Serum Albumin As a Prognostic Factor for Overall Survival at 6-Months in Acute Myeloid Leukemia (AML)

Abstract Introduction: The role of serum albumin as a prognostic factor has been well established in various medical conditions including some hematologic malignancies such as multiple myeloma and myelodysplastic syndromes . In this retrospective analysis, we examined the prognostic value of serum albumin at diagnosis prior to any therapy in a cohort of patients with acute myeloid leukemia (AML) irrespective of treatment modality. Methods: Data were collected retrospectively in a cohort of 257 AML patients who received treatment between 2002 to 2019. The cohort included patients who received conventional 7+3 induction, patients who were not candidates for induction receiving lower intensity chemotherapy +/- targeted drug, and patients who were placed on clinical trials. Patients under the age of 17 were excluded, as well as patients who received their initial diagnosis and induction at an outside hospital whose initial laboratory data for albumin were not available. We excluded patients who were not identified as Caucasian or African American in our final analysis. 46 patients were lost to follow up before 6-months and were excluded from all analysis. Analysis were performed with Epi Info software. Our patients were dichotomized by serum albumin ≥3.5 (normal albumin) and <3.5 (hypoalbuminemia [HA]). Chi-square test was performed for univariate analysis of categorical variables and logistic regression was performed for multivariable analysis. Results: Of the 211 patients, the median age was 59.4 years (17 - 83.4) with 1:1 male to female ratio. 171 patients survived to 6 months and were included in our analysis. There was no significant age difference between normal albumin and HA groups (median age 59 and 59.7 respectively, p=0.854). There was an equal distribution of patients with HA with respect to sex (33.0% male and 36.9% female, p=0.560). With regards to race, more African Americans were found to have hypoalbuminemia compared to Caucasians (46% African Americans vs. 30% Caucasians, p=0.027). Patients with HA had an overall survival rate of 72.2% at 6 months while those with normal albumin levels had a survival rate of 85.1% (p=0.027). Multivariate logistic regression analysis including age, race, sex and albumin levels showed that age, sex and albumin levels were statistically significant independent predictors of survival at 6 months [Table 1]. Patients with albumin ≥3.5 were significantly more likely to survive controlling for age, race, and sex (OR=2.16, p=0.044). Multivariate analysis additionally showed that age was inversely associated with survival at 6-months (p=0.003) and males were more likely to survive than females (p=0.034). Though African Americans were shown to have a higher incidence of HA in univariate analysis, race was not an independent predictor for survival in the multivariate analysis when controlling for age, sex, and albumin level. Conclusions: In this cohort of AML patients, we found that hypoalbuminemia is an independent predictor survival. Serum albumin <3.5 was associated with a significantly decreased overall survival at 6-months. Age and sex were additional independent predictors of 6-month survival. This data suggests that hypoalbuminemia, defined as albumin <3.5, has prognostic utility in AML patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Acute Myeloid Leukemia with Myelodysplasia-Related Changes (MRC) Did Not Show Inferior Outcomes Compared to Those without MRC,

Blood ◽

10.1182/blood.v118.21.3563.3563 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3563-3563

Author(s):

Jee Hyun Kong ◽

Hyun Ae Jung ◽

Hee Kyung Ahn ◽

Silvia Park ◽

Hee-Jin Kim ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Induction Chemotherapy ◽

