"Older People Want to Be in Their Own Homes": A Service Evaluation of Patient and Carer Feedback after Pathfinder Responded to Their Emergency Calls.

OBJECTIVE: Older people experience high rates of adverse outcomes following emergency department (ED) presentation. There is growing evidence to support alternative care pathways for certain types of emergency medical services (EMS) calls. Pathfinder is one such service and targets patients aged 65 years and over, whose presenting issues can be safely managed at home by immediate paramedic, occupational therapy, and/or physiotherapy interventions. The aim of this service evaluation was to understand how older people feel about being treated at home as a result of EMS calls and to understand their experiences of the Pathfinder service. METHODS: This was a thematic analysis of open-ended responses recorded from telephone interviews during routine service evaluation with service users (patients or their next-of-kin). RESULTS: Of 573 service users, telephone interviews were conducted with 429 (75%). Five primary themes were identified: (1) professionalism of the multidisciplinary clinical team; (2) "the right service, in the right place, at the right time"; (3) role of Pathfinder in "getting the ball rolling"; (4) lasting effects of the experience on the patient and his or her next-of-kin; (5) value of skilled communication with the older person. CONCLUSION: Older people and their next-of-kin voiced a clear preference for hospital avoidance, and strongly valued the opportunity to be treated in their homes at the time of an EMS call rather than default conveyance to the ED. They appreciated the importance of a skilled multidisciplinary team with a follow-up service that effectively positions itself between the acute hospital and community services.

Daratumumab for delayed RBC engraftment following major ABO mismatched haploidentical bone marrow transplantation.

BACKGROUND: Recent case reports have described the efficacy of daratumumab to treat refractory pure red cell aplasia (PRCA) following major ABO mismatched allogeneic hematopoietic stem cell transplantation (HSCT). In this report, we describe the use of daratumumab as a first-line agent for treatment of delayed red blood cell (RBC) engraftment following a major ABO mismatched pediatric HSCT and provide a review of the literature. STUDY DESIGN AND MATERIALS: We report on a 14-year-old with DOCK8 deficiency who underwent a myeloablative, haploidentical bone marrow transplant from her major ABO mismatched sister (recipient O+, donor A+) for treatment of her primary immunodeficiency. Despite achieving full donor chimerism, she had delayed RBC engraftment requiring ongoing transfusions. Due to iron deposition, symptomatic anemia, and persistence of anti-A iso-hemagglutinins despite discontinuation of immunosuppression, treatment for delayed RBC engraftment with the CD38-targeted monoclonal antibody daratumumab was selected as a less immunosuppressive agent that could more selectively target iso-hemagglutinin producing plasma cells without causing broad B-cell aplasia. RESULTS: Clinical effect with daratumumab was demonstrated by reduced iso-hemagglutinin titer, increased reticulocytosis, normalization of her hemoglobin, and transfusion independence. In the 11-month follow-up period to date, no additional transfusions or immunosuppression have been necessary, despite persistence of low-level anti-A iso-hemagglutinin. CONCLUSION: Our experience suggests that daratumumab was an effective first-line therapy for delayed RBC engraftment and that earlier consideration for daratumumab in treatment of delayed RBC engraftment may be warranted.

Characterization of COVID-19 disease in pediatric oncology patients: The New York-New Jersey regional experience.

PURPOSE: Pediatric oncology patients undergoing active chemotherapy are suspected to be at a high risk for severe disease secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection; however, data to support this are lacking. We aim to describe the characteristics of coronavirus disease 2019 (COVID-19) in this population and also its impact on pediatric cancer care in the New York region during the peak of the pandemic. PATIENTS AND METHODS: This multicenter, retrospective study included 13 institutions. Clinical and laboratory information on 98 patients ≤21 years of age receiving active anticancer therapy, who tested positive for SARS-CoV-2 by nasopharyngeal swab polymerase chain reaction (PCR), was collected. RESULTS: Of the 578 pediatric oncology patients tested for COVID-19, 98 were positive, of whom 73 were symptomatic. Most experienced mild disease, 28 required inpatient management, 25 needed oxygen support, and seven required mechanical ventilation. There is a slightly higher risk of severe disease in males and obese patients, though not statistically significant. Persistent lymphopenia was noted in severe cases. Delays in cancer therapy occurred in 67% of SARS-CoV-2-positive patients. Of four deaths, none were solely attributable to COVID-19. The impact of the pandemic on pediatric oncology care was significant, with 54% of institutions reporting delays in chemotherapy, 46% delays in surgery, and 30% delays in transplant. CONCLUSION: In this large multi-institutional cohort, we observed that mortality and morbidity from COVID-19 amongst pediatric oncology patients were low overall, but higher than reported in general pediatrics. Certain subgroups might be at higher risk of severe disease. Delays in cancer care due to SARS-CoV-2 remain a concern.

