Michele L. Nassin

Irreversible electroporation in the curative treatment of Ewing's sarcoma.

Ewings sarcoma (ES) is the second most common paediatric cancer of the bone. Standard therapy includes surgery or radiation for local control of primary and relapsed lesions and chemotherapy for systemic control. Irreversible electroporation (IRE), which uses short electrical pulses to induce pores and ablate neoplastic cells, has emerged as an alternative method of local control for inoperable metastatic liver and lung lesions. We present the first case in which IRE was used for local control of bony ES. This method has achieved successful local tumour control in our patient for 3 years.

Family Refusal of Chemotherapy for Pediatric Cancer Patients: A National Survey of Oncologists.

Background: Refusal of therapy is ethically acceptable for competent adults. Practitioner opinions regarding refusal of therapy in pediatric cancer patients has not been widely studied. This is the largest survey of oncology practitioners assessing support for refusal of chemotherapy. Procedure: Pediatric oncology nurses/physicians were asked: “As their provider I would support refusal of chemotherapy by a family,” with the following options: “Never support refusal,” “Always support refusal,” or “Support for refusal would depend on cure rate, age, or both.” Variables assessed were: age (0 to 7, 8 to 13, 14 to 17 y) and cure rate (0% to 33%, 34% to 66%, 67% to 100%). Results: A total of 957 practitioners responded. Fifty-six percent, 31%, and 0.2%, respectively, stated their support of chemotherapy refusal depended on “age and cure rate,” “cure rate alone,” or “age alone.” Two percent and 11% indicated they would “always” or “never” support refusal, respectively. For a “modest” or “good” cure rate, support for refusal was <20%, whereas for a “poor” cure rate, the majority would support a family’s refusal (53% to 78% age dependent). Within each cure rate, respondents were more likely to support refusal for older patients (P<0.001). Conclusions: The majority of practitioners surveyed viewed parental refusal of chemotherapy for children with a moderate or good expected cure rate as unacceptable, but were more accepting of refusal with a poor prognosis, especially for teenagers.

Killing Two Cells with One Stone: Pharmacologic BCL-2 Family Targeting for Cancer Cell Death and Immune Modulation

A crucial component of regulating organismal homeostasis is maintaining proper cell number and eliminating damaged or potentially malignant cells. Apoptosis, or programed cell death, is the mechanism responsible for this equilibrium. The intrinsic apoptotic pathway is also especially important in the development and maintenance of the immune system. Apoptosis is essential for proper positive and negative selection during B- and T-cell development and for efficient contraction of expanded lymphocytes following an immune response. Tight regulation of the apoptotic pathway is critical, as excessive cell death can lead to immunodeficiency while apoptotic resistance can lead to aberrant lymphoproliferation and autoimmune disease. Dysregulation of cell death is implicated in a wide range of hematological malignancies, and targeting various components of the apoptotic machinery in these cases is an attractive chemotherapeutic strategy. A wide array of compounds has been developed with the purpose of reactivating the intrinsic apoptotic pathway. These compounds, termed BH3 mimetics are garnering considerable attention as they gain greater clinical oncologic significance. As their use expands, it will be imperative to understand the effects these compounds have on immune homeostasis. Uncovering their potential immunomodulatory activity may allow for administration of BH3 mimetics for direct tumor cell killing as well as novel therapies for a wide range of immune-based directives. This review will summarize the major proteins involved in the intrinsic apoptotic pathway and define their roles in normal immune development and disease. Clinical and preclinical BH3 mimetics are described within the context of what is currently known about their ability to affect immune function. Prospects for future antitumor immune amplification and immune modulation are then proposed.

Anemia in the Neonate: The Differential Diagnosis and Treatment

Anemia is a common problem in the neonatal period. Presenting symptoms may suggest numerous possible diagnoses ranging from anemia seen as a normal part of development to anemia due to critical pathology. An illustrative case is presented to highlight the appropriate evaluation of the neonate with significant anemia. Several important features of the evaluation of neonatal anemia are highlighted. The constellation of signs and symptoms that occur in conjunction with the anemia are critical for the evaluation. The evaluation should be performed in a step-wise process that starts by eliminating common causes of anemia. Manual review of the peripheral blood smear with a hematologist can be helpful.

Immune Reconstitution Following Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma at the Time of Immunotherapy

Outcomes for patients with high-risk neuroblastoma (HR-NBL) are significantly improved with the addition of immunotherapy (dinutuximab + cytokines) following autologous hematopoietic stem cell transplantation (auto-HSCT). We hypothesized that the immune system is not fully reconstituted at the initiation of immunotherapy. To test this hypothesis, we evaluated hematologic and immune subsets in 34 patients with HR-NBL before and after auto-HSCT. We found that absolute T, B, and NK cell counts at the time of immunotherapy were below normal in 80% of patients. Patients with residual disease at the time of transplantation had significantly lower absolute lymphocyte counts (ALC; P = .008), lower CD16+ cell counts (P = .009), and an abnormal ratio of cytokine-releasing to cytotoxic NK cells at the time of dinutuximab treatment. In addition, the preparative regimen used for auto-HSCT predicted immune recovery. Finally, higher total white blood cell count (P = .013) and ALC (P = .013) at 3 months after completion of therapy were measured in patients who remained in remission compared with those who relapsed. Our results indicate that most patients with HR-NBL do not have full immune reconstitution at the time of dinutuximab treatment after auto-HSCT, and that immune recovery may correlate with disease-related outcomes in patients with high-risk disease.

Neonatal anemia: Revisiting the enigmatic pyknocyte

Department of Pediatrics, Section of Hematology/Oncology/Stem Cell Transplantation, University of Chicago, Comer Children’s Hospital, Chicago, Illinois, USA; Foundation Medicine, Inc., Cambridge, Massachusetts, USA; Division of Hematology/Oncology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA Correspondence James L. LaBelle, 900 East 57 Street, KCBD 5122, Chicago, IL 60637. Email: jlabelle@peds.bsd.uchicago.edu