Myeloid Leukemia ◽

Risk Group ◽

Univariate Analysis ◽

Group A ◽

Group B ◽

Group D ◽

Acute Myeloid

Abstract Abstract 3563 The distinctive features of the World Health organization (WHO) classification compared to French-America-British Co-operative group (FAB) classification of acute myeloid leukemia is the new morphological entity “AML with multilineage dysplasia (MLD)”, and now this subgroup has been renamed as 'AML with myelodysplasia-related change (MRC)”. It generally accepted that dysplasia was most frequently noted in older individual, is often associated with an unfavorable cytogenetic profiles and unfavourable response to therapy. However it is still controversial. Therefore, we evaluated the impact of MRC on overall survival (OS) and leukemia free survival (LFS) in acute myeloid leukemia patients. A total of 644 adult AML patients diagnosed at Samsung Medical Center (SMC) between Sep.1994 and Oct. 2010 were enrolled. We reviewed their medical histories, clinical parameters, hemogram data, bone marrow aspirate and cytogenetic studies, and reclassified them into AML with of MRC and without MRC groups. Of 664 patients, 543 patients were received induction chemotherapy, among them, 84 patients demonstrated MRC and 451 patients did not. Median age was 50 (15–88) years old, and 57.1% of patients were male. Median follow up period was 77.3 [0–191] months. AML without MRC group had more favorable cytogenetic risk, higher WBC counts and LDH levels than those with MRC. However, other variable such as age, sex, hemoglobin level, absolute neutrophil, and peripheral blast count, induction chemotherapy regimen, hematopoietic stem cell transplantation, CR1 (complete response after induction chemotherapy), CRp (complete recovery of platelet), and relapse rate were not different between two groups. Since FLT3-ITD and NPM1 tests were introduced into laboratory work after 2005, results of these tests were available only in 158 and 75 patients respectively, and these were not different between two groups. In univariate analysis, advanced age (>65 years) predicted worse LFS (median LFS [95% C.I.]; ° Â65 years vs >65 years; 9.3[7.2–11.4] vs 5.9[4.6–7.2] months, p =0.014). In terms of OS, young age (p=0.000), female (p=0.000), favorable cytogenetic risk (p=0.000), CR1 (p=0.000), CRp (p=0.000), absence of relapse (p=0.000), and HSCT (p=0.000) showed a higher probability of longer OS (Table 1). The presence of MRC, FLT3-ITD, and NPM1 did not affect OS (Table 1).Table 1.Summary of univariate analysis for overall survival.Median OS (months) [95% C.I.] or mean OS ± SD (months)pAge°Â65 years47.9 [17.1 – 78.6]0.000>65 years13.1 [5.9 – 20.4]SexMale23.2 [16.5 – 30.0]0.000¢Female112.2 [ – ]Cytogenetic risk¢Favorable107.0±7.40.000Intermediate28.0 [19.0 – 36.9]Unfavorable10.8 [7.8 – 13.7]Unknown17.5 [6.8 – 28.1]MRCAbsence35.9 [6.6 – 65.2]0.081Presence19.0 [6.9 – 31.0]CR1¢Yes112.2 [–]0.000No3.6 [1.1 – 6.1]CRp¢Yes70.9±4.40.000No54.8 [18.5 – 91.1]RelapseYes21.5 [17.2 – 25.9]0.000No17.5 [–]HSCT¢Auto86.2±5.60.000¢Allo83.8±6.5Not done17.5 [10.8 – 24.1]FLT3-ITDPositive8.2 [0–26.1]0.595Negative29.5 [20.9–38]NPM1¢Positive104.1±11.00.978¢Negative78.9±15.0¢“median survival not reached Next, we analyzed MRC effect in each variable to OS. The presence MRC did not affect OS of each group which divided according to the age (Figure 1. A and B), sex, cytogenetic risk groups (Figure 1. C and D), relapse, CR1, HSCT, and FLT3-ITD, though AML with MRC group had tendancy to have poor survival rate in intermediate cytogenetic risk group (Figure 1. C). However in patients who did not acheived CRp or showed NPM1, the presence of MRC correlated with shorter OS.Figure 1.Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).Figure 1. Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D). In this study, patients with MRC did not show inferior outcomes than those without MRC. Therefore it is not necessary to decide different treatment strategy according to the presence of MRC Disclosures: No relevant conflicts of interest to declare.

