scholarly journals Fungal diagnostic testing and therapy: navigating the neutropenic period in children with high-risk leukemia

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 361-367
Author(s):  
Brian T. Fisher
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Diagnostic Testing ◽  
Standard Of Care ◽  
Invasive Fungal Disease ◽  
Published Data ◽  
Therapeutic Approaches ◽  
Empirical Antifungal Therapy ◽  
Therapeutic Recommendations ◽  
The Impact

Abstract Children, adolescents, and young adults receiving intensive chemotherapy for acute myeloid leukemia or high-risk or relapsed acute lymphoblastic leukemia sustain prolonged periods of neutropenia that predispose them to invasive fungal disease (IFD). For many decades the standard of care for these patients was to initiate empirical antifungal therapy after a period of prolonged fever and neutropenia. Recent publications have yielded important evidence on the utility of different diagnostic and therapeutic approaches aimed at reducing the impact of IFD among these patients during these vulnerable periods. This case-based review highlights and interprets the published data to provide context for the IFD diagnostic and therapeutic recommendations proposed in multiple published guidelines. Personalized approaches are offered at points where evidence is lacking. Time points where specific knowledge gaps exist are identified along the clinical trajectory of the prolonged neutropenic period to illustrate areas for future investigation.

149 Use of Risk Model for Assessment of Residents Perception of Complexity of Surgical Steps

Neurosurgery ◽  
2015 ◽  
Vol 62 (CN_suppl_1) ◽  
pp. 214-214
Author(s):  
Ahmed M. Raslan ◽  
Jeffrey Steven Raskin ◽  
Jesse Jia-Xin Liu
Keyword(s):  
High Risk ◽  
Operative Time ◽  
Resident Education ◽  
Comfort Level ◽  
Matrix Analysis ◽  
Published Data ◽  
Dependent Manner ◽  
Risk Matrix ◽  
Danger Zone ◽  
The Impact

Abstract INTRODUCTION: Quality improvement projects have begun to standardize surgical work flow as a component to optimize operative room (OR) efficiency. Removing special cause variability resulting from nonsurgical waste is an obvious target; however, surgical resident education must be maintained even in the setting of process improvement. There are no published data describing the impact on operative time of resident-identified risky or uncomfortable procedural steps during posterior instrumented fusion (PIF). Self-identification of risk or discomfort in surgical steps may allow for shorter OR time and reduced cost, without sacrificing resident education. METHODS: PIF procedure steps were defined. An 8 two-part question survey regarding surgeon comfort level and perceived risk assessment at each step was developed, and completed by junior (17) and senior residents (10), and faculty (6) from orthopedic and neurological surgeons. A risk matrix was constructed defining 2 zones, a “danger zone” where responses were both high risk (3–5) and low comfort (1–3) and a “safe zone” where responses were low risk (1–2) and high comfort (4–5). One-tailed χ2 with Yates correction was performed. RESULTS: Risk matrix analysis showed a statistical difference among danger zone respondents between junior resident and faculty groups for exposure, pedicle screw placement, neural decompression, interbody placement, posterolateral fusion, and hemostasis (Table 2). Radar graph identifies percentage of respondents who fall within the danger zone (Figure 1). CONCLUSION: Resident perception of surgical complexity can be evaluated for procedural steps using a risk matrix survey. For PIF, residents assign more risk and are less comfortable performing steps in a training-dependent manner. Identification of particular high-risk steps, which are uncomfortable, should prompt strict faculty oversight to improve patient safety, monitor resident education, and reduce operative time.

scholarly journals Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia Randomly Assigned to Different Methotrexate and Corticosteroid Treatment Strategies: A Report From the Children’s Oncology Group

2017 ◽  
Vol 35 (23) ◽  
pp. 2700-2707 ◽  
Author(s):  
Kristina K. Hardy ◽  
Leanne Embry ◽  
John A. Kairalla ◽  
Shanjun Helian ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
Corticosteroid Treatment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Outcomes ◽  
Leucovorin Rescue ◽  
B Lineage ◽  
The Impact

Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.

