Incidence Of Early Death Research Articles

Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia.

In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117-) in 169 APL patients treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. The median follow-up period was 63.0 months. CD117- was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117- subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117- APL (p = 0.023). By multivariate analysis, CD117- was an independent adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) (p = 0.022 and p = 0.014, respectively). To sum up, CD117- is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk-adapted therapeutic strategies in APL management.

How to avoid early mortality in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL), a phenotypically and genotypically unique subtype of acute myeloid leukemia, has seen unprecedented advances in its management since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide. However, the phenomenal pharmacologic conversion of this once highly fatal disease to one with a long-term survival exceeding 90% among patients who survive induction remains impaired by the significant incidence of early death (ED) reaching 30% in some real-world studies. The key driver for ED in APL is catastrophic hemorrhage with a proclivity for cranial sites. Most EDs in APL are currently considered preventable. Here, we discuss the concept of early death in APL and its characteristics. Importantly, we outline implementable strategies to reduce the incidence of ED. Early recognition of APL underpins these preventive measures as significant delays in the diagnosis increase the likelihood of ED. While early administration of ATRA is often taught to all hematology trainees, this lifesaving intervention is only possible if providers, including those in emergency departments and urgent/immediate care settings, are trained to have a high index of suspicion and competence to recognize the morphologic and clinical characteristics of the disease. Other proposed strategies tackle the complications that can be present at diagnosis or arise during induction therapy and address the issues of expert consultation and protocol adherence in the management of these patients. While some of these measures appear intuitive and others aspirational, widespread adoption could bring about an era of cure for almost every patient with APL.

Influence of cytokines on early death and coagulopathy in newly diagnosed patients with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with a better prognosis. But early death (ED) rate remains high. APL patients are simultaneously accompanied by coagulopathy and hyperinflammation at the onset. It is not known what effects cytokines have on ED and coagulopathy in these patients. Therefore, the purposes of this study are to explore the clinical differences between APL and other types of AML, the link between cytokines and coagulopathy in newly diagnosed APL, and their roles in the ED for APL. This study retrospectively collected the information of 496 adult patients with AML (age ≥14 years at admission) newly diagnosed in the First People's Hospital of Yunnan Province between January 2017 to February 2022, including 115 APL patients. The difference of clinical manifestations between two groups [APL and AML (non-APL)] was statistically analyzed. Then, the factors affecting ED in APL patients were screened, and the possible pathways of their influence on ED were further analyzed. The results indicate APL at the onset have a younger age and higher incidence of ED and DIC than other types of AML. Intracranial hemorrhage (ICH), age, and PLT count are found to be independent factors for ED in newly APL, among which ICH is the main cause of ED, accounting for 61.54% (8/13). The levels of cytokines in newly APL are generally higher than that in AML (non-APL), and those in the group of ED for APL were widelymore than the control group. IL-17A and TNF-β are directly related to the ED in newly APL, especially IL-17A, which also affects ICH in these patients. Moreover, the increase of IL-17A and TNF-β cause the prolongation of PT in APL patients, which reflected the exogenous coagulation pathway. However, they have no effect on APTT prolongation and FIB reduction. Thus, it is speculated that IL-17A leads to early cerebral hemorrhage death in newly APL by inducing tissue factor (TF) overexpression to initiate exogenous coagulation and further leading to excessive depletion of clotting factors and prolongation of PT. In conclusion, compared with other types of AML, APL patients have a younger age of onset and high inflammatory state, and are more likely to develop into DIC and die early. Age, and PLT count at diagnosis are independent factors for ED of APL, especially ICH. IL-17A is confirmed to be an independent risk factor for ED and ICH of newly APL. Hence, IL-17A may serve as a predictor of ED in newly diagnosed APL patients, and controlling its expression probably reduce ED in these patients.

Impact of Qualified Dedicated APL Leukemia Specialist and Simplified Treatment Algorithm on Early Deaths in APL, a Monocenter Experience