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Impact of Day 28 Absolute Lymphocyte Count on Outcome of Adult Patients with Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v124.21.5256.5256 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5256-5256

Author(s):

Naresh Bumma ◽

Jing Ai ◽

Xuefei Jia ◽

Sean Hobson ◽

Donna Abounader ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Board Of Directors ◽

Lymphocyte Count ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Absolute Lymphocyte Count ◽

Advisory Committees ◽

The Impact ◽

Acute Myeloid

Abstract Introduction: Lymphocyte recovery after induction chemotherapy (IC) predicts outcome in adult patients (pts) with acute myeloid leukemia (AML) (Behl et al. Leukemia 2006; 20: 29-34). However, it is unknown whether absolute lymphocyte count (ALC) recovery after IC predicts outcome in those pts who are then treated with allogeneic hematopoietic stem cell transplant (AHCT) in first complete remission (CR1). We hypothesized that the prognostic impact of ALC might be nullified by AHCT in CR1 due to the abrogation of normal immunologic recovery. In this study, our aims were to (1) evaluate the impact of Day 28 ALC on all AML pts receiving IC and (2) to specifically, evaluate the impact of Day 28 ALC on the subset of AML pts proceeding to AHCT in CR1. Methods: A retrospective chart review of 180 adult AML pts (≥ 18 years of age) who were treated with IC during the years 2001- 2012 at the Cleveland Clinic was performed. Institutional Review Board approval was obtained. Pts with acute promyelocytic leukemia were excluded . Ninety-four of the 180 pts received AHCT in CR1. A total of 141 AML pts receiving IC and a total of 66 pts receiving IC and then receiving AHCT in CR1 were eligible for data analysis because Day 28 ALC was missing in the remainder of the pts. Prior studies in AML identified an ALC of < 500/ µL at Day 28 of IC as predictive of overall survival. We stratified Day 28 ALC into the following categories: (a)< 250/ µL (b) < 350/ µL (c) < 500/ µL and (d) < 500/ µL for Max ALC [Max ALC was defined as the maximum ALC value between days 26 and 30 after the initiation of IC]. Other variables collected included age at diagnosis, WBC at diagnosis, and cytogenetic (CG) risk. CG risk was ascribed by CALBG criteria. The Kaplan-Meier method was used to summarize overall survival (OS) and relapse-free survival (RFS), which were measured for all pts from the time of diagnosis. The log-rank test was used for univariate analysis of categorical factors and the Cox proportional hazards model was used for measured factors and multivariate analysis. We performed two separate analyses : one for all AML pts (n=141); and a second analysis only focusing on those receiving AHCT in CR1 (n=66). Results: Pt characteristics for the entire AML cohort: The median age was 58.0 years (20.0-80.0); 46.1% female. The median WBC at diagnosis was 11.6 K / µL (range 0.7-220.7) and median Day 28 ALC was 400/ µL (0-2.4). Twenty-seven pts (19.7%) had favorable CG, 84 (61.3%) intermediate, and 26 (19.0%) unfavorable. Most pts (91%) received "7+3" IC and 93 (66%) also received at least 1 cycle of post-remission chemotherapy. On univariate analysis, age ≥60 (HR 2.72, p< 0.001), CG risk (HR 2.13, p < 0.001), Day 28 ALC < 250/ µL (HR 1.60, p=0.022), Day 28 ALC < 350/ µL (HR 1.57, p=0.029), and max ALC < 500/ µL (HR 1.54, p=0.035) were associated with a worse OS from the initiation of treatment. Low ALC was associated with both a higher incidence of refractory disease and death during induction (p=0.015). In our second analysis of pts undergoing AHCT in CR1, although not statistically significant, max ALC < 500/ µL (during IC) was associated with a trend towards decreased OS from the start of treatment on both univariate (HR 1.88,p= 0.13) and multivariate (HR 2.16, p=0.075) analysis. Conclusions: Max ALC < 500/ µL is predictive of outcome in AML pts undergoing IC, and there is a suggestion that this effect may not be abrogated by AHCT. A larger study will be needed to further confirm these findings. Therapies to improve lymphocyte recovery may be important in the treatment of AML. Disclosures Sekeres: Boehringer-Ingelheim Corp: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Corp: Membership on an entity's Board of Directors or advisory committees.

