Prognostic Factors In Adult Patients Research Articles

Significance of absolute neutrophil count before allogeneic hematopoietic stem cell transplantation in adult patients with aplastic anemia.

The impact of absolute neutrophil count (ANC) before allogenic hematopoietic stem cell transplantation (HSCT) on the outcomes for patients with aplastic anemia (AA) remains unclear. We retrospectively evaluated the relationship between ANC before transplantation and patient outcomes, involving 883 adult Japanese patients with AA who underwent allogeneic HSCT as their first transplantation between 2008 and 2020. Patients were divided into three groups based on ANC: 0/µL (n = 116); 1-199 (n = 210); and ≥ 200 (n = 557). In the low ANC groups (ANC < 200), patient age was higher, previous anti-thymocyte globulin (ATG) treatments were infrequent, duration from diagnosis to transplantation was shorter, hematopoietic cell transplantation-comorbidity index (HCT-CI) was higher, ATG-based conditioning was used infrequently, and peripheral blood stem cell from related donor and cord blood were used frequently. In multivariate analysis, patient age, previous ATG treatment, HCT-CI, stem cell source, and ANC before transplantation were significantly associated with 5-year overall survival (OS) ("ANC ≥ 200": 80.3% vs. "ANC 1-199": 71.7% vs. "ANC 0": 64.4%). The cumulative incidence of bacterial infection, invasive fungal disease, and early death before engraftment were significantly higher in the low ANC groups. Among patients with ANC of zero before transplantation, younger patient age, shorter duration from diagnosis to transplantation, HCT-CI of 0, and bone marrow from related donor as stem cell source were significantly associated with better OS. Consequently, ANC before allogeneic HSCT was found to be a significant prognostic factor in adult patients with AA. Physicians should pay attention to ANC before transplantation.

Clinical characteristics and prognostic factors of adult brainstem gliomas: A retrospective analysis of histologically-proven 40 cases.

To illustrate the clinical characteristics and prognostic factors of adult patients pathologically confirmed with brainstem gliomas (BSGs). Clinical data of 40 adult patients pathologically diagnosed with BSGs admitted to Beijing Shijitan Hospital from 2009 to 2022 were recorded and retrospectively analyzed. The primary parameters included relevant symptoms, duration of symptoms, Karnofsky performance status (KPS), tumor location, type of surgical resection, diagnosis, treatment, and survival. Univariate and multivariate analyses were evaluated by Cox regression models. The gliomas were located in the midbrain of 9 patients, in the pons of 14 cases, in the medulla of 5 cases, in the midbrain and pons of 6 cases and invading the medulla and pons of 6 cases, respectively. The proportion of patients with low-grade BSGs was 42.5%. Relevant symptoms consisted of visual disturbance, facial paralysis, dizziness, extremity weakness, ataxia, paresthesia, headache, bucking, dysphagia, dysacousia, nausea, dysphasia, dysosmia, hypomnesia and nystagmus. 23 (57.5%) patients accepted stereotactic biopsy, 17 (42.5%) patients underwent surgical resection. 39 patients received radiotherapy and 34 cases were treated with temozolomide. The median overall survival (OS) of all patients was 26.2 months and 21.5 months for the median progression-free survival (PFS). Both duration of symptoms (P = .007) and tumor grading (P = .002) were the influencing factors for OS, and tumor grading was significantly associated with PFS (P = .001). Duration of symptoms for more than 2 months and low-grade are favorable prognostic factors for adult patients with BSGs.