Is Pathfinder a safe alternative to the emergency department for older patients? An observational analysis.

BACKGROUND: many patients brought to emergency departments (EDs) following an emergency medical services (EMS) call have non-urgent needs that could be treated elsewhere. Older people are particularly vulnerable to adverse events while attending the ED. Alternative care pathway models can reduce ED crowding and improve outcomes. Internationally, there is no consensus on which model is recommended. AIM: the aim of this study is to investigate the impact of the Pathfinder model on ED conveyance rates and patient safety. METHODS: the Pathfinder service is a collaboration between the National Ambulance Service and Beaumont Hospital Occupational Therapy and Physiotherapy Departments. It is supported by the Government of Ireland's Sláintecare Integration fund. This is a retrospective cohort study of the Pathfinder service over a 5-month period. RESULTS: one-hundred and seventy-eight patients were responded to by the Pathfinder 'Rapid Response Team'. Average age was 79.6 years (standard deviation 7.6), median clinical frailty score was 6 (interquartile range: 5-6). Sixty-four percent remained at home following initial review. None re-presented to the ED within 24 hours, and 10% re-presented within 7 days. The majority (67%) of patients required follow-up by the Pathfinder 'Follow-Up Team' and/or another community-based service. Feedback demonstrates 99% patient satisfaction with the service. CONCLUSION: the Pathfinder service is a safe alternative to ED conveyance for older people following an EMS call. It is the first model of this kind to be evaluated in Ireland. The overwhelmingly positive feedback confirms that older people want this service. This model could expand, with local adaptation, nationally and internationally.

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

Importance: Standard chemotherapy for first relapse of B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults is associated with high rates of severe toxicities, subsequent relapse, and death, especially for patients with early relapse (high risk) or late relapse with residual disease after reinduction chemotherapy (intermediate risk). Blinatumomab, a bispecific CD3 to CD19 T cell-engaging antibody construct, is efficacious in relapsed/refractory B-ALL and has a favorable toxicity profile. Objective: To determine whether substituting blinatumomab for intensive chemotherapy in consolidation therapy would improve survival in children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL. Design, Setting, and Participants: This trial was a randomized phase 3 clinical trial conducted by the Children's Oncology Group at 155 hospitals in the US, Canada, Australia, and New Zealand with enrollment from December 2014 to September 2019 and follow-up until September 30, 2020. Eligible patients included those aged 1 to 30 years with B-ALL first relapse, excluding those with Down syndrome, Philadelphia chromosome-positive ALL, prior hematopoietic stem cell transplant, or prior blinatumomab treatment (n = 669). Interventions: All patients received a 4-week reinduction chemotherapy course, followed by randomized assignment to receive 2 cycles of blinatumomab (n = 105) or 2 cycles of multiagent chemotherapy (n = 103), each followed by transplant. Main Outcome and Measures: The primary end point was disease-free survival and the secondary end point was overall survival, both from the time of randomization. The threshold for statistical significance was set at a 1-sided P <.025. Results: Among 208 randomized patients (median age, 9 years; 97 [47%] females), 118 (57%) completed the randomized therapy. Randomization was terminated at the recommendation of the data and safety monitoring committee without meeting stopping rules for efficacy or futility; at that point, 80 of 131 planned events occurred. With 2.9 years of median follow-up, 2-year disease-free survival was 54.4% for the blinatumomab group vs 39.0% for the chemotherapy group (hazard ratio for disease progression or mortality, 0.70 [95% CI, 0.47-1.03]); 1-sided P = .03). Two-year overall survival was 71.3% for the blinatumomab group vs 58.4% for the chemotherapy group (hazard ratio for mortality, 0.62 [95% CI, 0.39-0.98]; 1-sided P = .02). Rates of notable serious adverse events included infection (15%), febrile neutropenia (5%), sepsis (2%), and mucositis (1%) for the blinatumomab group and infection (65%), febrile neutropenia (58%), sepsis (27%), and mucositis (28%) for the chemotherapy group. Conclusions and Relevance: Among children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL, postreinduction treatment with blinatumomab compared with chemotherapy, followed by transplant, did not result in a statistically significant difference in disease-free survival. However, study interpretation is limited by early termination with possible underpowering for the primary end point. Trial Registration: ClinicalTrials.gov Identifier: NCT02101853.