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Minority Health Disparities in Acute Myeloid Leukemia: A Metropolitan, Single-Center Retrospective Analysis

Blood ◽

10.1182/blood-2021-153642 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1987-1987

Author(s):

Keri R. Maher ◽

Ian M. Bouligny

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

African American ◽

African Americans ◽

Myeloid Leukemia ◽

Insurance Coverage ◽

Rank Test ◽

Log Rank Test ◽

Disease Biology ◽

Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) is an aggressive bone marrow cancer affecting 20,000 adults in the United States yearly. Five-year relative survival remains poor at 29.5%, though this has been steadily increasing. There are no known differences in diagnostic rates between racial and ethnic groups. Previous work has shown being African American is an independent predictor of poorer survival - particularly in impoverished areas and those with Medicaid. We aimed to identify potential racial disparities amongst our AML population - with special attention to insurance coverage, access to care, disease biology, regimen selection, toxicities, referral for allogeneic hematopoietic stem cell transplant (alloHSCT), and overall survival with non-Hispanic Whites as a control. Methods: This study is a retrospective analysis of patients diagnosed with AML and treated at Virginia Commonwealth University/Massey Cancer Center identified by our data analytics core from June 2018 to December 2020. Data were extracted and manually verified from the electronic medical record into an AML database instrument created in RedCap. Race was determined by self-report. Statistical analysis was performed using GraphPad Prism. Descriptive and inferential statistics were performed with comparisons between groups using an unpaired t-test with Welch's correction or with Fischer's exact test. Overall survival rates were evaluated using Kaplan-Meier analyses and compared using log-rank test. The event date was death and patients were otherwise censored at the date of last contact. Results: Our cohort consisted of 160 patients: 26.3% African Americans, 68.8% Whites, 1.9% Hispanic/Latinos, 1.9% other or declined to state, and 1.3% were unknown. To analyze the impact of minority populations, Hispanic/Latino and "other" categories were combined with African American into a "Non-White" cohort (N = 48) and compared to the "White" cohort (N = 110). There was no baseline difference in age (p= 0.212), Charleson Comorbidity Index (CCI) at presentation (p = 0.692), or ECOG status (p = 0.920) at presentation (Table 1). Assessment of disease biology, including European Leukemia Network risk stratification (p = 0.507), presence of complex karyotype (p = 0.366) and presence of TP53 mutations (p = 0.776) did not detect a statistically significant difference between the two groups (Table 1). Choice of intensive (vs non-intensive) induction based on physician's discretion was also similar (62.5% in non-White, 68.2% in Caucasians, p = 0.583). Toxicity analysis such as ICU during induction (p = 0.519) and death within 60 days of induction (p = 0.8) showed no difference between groups. In parameters assessing access to care, non-Whites were more likely than Whites to have either Medicaid or no insurance coverage, opposed to private insurance or Medicare (p = 0.0166). Despite this, there was no difference in overall survival assessed by log-rank test (p = 0.068) across all cytogenetic cohorts or with respect to the adverse risk cohort (p = 0.143), though the non-White cohort had a mOS of 286 days (9.4 months) compared to 764 days (25.1 months) in the White cohort. Rates of being lost to follow up were not different between the two groups (p = 0.34). However, rates of alloHSCT were approaching significance with p = 0.0528 favoring Caucasians. Discussion: Our data suggest similar disease biology at presentation amongst racial and ethnic groups, as well as similar comorbidities, performance status at diagnosis, and choice of induction regimen. As previous research has shown, our minority cohort was more likely to have no insurance or Medicaid than the Caucasian population. However, this did not lead to a statistically significant overall survival difference. Rates of alloHSCT were approaching statistical significance between the groups. This suggests that improving access to transplant might be one of the more effective tools for improving outcomes in this group. Additionally, demographics in the Richmond metro area demonstrate a population of 47% African American and 48% Whites, whereas our data showed 26% African Americans and 69% Whites, with no known strong racial predilection of AML based on SEER data (46% vs 54%, respectively). Thus, concern remains that there may be a significant number of patients with AML who either do not seek care, or present in a condition where treatment is no longer possible. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Prognostic Value of Absolute Lymphocyte count, Lymphocyte percentage, Serum albumin, Aberrant Expression of CD7, CD19 and the Tumor Suppressors (PTEN and p53) in Patients with Acute Myeloid Leukemia

Asian Pacific Journal of Cancer Biology ◽

10.31557/apjcb.2020.5.4.131-140 ◽

2020 ◽

Vol 5 (4) ◽

pp. 131-140

Author(s):