Mortality and Prognostic Factors of Adult Patients with Acute Leukemia Admitted to the ICU: A Systematic Review

Introduction: Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are the most aggressive group of hematologic malignancies (Pulte et al, 2020) and will be responsible for approximately 12,700 deaths in the U.S. during 2023(Seiger et al,2023). Improved overall survival (OS) has been observed in the past decades in both diseases, but high mortality in the Intensive Care Unit (ICU) persists, which may prevent ICU admission of those patients. We aimed to review the literature on mortality data and survival predictors of patients with acute leukemia (AL) admitted to the ICU. Methods: Embase, Pubmed and Cochrane databases were searched for articles published from January of 2005 to December of 2020. Due to OS improvement of patients with AML, we only included studies published as of 2005 (Percival et al, 2015). Editorials, case reports and small case series were excluded. Results: Initial search revealed 1,015 manuscripts from database and references, 650 were screened and 115 were fully assessed, for which 24 met eligibility criteria (Figure 1). A total of 13,350 patients were included in the review. Median age was 54.8 years and 57.3% of patients were male. AML represented the majority of diagnoses (98.2%).Two studies included only newly diagnosed patients, 1 study only included patients with relapsed disease and the rest (N=21) included subjects regardless of the AL status. Only 0.7% of patients had a history of hematopoietic stem cell transplantation . 81.9% of patients required mechanical ventilation, 25.3% needed renal replacement therapy, and 65.9% used vasopressors in studies data was available. Median SOFA score in the first 24h of ICU admission was 10.85 . Pooled ICU mortality and hospital mortality were 45.0% and 43.1%, respectively; 58.2% of patients were deceased at 90-day mark (Table 1). The 12 months OS was 37.3%. Higher SOFA score, need for mechanical ventilation, sepsis, vasopressor use, and age greater than 60 years were the most common predictors of ICU, hospital and 90-day mortality. Relapsed or refractory status of underlying AL was the most significant risk factor for long-term mortality. Conclusions: Our systemic review showed that ICU mortality in patients with AL was 45.0%, which represents a survival improvement compared to prior studies on patients with hematological malignancies, where ICU mortality could be as high as 69% (Ashkenazi et al, 1986). Predictors of ICU mortality were closely related to the severity of acute illness rather than malignancy status. We acknowledge that our patient population was mostly comprised of AML cases and the majority of the original studies included a small number of patients with AL with exception of one large study (Halpern et al, 2017).

Clinicopathological Characteristics, Survival Outcomes, and Prognostic Factors in Adult Patients With Sinonasal Rhabdomyosarcoma: Insights from a Retrospective Cohort Study.

Rhabdomyosarcoma (RMS) is a rare tumor with distinct morphological types and challenging diagnosis. This study aimed to investigate clinicopathological characteristics, survival outcomes, and factors influencing prognosis in adult patients with sinonasal RMS, addressing a critical gap in knowledge. This retrospective cohort study employed various statistical analyses to investigate patients with RMS. Descriptive statistics summarized demographic and clinical characteristics, while survival analysis using the Kaplan-Meier method and Cox proportional hazards model explored the relationship between covariates and survival outcomes. We analyzed 13 cases (7 males, 6 females) of sinonasal RMS. The average age at onset was 42.5 years (standard deviation 18.9). Tumors were observed in multiple locations, predominantly in the maxillary sinus (n=7), followed by the ethmoid sinus (n=5), and the sphenoid sinus (n=1). The study revealed a low survival rate, with 12 patients succumbing to the disease and only one patient surviving. Over time, survival probabilities declined from 92.31% (at 0.5 months) to 7.69% (at 45 months). The analysis indicated a borderline statistically significant positive association between age at diagnosis below 40 years and survival (p=0.05). Sex was found to be significantly associated with survival (p=0.03), with male patients exhibiting a higher survival rate (hazard ratio=0.08, 95%CI=0.01-0.81). This study highlights the complex nature of sinonasal RMS in adults. The low survival rate and distinct tumor locations emphasize the need for further research to improve diagnosis and treatment outcomes.

Characteristics and prognostic factors of adult patients with osteosarcoma from the SEER database.