Introduction: Acute Promyelocytic Leukemia (APL) is a highly curable subtype of Acute Myelogenous Leukemia (AML). Since the incorporation of all-trans-retinoic acid ATRA and arsenic trioxide (ATO) survival rates for APL are reported to be >90% in clinical trials. Despite this, there is a discrepancy in survival rates in general practice, mainly due to significant early deaths (ED). Some national registries report 20-30% of patients die during induction. Major factors contributing to ED are due to rarity of the disease, advanced age, underlying comorbidities, lack of written guidelines for induction, delay in diagnosis, and physician experience level. Herein, we report our observations on the incorporation of a simple treatment algorithm and management by leukemia/APL experts on ED. Methods: Retrospective monocenter analysis of ED in APL patients who underwent induction therapy from 4/2007 to 3/2022. All APL patients who underwent induction therapy were stratified into 2 treatment groups. Patients in group 1 treated from 4/2007-12/2009 and 1/2014- 6/2017 by a hematologist without an algorithm. Group 2 patients were treated from 1/2010-12/2013 and 7/2017-03/2022 by an APL leukemia specialist using a written algorithm. Induction rate mortality was compared between both groups. The algorithm was a two-page set of guidelines directed at preventing or treating the major causes of early death. Institutional review board approval was obtained for this review. Results: Between 4/2007 and 3/2022, n=62 patients were analyzed. A total of n=5 patients were excluded from the study; n=3 passed away or were transitioned to hospice care prior to starting any form of induction therapy and n=2 were Jehovah's Witnesses who refused all blood products. A total of n=57 patients were stratified into their respective groups. Across all groups (n=10, 17.5%) reported ED, median age 68 (range 20-81), (n=6, 60%) patients >60 years of age. Group 1 consisted of n=23 patients, median age 53 (range 20-78), (n=12, 52.2%) were male, and (n=9, 39.1%) were high risk (WBC > 10,000/mm3). Incidence of ED was (n=9, 39.1%) from disseminated intravascular coagulation DIC (n=3), differentiation syndrome DS (n=4), multi-organ failure (n=1), infection (n=1). ATRA was initiated at suspicion of APL diagnosis in (n=23, 100%) of patients. ATRA given alone in (n=1, 4.3%) patients, combined with ATO in (n=8, 34.8%), with chemotherapy in (n=19, 82.6%), and (n=5, 21.7%) with ATO/ATRA/chemotherapy. Group 2 consisted of n=34 patients, median age 51 (range 10-88), (n=14, 41.2%) were male, (n=10, 41.2%) were reported as high risk. There were (n=1, 2.9%) reported ED from DIC. ATRA was initiated at suspicion of APL diagnosis in (n=34, 100%) of patients. ATRA was given alone in (n=7, 20.6%) patients, combined with ATO in (n=17, 50%) and chemotherapy in (n=8, 23.5%). ATRA/ATO/chemotherapy was administered in (n=6, 17.6%). Conclusions: Results of this retrospective study showed that a simplified treatment algorithm and management by APL experts decreased early death rates from 39.1% to 2.9%. This data is promising and has important implications for both academic centers and community practices.

Screening for Severe Illness at Diagnosis Has the Potential to Prevent Early TB Deaths: Programmatic Experience From Karnataka, India.

Due to the coronavirus disease (COVID-19) pandemic and its associated response, TB deaths increased for the first time in a decade. In any potentially fatal illness, an assessment of severity is essential. This is not systematically done for adults with TB, mostly due to a lack of policy and/or limited availability of diagnostic and clinical capacity. We developed a screening tool using simple and easily measurable indicators that can be used by paramedical TB program staff to quickly identify people with severe illness. During October-November 2020 in Karnataka, India, the paramedical program staff from 16 districts screened people with TB (aged ≥15 years) notified by public facilities for "high risk of severe illness," which was defined as the presence of any of the following indicators: (1) body mass index (BMI) ≤14.0 kg/m2; (2) BMI ≤16.0 kg/m2 with bilateral leg swelling; (3) respiratory rate >24/minute; (4) oxygen saturation <94%; (5) inability to stand without support. In this cohort study, we determined the incidence of program-recorded early deaths (within 2 months) and its association with high risk of severe illness. Of 3,010 people with TB, 1,529 (50.8%) were screened at diagnosis/notification, of whom 537 (35.1%) had a high risk of severe illness. There were 195 (6.5%, 95% CI=5.7, 7.4) early deaths: 59 (30.2%) within a week and 100 (51.3%) within 2 weeks of treatment initiation. The incidence of early deaths was significantly higher among those with high risk of severe illness (8.9%) at diagnosis compared to those without (3.8%) [adjusted relative risk: 2.36 (95% confidence interval=1.57, 3.55)]. To conclude, early deaths were especially high during the first 2 weeks and strongly associated with a high risk of severe illness at diagnosis/notification. Screening for severe illness should be explored as a potential strategy to end TB deaths.