Nadia Ali Sadek ◽

Suzan M Abd-eltawab ◽

Nagwa Mohamed Assem ◽

Hoda A-M Hamdy ◽

Fatma M. EL- sayed ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Serum Albumin ◽

Tumor Suppressors ◽

Lymphocyte Count ◽

Myeloid Leukemia ◽

Prognostic Value ◽

Absolute Lymphocyte Count ◽

Aberrant Expression ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) is a hematopoietic neoplasm. Tumor suppressors have a magnificent role in preventing the AML process. The absolute lymphocyte count is a simple yet statistically powerful estimate in patients with acute leukemia besides the lymphocyte’s percentage. Aim: Investigating the prognostic value of absolute lymphocyte count, lymphocyte percentage, serum albumin, the aberrant expression of CD7and CD19 and the tumor suppressor genes (PTEN and p53) in patients with AML. Methods: 35 de novo AML patients were included. They received the standard induction chemotherapy (3+7 protocol) and were followed up for one year after treatment. 15 normal healthy individuals, age and sex matched constituted the controls.Results: The mean overall survival of patients with lymphocyte percentage ≤25 was low compared to those with high lymphocyte percentage (>25%) (χ2 =5.808, P=0.016). AML patients with low levels of ALC showed significantly shorter overall survival than patients with high levels (χ2 =4.587, P= 0.032). AML patients with low serum albumin were of low overall survival compared to those with normal level (χ2 =8.698, P=0.003). Patients with aberrant CD7 expression showed short survival and unresponsiveness to treatment than CD7 negative patients. PTEN gene expression and p53 protein level were significantly lower in AML patients compared to the control group.Conclusion: The decrease in ALC, lymphocyte percentage, albumin concentration and the increase in monocyte percentage indicates bad prognosis in AML patients. The Aberrant CD7 expression, very low expression of PTEN and low level of p53 could estimate the unresponsiveness to standard chemotherapy.

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Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes

Blood ◽

10.1182/blood-2011-12-399337 ◽

2012 ◽

Vol 119 (15) ◽

pp. 3578-3584 ◽

Cited By ~ 257

Author(s):

Felicitas Thol ◽

Sofia Kade ◽

Carola Schlarmann ◽

Patrick Löffeld ◽

Michael Morgan ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Confidence Interval ◽

Myelodysplastic Syndromes ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Hazard Ratio ◽

Prognostic Impact ◽

Wild Type ◽

Acute Myeloid

Abstract Mutations in genes of the splicing machinery have been described recently in myelodysplastic syndromes (MDS). In the present study, we examined a cohort of 193 MDS patients for mutations in SRSF2, U2AF1 (synonym U2AF35), ZRSR2, and, as described previously, SF3B1, in the context of other molecular markers, including mutations in ASXL1, RUNX1, NRAS, TP53, IDH1, IDH2, NPM1, and DNMT3A. Mutations in SRSF2, U2AF1, ZRSR2, and SF3B1 were found in 24 (12.4%), 14 (7.3%), 6 (3.1%), and 28 (14.5%) patients, respectively, corresponding to a total of 67 of 193 MDS patients (34.7%). SRSF2 mutations were associated with RUNX1 (P < .001) and IDH1 (P = .013) mutations, whereas U2AF1 mutations were associated with ASXL1 (P = .005) and DNMT3A (P = .004) mutations. In univariate analysis, mutated SRSF2 predicted shorter overall survival and more frequent acute myeloid leukemia progression compared with wild-type SRSF2, whereas mutated U2AF1, ZRSR2, and SF3B1 had no impact on patient outcome. In multivariate analysis, SRSF2 remained an independent poor risk marker for overall survival (hazard ratio = 2.3; 95% confidence interval, 1.28-4.13; P = .017) and acute myeloid leukemia progression (hazard ratio = 2.83; 95% confidence interval, 1.31-6.12; P = .008). These results show a negative prognostic impact of SRSF2 mutations in MDS. SRSF2 mutations may become useful for clinical risk stratification and treatment decisions in the future.