Potential alternative treatment approach for pediatric patient with diffusely infiltrative primary rhabdomyosarcoma of the liver.

Primary hepatic rhabdomyosarcoma is rare, making decisions regarding locoregional management with resection and/or conventional radiation difficult. We present a novel treatment approach for a pediatric patient diagnosed with rhabdomyosarcoma diffusely involving the liver. This patient underwent treatment with yttrium-90 (Y-90) microspheres followed by external beam radiation therapy (EBRT ) to residual disease, interdigitated with systemic chemotherapy. Initial post-radiation imaging showed significant response to treatment, and she experienced minimal acute toxicities and no long-term toxicities. She developed recurrent PET-avid disease 23 months after Y-90 treatment, necessitating further local and continued systemic therapies. We report on the tumor control following Y-90 and EBRT treatment.

Neural correlates of working memory function in pediatric cancer survivors treated with chemotherapy: an fMRI study.

The goal of this study is to investigate the neural correlates of working memory function associated with chemotherapy in pediatric cancer survivors using event-related functional MRI (fMRI) analysis. Fifteen pediatric cancer survivors treated with chemotherapy and 15 healthy controls were studied. Blood oxygenation level dependent (BOLD) fMRI was acquired. A visual n-back task was used to test working memory function during the fMRI scan. Responses were recorded via an MRI compatible button box for analysis. fMRI scans were analyzed using statistical parametric mapping software. All statistics were corrected for multiple comparisons by false discovery rate, with p < 0.05 as significance. Patients however gave more incorrect responses (p < 0.05), more no responses (p < 0.05), and longer response times (p < 0.05) compared with healthy controls. Correct responses generated significantly lower BOLD responses in the posterior cingulate for pediatric cancer survivors compared with controls (p < 0.05). Incorrect responses generated significantly greater BOLD responses in the angular gyrus in survivors (p < 0.05), and no response trials generated greater BOLD responses within the superior parietal lobule (p < 0.05) compared with controls. Working memory impairment appears to be due to an inability to manipulate information and to retrieve information from memory. The ability to delineate the affected neural circuits associated with chemotherapy-induced cognitive impairment could inform treatment strategies, identify patients at high risk of developing cognitive deficits, and pre-emptively tailor behavioral enrichment to overcome specific cognitive deficits.

The Progression of Bone Mineral Density Abnormalities After Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

Although reduced bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL) is well documented, the degree of demineralization and relation to age are not well described. This is a retrospective chart analysis of 58 patients consecutively treated for ALL without relapse, cranial irradiation, or transplantation. Bone mineral densities were measured by dual-energy x-ray absorptiometry and patients were divided by sex and age (≤5, 6 to 10, and >10 y) at diagnosis. Serial scans for 6 years after therapy were analyzed as Z-scores. Over 6 years after therapy, 93.1% of patients exhibited a decreased Z-score in at least 1 anatomic site. The difference in Z-score among the age cohorts was significant at both the lumbar spine and femoral neck. Patients older than 10 years at diagnosis had the lowest Z-scores: -2.78 and -2.87 for boys and -2.39 and -2.91 for girls at the lumbar spine and femoral neck, respectively. Children after ALL therapy exhibit a significant bone mineral deficit shortly after completion of therapy that persists for at least 6 years. The degree of bone demineralization can be followed up by a dual-energy x-ray absorptiometry scan and is most severe in patients older than 10 years at the initiation of therapy.

Low-risk relapsed acute lymphoblastic leukemia in children and young adults: what have we learnt and what's next?

While outcomes for newly diagnosed children with acute lymphoblastic leukemia (ALL) have improved over the last few decades, 10-15% will relapse. Outcomes for those children with relapse remains a challenge, with 5-year overall survival of approximately 35-60%. Large cooperative group trials have identified factors associated with favorable (low risk, LR) outcome at relapse, including later relapse, B-cell phenotype, isolated extramedullary relapse and a good response to initial re-induction therapy. Contemporary therapeutic regimens are aimed at improving outcomes, while decreasing toxicity. A main focus of current research involves how immunotherapy can be best incorporated with cytotoxic chemotherapy to improve survival in relapsed ALL. Here we review therapeutic strategies for LR relapse, including review of recently completed and ongoing trials.

Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.

Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (< 36 months) and late (≥ 36 months) relapse. CNA analysis discovered CNAs that were shared at diagnosis and relapse and others that were new lesions acquired at relapse. DNA methylation analysis found increased promoter methylation at relapse. There were many genetic alterations that evolved from diagnosis to relapse, and in some cases these genes had previously been associated with chemoresistance. Integration of the results from all 3 platforms identified genes of potential interest, including CDKN2A, COL6A2, PTPRO, and CSMD1. Although our results indicate that a diversity of genetic changes are seen at relapse, integration of gene expression, CNA, and methylation data suggest a possible convergence on the WNT and mitogen-activated protein kinase pathways.

Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse.

PURPOSE: Blinatumomab, a bispecific T-cell engager immunotherapy, is efficacious in relapsed/refractory B-cell ALL (B-ALL) and has a favorable toxicity profile. One aim of the Children's Oncology Group AALL1331 study was to compare survival of patients with low-risk (LR) first relapse of B-ALL treated with chemotherapy alone or chemotherapy plus blinatumomab. PATIENTS AND METHODS: After block 1 reinduction, patients age 1-30 years with LR first relapse of B-ALL were randomly assigned to block 2/block 3/two continuation chemotherapy cycles/maintenance (arm C) or block 2/two cycles of continuation chemotherapy intercalated with three blinatumomab blocks/maintenance (arm D). Patients with CNS leukemia received 18 Gy cranial radiation during maintenance and intensified intrathecal chemotherapy. The primary and secondary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The 4-year DFS/OS for the 255 LR patients accrued between December 2014 and September 2019 were 61.2% ± 5.0%/90.4% ± 3.0% for blinatumomab versus 49.5% ± 5.2%/79.6% ± 4.3% for chemotherapy (P = .089/P = .11). For bone marrow (BM) ± extramedullary (EM) (BM ± EM; n = 174) relapses, 4-year DFS/OS were 72.7% ± 5.8%/97.1% ± 2.1% for blinatumomab versus 53.7% ± 6.7%/84.8% ± 4.8% for chemotherapy (P = .015/P = .020). For isolated EM (IEM; n = 81) relapses, 4-year DFS/OS were 36.6% ± 8.2%/76.5% ± 7.5% for blinatumomab versus 38.8% ± 8.0%/68.8% ± 8.6% for chemotherapy (P = .62/P = .53). Blinatumomab was well tolerated and patients had low adverse event rates. CONCLUSION: For children, adolescents, and young adults with B-ALL in LR first relapse, there was no statistically significant difference in DFS or OS between the blinatumomab and standard chemotherapy arms overall. However, blinatumomab significantly improved DFS and OS for the two thirds of patients with BM ± EM relapse, establishing a new standard of care for this population. By contrast, similar outcomes and poor DFS for both arms were observed in the one third of patients with IEM; new treatment approaches are needed for these patients (ClinicalTrials.gov identifier: NCT02101853).

Pcsk6 mutant mice exhibit progressive loss of ovarian function, altered gene expression, and formation of ovarian pathology.

Bioactivation of precursor proteins by members of the proprotein convertase (PC) family is essential for normal reproduction. The Pcsk6 gene is a member of the PC family that is expressed in numerous ovarian cell types including granulosa cells and oocytes. We hypothesized that loss of PCSK6 would produce adverse effects in the mouse ovary. Mice incapable of expressing PCSK6 (Pcsk6(tm1Rob)) were obtained, and reproductive parameters (serum hormones, whelping interval, estrus cyclicity, and fertility) were compared to Pcsk6(+/+) mice. While Pcsk6(tm1Rob) female mice are fertile, they manifest reduced reproductive capacity at an accelerated rate relative to Pcsk6(+/+) mice. Reproductive senescence is typically reached by 9 months of age and is correlated with loss of estrus cyclicity, elevated serum FSH levels, and gross alterations in ovarian morphology. A wide range of ovarian morphologies were identified encompassing mild, such as an apparent reduction in follicle number, to moderate--ovarian atrophy with a complete absence of follicles--to severe, manifesting as normal ovarian structures replaced by benign ovarian tumors, including tubulostromal adenomas. Targeted gene expression profiling highlighted changes in RNA expression of molecules involved in processes such as steroidogenesis, gonadotropin signaling, transcriptional regulation, autocrine/paracrine signaling, cholesterol handling, and proprotein bioactivation. These results show that PCSK6 activity plays a role in maintaining normal cellular and tissue homeostasis in the ovary.

