Prognostic Impact of High Hematogones in Acute Myeloid Leukemia

Abstract Abstract 1435 Introduction: The response to AML treatment is very heterogeneous and relapse risk is high. Hematogones (HG) are B lymphoid cell precursors present in all individuals. HG absolute count grows after chemotherapy, during medullar recovery and it seems to be related to prognosis. Objectives: Determination of HG number in AML patients with intermediate-risk karyotype, with complete response (CR). Determine prognostic value for HG number in these patients. Methods: Retrospective analysis of 148 patients with non promyelocytic AML, treated with “7+3” chemotherapy induction, followed in our centre, from 1998 to 2011. HG quantification was executed after induction chemotherapy, with flow cytometry pannel (4 colours - CD34, CD10, CD19, CD20 e CD45) in blood marrow samples in patients with CR, according to Cheson et al. (JCO 2003). The patients characteristics were compared with a X2test for binary variables and a Mann-Whitney test for continuous variables. Survival was plotted with Kaplan-Meier curves and the data for the various groups were compared with a log-rank test. Multivariate analysis was performed with a Cox model after the proportional hazard assumption was checked. A p value less than 0.1 was considered to be statistically significant. Results: There were 124 patients achieving CR after induction chemotherapy “7+3”, with a median follow up of 32 months ([0–141]), 46,8% (n=58) were male, median age of 50 years ([17–66]). There were 91,1% (n=113) patients with de novo AML and 63,9% (n=76) with intermediate-risk karyotype. In this study 16,3% (n=20) went on transplantation. Relapse occurred in 53,2% (n=66), with a disease free survival (DFS) of 15 months ([0–140]). HG quantification was possible in 33,1% (n=41) of the patients. Applying a cutoff of 0.01% (Chantepie S et al. Blood 2011) we can find 31,7% (n=13) with HG>0.01%. These patients had better DFS, when comparing to patients with HG≤0.01% (median 16 vs 9 months, p=0,05), to equal overall survival. According to multivariate Cox model, the HG>0,01% is a independent predictive value for DFS (IC 95% [0,8533-54.259], p<0,07), when comparing to HG≤0,01%, age, leucocytosys (>20000/μL), karyotype-risk groups and WHO classification of AML. We established a good prognosis associated to HG>0,01% group: patients with HG≤0,01% have a 6.8 hazard ratio (HR) or relapse comparing with HG>0,01% group. Considering this information and applying it to karyotype-intermediate risk patients, it was possible to obtain two different groups with prognostic impact on the DFS: low intermediate risk (HG>0,01%) and high intermediate risk (HG<0,01%).The 3 year-DFS is 83,3% for low intermediate risk group and 50% for high intermediate risk patients (p<0,094). Conclusion: Using flow cytometry is a simple and reproductively method for detecting HG. This quantification in AML patients with CR has clinically relevance, with prognostic impact in DFS (16 vs 9 months, p=0,05). For HG levels superior to 0,01% after induction chemotherapy the risk of relapse is decreased. The HR associated to HG value allowed the stratification of the intermediate-risk group in two subgroups of patients (low intermediate risk group and high intermediate risk patients) with different DFS (83.3% vs 50% 3-y EFS, p<0,094). This subdivision can have implications on clinical decision for therapeutic strategy, in the heterogeneous intermediate-risk karyotype group. This cohort needs to be enhanced in order to validate this approach. Disclosures: No relevant conflicts of interest to declare.

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The Prognostic Impact of Blast Cell Immunophenotyping in Intermediate Risk AML Patients at Diagnosis.

Blood ◽

10.1182/blood.v104.11.2990.2990 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2990-2990

Author(s):

Marianne H. Hoffmann ◽

Eva B. Leinoe ◽

Tobias W. Klausen ◽

Ronnie C. Danielsen ◽

Erik Kjaersgaard ◽

...

Keyword(s):

