scholarly journals Peripheral blood blast clearance is an independent prognostic factor for survival and response to acute myeloid leukemia induction chemotherapy

2016 ◽  
Vol 91 (12) ◽  
pp. 1221-1226 ◽  
Author(s):  
Nicholas J. Short ◽  
Christopher B. Benton ◽  
Hsiang‐Chun Chen ◽  
Peng Qiu ◽  
Lisa Gu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Independent Prognostic Factor ◽  
Acute Myeloid

scholarly journals Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia

Cancer ◽  
2012 ◽  
Vol 118 (21) ◽  
pp. 5278-5282 ◽  
Author(s):  
Martha Arellano ◽  
Suchita Pakkala ◽  
Amelia Langston ◽  
Mourad Tighiouart ◽  
Lin Pan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Acute Myeloid

EVI1 Overexpression in Pediatric Acute Myeloid Leukemia Associated with Unfavorable Subtypes.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1802-1802
Author(s):  
Brian V Balgobind ◽  
Sanne Lugthart ◽  
Iris H.I.M. Hollink ◽  
Susan T.J.C.M. Arentsen-Peters ◽  
Elisabeth R van Wering ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Independent Prognostic Factor ◽  
Older Children ◽  
Microarray Gene Expression ◽  
Treatment Protocols ◽  
Monosomy 7 ◽  
Pediatric Aml ◽  
Acute Myeloid

Abstract The EVI1 (ecotropic virus integration-1) gene plays an important role in hematopoiesis especially in megakaryocyte development. The MDS1 gene is located upstream of EVI1, and its function is currently unknown. Normally the MDS1/EVI1 intergenic splice variant is co-expressed with EVI1. In adult acute myeloid leukemia (AML) overexpression of EVI1 (EVI1+) can be found in patients with chromosome 3q26-rearrangements. Often, these patients do not co-express MDS1/EVI1. Recently high EVI1 expression was also discovered in a separate subgroup of patients that did not have 3q26-rearrangements. Occasionally, they did not show overexpression of MDS1/EVI1. In these patients cryptic inversions of chromosome 3 were identified with fluorescence in situ hybridization (FISH). Of interest, EVI1+ was found to be an independent poor prognostic marker in adult AML (Lugthart et al, Blood 2008). In pediatric AML, 3q26-rearrangements are rare and the role of EVI1 is unknown. In this study, we investigated the frequency and clinical relevance of EVI1+ in pediatric AML. EVI1 expression was analyzed in 233 pediatric AML patients, of whom microarray gene expression profiling data were available. EVI1+ was found in 25 pediatric AML patients (11%), and confirmed with real-time quantitative PCR. This included 13/49 (26%) patients with MLL-rearranged AML: 5/22 (23%) cases with t(9;11); and all (n=4) cases with t(6;11). Moreover, EVI1+ was found in 4/7 (57%) cases with AML M7; in 2/3 (66%) cases with AML M6; in both cases with monosomy 7; in 1/43 (2%) cases with normal cytogenetics; in 2 patients with random cytogenetics, and in 1 patient with a cytogenetic failure. EVI1+ was not found in the t(8;21), inv(16) and t(15;17) subgroups. 3/25 EVI1+ patients lacked the MDS/EVI1 transcript, but no cryptic 3q26-rearrangements were detected with FISH. Molecular analysis showed that one patient had a CEBPα mutation; one patient had an FLT3-ITD; and 3 patients showed a mutation in the RAS oncogene. EVI+ was not correlated with sex or white blood cell count. However, the frequency in children younger than 10 years old was twice as high when compared to older children (14% vs 7%, p=0.12). Survival analysis was restricted to the subset of patients who were treated using uniform DCOG and BFM treatment protocols (n=204). In this cohort, EVI1+ patients had a worse 5-years event-free survival (pEFS) compared to patients without EVI1+ (30 vs. 43%, p=0.02). However, multivariate analysis, including cytogenetics (favorable [t(8;21, inv(16), t(15;17)] vs. other), FLT3-ITD, age and WBC, showed that EVI1+ was not an independent prognostic factor for survival. Moreover, within the unfavorable/normal cytogenetic subgroup, there was no difference in outcome between patients with and without EVI1+. We conclude that EVI1+ is found in ~10% of pediatric AML, and highly correlated with specific unfavorable cytogenetic (MLL-rearrangements) and morphologic (FAB M6/7) subtypes. In contrast to adult AML, no 3q26-rearrangements or cryptic inversions were found, and EVI1+ was not an independent prognostic factor. This difference in prognostic relevance may be due to differences in treatment. Alternatively, these results may indicate that EVI1 plays a different role in disease biology between adult and pediatric AML. This is at least suggested by the lack of 3q26 aberrations in pediatric AML.