T Cell Interactions in Mycobacterial Granulomas: Non-Specific T Cells Regulate Mycobacteria-Specific T Cells in Granulomatous Lesions.

Infections with pathogenic mycobacteria are controlled by the formation of a unique structure known as a granuloma. The granuloma represents a host-pathogen interface where bacteria are killed and confined by the host response, but also where bacteria persist. Previous work has demonstrated that the T cell repertoire is heterogenous even at the single granuloma level. However, further work using pigeon cytochrome C (PCC) epitope-tagged BCG (PCC-BCG) and PCC-specific 5CC7 RAG-/- TCR transgenic (Tg) mice has demonstrated that a monoclonal T cell population is able to control infection. At the chronic stage of infection, granuloma-infiltrating T cells remain highly activated in wild-type mice, while T cells in the monoclonal T cell mice are anergic. We hypothesized that addition of an acutely activated non-specific T cell to the monoclonal T cell system could recapitulate the wild-type phenotype. Here we report that activated non-specific T cells have access to the granuloma and deliver a set of cytokines and chemokines to the lesions. Strikingly, non-specific T cells rescue BCG-specific T cells from anergy and enhance the function of BCG-specific T cells in the granuloma in the chronic phase of infection when bacterial antigen load is low. In addition, we find that these same non-specific T cells have an inhibitory effect on systemic BCG-specific T cells. Taken together, these data suggest that T cells non-specific for granuloma-inducing agents can alter the function of granuloma-specific T cells and have important roles in mycobacterial immunity and other granulomatous disorders.

The effects of sample handling on proteomics assessed by reverse phase protein arrays (RPPA): Functional proteomic profiling in leukemia.

Reverse phase protein arrays (RPPA) can assess protein expression and activation states in large numbers of samples (n > 1000) and evidence suggests feasibility in the setting of multi-institution clinical trials. Despite evidence in solid tumors, little is known about protein stability in leukemia. Proteins collected from leukemia cells in blood and bone marrow biopsies must be sufficiently stable for analysis. Using 58 leukemia samples, we initially assessed protein/phospho-protein integrity for the following preanalytical variables: 1) shipping vs local processing, 2) temperature (4 °C vs ambient temperature), 3) collection tube type (heparin vs Cell Save (CS) preservation tubes), 4) treatment effect (pre- vs post-chemotherapy) and 5) transit time. Next, we assessed 1515 samples from the Children's Oncology Group Phase 3 AML clinical trial (AAML1031, NCT01371981) for the effects of transit time and tube type. Protein expression from shipped blood samples was stable if processed in ≤72 h. While protein expression in pre-chemotherapy samples was stable in both heparin and CS tubes, post-chemotherapy samples were stable in only CS tubes. RPPA protein extremes is a successful quality control measure to identify and exclude poor quality samples. These data demonstrate that a majority of shipped proteins can be accurately assessed using RPPA. SIGNIFICANCE: RPPA can assess protein abundance and activation states in large numbers of samples using small amounts of material, making this method ideal for use in multi-institution clinical trials. However, there is little known about the effect of preanalytical handling variables on protein stability and the integrity of protein concentrations after sample collection and shipping. In this study, we used RPPA to assess preanalytical variables that could potentially affect protein concentrations. We found that the preanalytical variables of shipping, transit time, and temperature had minimal effects on RPPA protein concentration distributions in peripheral blood and bone marrow, demonstrating that these preanalytical variables could be successfully managed in a multi-site clinical trial setting.

Anatomical brain MRI study of pediatric cancer survivors treated with chemotherapy: Correlation with behavioral measures.

The negative impacts of chemotherapy on pediatric patients treated with chemotherapy during the formative years of brain development are understudied compared to adult chemotherapy cancer patients. This work investigated the morphometry, cortical thickness, and subcortical volumes using MRI and their correlations with behavioral measures in pediatric oncology survivors treated with chemotherapy. Chemotherapy-treated childhood cancer survivors (N = 15, 15.12 ± 5.98 years old) diagnosed with a non-central nervous system malignancy and healthy age-matched controls (N = 15, 15.13 ± 4.21 years old) were studied. MRI was acquired at 3 Tesla. Behavioral Rating Inventory of Executive Functioning (BRIEF) Parental Rating, Purdue Pegboard manual dexterity and n-back working memory measures were administered. Structural MRI scans at 3 Tesla were acquired. Voxel-based morphometry, cortical thickness and subcortical volumes were analyzed and correlated with behavioral scores. Parametric statistics with a p < .05 and adjusted for multiple comparison corrections were performed. Patients exhibited significantly smaller gray-matter volumes in the left globus pallidum, bilateral thalami, left caudate and left nucleus accumbens (p < .05) and thinner cortex in the right parahippocampal gyrus (p < .05) compared to controls. BRIEF scores were similar to normative values. Purdue Pegboard revealed manual dexterity deficits compared to normative values, and the n-back task showed working-memory deficits in patients compared to controls. Left thalamus volume positively correlated with dexterity performance (p = .029). The number of correct answers positively correlated and the number of incorrect answers negatively correlated with total-brain and white-matter volume (p < .05), but not gray-matter volume (p > .05). Our results support the hypothesis that the neurotoxicity of systemic chemotherapy has widespread negative effects on brain development in pediatric oncology patients with relatively mild cognitive deficits. MRI identified neuroanatomical changes have the potential to provide neural correlates of the sequelae associated with pediatric chemotherapy.