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Addition of Lomustine to Idarubicin and Cytarabine Improves the Outcome of Elderly Patients With De Novo Acute Myeloid Leukemia: A Report From the GOELAMS

Journal of Clinical Oncology ◽

10.1200/jco.2009.26.4648 ◽

2010 ◽

Vol 28 (18) ◽

pp. 3028-3034 ◽

Cited By ~ 24

Author(s):

Arnaud Pigneux ◽

Jean-Luc Harousseau ◽

Francis Witz ◽

Mathieu Sauvezie ◽

Marie-Christine Bene ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Elderly Patients ◽

Induction Therapy ◽

Myeloid Leukemia ◽

De Novo ◽

Group I ◽

Acute Myeloid

Purpose No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML. Patients and Methods The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005. Induction therapy consisted of idarubicin (8 mg/m2, days 1 through 5) and cytarabine (100 mg/m2, days 1 through 7; group I, 339 patients) or the same drugs plus lomustine (200 mg/m2 orally on day 1; group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course of intermediate-dose cytarabine. Results The rate of CR was significantly higher in patients in group II compared with group I (68% v 58%; P = .002). The rate of toxic death was similar in the two groups. In multivariate analysis, two prognostic factors were linked to CR: nonadverse cytogenetic (P < .003) and addition of lomustine to induction chemotherapy (P = .002). Median overall survival was significantly improved in patients treated with lomustine (median and SE, 12.7 ± 2.2 months v 8.7 ± 2.7 months; P = .004). In multivariate analysis, five prognostic factors positively affected overall survival: addition of lomustine (P = .002), age ≤ 69 years (P < .001), Eastern Cooperative Oncology Group performance status lower than 2 (P = .002), French-American-British subgroup 1/2 (P = .02), and nonadverse cytogenetic (P < .001). Conclusion Lomustine improves the rate of CR and survival in elderly patients with de novo AML when added to standard induction therapy.

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Can Early Removal of Central Venous Catheter Influence Duration of Fever in Febrile Neutropenic Patients with Acute Myeloid Leukemia?

Blood ◽

10.1182/blood.v128.22.1615.1615 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1615-1615

Author(s):

Tae Hwan Kim ◽

Yong Won Choi ◽

Seong Hyun Jeong ◽

Joon Seong Park

Keyword(s):

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Febrile Neutropenia ◽

Blood Sample ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Blood Stream ◽

Central Catheter ◽

Early Removal ◽

Acute Myeloid

Abstract Background: Febrile neutropenia is considered a medical emergency and generally prompts immediate hospitalization. For this reason, many physicians and researchers have tried some attempts to reduce the duration of febrile neutropenia. Patients with hematologic disorders frequently require the insertion of medium or long-term central venous catheters (CVCs) for stem-cell transplantation, the administration of chemotherapy, or transfusion of blood products. We have already known that the CVC is a major source of bloodstream infections in the neutropenic patients, but, there have been no reports about the duration of febrile neutropenia in the cases with early removal of CVCs except for catheter-related blood stream infections (CRBSIs). In this study, we want to investigate the factors influencing the duration of febrile neutropenia including early removal of CVCs except for CRBSIs in the patients diagnosed with acute myeloid leukemia. Methods: A total of 161 central catheter insertion cases with febrile neutropenia except for CRBSIs in 102 patients were eligible for analysis. CRBSI was defined as the same microorganism grown from at least one percutaneous blood culture and from a culture of the catheter tip (>15 colony-forming units), or a growth of microbes from blood sample drawn from a catheter hub at least 2 hours before microbial growth was detected in a blood sample obtained from a peripheral vein. Patients with blood stream infection (BSI) were defined as those with clinical signs of infection and the microorganism grown from at least one percutaneous blood culture without detecting microorganism from a culture of the catheter tip or from blood sample drawn from a catheter hub. The early removal of CVCs was defined as the removal of CVCs before 21 days from the insertion date of CVC. Duration of fever was investigated according to age, gender, body mass index (BMI), type of chemotherapy, presence of baseline fever, presence of BSI and/or early removal of central catheter by the Kaplan-Meier method and the Log Rank method. Statistical analysis was performed using SPSS software version 13.0 (IBM, Armonk, NY, USA). Results: Baseline characteristics of total cases were described in Table 1. Univariate and multivariate analysis about duration of fever are summarized in Table 2 and Table 3. Age, type of chemotherapy, presence of baseline fever and early removal of central catheter were significant in the univariate analysis and age, type of chemotherapy and early removal of central catheter were also significant, but, baseline fever was not significant in the multivariate analysis. Furthermore, duration of fever in the remission induction chemotherapy was significantly longer than consolidation chemotherapy, on the other hand, not significantly longer than salvage chemotherapy. Conclusion : In this retrospective study, age, type of chemotherapy, presence of baseline fever and early removal of central catheter were significant in the univariate analysis. They were equally significant in the multivariate analysis, only except for the presence of baseline fever. It is noteworthy that the cases with early removal of CVCs except for CRBSIs had significant reduction of the duration of febrile neutropenia. We may need active consideration about the early removal of CVCs in the acute myeloid leukemia patients with febrile neutropenia for the purpose of reduction of the duration of febrile neutropenia. Disclosures No relevant conflicts of interest to declare.

