burden. In this study, we report that bioluminescent imaging can be reproducibly achieved with primary human ALL samples.

Part 1: Hormone replacement for survivors of childhood cancer with ovarian failure--when is it worth the risk?

Survivors of childhood cancer represent a rapidly growing population of patients, some of whom experience temporary or permanent premature ovarian failure (POF) as a consequence of their disease or treatment. Although the risks and benefits of exogenous hormones have been extensively explored in menopausal women 50 years of age and older, there is scant data on the long-term safety of exogenous hormones in childhood cancer survivors. Although there are certainly benefits that can be achieved through hormone replacement for this unique population, many of these patients also have very long hormone exposure times and a markedly increased baseline risk for second malignancies, including breast cancer.

Insidious iron burden in pediatric patients with acute lymphoblastic leukemia.

Background: A significant iron burden may occur after only 10 blood transfusions in patients with hematologic disorders. Children with acute lymphoblastic leukemia (ALL) routinely receive blood transfusions during therapy, although few studies to date have quantified transfusion-related iron burden in these patients. This study quantifies the transfused blood volume and resultant iron load in a large cohort of pediatric patients with ALL, and evaluates risk factors that may impact transfusion volume.

Autologous and allogeneic cellular therapies for high-risk pediatric solid tumors.

Since the 1950s, the overall survival of children with cancer has gone from almost zero to approaching 80%. Although there have been notable successes in treating solid tumors such as Wilms tumor, some childhood solid tumors have continued to elude effective therapy. With the use of megatherapy techniques such as tandem transplantation, dose escalation has been pushed to the edge of dose-limiting toxicities, and any further improvements in event-free survival will have to be achieved through novel therapeutic approaches.

Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo.

Persistence of T cells engineered with chimeric antigen receptors (CARs) has been a major barrier to use of these cells for molecularly targeted adoptive immunotherapy. To address this issue, we created a series of CARs that contain the T cell receptor-zeta (TCR-zeta) signal transduction domain with the CD28 and/or CD137 (4-1BB) intracellular domains in tandem. After short-term expansion, primary human T cells were subjected to lentiviral gene transfer, resulting in large numbers of cells with >85% CAR expression.

Targeting Notch signaling in autoimmune and lymphoproliferative disease.

Patients with autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosis (SLE) have T-cell dysregulation and produce abnormal, activated T lymphocytes and an atypical peripheral T-cell population, termed double negative T cells (DNTs). T-cell functions, including DNT transition in T-cell development and T-cell activation, are critically dependent on Notch signaling. We hypothesized that inhibiting Notch signaling would be effective in ALPS and SLE by reducing the production of abnormal DNTs and by blocking aberrant T-cell activation.

A caution regarding the use of low-molecular weight heparin in pediatric otogenic lateral sinus thrombosis.

Lateral sinus thrombosis (LST), a rare complication of otitis media, is managed by antibiotics, surgery and anticoagulation. Traditionally, post-operative anticoagulation has been achieved by intravenous unfractionated heparin followed by oral warfarin. Fractionated, or low-molecular weight heparin derivatives (LMWH) have been introduced recently.

In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides.

Despite considerable success in treating newly diagnosed childhood acute lymphoblastic leukemia (ALL), relapsed disease remains a significant clinical challenge. Using a NOD/SCID mouse xenograft model, we report that immunostimulatory DNA oligonucleotides containing CpG motifs (CpG ODNs) stimulate significant immune activity against primary human ALL cells in vivo. The administration of CpG ODNs induced a significant reduction in systemic leukemia burden, mediated continued disease control, and significantly improved survival of mice with established human ALL.