The Association between Evidence-Based Healthcare Practices and Outcomes among Preterm Births in China

Introduction: Very preterm infants are at high risk of early death or severe brain injury, with potential for impaired long-term neurodevelopmental function and physical health. There are evidence-based healthcare practices that can reduce the incidence. Materials and Methods: Infants born at 24–316 weeks gestational age and admitted within 24 h to NICUs participating in the Chinese Neonatal Network in 2019 were included. We examined the association between 4 evidence-based practices: inborn (born in a tertiary hospital in the Chinese Neonatal Network), ACS (any antenatal corticosteroid), MgSO4 (prenatal magnesium sulfate), and NT (normothermic temperature [36.0–37.5°C] at admission) and early death and/or severe brain injury in the study population. Results: Of 6,035 eligible infants, the incidence of early death and/or severe brain injury was 10.6%. Exposure to ACS only was associated with significant lower incidence of death and/or severe brain injury than none (aOR, 0.71; 95% CI: 0.57–0.88), but not MgSO4 only (aOR, 0.97; 95% CI: 0.81–1.17), NT only (aOR, 0.91; 95% CI: 0.76–1.08), or inborn only (aOR, 0.91; 95% CI: 0.72–1.15). The association between number of practices and incidence of early death and/or severe brain injury is as follows: none = 23% (31/138), any 1 = 14% (84/592), any 2 = 12% (185/1,538), any 3 = 9% (202/2,285), and all 4 = 9% (140/1,482). Discussion/Conclusion: More comprehensive use of evidence-based practices was associated with improved survival without severe brain injury among very preterm infants born at <32 weeks gestational age.

Early Deaths after Arterial Ischemic Stroke in Pediatric Patients: Incidence and Risk Factors.

In developed countries, cerebrovascular diseases are among the 10 most common causes of death in both the pediatric and adult population. The prevalence of fatal outcomes following arterial ischemic stroke (AIS) in various groups of pediatric patients ranges from 1% to almost 32%. However, a constant improvement in stroke mortality among children has been observed. The extent of the decline differs among studies (from nearly tenfold to twofold decline), as it depends on the study population. While a portion of this variability might be explained by factors such as health care access, population age, diseases related to ethnicity, and different etiologies of stroke in studied populations, the understanding of such differences is still insufficient. Risk factors for death in the early stages of the disease are poorly understood and are usually based on the clinical presentations of relatively small groups of pediatric patients. Familiarity with these factors may be of significant importance for prognosis, but also for the early selection of patients requiring careful supervision. The present study aimed to analyze and discuss the current literature data on the incidence of early death and risk factors for early death in children suffering from stroke.

Early Mortality Risk in Patients with Multiple Myeloma

BACKGROUND: Advances in treatment has improved greatly survival of multiple myeloma in the last two decades, and this improvement has been endorsed by wider use of novel drugs and tandem autologous stem cell transplantation. However, still there were cases died earlier post diagnosis OBJECTIVES: To study the risk factors of early mortality in patients with multiple myeloma In Kurdistan region of Iraq PATIENTS AND METHODS: A 176 cases that were diagnosed with symptomatic multiple myeloma between (January 2012 – July 2019) in cancer centers in Kurdistan region of Iraq. A total of 152 were continued within the study through their recorded sheet. Their data were analysed to determine what are the main risk factors that have an impact on early mortality among our myeloma patients. RESULTS: Among the total of 152 studied patients nine of them (5.9%) died early. The highest proportion (32.2%) of the sample aged 60-69 years, more than half (57.2%) of the them were male. The majority of the patients (80.9%) have been diagnosed during 2016-2019. The incidence of early death was 8.7% among patients who didn’t take the cytotoxic treatment compared with 1.7% of patients who took that treatment, but the difference was not significant (p = 0.089). The early death rate was significantly high (22.2%) among patients who didn’t take the immunomodulatory drugs, versus 2.4% of patients who took the immunomodulatory drugs (p = 0.001). The incidence of early mortality was 9.6% among patients with lactate dehydrogenase of ≥ 250 U/L compared with 0%

Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group

BACKGROUND: Children with acute myeloid leukemia (AML) still experience high rates of relapse. Facing increasing survival after first relapse, it appears critically important to examine the consequences of a second relapse in more detail. However, there is no population-based data available in pediatric AML and no reliable statement about general survival, patients' characteristics or treatment approaches can be made. Herein, we report current survival results following second relapse from the BFM study group, which represents to our knowledge the largest available dataset for this subgroup of patients. PATIENTS AND METHODS: Between 2004 and 2017, 1222 pediatric patients (age less than 18 years at initial AML diagnosis) with AML (no secondary leukemia, no Down syndrome, no acute promyelocytic leukemia) were registered in the population-based AML-BFM registry and trials in Germany, Austria, Czech Republic and Switzerland providing a longitudinal data collection with treatment, response rates, survival and disease characteristics. Central review of source documentation confirmed accuracy and consistency of all reported data. Only patients with a documented date of first and second complete remission (CR1 and CR2) and a diagnosed second relapse until the age of 21 are included. Statistical analyses were performed with SAS version 9.4 (SAS Institute). All living patients were censored at the time of last follow-up, but no patient later than 03/27/2020. The median follow-up after diagnosis of second relapse was 6,5 years. RESULTS: In all registered patients, 7% (83 out of 1222) met the strict criteria for a second relapse. For further analyses patients with a date of second relapse diagnosis after 12/31/2017 (n=6), two patients with isolated CNS relapse, who did not receive systemic chemotherapy, one patient with an underlying syndrome and one patient with insufficient data have been excluded. The median age at second relapse was 9,2 years. Sixty percent (n=44) of the patients, who experienced a second relapse, did so within a year after first relapse diagnosis. Eighty percent (n=58) and 7% (n=5) had one or two previous HSCTs, respectively. Eighty-nine percent (n=65) received an anthracycline-containing re-induction (DNX-FLA) followed by FLA or another intensive treatment regimen before at first relapse. In contrast to the standardized treatment approaches in first relapse, patients with second relapse received a wide range of therapy. Forty-six patients (63%) have been treated with an intensive cytotoxic treatment (Table 1). Seventeen patients (23%) got palliation only. Among the 25 patients (35%) who proceeded to HSCT, 21 patients (88%) had a prior HSCT. Survival after second relapse was very poor with a 5-year pOS of 15±4% (see Figure 1A) and a considerable cumulative incidence of early deaths (until day 56 after diagnosis: CI ED 19±5%). Prognosis did not improve over time with consistent overall survival rates until 2017 (see Figure 1B). Causes of death include disease progression (n= 51, 70% of all patients), a combined SCT-related and disease-related cause (n=3, 5%) and SCT-related complications (n=4, 4%) or treatment-associated toxicity (n=5, 7%). The 5-year pOS was 2±2% for patients with an early second relapse vs. 33±9% for those experiencing a second relapse more than a year after the first. (p&amp;lt;0.0001; Figure 1C). The timing of a first relapse and age did not show any influence on overall survival. The best response achieved in the respective bone marrow sample after up to two cycles with cytotoxic treatment have been categorized. Out of 45 patients with conclusive data 31.1% (n=14) achieved a third CR with a pOS of 36±13%, while 62.2% of the patients showed a nonresponse to the treatment (n=28, pOS 7±5%) or no evidence of leukemia, but also no peripheral regeneration (6.7%, n=3, pOS 0±0%). CONCLUSION: These data provide new insights into treatment strategies, prognostic factors and outcome of children with second relapse in pediatric AML. As expected, survival is poor, but nonetheless possible in this increasingly relevant subgroup of patients. These data may serve as foundation for urgently needed international clinical trials for relapsed and refractory AML in children. Disclosures Bourquin: Servier: Other: Travel Support. Reinhardt:CLS Behring: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees.

Causes of early death and treatment-related death in newly diagnosed pediatric acute myeloid leukemia: Recent experiences of the Dutch Childhood Oncology Group.

With the current more effective treatment regimens for pediatric acute myeloid leukemia (AML), research on early death (ED), treatment-related mortality (TRM), and toxicity becomes increasingly important. The aim of this study was to give an overview of the frequency, clinical features, and risk factors associated with ED and TRM in first complete remission (CR1) during the last three consecutive treatment protocols of the Dutch Childhood Oncology Group (DCOG) between 1998 and 2014. Incidence and risk factors associated with ED and TRM in CR1 were retrospectively studied in 245 patients treated according to the Dutch ANLL-97/AML-12 (n=118), AML-15 (n=60), or DB AML-01 (n=67) protocols. The incidence of ED was, respectively, 5.1%, 6.7%, and 3.0% excluding deaths before treatment (P=NS), and 7.4%, 11.1%, and 4.4% including deaths before the onset of treatment. Severe underweight at initial diagnosis was significantly associated with more frequent ED. When relapse was included as a competing risk, cumulative incidence of death in CR1 were 5.9%, 5.0%, and 4.6% for ANLL97, AML15, and DB01, respectively (P=NS). The most important cause of TRM included infectious and SCT-related complications. We report relatively stable rates of ED and TRM in CR1 in the latest completed DCOG protocols for newly diagnosed AML patients. The most important causes of TRM were SCT- or infection-related, warranting further evaluation and awareness.

Early Intracranial Hemorrhages in Acute Promyelocytic Leukemia: Analysis of Neuroradiological and Clinico-Biological Parameters