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Expression of high Km 5′-nucleotidase in leukemic blasts is an independent prognostic factor in adults with acute myeloid leukemia

Blood ◽

10.1182/blood.v98.6.1922 ◽

2001 ◽

Vol 98 (6) ◽

pp. 1922-1926 ◽

Cited By ~ 64

Author(s):

Carlos M. Galmarini ◽

Kathryn Graham ◽

Xavier Thomas ◽

Fabien Calvo ◽

Philippe Rousselot ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Cytotoxic Activity ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Young Patients ◽

Independent Prognostic Factor ◽

Blast Cells ◽

Acute Myeloid

Abstract Cytarabine (ara-C) requires activation into its triphosphorylated form, ara-CTP, to exert cytotoxic activity. Cytoplasmic 5′-nucleotidase (5NT) dephosphorylates ara-CMP, a key intermediate, preventing accumulation of ara-CTP and may reduce cellular sensitivity to the cytotoxic activity of ara-C. To determine whether the level of expression of 5NT is correlated with clinical outcome in patients with acute myeloid leukemia (AML) treated with ara-C, this study analyzed the levels of messenger RNA expression of high Km 5NT by real-time polymerase chain reaction at diagnosis in blast cells of 108 patients with AML. High Km 5NT was expressed at diagnosis in the blast cells of 54% of patients. In univariate analysis, (1) patients whose blast cells contained high levels (values greater than the median value for total population) of high Km 5NT at diagnosis had significantly shorter disease-free survival (DFS) than patients with low levels of high Km 5NT (11 months versus 17.5 months, P = .02) and (2) high levels of high Km 5NT also predicted significantly shorter overall survival (15.7 months versus 39 months, P = .01) in young patients (≤ 57 years; median value for the entire population). In a multivariate analysis taking into account age, karyotype risk, and other factors found to have prognostic significance in univariate analysis, (1) high Km 5NT expression was an independent prognostic factor for DFS and (2) high levels of high Km 5NT also predicted significantly shorter overall survival in young patients. These results demonstrate that the expression of high levels of high Km 5NT in blast cells is correlated with outcome in patients with AML.

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Vascular Endothelial Growth Factor 121 (VEGF121) Isoform mRNA Is Predictive of Poor Prognosis in Acute Myeloid Leukemia (AML) .

Blood ◽

10.1182/blood.v104.11.2007.2007 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2007-2007

Author(s):

Fabien Calvo ◽

Philippe Rousselot ◽

Herve Dombret ◽

Jacques Medioni ◽

Samia Mourah

Keyword(s):

