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

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 In unpublished work, we have successfully used mathematical modeling of peripheral blood blast kinetics following induction chemotherapy to accurately predict the likelihood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.

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

The Time to Clearance of Peripheral Blood Blasts Predicts Complete Remission and Survival in Chinese Adults with Acute Myeloid Leukemia

2016 ◽  
Vol 135 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Xiaoyang Li ◽  
Hongming Zhu ◽  
Yunxiang Zhang ◽  
Weili Zhao ◽  
Jianqing Mi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Prognostic Significance ◽  
Chinese Patients ◽  
Characteristic Analysis ◽  
Chinese Adults ◽  
Acute Myeloid

The value of clearance of peripheral blood blasts (PBB) as a predictor of outcomes in acute myeloid leukemia (AML) is controversial. To investigate the prognostic significance of the time to clearance of PBB after induction in Chinese patients with AML, a retrospective analysis of 146 patients with newly diagnosed AML at Shanghai Ruijin Hospital was performed. Patients were categorized into early blast clearance (EBC; ≤5 days) and delayed blast clearance (DBC; >5 days) groups based on a receiver operating characteristic analysis. Complete remission (CR) after induction chemotherapy was related to the time to clearance of PBB (p < 0.001). Relapse-free survival (RFS; p = 0.003) and overall survival (p < 0.001) were longer in the EBC group. Multivariate analysis demonstrated that the time to clearance of PBB and cytogenetic risk independently predicted CR and RFS. Early clearance of PBB after induction chemotherapy can be a significant predictor of survival outcomes in AML patients.

scholarly journals Myeloid-derived suppressor cells level and MUC1 expression in de novo acute myeloid leukemia

2020 ◽  
Vol 51 (4) ◽  
pp. 245-252
Author(s):  
Sarah M. Nawar ◽  
Hala K. Sultan ◽  
Ahmed M. Bedewy ◽  
Amel A. ElNaggar ◽  
Irene L. Mikhael
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Normal Controls ◽  
Acute Myeloid

AbstractBackgroundAcute myeloid leukemia (AML) is the most common acute leukemia occurring in adults. It is an aggressive myeloid neoplasm with maturation arrest of myelopoiesis, leading to an accumulation of myeloblasts in the bone marrow and peripheral blood.ObjectiveTo evaluate alterations in myeloid-derived suppressor cells level and MUC1 gene expression in patients with de novo acute myeloid leukemia concerning disease characteristics and response to induction chemotherapy.Patients and methodsThe study was performed on 50 AML patients and 50 healthy controls. Detection of myeloid-derived suppressor cells (MDSCs) in peripheral blood was performed by mononuclear separation and flow cytometry. MUC1 gene expression was performed by RNA extraction, reverse transcription, and real-time PCR at Hematology Department Medical Research Institute, Alexandria University.ResultsWe have demonstrated that AML patients had both increased presence of MDSCs in peripheral blood as well as MUC1 overexpression in comparison to normal controls. MDSCs showed a significant correlation regarding response to induction chemotherapy on day 28. While MDSCs and not MUC1 are associated with inferior response to induction chemotherapy on day 28.ConclusionThe current data suggested that AML patients exhibit an increased presence of MDSCs as well as MUC1 gene overexpression in comparison with normal controls. While MDSCs showed a significant correlation regarding response to induction chemotherapy on day 28, MDSCs and not MUC1 are associated with inferior response to induction chemotherapy on the same day.

Clinical Impact of Different Levels of VEGF-C on Leukemic Blasts in the Bone Marrow and Peripheral Blood of Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1670-1670
Author(s):  
Sung-Eun Lee ◽  
Ji Yoon Lee ◽  
A-Reum Han ◽  
Woo-Sung Min ◽  
Heeje Kim
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Growth Factor ◽  
Cancer Cells ◽  
Predictive Model ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract Background: Vascular endothelial growth factor-C (VEGF-C) is a lymph-angiogenic growth factor and in general, transmits intracellular signals, resulting in cell proliferation and survival. Previous studies have reported that VEGF-C is important for cancer progression based on the autocrine VEGF-C loop promoting the invasion and metastasis of cancer cells as well as the spread of cancer cells by active recruitment of new lymphatics by tumor-derived VEGF-C. Acute myeloid leukemia (AML) blasts express VEGF-C and its receptors. A few studies demonstrated that high VEGF-C mRNA expression of AML blasts were related to increased in vitro and in vivo drug resistance and could predict adverse long-term outcomes. However, whether the expression of VEGF-C in the bone marrow (BM) and peripheral blood (PB) has a similar role in the pathophysiology of AML remains unclear. Methods: In this study, we analyzed plasma levels of VEGF-C in both BM and PB samples of AML patients. The levels of VEGF-C were measured using a commercially available ELISA in the newly diagnosed AML patients (58 in BM, 26 in PB), patients in complete remission (CR) (26 in BM, 20 in PB), and refractory/relapsed AML (15 in BM, 10 in PB). In addition, response after 1st induction chemotherapy was assessed in 67 evaluable patients and to create the predictive model for an achievement of CR, logistic regression was used after log transformation of VEGF-C levels. Results: In the BM of patients with newly diagnosed AML, the level of VEGF-C was 47.87 ± 12.4 pg/ml which was significantly lower than that of refractory/relapsed AML [518.3 ± 320.0 pg/ml (P=0.005)] but there was no difference, compared to that of patients in CR [44.57 ± 8.44 pg/ml (P = 0.865)]. In contrast no trend was observed in the PB samples. Next, to create the predictive model for an achievement of CR, sixty-seven evaluable patients who received standard induction chemotherapy were analyzed. Thirty-seven men and 30 women were included. With a median age of 49 years (range, 20-78), the distribution of favorable, intermediate-I, intermediate-II, and adverse cytogenetic risk (ELN) were 25%, 31%, 21%, and 22%, respectively. The patients with continuous values of Log10VEGF-C were divided into 2 groups (low vs. high levels) by a ROC curve analysis. Univariate analysis showed that high levels in BM samples were associated with achievement of CR after 1st induction chemotherapy. Ultimately, multivariate analyses revealed that low levels of Log10VEGF-C showed a trend for failure to achieve a response of CR (RR of 0.24, P = 0.065) and intermediate II/adverse cytogenetic risk was associated with a failure of CR, compared to favorable/intermediate I (RR of 0.21, P = 0.036). In contrast, in the PB samples, a low value of Log10VEGF-C was an independent factor for achievement of CR (RR of 28.7, P = 0.043). Conclusion: Our data demonstrate that the high VEGF-C level in the BM samples at diagnosis was associated with a trend toward higher CR rate and high VEGF-C level in the PB samples was significantly related to a failure of CR, suggesting discrepancy of the role of VEGF-C level in the BM and PB. Further studies on the different mechanism of the VEGF-C/VEGF-receptor pathway in the BM and PB are warranted. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document