Osteosarcoma is the most common bone malignancy. There are many studies on the prognostic factors of children and adolescents, but the characteristics and prognostic factors of adult osteosarcoma are rarely studied. The aim of this study was to construct a nomogram for predicting the prognosis of adult osteosarcoma. Information on all osteosarcoma patients aged ≥ 18 years from 2004 to 2015 was downloaded from the surveillance, epidemiology and end results database. A total of 70% of the patients were included in the training set and 30% of the patients were included in the validation set. Univariate log-rank analysis and multivariate cox regression analysis were used to screen independent risk factors affecting the prognosis of adult osteosarcoma. These risk factors were used to construct a nomogram to predict 3-year and 5-year prognosis in adult osteosarcoma. Multivariate cox regression analysis yielded 6 clinicopathological features (age, primary site, tumor size, grade, American Joint Committee on Cancer stage, and surgery) for the prognosis of adult osteosarcoma patients in the training cohort. A nomogram was constructed based on these predictors to assess the prognosis of adult patients with osteosarcoma. Concordance index, receiver operating characteristic and calibration curves analyses also showed satisfactory performance of the nomogram in predicting prognosis. The constructed nomogram is a helpful tool for exactly predicting the prognosis of adult patients with osteosarcoma, which could enable patients to be more accurately managed in clinical practice.

Prognostic factors for adult patients with Burkitt lymphoma treated with dose-adjusted EPOCH-R.

Prognostic factors for adult patients with Burkitt lymphoma treated with dose-adjusted EPOCH-R.

Next-generation sequencing-based MRD in adults with ALL undergoing hematopoietic cell transplantation.

Measurable residual disease (MRD) is an adverse prognostic factor in adult patients with acute lymphoblastic leukemia (ALL) undergoing hematopoietic cell transplant (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10-6, but the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult patients with ALL undergoing HCT, patients aged ≥18 years with ALL who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014 and April 2021 and were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed before HCT (MRDpre) and up to 1 year after HCT (MRDpost). Patients were followed up for leukemia relapse and survival for up to 2 years after HCT. In total, 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10-4 (hazard ratio [HR], 3.56; 95% confidence interval [95% CI], 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR, 4.60; 95%CI, 3.01-7.02). In exploratory analyses limited to patients with B-cell ALL, the detection of post-HCT immunoglobulin H (IgH) MRD clonotypes, rather than non-IgH MRD clonotypes, was associated with relapse. In this analysis across 2 large transplant centers, we found that the detection of MRD by NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT.

Obesity and risk of relapse in patients with Acute Lymphoblastic Leukemia: A retrospective study

Obesity has been associated with a low-grade proinflammatory state, and it has been related to the development of cancer in general, including hematologic cancer. The present work aimed to identify the association of the diagnosis of obesity according to the body mass index (BMI) with prognostic factors of adult patients with Acute Lymphoblastic Leukemia (ALL). This observational, retrospective study included hospitalized patients diagnosed with ALL of the B-cell lineages. BMI was estimated based on the weight and height registered on clinical records at the admission of the patients. The relapse risk and bone marrow relapse were determined, and the survival rate was measured. The statistical analysis included the Kaplan-Meier method using the log-Rank test. This study included 128 clinical records of patients. Weight had no significant association with relapse risk. The frequency of bone marrow relapse was 43.8%. Obesity did not impact overall survival (p = 0.640) or disease-free survival (p = 0.527). The presence of obesity does not behave as a relapse risk variable (p = 0.873). BMI with a 30 kg/m2 cut-off point did not influence relapse risk (OR 1.078). Obesity is not an independent risk factor for the prognosis of adult patients with Acute Lymphoblastic Leukemia B-lineage.