Predicting Duration of Neutropenia After Successful Intensive Induction Chemotherapy for Acute Myeloid Leukemia or High-Grade Myelodysplastic Syndromes

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4336-4336 ◽  
Author(s):  
Sarah A. Buckley ◽  
Vladimir Vainstein ◽  
Janis L. Abkowitz ◽  
Elihu H. Estey ◽  
Roland B. Walter
Keyword(s):  
Mathematical Modeling ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Blood Neutrophil ◽  
Neutrophil Recovery ◽  
Peripheral Blood Neutrophil ◽  
Acute Myeloid

Abstract Abstract 4336 Background: Chemotherapy-induced neutropenia (CIN) is a major cause of morbidity and mortality in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) due to the risk of overwhelming infection. Although the risk for infections increases with longer duration of neutropenia, no attempts have been undertaken to predict time of neutrophil recovery in AML/MDS patients following intensive chemotherapy. In unpublished work, we have successfully used mathematical modeling of peripheral blood blast kinetics following induction chemotherapy to accurately predict the likelihood of subsequent complete remission (CR). In this retrospective study, we investigated whether data derived from mathematical modeling of early peripheral blood neutrophil or blast dynamics could predict the duration of CIN in AML/MDS patients undergoing intensive induction chemotherapy. Patients and Methods: We retrospectively analyzed a cohort of 59 consecutive patients with newly diagnosed AML or MDS who achieved CR after induction chemotherapy after 1 course of chemotherapy with a 7 + 3-like regimen. Daily peripheral blood neutrophil and blast counts were recorded from the initiation of chemotherapy until the day of neutrophil recovery (defined as an absolute neutrophil count [ANC] ≥ 500 cells/μL). In patients with ≥ 3 measurable neutrophil or blast counts within the first five days of data collection, the rate of peripheral blood neutrophil and blast clearance was calculated by fitting an exponential decay curve to the data points starting on day 1 of chemotherapy. Results: The average age of the study cohort was 54 years (range 25 to 78). Seventy-six percent had primary AML. Cytogenetic risk was favorable in 32%, intermediate in 37%, and adverse in 27% of patients. The 23 patients with initial ANC < 500 cells/μL had a significantly longer duration of neutropenia than the 36 patients with initial ANC ≥ 500 cells/μL (mean: 29 versus 26 days, range: 21 – 39 versus 21 – 34, p=0.045). Neither age nor percentage of blasts in the bone marrow at diagnosis predicted neutropenia duration. In patients for whom decay rates could be modeled, there was no association between duration of neutropenia and decay rate for neutrophils (n = 36) or blasts (n = 20). There was also no association with the day that neutrophils first started to decline (defined as the first drop < 70% of the initial neutrophil count) or the first day of blast clearance from peripheral blood. Seven patients received granulocyte colony-stimulating factor (G-CSF; 1 prior to chemotherapy for antecedent myelodysplastic syndrome and 6 between days 15 and 43 for prolonged neutropenia and/or febrile neutropenia); the duration of neutropenia in this group did not differ significantly from that of the cohort as a whole. Conclusion: While kinetics of normal blood counts following initiation of intensive chemotherapy do not appear helpful to predict the duration of subsequent neutropenia, pre-treatment ANC levels provide limited information, with patients who are severely neutropenic prior to induction chemotherapy for AML having a longer average duration of CIN. This observation may provide some clinical guidance on the risk-adapted use of G-CSF in patients with AML/MDS undergoing induction chemotherapy. Disclosures: Vainstein: Neumedicines Inc: Employment.