scholarly journals Unique Molecular Features in High-Risk Histology Endometrial Cancers

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1665 ◽  
Author(s):  
Pooja Pandita ◽  
Xiyin Wang ◽  
Devin E. Jones ◽  
Kaitlyn Collins ◽  
Shannon M. Hawkins
Keyword(s):  
Endometrial Cancer ◽  
High Risk ◽  
Early Stage ◽  
Standard Of Care ◽  
The United States ◽  
Model Systems ◽  
Low Grade ◽  
Cell Of Origin ◽  
Molecular Features ◽  
The Impact

Endometrial cancer is the most common gynecologic malignancy in the United States and the sixth most common cancer in women worldwide. Fortunately, most women who develop endometrial cancer have low-grade early-stage endometrioid carcinomas, and simple hysterectomy is curative. Unfortunately, 15% of women with endometrial cancer will develop high-risk histologic tumors including uterine carcinosarcoma or high-grade endometrioid, clear cell, or serous carcinomas. These high-risk histologic tumors account for more than 50% of deaths from this disease. In this review, we will highlight the biologic differences between low- and high-risk carcinomas with a focus on the cell of origin, early precursor lesions including atrophic and proliferative endometrium, and the potential role of stem cells. We will discuss treatment, including standard of care therapy, hormonal therapy, and precision medicine-based or targeted molecular therapies. We will also discuss the impact and need for model systems. The molecular underpinnings behind this high death to incidence ratio are important to understand and improve outcomes.

Treatment Intensification of Traditional BFM Therapy with 3 Chemotherapy Blocks and Double Delayed Intensification (Protocol II) Improves Outcome in Infants with High Risk (HR) Acute Lymphoblastic Leukemia (ALL): Results of Two Consecutive AIEOP Studies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 871-871 ◽  
Author(s):  
Carmelo Rizzari ◽  
Maria Grazia Valsecchi ◽  
Paola De Lorenzo ◽  
Maurizio Aricò ◽  
Giuseppe Basso ◽  
...  
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Strategies ◽  
High Dose Chemotherapy ◽  
P Value ◽  
High Dose ◽  
Treatment Intensification ◽  
Treatment Protocols ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Introduction: Cure rates of ALL in children aged less than one year (i.e. infants) at diagnosis are in the range of 35–40%. Encouraging results have been recently reported in infants by using intensified treatment, including high dose chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR). Aim: To evaluate the impact of the two treatment strategies adopted in the AIEOP ALL 91 and 95 studies on the outcome of ALL in infants. Patients and Methods: Fifty-two infants with ALL were enrolled between 1991 and 1999 in two consecutive studies, named AIEOP ALL 91 and ALL 95. Infants with an identified t(4;11) translocation had to be included in the high risk (HR) groups whilst those without this genetic abnormality could be treated in the intermediate (IR) or HR groups according to presenting features and treatment response. Patients belonging to the IR groups received a traditional BFM back-bone based treatment (protocols I, M and II), while those classified in the HR groups underwent an tensified treatment including induction (BFM protocol IA only, in study AIEOP ALL 91, and IA+IB in study ALL 95), consolidation with either 9 blocks of non-cross-resistant drugs (ALL 91) or 3 blocks followed by the 8-drug reinduction regimen - BFM protocol II - repeated twice (ALL 95). All patients were given a continuation phase (reinforced in HR patients of study ALL 95 by vincristine/prednisone pulses). Overall treatment duration was 2 years in both studies. Results: Infants in studies ALL 91 (n=21) and ALL 95 (n=31) had similar biological and clinical characteristics. The overall event-free survival (EFS) at 5 years was 45.0% (SE 7.0%). The EFS, after censoring for HSCT in 1st CR, was 38.1% (SE 11.4%) in ALL 91 and 51.6% (SE 9.9%) in ALL 95 (p-value=0.29). Patients treated in the IR arm of the two studies had a similar outcome. Better results were obtained in patients treated in the HR arm of ALL 95 study, where 9/17 chemotherapy-only patients and 3/4 HSCT patients are alive in CCR as compared to 1/7 and 0/2, respectively, in patients treated in the ALL 91 study. Discussion: These data show that full traditional BFM therapy intensified by 3 post-induction chemotherapy blocks and double protocol II (adopted in study ALL 95), is associated with a better outcome in infants with HR ALL.