Implications of VP-Shunt, Sodium Level, Glucose Level Ratio and Neurologic Deficit as Clinical Outcome Prognostic Factor in Adult Meningitis Tuberculosis with Acute Hydrocephalus in Dr. Hasan Sadikin General Hospital

Introduction: Meningitis is the most severe and dangerous complication of tuberculosis, and can be fatal if not treated adequately. Acute hydrocephalus is often accompanied by tuberculous meningitis. This study aims to assess the prognostic factors in adult patients with tuberculous meningitis accompanied by hydrocephalus.&#x0D; Methods: The study was conducted retrospectively by collecting data from the medical records of patients with TB meningitis. Patient data were collected and analyzed using multiple logistic regression to obtain significant prognostic factors.&#x0D; Result: Fifty-four patients had Grade II TB meningitis and 42 patients had Grade III TB meningitis. In this study, it was found that patients with Grade III had higher mortality than patients with Grade II, especially within 30 days of treatment (HR = 3.73 (2.02-6.89), p&lt;0.0001). In patients with Grade II, low sodium levels increased the risk of mortality compared to near-normal sodium levels (HR = 4.22 (1.44-12.43), p = 0.0088). In patients with Grade III, VP-shunt action reduced the risk of mortality (HR = 0.23 (0.09-0.55), p = 0.0011). Meanwhile, the ratio of glucose levels and neurological deficits was not significant as a prognostic factor (p&gt;0.05).&#x0D; Conclusions: Patients with grade III TB meningitis generally have a high risk of mortality and require VP-Shunt intervention to increase life expectancy. In patients with grade II tuberculous meningitis, sodium level plays a role in determining the prognosis.

Prognostic factors of pediatric hematopoietic stem cell transplantation recipients admitted to the pediatric intensive care unit.

BackgroundPediatric patients who received hematopoietic stem cell transplantation (HSCT) tend to have high morbidity and mortality. While, the prognostic factors of adult patients received bone marrow transplantation were already known, there is little known in pediatric pateints. This study aimed to identify the prognostic factor for pediatric intensive care unit (PICU) mortality of critically ill pediatric patients with HSCT.MethodsRetrospectively reviewed that the medical records of patients who received HSCT and admitted to PICU between January 2010 and December 2019. Mortality was defined a patient who expired within 28 days.ResultsA total of 131 patients were included. There were 63 boys (48.1%) and median age was 11 years (interquartile range, 4–15 years). The most common HSCT type was haploidentical (38.9%) and respiratory failure (44.3%) was the most common reason for PICU admission. Twenty-eight–day mortality was 22.1% (29/131). In comparison between survivors and non-survivors, the number of HSCTs received, sepsis, oncological pediatric risk of mortality-III (OPRISM-III), pediatric risk of mortality-III (PRISM-III), pediatric Sequential Organ Failure Assessment (pSOFA), serum lactate, B-type natriuretic peptide (BNP) and use of mechanical ventilator (MV) and vasoactive inotropics were significant predictors (P<0.05 for all variables). In multivariate logistic regression, the number of HSCTs received, use of MV, OPRISM-III, PRISM-III and pSOFA were independent risk factors of PICU mortality. Moreover, three scoring systems were significant prognostic factors of 28-day mortality.ConclusionsThe number of HSCTs received and use of MV were more accurate predictors in pediatric patients received HSCT.

Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis

The present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.

Critical analysis of acute kidney injury in pediatric COVID-19 patients in the intensive care unit.

Background and objectivesCOVID-19 is responsible for the 2019 novel coronavirus disease pandemic. Despite the vast research about the adult population, there has been little data collected on acute kidney injury (AKI) epidemiology, associated risk factors, treatments, and mortality in pediatric COVID-19 patients admitted to the ICU. AKI is a severe complication of COVID-19 among children and adolescents.MethodsA comprehensive literature search was conducted in PubMed/MEDLINE and Cochrane Center Trials to find all published literature related to AKI in COVID-19 patients, including incidence and outcomes.ResultsTwenty-four studies reporting the outcomes of interest were included. Across all studies, the overall sample size of COVID positive children was 1,247 and the median age of this population was 9.1 years old. Among COVID positive pediatric patients, there was an AKI incidence of 30.51%, with only 0.56% of these patients receiving KRT. The mortality was 2.55% among all COVID positive pediatric patients. The incidence of multisystem inflammatory syndrome in children (MIS-C) among COVID positive patients was 74.29%.ConclusionAKI has shown to be a negative prognostic factor in adult patients with COVID-19 and now also in the pediatric cohort with high incidence and mortality rates. Additionally, our findings show a strong comparison in epidemiology between adult and pediatric COVID-19 patients; however, they need to be confirmed with additional data and studies.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00467-021-05084-x.