scholarly journals Peripheral Blood Blast Clearance As an Independent Predictor of Clinical Response and Outcomes in Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2684-2684
Author(s):  
Noa G. Holtzman ◽  
Firas El Chaer ◽  
Omer Ali ◽  
Ameet Patel ◽  
Maria R. Baer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcomes ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Total Leukocyte Count ◽  
Risk Category ◽  
The Absolute ◽  
Acute Myeloid

Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease that depends on precise risk-stratification for predicting outcomes and optimizing therapy plans. Despite the current clinical landscape of incorporating karyotype and mutations into prognostic models, chemosensitivity (or lack thereof) is usually not evaluated or appreciated until a patient undergoes a day 14 bone marrow (D14BM) evaluation during induction treatment. While the D14BM aspirate and biopsy are regularly used to predict achievement of CR versus need for further reinduction therapy, some have questioned its utility. Further, the invasive nature of the procedure leads to significant patient discomfort, anxiety, increased risk of complications (infections, bleeding, damage to surrounding tissues) and, at times, is not feasible due to a patient's critical state. Therefore, alternative criteria are needed to help risk-stratify these patients and predict treatment responses. We report here a single center analysis of the relationship between the rate of peripheral blood blast (PBB) clearance with cytotoxic induction therapy and clinical outcomes. Methods Patients diagnosed with AML (non-M3) with detectable PBB via manual differential or flow cytometry at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC) during 2007-2018 were identified. Only patients who underwent induction with a "7+3" regimen with cytarabine and an anthracycline (idarubicin or daunorubicin), or "7+3" plus a third agent, were included. Patient and disease characteristics, treatment courses, and clinical outcomes were collected. The absolute PBB count was calculated by percent PBB multiplied by total leukocyte count (103/mcL). PBB rate of clearance (PBB-RC) was defined as the percentage of the absolute PBB count at diagnosis that was cleared each day, on average, until clearance or D14 of induction chemotherapy. Patients were divided into three groups based on PBB-RC: high, if PBB-RC >30% (n=15); low, if PBB-RC <10% (n=16); and intermediate, if PBB-RC fell between 10-30% (n=133). Primary outcomes included D14BM status, achievement of complete remission (CR) with or without full count recovery, and overall survival (OS). Multivariate logistic regression and Cox proportional hazards models were conducted and adjusted for the disease risk category, age, sex, ethnicity, and use of leukapheresis or hydroxyurea. Cox models were also adjusted for allogeneic stem cell transplantation (SCT) status. Results Treatment-naive AML patients with PBB at diagnosis and who underwent cytotoxic induction therapy were identified (n=164). Patient characteristics are shown in Table 1. Sixty-eight percent of patients underwent induction with "7+3", and 28% with "7+3" with a third agent. Pre-induction leukoreduction included hydroxyurea (29%) and/or leukapheresis (12%). Most (68%) patients received only one course of induction; 18% received 2 courses, and 8% received ≥3. Chemoablation on D14BM was achieved in 70% of patients (n=113); 27% (n=45) had residual disease, and 4% (n=6) were indeterminate. CR was achieved in 74% of patients (n=121), 19 of which required ≥ 2 induction courses. Forty-one patients proceeded to SCT. Median OS was 18.5 months (range 0.5-122). Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR=1.97; 95% CI: 1.39-2.80, p<0.001). The adjusted area under the ROC curve of PBB-RC for predicting D14BM clearance was 0.72, with a positive predictive value (PPV) of high PBB-RC of 93% and negative PV (NPV) of low PBB-RC of 81%. PBB-RC was also significantly associated with CR (OR per 5% =2.08; 95% CI: 1.38-3.14, p<0.001). CR was achieved in all patients in the high PBB-RC group, while only 44% in the low PBB-RC group. PBB-RC was significantly associated with improved OS (HR per 5%=0.67; 95% CI: 0.52-0.85, Figure 1). Other factors associated with longer OS included favorable risk category (HR=0.03; 95% CI: 0.01-0.23) and SCT (HR=0.50; 95% CI: 0.26-0.95). African American patients had poorer OS adjusted for PBB-RC (HR=2.22; 95% CI: 1.16-4.25), while race was not associated with D14BM or CR rate. Conclusion PBB-RC during induction chemotherapy is predictive of achievement of CR and improved OS in AML. PBB-RC is also significantly associated with D14BM clearance and can therefore serve as a surrogate predictive marker for treatment response in AML patients with PBB at diagnosis. . Disclosures Emadi: NewLink Genetics: Research Funding.