Introduction In the last decades, survival outcomes tremendously improved in acute promyelocytic leukemia (APL) due to all‐trans retinoic acid (ATRA)/anthracycline‐based chemotherapy, and more recently ATRA/arsenic trioxide (ATO) combinations. Despite the excellent results, with response rates exceeding 90%, early death (ED), mainly due to hemorrhagic complications occurring during the first 30 days after diagnosis, remains an unsolved issue. The prevalence of ED is largely underestimated due to discrepancies between data deriving from clinical trials, reporting 3-10% rates, and real-life, where it ranges from 10 to 30% of cases, and still remains the dominant cause of poor outcome. The most common site of bleeding is the brain (65%), particularly in fatal cases. Many theories have been proposed to elucidate the pathophysiology of this complication, considering the coagulopathy of APL and the perturbed homeostasis as primum movens, but no specific neuroradiologic studies have been conducted so far. Moreover, there is no specific predictor for bleeding events in APL, with exception of increased white blood cell counts (WBC). Patient and Methods We retrospectively identified 38 patients with APL (23 males and 15 females with a median age of 51.83 years, range 11-82), consecutively diagnosed at our Institution between 2004 and 2019, and treated with standard ATRA-based induction (Table 1). Occurrence of ED and ICH was then correlated with clinico-biological parameters, selecting for commonly reported variables predictors of these complications. In addition, CT scans of the 5 patients who experienced an intracranial hemorrhage (ICH) were revised by an expert neuroradiologist, looking for radiographic predictors of poor outcome (Al-Mufti et al 2018). Results Approximately 13% (5/38) of our APL patients experienced an ICH during induction therapy, which was fatal in 3 cases, while the overall incidence of ED was about 10% (4/38, including 1 case of death due to a differentiation syndrome). Looking at clinico-biological variables, the only predictor of ICH was a lower albumin level at baseline (3.8 vs 4.2 gr/dl; p=0.022), as compared to patients who did not experience ICH. A high Sanz-risk score was present in 2 of 3 pts with a fatal outcome of ICH (67% of cases), together with a shorter activated partial thromboplastin time (aPTT, 0.75 vs 0.86 ratio)(Table 1). Looking at neuroradiological findings (Figure 1) the three fatal cases showed a wider ICH volume, with perilesional edema and, interestingly, a positive "swirl" sign, which is defined as a marker of ongoing extravasation of blood within a hematoma. Both cases with a favourable outcome had a cerebellar involvement, without perilesional edema, and no major involvement of basal ganglia or thalamus. None of the patients had radiological signs of arteriovenous malformations. Conclusions Our data remark the impact of lower albumin levels at baseline and of a high Sanz-risk category on ED in patients with APL. In APL cases with fatal ICH, the thrombo-hemorrhagic imbalance is more profound than in other AMLs and results in a more devastating clinical picture. Taking into account the limitations of the small sample size, we found that a wide hemorrhage volume with perilesional edema, and the presence of the "swirl" sign are characteristic of fatal cases, while arteriovenous malformations did not seem to play a predisposing role. Further studies including large series of patients are warranted to identify the characteristics and the possible strategies to ameliorate the outcome of ICH in APL. Disclosures Venditti: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees.

The Prognostic Factors for Early Fatal Outcome in Patients with Multiple Myeloma

Introduction: Survival of Multiple Myeloma (MM) patients has improved in recent decades due to the advent of novel agents and broader utilization of stem cell transplant. Fatal outcomes occur mostly after multiple lines of therapy due to increasingly resistant disease. Indeed, early mortality after diagnosis is unusual in front line treatment MM trials, where patients are often selected on the basis of good performance status and absence of organ dysfunction. The real world incidence of early deaths is largely unknown. Hereby, we analyze the factors impacting early mortality in the National Cancer Database (NCDB) which covers more than 70% of MM patients in United States. Methods: Patients with MM diagnosed from 2005-2014 were identified in the NCDB. Early mortality (EM) was defined as death within six months of MM diagnosis. The effect of demographic and clinical factors, insurance type, distance to treatment facility, medical facility and facility volume on the probability of EM was estimated by univariate logistic model. The effect of these factors on the probability of EM was further estimated by multivariable logistic regression. The overall performance of multivariable logistic regression was evaluated using the receiver operating characteristic curve (ROC) analysis. The difference of continuous measurements between groups was examined using t-test. The association between categorical variables was examined using Chi-square test. All tests are two-sided and p-value ≤ 0.05 were considered statistically significant. Results: 90,258 patients with ICD-O 9732 were included. 49949 (55%) were male. EM was reported in 15729 (17%) within the first 6 months after MM diagnosis. Median age at diagnosis was 67 years (19-90). 15729 patients (17%) died in the first 6 months after diagnosis. There was no significant change in the percentage of EM over the years from 2005-2014. 11963 (76%) of patients with EM were older than 65 years while 3766 (23%) patients were less than 65 years. 12300 (78.1%) of the patients with EM were white and 2822 (17.9%) were African American. In a multivariable analysis, variables that confer the worst prognosis were increasing age, higher charlson co-morbidity score, lower annual median income of less than 30,000, and being treated in a community hospital. Controlling the effects of other factors (charlson co-morbidity score, hospital type and transplant), the odds ratio of EM was 1.04 per year increase of age (p&amp;lt;0.0001), 0.52 with treatment in academic center compared to community hospital (p&amp;lt;0.0001). Conclusion: Taken together our data suggest almost 1 out of 6 MM patients died at the first 6 months after diagnosis. Therefore, EM remains high in MM and a major barrier for continued improvement in survival outcomes. In addition to well-known MM-specific determinants of survival, socioeconomic factors were significantly associated with early mortality. Disclosures Malek: Adaptive: Consultancy; Medpacto: Research Funding; Janssen: Speakers Bureau; Sanofi: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Amgen: Speakers Bureau.