Clonal evolution detected with conventional cytogenetic analysis is a potent prognostic factor in adult patients with relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia

Additional cytogenetic abnormality (ACA) acquisition at relapse has been recognized as clonal evolution at the cytogenetic level, and has a significant prognostic impact on relapsed acute myeloid leukemia (AML) patients. We retrospectively investigated 48 relapsed Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients to clarify the clinical significance of ACA acquisition at the first relapse. Twenty-seven patients (56 %) acquired ACA at the first relapse. No significant predisposing factor for ACA acquisition was identified. Notably, patients with ACA acquisition showed a significantly lower second complete remission rate compared to those without ACA acquisition (14.8 % vs. 76.2 %, respectively; p < 0.01), and furthermore, the overall survival rates after the first relapse were significantly different between patients with and without ACA acquisition (25.9 % vs. 55.3 % at 1 year, respectively; p < 0.01). Multivariate analysis extracted ACA acquisition as the only negative prognostic factor (hazard ratio: 2.55, p < 0.01). All seven patients with ACA acquisition who underwent allogeneic transplant died within 2 years after relapse. These findings suggested that clonal evolution detected with conventional cytogenetic analysis at the first relapse triggers severe chemo-refractoriness in Ph-negative ALL cells, just like AML cells. Novel therapeutic strategies are warranted for this subset of patients.

Clinical characteristics and prognostic factors of adult patients with acute respiratory failure due to influenza infection

To investigate the clinical characteristics and prognostic predictors of adult patients with acute respiratory failure due to influenza infection. A retrospective analysis was performed on adult patients with acute respiratory failure due to confirmed influenza infection admitted to intensive care units (ICU) of the First Affiliated Hospital of Zhengzhou University and the Sixth People's Hospital of Zhengzhou between January 2018 and January 2020. The subjects were divided into survival and death groups according to whether the patients died before discharge. Demographic and clinical data including underlying conditions, laboratory variables, therapy and prognostic factors of hospital mortality between the two groups were analyzed. The risk factors of mortality were evaluated by univariate and multivariate Logistic regression analysis. Then, the correlation between lymphocyte (LYM) count and LYM subsets were analyzed. The survival rates of different acute physiologic and chronic health evaluation II (APACHE II) and LYM level subgroups were compared. A total of 104 patients were enrolled. Among them, 67 cases (64.4%) had underlying conditions, 91.3% of the patients (95 cases) were infected by influenza A virus, and the hospital mortality rate was 39.4% (41 cases). Compared with survival group, the patients of death group had higher respiratory rate (times/min: 26.0±5.6 vs. 23.7±5.0), APACHE II score (18.20±4.88 vs. 12.35±4.58), procalcitonin [PCT (μg/L): 0.82 (0.23, 4.63) vs. 0.39 (0.11, 0.92)], higher percentage of cardiovascular disease [24.4% (10/41) vs. 7.9% (5/63)] and invasive mechanical ventilation [63.4% (26/41) vs. 17.5% (11/63), all P < 0.01], but had lower oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 131.8±34.5 vs. 181.7±31.6] at ICU admission, LYM (×109/L: 0.53±0.40 vs. 0.92±0.44), hemoglobin [Hb (g/L): 105.66±28.17 vs. 118.29±28.29], platelet count [PLT (×109/L): 135.12±85.40 vs. 199.81±110.11], T lymphocyte count [cells/μL: 181 (131, 275) vs. 319 (238, 528)], CD4+ count [cells/μL: 110 (71, 161) vs. 190 (120, 311)] and CD8+ count [cells/μL: 71 (33, 100) vs. 121 (81, 188), all P < 0.01]. Patients of death group also had a shorter length of hospital stay [days: 7.0 (4.0, 11.0) vs. 12.0 (8.0, 20.0), P < 0.01]. Univariate analysis showed that APACHE II score [odds ratio (OR) = 1.207, 95% confidence interval (95%CI) was 1.094-1.332, P < 0.001], LYM (OR = 0.070, 95%CI was 0.018-0.271, P < 0.001), Hb (OR = 0.984, 95%CI was 0.970-0.999, P = 0.031), PLT (OR = 0.992, 95%CI was 0.987-0.997, P = 0.003), T lymphocyte count (OR = 0.996, 95%CI was 0.993-0.998, P = 0.001) and PaO2/FiO2 (OR = 0.955, 95%CI was 0.938-0.972, P < 0.001) were the risk factors for the prognosis of influenza patients with acute respiratory failure. Further multivariate Logistic analysis also showed that APACHE II score (OR = 1.195, 95%CI was 1.041-1.372, P = 0.011), LYM (OR = 0.063, 95%CI was 0.011-0.369, P = 0.002) and PaO2/FiO2 (OR = 0.953, 95%CI was 0.933-0.973, P < 0.001) were the predictors of mortality. Moreover, patients with peripheral blood LYM < 0.65×109/L or APACHE II score > 14 had a higher risk of poor outcome. There were significantly positive correlation between LYM and LYM subsets (T lymphocyte, CD4+ and CD8+ lymphocyte, r value was 0.593, 0.563, and 0.500, respectively, all P < 0.001). Influenza patients with acute respiratory failure were critically ill and had a high mortality rate. APACHE II score, PaO2/FiO2 and LYM at ICU admission were independent risk factors affecting the prognosis of patients.