Intensification of Chemotherapeutic Regimens and Hematopoietic Stem Cell Transplantation Are Responsible for Improved Overall Survival in Adult Acute Lymphoblastic Leukemia in a Single Center Over the Last Forty Years

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4227-4227
Author(s):  
Estrella Carrillo ◽  
Nancy Rodriguez ◽  
Juan Francisco Dominguez ◽  
Jose Gonzalez ◽  
Jose Francisco Falantes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Central Nervous System Involvement ◽  
Male Gender ◽  
Hematopoietic Stem ◽  
System Involvement ◽  
The Impact

Abstract Abstract 4227 Background Acute lymphoblastic leukemia (ALL) of adults is an infrequent and heterogeneous disease according to presentation pattern, prognosis and treatment. It is widely assumed that age above 30 years, leukocytosis >25 ×109/L, central nervous system involvement and specific cytogenetic disorders such as t(9;22) or MLL rearrangement entail bad prognosis. There are controversial studies on the impact of intensification chemotherapy and hematopoietic stem cell transplantation (HSCT) on survival of these high-risk groups. Aims To identify biological, clinical and prognostic characteristics in adult ALL patients diagnosed and followed in a single center throughout 40 years as long as the impact on clinical outcome of different consecutive therapeutic approaches, including HSCT, in different periods. Patients and methods Throughout 1970 to 2011, 230 patients were prospectively registered and retrospectively analyzed. Most patients accomplishing pre-determined criteria received treatment according to PETHEMA or locally developed therapeutic protocols (including HSCT in relapse high-risk patients, since 1978). Critical variables at diagnosis such as age, gender, phenotype (from 1978), cytogenetic (from 1999), white blood cells count (WBC) and central nervous system involvement, were analyzed. Response to induction chemotherapy, relapse rate (RR) and 5 year overall survival (OS) were analyzed in the whole cohort and separately by decade when treatment protocols were different. The clinical impact of HSCT was analyzed on a subgroup of patients homogeneously treated since 1994. Statistical analysis was performed by mean of Chi-square and Kaplan Meier tests, as appropriate. Outcome Table 1 summarizes the presentation pattern and its prognostic value. At diagnosis features such male gender, age above 30 years, central nervous system involvement, leukocytosis >10×109/L, MLL rearrangement, t(9:22) and complex karyotype entailed a worse prognosis. For the whole cohort the 5 years OS was 30%. CR was achieved in 73% and the RR was 38%. 5 years OS has improved by decades: 11% in the 70s, 24% in the 80s, 30% in the 90s, and 41% in XXI century (p<0,01). Patients selected for intensive chemotherapeutic protocols achieved a similar CR rate in each decade (nearly 80%) while the RR decreased through the years (70s: 68%, 80s: 44%, 90: 42%, 00–11: 25%; p<0,01). Patients treated with chemotherapy plus HSCT achieved in 5 years (from 1994) an OS of 69% in comparison with the 30% obtained in those patients who only received chemotherapy (p<0,01). Conclusion Male gender, age above 30, WBC >10×10e9/L, t(9;22), MLL-rearrangement, complex karyotype and CNS involvement conferred poor prognosis in adult ALL. Intensification of chemotherapeutic regimens produced a progressive decrease in relapse rate, leading to an improvement in overall survival over the years. HSCT seems to partially overcome the poor prognosis related to high risk factors. Disclosures: Perez-Simón: Janssen-Cilag: Patents & Royalties.

scholarly journals Improved Survival for Children and Adolescents With Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report From the Children's Oncology Group

2012 ◽  
Vol 30 (14) ◽  
pp. 1663-1669 ◽  
Author(s):  
Stephen P. Hunger ◽  
Xiaomin Lu ◽  
Meenakshi Devidas ◽  
Bruce M. Camitta ◽  
Paul S. Gaynon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Population Based ◽  
Oncology Group ◽  
Clinical Covariates ◽  
The Impact