Flow Cytometry ◽

Prognostic Model ◽

Cox Regression ◽

Risk Group ◽

Blast Cell ◽

Prognostic Impact ◽

Intermediate Risk ◽

Cox Regression Analysis ◽

Risk Patients ◽

Blast Cells

Abstract The most important prognostic factor in current clinical management of acute myeloid leukemia (AML) is the leukemic karyotype, identifying patients with relatively favorable, intermediate and adverse prognosis. Unfortunately, the majority of patients are assigned to the intermediate risk group although they represent a broad spectrum regarding prognosis. While molecular mapping may diminish this problem in the future, an approach to prognostic stratification of patients within the intermediate risk group is urgently needed in order to develop risk-adapted treatment strategies and evaluate the efficacy of new treatments. The aim of this retrospective study was to evaluate the prognostic impact of diagnostic multiparametric flow cytometry (MFC) in the cytogenetic intermediate risk group of AML patients. Diagnostic samples were obtained from 162 AML patients (median age 66 years, range 0–88; cytogenetic risk group favorable/intermediate/adverse/unknown 11/91/17/43; bone marrrow/blood 141/21). Four-color flow cytometry and a panel of 35 monoclonal antibodies was used to characterize the immunophenotype of AML blast cells, defined by side scatter and CD45 expression. For each antigen in the panel, mean fluorescence intensity (MFI) of the blast cell population was recorded. For each antigen, the expression pattern was characterized as homogeneous or heterogeneous. Heterogeneous antigen expression was defined as the presence of two or more subpopulations, within the blast cell gate, expressing the antigen in question with distinctly different intensities. Flow cytometry data, biological and clinical variables for the cytogenetic intermediate risk group and for patients with unknown cytogenetic risk were analysed by univariate Cox regression analysis and selected variables were analysed by multivariate Cox regression analysis (backward likelihood-ratio statistics, p<0.05 considered significant) with overall survival as outcome variable. Four conventional variables and four blast cell phenotype variables significantly predicting inferior survival were identified: FAB type other than 0/1 (p<0.03), presence of extramedullary disease (p<0.007), high white blood count (p<0.0005) and high age (p<0.0005); a heterogeneous CD117 expression (p<0.009), heterogeneous CD90 expression (p<0.03) as well as high MFI of CD56 expression (p<0.0005) and low MFI of CD58 expression (p<0.001) for CD45/SSC gated blast cells. The prognostic model identified two subsets of cytogenetic intermediate risk patients with a median overall survival of 0.1 and 1.5 years respectively. The subset of cytogenetic intermediate risk patients with high risk according to the prognostic model had an outcome inferior to that of the cytogenetically defined adverse risk group. This prognostic model was also valid for patients with unknown cytogenetic risk and for patients assigned to the favorable and adverse risk groups by cytogenetics. Informative MFC was applicable in 96% of the cases analysed. The prognostic model should be evaluated in a prospective clinical multicentre trial.

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Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920928214 ◽

2020 ◽

Vol 12 ◽

pp. 175883592092821

Author(s):

Li-Ting Liu ◽

Yu-Jing Liang ◽

Shan-Shan Guo ◽

Hao-Yuan Mo ◽

Ling Guo ◽

...

Keyword(s):

High Risk ◽

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Risk Group ◽

Risk Groups ◽

Rank Test ◽

Intermediate Risk ◽

Free Survival ◽

Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

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Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia (AML)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7015 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7015-7015

Author(s):

F. P. Santos ◽

W. Qiao ◽

J. E. Cortes ◽

D. Jones ◽

F. Ravandi ◽

...

Keyword(s):

Risk Group ◽

Cox Model ◽

Tyrosine Kinase Domain ◽

P Value ◽

Prognostic Impact ◽

Intermediate Risk ◽

Poor Risk ◽

Flt3 Mutations ◽

The Impact ◽

Good Risk

7015 Background: Mutations of the FLT3 gene (in special internal tandem duplication -ITD) are common in normal karyotype AML (NK-AML) and are associated with shorter relapse free and overall survival (OS). The frequency of FLT3 mutations is lower in other cytogenetic subgroups and the impact on outcome is unclear. Methods: The records of patients (pts) with newly diagnosed AML (from 2003 to 2007) were reviewed. Pts were divided among three cytogenetic subgroups: Good-risk (t(8;21), Inv(16)/t(16;16)) Intermediate-Risk (Diploid,-Y) and Poor Risk (-5,-7, 11q abnormalities). FLT3 ITD and tyrosine kinase domain (TKD) mutations were determined on baseline DNA samples by a PCR based method with 1% sensitivity. Since the frequencies of FLT3 mutations were lower in good- and poor-risk subgroups, ITD/TKD mutations were considered together in the analysis, while in the intermediate risk group they were analyzed separately. Survival curves stratified by FLT3 mutation were estimated by Kaplan Meier plots and compared by logrank test. A Cox model was fit for OS, and non-significant variables were eliminated in a step-down fashion with a p- value cut-off of p = .10. Results: A total of 481 pts were included (65 pts=good risk, 272 pts=intermediate risk and 144 pts= poor risk). Prevalence of FLT3 mutations is shown in the Table. No difference was found in median OS between FLT3-mutated and FLT3- wild type pts in the good risk group (not reached (NR) vs NR, P = 0.57) nor in the poor risk group (55 vs 24 weeks, P = 0.44). In intermediate risk, OS was worse in FLT3-ITD positive pts (33 vs 89 weeks, P < 0.0001) but not in FLT3-TKD positive pts (77 vs 70 weeks, P = 0.89). In the Cox model, FLT3 mutations were prognostic for OS only in intermediate risk pts with FLT3-ITD (HR 2.63, P < 0.0001). Conclusions: In our cohort of pts, FLT3 mutations did not have a prognostic impact in AML with good and poor risk karyotype. [Table: see text] No significant financial relationships to disclose.

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Differential Prognostic Impact Of Peripheral Blood Blast Clearance In AML Based On Type Of Therapy and FLT3 Mutation Status

Blood ◽

10.1182/blood.v122.21.2584.2584 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2584-2584

Author(s):

Christopher B. Benton ◽

Lisa Gu ◽

Hagop M. Kantarjian ◽

Peng Qiu ◽

Farhad Ravandi ◽

...