A CASE OF FATAL SEPTIC SHOCK IN SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) ASSOCIATED WITH BACTERIAL INFECTION IN THE ICU SETTING

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: HLH is a rare systemic inflammatory disease with a high rate of mortality. Early diagnosis and urgent intervention are therefore crucial for survival. Primary HLH is mostly seen in children and is caused by an underlying genetic mutation. Secondary HLH is a rare clinical condition, and its underlying pathophysiology isn’t well studied, but common triggers include underlying infections, malignancies, and autoimmune diseases. We present a case of an 80 yo F presenting with altered mental status (AMS) and fever progressing to septic shock. CASE PRESENTATION: 80 yo F from Bangladesh with PMH of HTN, Asthma, Afib, CVA admitted with worsening AMS for 3 months. Urine culture grew E.coli. Chest X-ray revealed bilateral pneumonia. She was started on antibiotics. Labs on presentation were notable for pancytopenia, requiring transfusion of blood products, ferritin >9900, Total Bilirubin/Direct/ALKP/ALT/AST - 20.4/16.3/857/808/3485. HIV, Hep A, B, C negative with unremarkable right upper quadrant ultrasound. CT chest showing mediastinal lymphadenopathy with the largest subcarinal node of 2.5 cm. Despite aggressive treatment, the patient developed septic shock. Her hemodynamic status deteriorated requiring mechanical ventilation and vasopressors. Bone marrow biopsy (BMP) was considered to rule out underlying hematologic disorder given mediastinal lymphadenopathy and bicytopenia. The patient expired before the biopsy results were reported. BMP confirmed the diagnosis of HLH showing histiocytes with hemophagocytosis. DISCUSSION: Secondary HLH can be triggered by infections, autoimmune diseases and malignancies, with the majority of cases occurring in ICU going underdiagnosed and carrying a poor prognosis with a high mortality rate. Manifestation varies between individual cases and It can present with a combination of various symptoms and signs. Secondary HLH is difficult to identify as it can mimic septic shock with progressive multiorgan failure. HLH 2004 diagnostic criteria require 5/8 findings (Table 1). Modified criteria are useful as it’s common for a patient with HLH to exhibit only 3-4/8. Retrospective studies have identified infections as common precipitating factors, with one study showing bacterial organisms to be the predominant trigger among infectious agents, and another one showing viral infection as a more common provoking factor. The mainstay of treatment involves immuno/myelosuppressive agents. CONCLUSIONS: Secondary HLH is a multisystem disorder caused by uncontrolled immune activation. Although big prospective studies for data analysis of diagnostic modalities and prognostic factors are lacking, a high index of suspicion for HLH should be maintained for adults presenting with the above-mentioned manifestations. Further understanding and refined diagnostic criteria are important for early diagnosis and implementing disease-modifying therapies for this life-threatening syndrome. Reference #1: Raschke RA1, Garcia-Orr R2. Hemophagocytic lymphohistiocytosis: a potentially underrecognized association with systemic inflammatory response syndrome, severe sepsis, and septic shock in adults. Chest. 2011 Oct;140(4):933-938. Reference #2: Jae-Ho Yoon, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, and Jong Wook Lee. Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis not associated with malignancy. Chest. 2011 Oct;140(4):933-938. Reference #3: Sameer A Parikh, Prashant Kapoor, Louis Letendre, Shaji Kumar, Alexandra P Wolanskyj. Prognostic Factors and Outcomes of Adults With Hemophagocytic Lymphohistiocytosis. Mayo Clinic Proceedings 2014, 89 (4): 484-92 DISCLOSURES: No relevant relationships by Mariam Agladze, source=Web Response No relevant relationships by Theo Trandafirescu, source=Web Response