Purpose To examine population-based improvements in survival and the impact of clinical covariates on outcome among children and adolescents with acute lymphoblastic leukemia (ALL) enrolled onto Children's Oncology Group (COG) clinical trials between 1990 and 2005. Patients and Methods In total, 21,626 persons age 0 to 22 years were enrolled onto COG ALL clinical trials from 1990 to 2005, representing 55.8% of ALL cases estimated to occur among US persons younger than age 20 years during this period. This period was divided into three eras (1990-1994, 1995-1999, and 2000-2005) that included similar patient numbers to examine changes in 5- and 10-year survival over time and the relationship of those changes in survival to clinical covariates, with additional analyses of cause of death. Results Five-year survival rates increased from 83.7% in 1990-1994 to 90.4% in 2000-2005 (P < .001). Survival improved significantly in all subgroups (except for infants age ≤ 1 year), including males and females; those age 1 to 9 years, 10+ years, or 15+ years; in whites, blacks, and other races; in Hispanics, non-Hispanics, and patients of unknown ethnicity; in those with B-cell or T-cell immunophenotype; and in those with National Cancer Institute (NCI) standard- or high-risk clinical features. Survival rates for infants changed little, but death following relapse/disease progression decreased and death related to toxicity increased. Conclusion This study documents ongoing survival improvements for children and adolescents with ALL. Thirty-six percent of deaths occurred among children with NCI standard-risk features emphasizing that efforts to further improve survival must be directed at both high-risk subsets and at those children predicted to have an excellent chance for cure.

scholarly journals The impact of donor type on the outcome of pediatric patients with very high risk acute lymphoblastic leukemia. A study of the ALL SCT 2003 BFM-SG and 2007-BFM-International SG

2020 ◽  
Vol 56 (1) ◽  
pp. 257-266
Author(s):  
Jean-Hugues Dalle ◽  
Adriana Balduzzi ◽  
Peter Bader ◽  
Anna Pieczonka ◽  
Isaac Yaniv ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Pediatric Patients ◽  
Ex Vivo ◽  
Lymphoblastic Leukemia ◽  
Stem Cell Source ◽  
Donor Type ◽  
The Impact ◽  
Very High

AbstractAllogeneic HSCT represents the only potentially curative treatment for very high risk (VHR) ALL. Two consecutive international prospective studies, ALL-SCT-(I)BFM 2003 and 2007 were conducted in 1150 pediatric patients. 569 presented with VHR disease leading to any kind of HSCT. All patients >2 year old were transplanted after TBI-based MAC. The median follow-up was 5 years. 463 patients were transplanted from matched donor (MD) and 106 from mismatched donor (MMD). 214 were in CR1. Stem cell source was unmanipulated BM for 330 patients, unmanipulated PBSC for 135, ex vivo T-cell depleted PBSC for 62 and cord-blood for 26. There were more advanced disease, more ex vivo T-cell depletion, and more chemotherapy based conditioning regimen for patients transplanted from MMD as compared to those transplanted from MSD or MD. Median follow up (reversed Kaplan Meier estimator) was 4.99 years, median follow up of survivals was 4.88, range (0.01–11.72) years. The 4-year CI of extensive cGvHD was 13 ± 2% and 17 ± 4% (p = NS) for the patients transplanted from MD and MMD, respectively. 4-year EFS was statistically better for patients transplanted from MD (60 ± 2% vs. 42 ± 5%, p < 0.001) for the whole cohort. This difference does not exist if considering separately patients treated in the most recent study. There was no difference in 4-year CI of relapse. The 4-year NRM was lower for patients transplanted from MD (9 ± 1% vs. 23 ± 4%, p < 0.001). In multivariate analysis, donor-type appears as a negative risk-factor for OS, EFS, and NRM. This paper demonstrates the impact of donor type on overall results of allogeneic stem cell transplantation for very-high risk pediatric acute lymphoblastic leukemia with worse results when using MMD stem cell source.