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Myeloid Leukemia ◽

Univariate Analysis ◽

Disease Free Survival ◽

Dose Intensity ◽

Response To Therapy ◽

Induction Treatment ◽

Worse Prognosis ◽

Acute Myeloid

Abstract Bone marrow microvascular organisation has been shown to play an important role in Acute Myeloid Leukemia (AML). VEGF has four main isoforms produced by alternative splicing: VEGF121, VEGF165, VEGF189 and VEGF206. The VEGF121 protein which lacks the basic amino acids responsible for heparin binding, is the more soluble and potent isoform. The present work aimed at quantitatively measure the shortest transcript for soluble VEGF121 isoform by quantitative RT-PCR in peripheral blood mononuclear cells (PBMC) from AML patients and to evaluate its value as a prognostic marker for response to therapy and survival. We conducted a single institution prospective study in 67 consecutive AML patients at diagnosis. VEGF121 transcript levels in AML PBMC were significantly higher than in normal controls (25.9 copies/1000 copies of β2 microglobulin (β2m) compared to 1.9 copies in normal participants, p<0.001). No relation was found between VEGF121 level and sex, age, white blood cells counts or the dose intensity of aracytine during induction treatment. Both univariate and multivariate analysis of overall survival showed that high levels of VEGF121 transcripts (VEGF121 in AML patients > 5 copies of VEGF121/1000 copies of β2m; 25th centile, this cut-point were designed after systematic searches) were significantly related with a worse prognosis (p<0.0001 for univariate analysis and OR=11.6 [2.76–48.6, p=0.008 for multivariate analysis). Neither sex (p=0.08) nor age (p=0.90) nor WBC (p=0.96) nor caryotype (p=0.29), nor AraC dose intensity (p=0.29) were related with a bad prognosis in this group of patients. Analysing disease free survival, only high levels of VEGF121 transcripts were significantly related to a worse prognosis (p<0.0001, using univariate analysis). Of note, 94% of the patients who relapsed had an initial high level of VEGF121 transcripts. Our findings support the use of this test as a predictive and prognostic tool, helping the clinician to identify patients who should benefit for alternative therapeutic strategies. This test has advantages over ELISA or RIA monitoring cellular or plasma VEGF protein, since it is more specific of this isoform, independant of the number of circulating cells, of binding to α2 macroglobulin and of contaminating sources of VEGF such as platelets which sequester this cytokine. Monitoring of antiangiogenic treatment through QRT-PCR of VEGF121 could therefore be useful in these patients.

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The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a prognostic score

Blood ◽

10.1182/blood.v96.3.870.015k16_870_877 ◽

2000 ◽

Vol 96 (3) ◽

pp. 870-877 ◽

Cited By ~ 3

Author(s):

Ollivier Legrand ◽

Jean-Yves Perrot ◽

Marion Baudard ◽

Annie Cordier ◽

Régine Lautier ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Multivariate Analysis ◽

Treatment Outcome ◽

Myeloid Leukemia ◽

Prognostic Score ◽

Univariate Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Biological Variables ◽

Acute Myeloid

In acute myeloid leukemia (AML) patients, a variety of clinical and biologic parameters, including phenotype, have been examined for potential value in predicting treatment response and survival. The European Group for the Immunological Classification of Leukaemias (EGIL) has proposed that AML be defined immunologically by the expression of 2 or more of the following myeloid markers: myeloperoxidase, CD13, CD33, CDw65, and CD117. With regard to this classification, the prognostic significance of 21 antigens taken separately and with immunophenotypic subgroups were evaluated and compared with other clinical and biological variables in 177 adult AML patients. None of the antigens tested were associated with treatment outcome. In contrast, patients with blasts disclosing a full expression of panmyeloid phenotype (defined by the expression of all 5 myeloid markers) had a higher complete remission rate (P < .0001) and differed significantly in disease-free survival (P = .02) and overall survival (P = .008) than patients whose cells expressed fewer than 5 of these markers. In multivariate analysis, only age, panmyeloid phenotype, performance status, and permeability glycoprotein activity influence treatment outcome. Cytogenetics was significant in univariate analysis but not in multivariate analysis, most likely because of the redundancy with panmyeloid phenotype and a higher sensitivity of immunophenotyping. Patients whose cells exhibit the panmyeloid phenotype appear to define a relatively homogeneous biological subset of AML. The 4 independent prognostic factors were used to create a prognostic score, defined by the number of factors present. This score permitted a stratification of patients with AML, thereby allowing for the consideration of innovative therapies to improve outcome in the poorer outcome groups.

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