Long-term follow-up of children with acute promyelocytic leukemia treated with Beijing Children’s Hospital APL 2005 protocol (BCH-APL 2005)

We studied the outcomes of children with APL treated by the Beijing Children’s Hospital’s (BCH) acute promyelocytic leukemia (APL) 2005 protocol (BCH-APL2005). The clinical data of 77 patients enrolled from January 2005 to June 2015 were analyzed retrospectively. The hematologic complete remission (CR) rate and overall survival (OS) rate were evaluated between standard-risk (SR) and high-risk (HR) groups. Prognostic factors and complications were investigated in these two groups. CR in the SR and HR groups was 96.4% (54/56) and 85.7% (18/21), respectively, while the 10-year OS was 94.6% (53/56) and 76.2% (16/21), respectively. The cumulative incidence of early death was 6.5% (5/77), and the SR and HR groups were 1.8% (1/56) and 19.0% (4/21), respectively. Only two patients relapsed, and the relapse rate was 2.6% (2/77). According to Kaplan–Meier analysis, the SR group had a significantly better long-term survival than HR counterparts (p= .016). Initial leukocyte count was the only prognostic factor (p= .016) by univariate analysis, while other factors, such as FLT3-ITD and platelet count, had no correlation with prognosis. In addition, early deaths were mainly due to intracranial hemorrhage. Although the combination of all-trans retinoic acid (ATRA) and chemotherapy can improve the outcome of APL patients, the early deaths and anthracycline-related cardiac toxicity were relatively higher in our study. Current efforts focus on reducing or even avoiding chemotherapy in APL children and rest on the frontline regimen of intravenous arsenic trioxide or oral realgar-indigo naturalis formula plus ATRA, which is the direction for APL treatment.

Analysis of CDSS Experimental Indexes in 333 Cases of Newly Diagnosed Acute Leukemia

To analyze the 5 experimental indexes of CDSS in the patients with acute leukemia (AL) so as to provide the laboratorial basis for the early diagnosis and treatment of the secondary DIC in AL. Three hundred and thirty three patients with AL were divided into 7 groups, such as AML-M1-M5, other AML and ALL. The experimental indexes and CDSS scores of all AL groups were compared and analyzed in pairs, meanwhile 100 healthy persons were taken in the control group. Clinical events such as early death in all cases were also analyzed. The highest positive rate of Platelet was 59.76%, among the 5 experimental indexes, followed by D-D (30.93%), and the lowest APTT with only 2.70%. Compared with the control group, the differences of remaining indexes were statistically significant (P＜0.01), except APTT in group AML-M3 and FIB in the other AML groups. The score of laboratory index was (1.50±1.51) in all AL patients, and the positive rate of overt DIC ( score≥4) was 14.11% ( 47 cases). The highest score of CDSS was (3.34 ±1.71) in group AML-M3. The difference in the incidence of early death and cerebral (pulmonary) hemorrhage in DIC patients were statistically significant (P＜0.05 and P＜0.01). The application of quantitative integral method of experimental indexes in CDSS is objective and feasible, which is of great significance for early diagnosis and early treatment of acute leukemia complicated with DIC.

Survival and risk factors for mortality in pediatric patients with acute myeloid leukemia in a single reference center in low-middle-income country.

Despite advances in therapy and care for children with acute myeloid leukemia (AML), survival rates for children in low- and middle-income countries (LMICs) remain poor. We studied risk factors for mortality and survival in children with AML in a LMIC to develop strategies to improve survival for AML children in these countries. This retrospective cohort (2000-2014) analyzed newly diagnosed AML patients (age < 19years) at a reference center in Brazil. Demographic and clinical variables were reviewed by AML subtype: acute promyelocytic leukemia (APL), AML with Down syndrome (AML-DS), and other AML subtypes. Cumulative hazard risk for early death (ED) until 6weeks of treatment and risk factors for mortality were determined by the multivariate Cox hazard models. Survival was assessed for each AML subtypes. A total of 220 patients were diagnosed: APL 50 (22.7%), AML-DS 16 (7.3%), and other AML subtypes 154 (70.0%). The cumulative hazard function values for ED for all patients with AML were 12.5% (95% CI 8.5-18.4%); for each AML patients subtypes: APL, 21.7% (95% CI 11.7-40.5%); AML-DS, 6.2% (95% CI 0.9-44.4%); and other AML subtypes, 10.2% (95% CI 6.2-17.0%). White blood cell count (cutoff 10 × 109/L for APL and 100 × 109/L for other AML subtypes) and Afro-descendance were significant risk factors for mortality in APL and other AML subtypes, respectively. Overall survival for patients with APL, AML-DS, and other AML subtypes was 66.8%, 62.5%, and 38.0%, respectively. APL patients had the highest incidence of ED and those with other subtypes had increased relapse risk. We also observed high rates of death in complete remission mainly due to infection. Better risk classification and identification of risk factors for infection may improve the survival of these patients.

Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia.

Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 109/L, and fibrinogen < 1g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 109/L, elevated serum uric acid level, and D-dimer > 4mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.

Analysis of early death in newly diagnosed acute promyelocytic leukemia patients.

The aim of this study was to identify risk factors for early death (ED) in acute promyelocitic leukemia (APL) patients.Clinical records of 49 APL patients who suffered ED were divided into 4 groups: death before treatment or within the first 3 days (immediate death; iED group), death during treatment at least 3 days after commencement (ED after treatment), low/intermediate risk, and high-risk groups.White blood cell (WBC) count, high-risk cases, prothrombin time (PT) prolongation, international society on thrombosis and hemostasis (ISTH) scores (P < .05), bleeding (P = .05), and death due to severe hemorrhage (P = .010) were higher in iED group than ED after treatment. And the time from onset to initial hospitalization or death was significantly shorter (P < .05) in iED patients. LDH level (P = .002), PT prolongation (P = .014), and incidence of grades 3 or 4 bleeding (P = .049) were higher in high-risk group than in ED and low/intermediate-risk groups, while the times from onset to the initial hospitalization or death were lower for ED patients in high-risk group (P = .037).We found that different types of EDs have different clinical features. A high WBC count contributes to the occurrence of more ED, which is usually not associated with delay of diagnosis and hospitalization. Current therapeutic strategies to reduce the incidence of ED in these cases are not adequate and will benefit from focused research attention.

Minimal access versus conventional aortic valve replacement: a meta-analysis of propensity-matched studies.

Conventional aortic valve replacement (CAVR) via a full sternotomy is the standard surgical approach for aortic valve replacement. Minimal access aortic valve replacement (MAAVR) is commonly performed via a partial sternotomy and a right minithoracotomy. Such procedures aim not only to reduce the invasiveness but to offer the same quality, safety and results of the conventional approach. Our goal was to compare both procedures by performing a meta-analysis of reports with risk adjustment that performed a propensity-matched analysis. Relevant articles were searched for in Medline, the Cochrane Database of Systematic Reviews and the Scopus database based on predefined criteria and end-points. The early and late outcomes and complications were compared in the selected studies. A total of 4558 patients from 9 studies were enrolled; 2279 (50%) underwent CAVR and 2279 (50%) underwent MAAVR. There was a significantly lower rate of postoperative low output syndrome (1.4% vs 2.3%, P = 0.05) and atrial fibrillation (11.7% vs 15.9%, P = 0.01) in the MAAVR than in the CAVR group, respectively. In contrast, aortic cross-clamp and cardiopulmonary bypass times were significantly longer in the MAAVR group (P < 0.05). Finally, the incidence of early deaths (1.5% vs 2.2%, P = 0.14), stroke (1.4% vs 2%, P = 0.20), myocardial infarction (0.4% vs 0.5%, P = 0.65), renal injury (4.5% vs 6%, P = 0.71), respiratory complications (9% vs 10.1%, P = 0.45), re-exploration for bleeding (4.9% vs 4.1%, P = 0.27) and pacemaker implantation (3.3% vs 4.1%, P = 0.31) was similar in both groups, respectively. In summary, even though MAAVR procedure, either through partial sternotomy or right minithoracotomy, provides patient satisfaction due to the smaller incision and better cosmetics, MAAVR is as safe as the CAVR procedure. Although MAAVR takes slightly longer, it was not associated with greater cardiopulmonary bypass-related adverse effects. Interestingly, MAAVR shows a lower incidence of low cardiac output syndrome and atrial fibrillation.

