Nicholas D. Yeager

Mifamurtide in Metastatic and Recurrent Osteosarcoma: A Patient Access Study with Pharmacokinetic, Pharmacodynamic, and Safety Assessments

This non‐randomized, patient‐access protocol, assessed both safety and efficacy outcomes following liposomal muramyl‐tripeptide‐phosphatidylethanolamine (L‐MTP‐PE; mifamurtide) in patients with high‐risk, recurrent and/or metastatic osteosarcoma.

Adolescent and young adult (AYA) oncology in the United States: A specialty in its late adolescence

Over the last 30 years, it has become apparent that oncology patients ages 15 to 39 have not reaped the same rewards of improved survival that we have seen in younger and older patients. As a result, in 2006 the Adolescent and Young Adult (AYA) Oncology Progress Review Group convened and examined the factors that impact the care of the 70,000 new cases per year (approximately 7% of all new cases) in the United States and published their findings. The reasons for inferior survival gains are of course multiple and include the settings in which patients are cared for, clinical trial enrollment, insurance coverage, varied treatment of sarcomas, varied treatment of acute lymphoblastic leukemia, the psychosocial impact of cancer and cancer survivorship. A new area of a yet-to-be completely defined subspecialty was born out of this meeting: AYA oncology. As a medical community we realized that these patients do not fit neatly into the pediatric nor adult world and, therefore, require a unique approach which many individuals, oncology centers, advocacy groups, and cooperative trial groups have started to address. This group of dedicated providers and advocates has made strides but there is still much work to be done on the local, national, and international level to make up for shortcomings in the medical system and improve outcomes. We review key components of AYA cancer care in 2015 that all providers should be aware of, how far we have come, where this movement is headed, and the obstacles that continue to stand in the way of better cure rates and quality of life after cure for this unique group of patients. Like an adolescent maturing into adulthood, this movement has learned from the past and is focused on moving into the future to achieve its goals.

Health literacy variables related to parents' understanding of their child's cancer prognosis

Obtaining an accurate understanding of a childs cancer prognosis can help parents make informed decisions about treatment. Research has shown that parents tend to overestimate their childs cancer prognosis relative to physicians. Thus, we examined whether the content of physician communication, parent sources of medical information, and parent demographic factors affected the association between oncologist and parent estimates of a childs cancer prognosis.

Mobilization of PML-RARA negative blood stem cells and salvage with autologous peripheral blood stem cell transplantation in children with relapsed acute promyelocytic leukemia†

Relapsed acute promyleocytic leukemia (APL) is treated with re‐induction chemotherapy, commonly arsenic trioxide, and stem cell transplantation (SCT). The effect of arsenic trioxide on autologous peripheral blood stem cell collection is unknown.

Unique diagnostic features and successful management of a patient with disseminated lymphangiomatosis and chylothorax.

Disseminated lymphangiomatosis is a rare vascular tumor characterized by a proliferation of abnormal lymphatic channels that often involves multiple organ systems. One particularly morbid manifestation of this disorder is the presence of bony lytic lesions with associated chylothorax. Because of its unusual nature, this condition is often a diagnostic and therapeutic challenge. In this report, we present the diagnostic features, including a unique radiologic finding, and successful management of a 7-year-old girl with this condition using a combination of aggressive surgery and medical treatment with interferon and pamidronate.

Chemoresistant hepatoblastoma in a patient with mosaic trisomy 18 treated with orthotopic liver transplantation

We present a 9‐month‐old male with mosaic trisomy 18 with a right hepatic lobe mass. The tumor was completely resected and identified as pure fetal histology hepatoblastoma but contained increased mitotic activity. Adjuvant chemotherapy consisted of cisplatin, vincristine, and 5‐fluorouracil. After the first and fourth cycles of chemotherapy, recurrent tumor developed. The patient underwent rescue orthotopic liver transplantation, and is currently alive without evidence of hepatoblastoma 28 months after transplantation. This report demonstrates the use of orthotopic liver transplantation in a child with mosaic trisomy 18 and hepatoblastoma. Pediatr Blood Cancer 2011;56:498–500.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

O6-Methylguanine-DNA methyltransferase activity and promoter methylation status in pediatric rhabdomyosarcoma

Objectives To determine the activity of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) and MGMT promoter methylation status of pediatric rhabdomyosarcoma (RMS) and examine MGMT in RMS tumors from different prognostic groups. Methods Fifteen samples each of the alveolar (ARMS) and embryonal (ERMS) subtypes were obtained for analysis of MGMT activity and promoter methylation status. MGMT activity was assayed by measuring the removal of O6-[3H] methylguanine from [3H]-methylated substrate by a tumor extract containing the enzyme. Promoter methylation status was examined using methylation-specific polymerase chain reaction (PCR). Results MGMT activity was successfully assayed from 25 samples, 10 ERMS and 15 ARMS. All ERMS and 11 of the 15 ARMS samples displayed high activity levels. There was significant intertumor variability among both subtypes but no significant difference in mean activity between the two histologic groups. There were trends toward increased activity in ERMS tumors and tumors from anatomically unfavorable locations. Only one tumor was hypermethylated at the MGMT promoter region. Conclusions This analysis suggests that a low percentage of RMS samples are hypermethylated at the MGMT promoter and that most have significant MGMT activity, implying that clinical trials with MGMT-modulating agents may have a role in the treatment of these tumors. This analysis does not support MGMT activity as an explanation of the differential response to chemotherapy demonstrated by ARMS and ERMS, but does suggest that MGMT may be involved in RMS treatment failure regardless of subtype and in the poorer response shown by tumors from unfavorable locations.

Fertility perspectives and priorities among male adolescents and young adults in cancer survivorship

Infertility is a common and distressing late effect of cancer treatment among male survivors. Investigators examined desire for parenthood, prioritization of fertility compared to other life goals, and reports of fertility‐related discussions among a cohort of male adolescent and young adult survivors. Eighty percent desired a biological child, yet only 31% ranked having a child among their “top 3” life goals. Only 40% reported fertility‐related discussions with their health care providers in survivorship. Given the importance of biological children among this cohort, future guidelines should encourage a more proactive approach to providing fertility counseling and offering testing, to mitigate distress and prevent unplanned pregnancies.

Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia†

Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count <0.5 × 109/L and recurrent bacterial infections. Homozygous mutations of either HAX‐1 or ELA‐2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem‐cell transplant. He was found to be heterozygous for the M1V variant of the ELA‐2 gene that we postulate to be causative for his severe neutropenia. Pediatr Blood Cancer 2011; 57: 514–515.