Panel-based next-generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings.

Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30-40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next-generation sequencing (NGS) of >150 cancer-related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3-ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel-based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel-based NGS approach into the clinical setting may allow for a patient-oriented strategy of precision treatment for childhood AML.

Clinical characteristics and prognostic factors of adult patients with pilocytic astrocytoma

IntroductionPilocytic astrocytoma (PA) is the most common primary brain neoplasm in children and treated in curative intent with gross total resection (GTR). However, PA is rare in adults, resulting in limited knowledge on the natural clinical course. This study aimed to describe the clinical course and identify prognostic factors of adult patients with PA.Methods46 patients ≥ 18 years at diagnosis of PA and neurosurgical resection or biopsy between 2000 and 2018 were identified from the Neuro-Biobank of the Medical University of Vienna. In two cases with differing histopathological diagnosis at recurrence, DNA methylation analysis was performed using Illumina Infinium HumanMethylation850 BeadChip (850 k) arrays and the Molecular Neuropathology classifier. Clinico-pathological features were correlated with patient outcomes.ResultsMedian age at diagnosis was 32.5 years (range: 19–75) and median Ki67 proliferation index was 2.8% (0.5–13.4%). Tumor location significantly correlated with resectability (p < 0.001). Tumor progression or recurrence was observed in 9/46 (19.6%) patients after a median follow up time of 53.0 months (range 0.5–300). 5-year overall and progression-free survival rates were 85.3% and 70.0%, respectively. 2/9 (22.2%) patients presented with histological changes in the recurrent tumor specimen. In detail, methylation classification redefined the histological diagnosis to anaplastic astrocytoma with piloid features and glioma in one patient, each. Age > 40 and higher body mass index (BMI) were associated with impaired progression-free and overall survival (p < 0.05).ConclusionsTumor recurrence or progression in adult PA patients was higher than the one reported in pediatric patients. Higher age and BMI were associated with impaired prognosis.