A rare case of near-haploid acute lymphoblastic leukemia.

Near-haploid acute lymphoblastic leukemia is seen in <1% of cases and carries an unfavorable prognosis. We report a case in an 18-year old male. He presented with two abnormal clones, one with 27-28 and one with 54-56 chromosomes. Near-haploidy (27-28) carries a poor prognosis and hyperdiploidy (>50) has a good prognosis. The correct diagnosis was critical for this patient's prognosis and treatment. The patient achieved remission after a bone marrow transplant from a 10/10 HLA matched sibling donor. He relapsed six months later and expired seven months later. This case illustrates the need for careful standard and molecular cytogenetic analysis for accurate diagnosis and treatment for this rare type of ALL.

Anti-CD19 chimeric antigen receptor targeting of CD19 + acute myeloid leukemia.

Aberrant expression of CD19 in acute myeloid leukemia (AML) is commonly associated with t(8;21)(q22;q22), although AML cases lacking this translocation occasionally express CD19. Mixed-phenotype acute leukemia also frequently expresses CD19. Chimeric antigen receptor (CAR) technology is a major breakthrough for cancer treatment, with the recent approval of CD19-directed CAR (CD19CAR) for treating B-cell malignancies. However, little information exists on using CD19CAR for other CD19 positive neoplasms such as AML. Our findings indicate that CD19CAR therapy can potentially be used for those with mixed phenotype leukemia and a subset of AML cases.

Enrolling in Medicaid through the National School Lunch Program: outcome of a pilot project in California schools.

California has several health insurance programs for children. However, the system for enrolling into these programs is complex and difficult to manage for many families. Express Lane Eligibility is designed to streamline the Medicaid (called Medi-Cal in California) enrollment process by linking it to the National School Lunch Program. If a child is eligible for free lunch and the parents consent, the program provides two months of presumptive eligibility for Medi-Cal and a simplified application process for continuation in Medi-Cal. For those who are ineligible, it provides a referral to other programs. An evaluation of Express Lane shows that while many children were presumptively enrolled, nearly half of the applicants were already enrolled in Medi-Cal. Many Express Enrolled children failed to complete the full Medi-Cal enrollment process. Few were referred to the State Children's Health Insurance Program or county programs. Express Lane is less useful as a broad screening strategy, but can be one of many tools that communities use to enroll children in health insurance.

New targeted therapies for relapsed pediatric acute lymphoblastic leukemia.

INTRODUCTION: The improvement in outcomes for children with acute lymphoblastic leukemia (ALL) is one of the greatest success stories of modern oncology however the prognosis for patients who relapse remains dismal. Recent discoveries by high resolution genomic technologies have characterized the biology of relapsed leukemia, most notably pathways leading to the drug resistant phenotype. These observations open the possibility of targeting such pathways to prevent and/or treat relapse. Likewise, early experiences with new immunotherapeutic approaches have shown great promise. Areas covered: We performed a literature search on PubMed and recent meeting abstracts using the keywords below. We focused on the biology and clonal evolution of relapsed disease highlighting potential new targets of therapy. We further summarized the results of early trials of the three most prominent immunotherapy agents currently under investigation. Expert commentary: Discovery of targetable pathways that lead to drug resistance and recent breakthroughs in immunotherapy show great promise towards treating this aggressive disease. The best way to treat relapse, however, is to prevent it which makes incorporation of these new approaches into frontline therapy the best approach. Challenges remain to balance efficacy with toxicity and to prevent the emergence of resistant subclones which is why combining these newer agents with conventional chemotherapy will likely become standard of care.