A Multi-Center Prospective Study Utilizing a Simplified Treatment Algorithm Complemented By Expert Support Decreases Induction Mortality and Improves Survival in Acute Promyelocytic Leukemia (APL). Results of the APL Trial in Georgia, South Carolina and Neighboring States

Background: APL is a highly curable malignancy with reported survival above 90% in many co-operative group studies. However these spectacular results are not evident in the general population. US SEER data and other population based studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be as high as 30%, leading to a considerably lower survival compared to clinical trials where ED is around 5-10%. Decreasing ED remains a global challenge and the highest priority at all leukemia treatment centers and will result in population wide survival in this most curable leukemia. We report results of our prospective trial using a set of simplified treatment guidelines along with expert support designed to decrease ED.Methods: A network of leukemia treatment centers was established in Georgia, South Carolina and neighboring states. An aggressive outreach effort was made by visiting most of the leukemia treatment centers to publicize the concept and educate treating physicians in the community about ED in APL. The protocol provides a simplified two page treatment algorithm that emphasizes quick diagnosis, prompt initiation of therapy and proactive and aggressive management of the major causes of death during induction. Expert and treating physician communication was established very early when a diagnosis of APL was suspected and was maintained until the completion of induction. Study was approved by local IRBs (if applicable) and funded by the Lymphoma Leukemia Society (LLS). Informed consent was obtained upon confirmation of a diagnosis of APL and there were no exclusion criteria. Patient accrual was initiated in July 2013 and continued till May 2016 when the accrual goal of 120 was met on an intent to treat basis. Statistics are descriptive.Results: Between 7/2013 and 5/2016, 120 patients were enrolled at 5 large leukemia centers (n=54, 45%) and 24 community hospitals (n=66, 55%). Only 3 hospitals treated more than 3 APL patients/year. Median age was 54 years (range 21-84 years). 68 were male. 84% were low risk (WBC < 10,000/mm3) and median WBC count was 4.3 (range 0.3-170,000/mm3). ATRA was initiated at suspicion of APL diagnosis in 100% of patients and was the only treatment in 2(1.5%) patients. Arsenic was combined with ATRA in 93 (81.5%) patients while the other 17% received chemotherapy. 15(13%) had bleeding complications at presentation. Treatment course was complicated by infection and differentiation syndrome (DS) in 31(28%) and 40(34%) patients respectively.There were 12 early deaths, of which 1 was a Jehovah's Witness who declined transfusions and 1 who enrolled 12 days after diagnosis while in multi-organ failure. Incidence of ED was 10/118 (8.5%). The cause of death was disseminated intravascular coagulation (DIC) (n=4), DS (n=2), infection (n=1), anemia (n=1), multi-organ failure (n=4). With a median follow-up of 10.6 months, 2 low risk patients relapsed: I due to non-compliance 1 year after diagnosis and 1 with CNS relapse 3 months after completing consolidation. With a median follow up of 320 days (range 1-965) overall survival (Figure 1) was 87%. There were four late deaths; relapse (n=1), second cancer (n=1) and non-APL related comorbidities (n=2).Conclusions: Results of this prospective trial showed that a simplified treatment algorithm along with support from experts and co-management with treating physicians in the community decreased induction mortality (8.5%) and improved survival (87%) compared to SEER data (1 year relative survival of 71%). We believe our experience warrants large scale implementation and is presently approved as an ECOG/ACRIN trial (EA9131). This model can be applicable to other cancers and life-threatening diseases. [Display omitted] DisclosuresJillella:Leukemia Lymphoma Society: Research Funding. Heffner:AbbVie: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Millennium: Research Funding. Stuart:Astellas: Research Funding; Celator: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Agios: Research Funding; Bayer: Research Funding; Incyte: Research Funding. Gerber:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding. Grunwald:Medtronic: Equity Ownership; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Amgen: Research Funding; Janssen: Research Funding. Kota:Pfizer: Membership on an entity's Board of Directors or advisory committees; Ariad Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

Early Mortality Was Highly and Strongly Associated with Functional Status in Incident Japanese Hemodialysis Patients: A Cohort Study of the Large National Dialysis Registry.

BackgroundAlthough dialysis is typically started in an effort to prolong survival, mortality is reportedly high in the first few months. However, it remains unclear whether this is true in Japanese patients who tend to have a better prognosis than other ethnicities, and if health conditions such as functional status (FS) at initiation of dialysis influence prognosis.MethodsWe investigated the epidemiology of early death and its association with FS using Japanese national registry data in 2007, which included 35,415 patients on incident dialysis and 7,664 with FS data. The main outcome was early death, defined as death within 3 months after initiation of hemodialysis (HD). The main predictor was FS at initiation of HD. Levels of functional disability were categorized as follows: severe (bedridden), moderate (overt difficulties in exerting basic activities of daily living), or mild/none (none or some functional disabilities).ResultsEarly death remained relatively common, especially among elderly patients (overall: 7.1%; those aged ≥80 years: 15.8%). Severely and even only a moderately impaired FS were significantly associated with early death after starting dialysis (adjusted risk ratios: 3.93 and 2.38, respectively). The incidence of early death in those with impaired FS increased with age (36.5% in those with severely impaired FS and aged ≥80 years).ConclusionsEarly death after starting dialysis was relatively common, especially among the elderly, even in Japanese patients. Further, early death was significantly associated with impaired FS at initiation of HD.