Embryonal and Alveolar Rhabdomyosarcoma in Adults: Real-Life Data From a Tertiary Sarcoma Centre

AimsEmbryonal and alveolar rhabdomyosarcoma (ERMS, ARMS) are subtypes of RMS that mainly occur in children, with relatively good outcomes. The incidence in adults is extremely low and survival is significantly worse compared with children. Data are scarce and literature generally combines all RMS subtypes, including pleomorphic RMS, which primarily occurs in adults and behaves more like undifferentiated pleomorphic sarcoma. The aim of this study was to evaluate patient and tumour characteristics, outcome and prognostic factors in adult patients with ERMS and ARMS. Materials and methodsAll adult (18 years or older) ERMS and ARMS patients (presenting 1990–2016) were identified from a prospectively maintained database and were included in this analysis. ResultsOverall, 66 patients were included (42 men, 24 women). The median age at presentation was 28 years (range 18–71). The median overall survival for all ARMS (n = 42) and ERMS (n = 24) patients was 18 months, with a 5-year overall survival rate of 27%. Patients presenting with localised disease (n = 38, 58%) and metastatic disease (n = 25, 42%), had a 5-year overall survival rate of 36% and 11%, respectively. In univariate analysis we found alveolar subtype, fusion gene positivity, infiltrative tumour and metastatic presentation to be negative prognostic factors. ConclusionSurvival in adult ERMS and ARMS patients is poor and the current data may be useful in the design of trials with novel agents. Ideally, paediatric and adult oncologists should set up trials together to get a better understanding of biological, genetic and clinically relevant factors in this disease.

Prognostic factors for adult patients with hemorrhagic moyamoya disease in the acute stage

ObjectivesHemorrhagic moyamoya disease (MMD) is one common subtype in adult patients. However, the study about outcome of hemorrhagic MMD patients in the acute stage is still lacking. This study is aimed to explore the short-term prognostic factors for adult patients with hemorrhagic MMD in the acute stage. Patients and MethodsAdult hemorrhagic MMD patients in the acute stage awere retrospectively analyzed. Both clinical and imaging data were collected. Unfavorable functional outcome at discharge was considered when modified Rankin Scale score ≥3. Multivariate logistic regression was used to investigate the prognostic factors in patients with hemorrhagic MMD in the acute stage. ResultsA total of 107 patients were included in this study. Among these patients, 17 died and 59 had unfavorable functional outcome at 9.6 ± 7.8 days. In multivariate logistic regression, admission blood glucose (odds ratio (OR) = 1.457, 95% confidence interval (CI) 1.156–1.836, P = 0.001), midline shift >5 mm (OR = 24.268, 95%CI 4.324–136.191, P < 0.001), and subarachnoid hemorrhage (OR = 13.067, 95%CI 2.020–84.512, P = 0.007) were independently associated with death at discharge. Moreover, admission Glasgow Coma Scale (GCS) score (OR = 0.420, 95%CI 0.296–0.598, P < 0.001), midline shift >5 mm (OR = 6.685, 95%CI 1.226–36.455, P = 0.028), and intraparenchymal hemorrhage (OR = 4.790, 95%CI 1.184–19.381, P = 0.028) were independently associated with unfavorable functional outcome at discharge. ConclusionThis study shows that admission blood glucose, midline shift >5 mm, and subarachnoid hemorrhage are independent predictors of short-term mortality in hemorrhagic MMD in the acute stage. In addition, admission GCS score, midline shift >5 mm, and intraparenchymal hemorrhage are independent predictors of short-term unfavorable functional outcome in hemorrhagic MMD in the acute stage.

NPM1 High Mutant Allele Burden is an Adverse Prognostic Factor for AML Patients with Mutated NPM1

To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1+AML). Seventy-three patients with newly diagnosed adult NPM1+AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors. A total of 74 NPM1 site mutations were detected in 73 patients with NPM1+AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1+AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1highAML) and NPM1 VAF≤38.4% (NPM1lowAML). Compared with NPM1lowAML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 d，95%CI 58-238 d vs 372 d，95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1high AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1+AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1+AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01). The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.