Raising the standard of care in the treatment of schizophrenia: Yes we can!

2017 ◽  
Vol 51 (5) ◽  
pp. 438-440 ◽  
Author(s):  
Stanley Victor Catts ◽  
Brian O’Toole
Keyword(s):  
Communication Skills ◽  
Critical Review ◽  
Treatment Effectiveness ◽  
Standard Of Care ◽  
Financial Resources ◽  
First Episode ◽  
Published Data ◽  
Decision Making Capacity ◽  
The Impact

Objective: In response to evidence of deteriorating outcomes of people with schizophrenia we recently published a critical review in the journal concerning why outcomes for schizophrenia are not improving. A published commentary on our review raised criticisms that we aim to address herein. Method: Published data related to four issues raised in the commentary were reviewed. Results: There is a body of evidence that supports the possibility of dramatic improvements in treatment effectiveness, presented in our critical review, and these can be achieved within existing financial resources and present day understanding of the pathophysiology of schizophrenia. However, the commentary leads us to highlight four current obstacles to improving treatment effectiveness: (1) the belief of many psychiatrists that long-term antipsychotic medication raises the cardiovascular mortality rate in schizophrenia when the opposite is almost certainly the case; (2) the need to improve psychiatrist training in diagnostic and communication skills, especially with first episode presentations; (3) the requirement for comprehensive and structured assessment of the highly prevalent deficits in insight and decision making capacity associated with schizophrenia; and (4) the need for improved intervention design to minimise the impact of these deficits on treatment choice and refusal. Conclusion: With a sense of professional urgency, a genuinely respectful and caring partnership between clinicians, affected individuals and their families, and researchers, with relative little innovation, we conclude that the standard of care can definitely be raised now in the treatment of schizophrenia.

Impact of a PERT initiative on hospital mortality of patients with bilateral pulmonary embolism

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Ramos Lopez ◽  
T Luque Diaz ◽  
C Ferrera ◽  
D Enriquez Vazquez ◽  
P Mahia Casado ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Hospital Mortality ◽  
Troponin I ◽  
Secondary Analysis ◽  
Standard Of Care ◽  
Orotracheal Intubation ◽  
Risk Profile ◽  
Rapid Response Teams ◽  
The Impact

Abstract Background Implication of rapid-response teams have demonstrated significant improvement in several cardiovascular diseases, such as myocardial infarction and stroke. Thus, pulmonary embolism (PE) response teams (PERT) for the management of high-risk PE are encouraged in the guidelines. Purpose We aimed to assess the impact of a PERT initiative on hospital mortality. PERT was designed to manage patients with bilateral PE with RV/LV ratio &gt;0.9 and positive biomarkers. Methods We prospectively recruited all consecutive patients with intermediate-high and high-risk bilateral PE who required PERT activation from February-2018 to September-2019 (PERT group, n=56 patients). We compared them with patients with bilateral PE admitted to our hospital in a previous 2-year period (2014–2016), managed with standard of care (SC-group, n=172 patients). As a secondary analysis, we focused on patients with a RV/LV ratio&gt;0.9 (n=52, in the SC-group; n=55, 98% in the PERT-group). Results Results are shown on Table. The SC-group had a lower risk profile at admission (lower PESI score, heart rate, and higher oxygen saturation), compared to PERT-group. The proportion of patients with RV enlargement on CT (RV/LV &gt;0.9) was lower in the retrospective cohort (p&lt;0.001). Peak Troponin I was significantly higher in the PERT-group (Table). Reperfusion treatment was more frequently needed in PERT patients. On the contrary, there was no difference in the use of vasopressors (5.8% vs 12.5%, p=0.098) and orotracheal intubation (4.1% vs 5.4%, p=0.689) between groups. In-hospital mortality was lower in the PERT-group in the whole cohort (Table) and much lower when considering patients with RV/LV ratio&gt;0.9 (17.6% vs 1.8%, p=0.005). Conclusion PERT initiative is associated with a significant reduction in mortality compared to the standard of care in patients with bilateral high-risk PE. Funding Acknowledgement Type of funding source: None

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