scholarly journals Risk Stratification in Acute Myeloid Leukemia Using CXCR Gene Signatures: A Bioinformatics Analysis

2020 ◽  
Vol 10 ◽  
Author(s):  
Cong Lu ◽  
Jiang Zhu ◽  
Xiangjun Chen ◽  
Yanjie Hu ◽  
Wei Xie ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Chemokine Receptors ◽  
Myeloid Leukemia ◽  
Independent Prognostic Factor ◽  
Cxcr2 Expression ◽  
Relationship Of ◽  
The Relationship ◽  
Acute Myeloid

The role of CXC chemokine receptors in tumors has been an increasingly researched focus in recent years. However, significant prognostic values of CXCR members in acute myeloid leukemia are yet to be explored profoundly. In this study, we firstly made an analysis of the relationship of CXCR family members and AML using samples from TCGA. Our results suggested that transcriptional expressions of CXCRs serve an important role in AML. CXCR transcript expressions, except CXCR1 expression, were significantly increased in AML. It displayed the expression pattern of CXCR members in different AML subtypes according to FAB classification. The correlations of CXCR transcript expression with different genotypes and karyotypes were also present. High CXCR2 expression was found to have a significantly worse prognosis compared with that of low CXCR2 expression, and CXCR2 was also found to be an independent prognostic factor. We also established a CXCR signature to identify high-risk subgroups of patients with AML. It was an independent prognostic factor and could become a powerful method to predict the survival rate of patients.

Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival

Blood ◽  
2007 ◽  
Vol 110 (13) ◽  
pp. 4172-4174 ◽  
Author(s):  
Michelle A. Elliott ◽  
Mark R. Litzow ◽  
Louis L. Letendre ◽  
Robert C. Wolf ◽  
Curtis A. Hanson ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Rapid Decline ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Acute Myeloid

In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating leukemic blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors, not only for achieving remission but also for relapse-free survival (RFS). However, in acute myeloid leukemia (AML) parameters of chemosensitivity have been restricted mainly to the rapidity of achievement of complete remission (CR) or the assessment of residual leukemic bone marrow blasts during aplasia. We hypothesized that the time to circulating peripheral blood blast clearance, as a potential surrogate for in vivo chemosensitivity, would have prognostic relevance in AML also. In a retrospective analysis of a cohort of 86 adult patients with AML receiving uniform induction and consolidation chemotherapy, we demonstrate that the time to clearance of circulating blasts during induction chemotherapy is an independent prognostic marker of RFS, superseding other known or established risk factors, including karyotype and number of inductions to achieve CR.

Enhanced pretreatment CD25 expression on peripheral blood CD4+ T cell predicts shortened survival in acute myeloid leukemia patients receiving induction chemotherapy

2016 ◽  
Vol 68 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Łukasz Bołkun ◽  
Małgorzata Rusak ◽  
Andrzej Eljaszewicz ◽  
Lothar Pilz ◽  
Urszula Radzikowska ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Cd4 T Cell ◽  
Cd25 Expression ◽  
Acute Myeloid
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