Atezolizumab for Advanced Alveolar Soft Part Sarcoma.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported. METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action. RESULTS: A total of 52 patients were evaluated. An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses. The median time to response was 3.6 months (range, 2.1 to 19.1), the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months. Seven patients took a treatment break after 2 years of treatment, and their responses were maintained through the data-cutoff date. No treatment-related grade 4 or 5 adverse events were recorded. Responses were noted despite variable baseline expression of programmed death 1 and PD-L1. CONCLUSIONS: Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03141684.).

Pediatric Chronic Myelogenous Leukemia in T-lineage Blast Crisis: A Reminder in Relevance.

Pediatric Philadelphia chromosome positive (Ph+) acute T-cell lymphoblastic leukemia can mimic chronic myelogenous leukemia (CML) in T-lineage blast crisis (BC). Differentiating the 2 is critical in guiding therapy as most children with de novo Ph+ acute T-cell lymphoblastic leukemia are treated with chemotherapy and tyrosine kinase inhibitors, whereas T-lineage BC of CML can include hematopoietic stem cell transplantation. We present a unique case of CML in T-lineage BC. The patient was treated with induction chemotherapy plus imatinib followed by matched unrelated donor hematopoietic stem cell transplantation. She is currently off all medications and in complete disease remission.

An ethical framework for responding to drug shortages in pediatric oncology.

The frequency of drug shortages has increased considerably over the last decade. Important ethical issues arise whenever the supply of an effective drug is insufficient to meet demand. Using the ethical principles of beneficence, non-maleficence, and justice, institutions can guide prioritization of drug distribution before a shortage occurs to avoid unfair and unethical distribution of resources. This analysis will give a historical context for drug shortages, identify, and explore the central ethical concerns raised by drug shortages, and propose an ethical framework for addressing them in the context of pediatric oncology.

Liver transplant for congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is a rare, autosomal recessive bleeding disorder with a spectrum of phenotypes ranging from asymptomatic to life-threatening intra-cranial hemorrhage (ICH). Orthotopic liver transplantation has been described for definitive treatment in a few patients with severe manifestations. We report a patient with congenital FVII deficiency and recurrent ICH, despite twice-weekly prophylaxis with recombinant activated FVII. At 17 months of age, he underwent an orthotopic liver transplant. He is now 1-year post-transplant, on maintenance immunosuppression with no hemorrhage or other complications.

Impact of cytomegalovirus (CMV) reactivation after umbilical cord blood transplantation.

This study investigated the impact of pretransplant cytomegalovirus (CMV) serostatus and posttransplant CMV reactivation and disease on umbilical cord blood transplant (UCBT) outcomes. Between 1994 and 2007, 332 patients with hematologic malignancies underwent UCBT and 54% were CMV seropositive. Pretransplant recipient CMV serostatus had no impact on acute or chronic graft-versus-host disease (aGVHD, cGVHD), relapse, disease-free survival (DFS), or overall survival (OS). There was a trend toward greater day 100 treatment-related mortality (TRM) in CMV-seropositive recipients (P=.07). CMV reactivation occurred in 51% (92/180) of patients with no difference in myeloablative (MA) versus reduced-intensity conditioning (RIC) recipients (P=.33). Similarly, reactivation was not influenced by the number of UCB units transplanted, the degree of HLA disparity, the CD34(+) or CD3(+) cell dose, or donor killer cell immunoglobulin-like receptor (KIR) gene haplotype. Rapid lymphocyte recovery was associated with CMV reactivation (P=.02). CMV reactivation was not associated with aGVHD (P=.97) or cGVHD (P=.65), nor did it impact TRM (P=.88), relapse (P=.62), or survival (P=.78). CMV disease occurred in 13.8% of the CMV-seropositive patients, resulting in higher TRM (P=.01) and lower OS (P=.02). Thus, although recipient CMV serostatus and CMV reactivation have little demonstrable impact on UCB transplant outcomes, the development of CMV disease remains a risk, associated with inferior outcomes.

Physician approaches to drug shortages: Results of a national survey of pediatric hematologist/oncologists.

AIM: To evaluate personnel involved in scarce drug prioritization and distribution and the criteria used to inform drug distribution during times of shortage among pediatric hematologists/oncologists. METHODS: Using the American Society of Pediatric Hematology/Oncology (ASPHO) membership list, a 20 question survey of pediatric hematologists/oncologists was conducted via email to evaluate personnel involved in scarce drug prioritization and distribution and criteria used to inform scarce drug distribution. RESULTS: Nearly 65% of the 191 study respondents had patients directly affected by drug shortages. Most physicians find out about shortages from the pharmacist (n = 179, 98%) or other doctors (n = 75, 41%). One third of respondents do not know if there is a program or policy for handling drug shortages at their institution. The pharmacist was the most commonly cited decision maker for shortage drug distribution (n = 128, 70%), followed by physicians (n = 109, 60%). One fourth of respondents did not know who makes decisions about shortage drug distribution at their institution. The highest priority criterion among respondents was use of the shortage drug for curative, rather than palliative intent and lowest priority criterion was order of arrival or first-come first-served. CONCLUSION: Despite pediatric hematology/oncology physicians and patients being heavily impacted by drug shortages, institutional processes for handling shortages are lacking. There is significant disparity between how decisions for distribution of shortage drugs are currently made and how study respondents felt those decisions should be made. An institution-based, and more importantly, a societal approach to drug shortages is necessary to reconcile these disparities.

Improving pediatric hematology/oncology care in the emergency department.

PURPOSE: Pediatric hematology/oncology patients frequently use the emergency department (ED) for prompt care during potentially life-threatening events, such as sepsis and bleeding. One challenge of these visits is the unavailability of appropriate patient-specific medical information. Lack of information may result in ineffective ED visits for these patients with complex conditions. METHODS: A cross-sectional survey to determine ways to improve the care of pediatric hematology/oncology patients in the ED setting was conducted among parents at two affiliated pediatric hematology/oncology clinics. ED physicians in the catchment area of the clinic completed a separate survey. RESULTS: All physicians surveyed were confident in caring for pediatric patients in the ED; however, fewer were confident in caring for pediatric hematology/oncology patients. Physicians and parents reported that the patient's written medical history (physicians, 30%; parents, 33%), medication list (physicians, 28%; parents, 24%), on-call pediatric hematologist/oncologist contact information (physicians, 34%; parents, 31%), and needle size and gauge to access the patient's port (physicians, 8%; parents, 12%) would be valuable information to have when presenting to the ED. CONCLUSION: Parents were satisfied with ED care, but both physician and parent respondents thought additional information would be valuable to have available at the visit to help facilitate effective care.

Cutaneous leishmaniasis with boggy induration and simultaneous mucosal disease.

A woman had cutaneous, mucosal, and possible visceral leishmaniasis simultaneously. Many of her cutaneous lesions consisted of boggy indurations rather than customary papules, nodules, or ulcers. This unusual case was finally cured after four courses of miltefosine, one course of antimony, and two courses of Ambisome.