Keyword(s):

Induction Chemotherapy ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Prognostic Significance ◽

Specific Treatment ◽

Rank Test ◽

P Value ◽

Prognostic Impact ◽

Mutation Status ◽

Mutational Status

Abstract Background The day of clearance of peripheral blood blast cells (PBBC) is a prognostic marker in patients with acute myeloid leukemia (AML) treated with induction chemotherapy with cytarabine (ara-C) plus idarubicin (AI regimen: ara-C 1.5g/m2 x 4 days, idarubicin 12mg/m2 x 3 days). Earlier PBBC clearance correlates with improved overall survival (OS). We extended this observation to subsets of patients receiving the AI regimen in combination with a targeted agent such as the FLT3 inhibitor sorafenib (AI regimen plus sorafenib 400mg orally twice daily x 7 days) and vorinostat (vorinostat 500mg three times daily x 3 days followed by AI regimen), and examined the interaction of FLT3 mutational status and PBBC clearance. Patients and Methods PBBC clearance (defined as PBBC=0% by CBC differential) was examined for patients with non-APL AML undergoing AI alone (n=168), AI+sorafenib (n=75), and AI+vorinostat (n=102). Patient characteristics for all patients (n=345) were as follows: median age 54 years (range, 18-72), FLT3-mutated (FLT3+, includes FLT3-ITD and FLT3-D385) (95, 28%), wild-type FLT3 (FLT3-neg) (207, 60%), median WBC 5.0x109/dL (range, 0-229), median PBBC 17% (range, 0-99), median BM blasts 46% (range, 1-98). Patients for each cohort were divided based on day of PBBC clearance and survival evaluated by Kaplan-Meier curves. Comparisons of curves were carried out using a log-rank test. Results The overall response rates (ORR=CR+CRp) for the AI, AI+sorafenib, and AI+vorinostat induction cohorts were 63%, 79%, and 76% respectively. We evaluated OS for each of the three cohorts individually. In our first analysis, we divided patients into 5 groups according to PBBC clearance day: group A (0-1 days), B (2-3 days), C (4-5 days), D (6-8 days), and E (>8 days). We found that OS for patients in groups A-E was significantly different only in the AI therapy cohort (p-value<0.01), and not in the AI+sorafenib (p-value=0.15) or AI+vorinostat (p-value=0.1) cohorts. Noting that earlier blast clearance generally correlated with improved OS, we simplified our analysis by dividing patients into only two groups based on blast clearance. We performed two separate analyses using a 3-day cutoff (0-3 days vs. >3 days) or a 5-day cutoff (0-5 days vs. >5 days). For a blast clearance cutoff of 3 days, OS was significantly different in the AI+vorinostat cohort (p-value=0.02) and not in the AI alone (p-value=0.27) or AI+sorafenib (p-value=0.1) cohorts. For a 5-day cutoff, OS was significantly different in the AI (p-value<0.001) and AI+vorinostat (p-value=0.04) cohorts, but not the AI+sorafenib (p-value=0.13) cohort. We next evaluated FLT3+ and FLT3-neg patients individually for all three cohorts. Using a 3-day cutoff for blast clearance, the prognosis of FLT3+ patients could be significantly differentiated for patients treated with the FLT3 targeted regimen AI+sorafenib (p-value=0.04), but not AI alone (p-value=0.64) or AI+vorinostat (p-value=0.48). In distinction, FLT3-neg patients receiving AI+vorinostat could be well differentiated (p-value=0.06), but not FLT3-neg patients receiving AI alone (p-value=0.21) or AI+sorafenib (p-value=0.6). Conclusions The prognostic significance of the day of PBBC clearance during induction chemotherapy in AML is dependent on the specific treatment used and the mutation status of the patients being treated. For patients treated with AI alone, disappearance of blasts within 5 days of induction strongly predicts superior survival compared to patients who clear blasts after 5 days. For patients treated with AI+sorafenib, there is not a strong correlation between day of blast clearance and prognosis, unless FLT3+ patients are investigated alone, where there is a significant correlation between clearing blasts within 3 days of induction and prognosis. For patients treated with AI+vorinostat, disappearance of blasts within 3 days suggests a better survival in FLT3-neg but not FLT3+ patients. Additional approaches are needed to evaluate the prognostic value of clearance of PBBC in AML in the context of targeted therapy and mutational status of disease. Disclosures: No relevant conflicts of interest to declare.

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The Prognostic Significance of Blast Aberrancies By Flow Cytometry in Low/Int Risk MDS

Blood ◽

10.1182/blood-2019-130511 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5430-5430

Author(s):

Kristen M Corrao ◽

Alexandra M. Harrington ◽

Steven H. Kroft ◽

Laura C. Michaelis ◽

Karen-Sue B. Carlson ◽

...

Keyword(s):

Flow Cytometry ◽

Median Time ◽

Research Funding ◽

Prognostic Significance ◽

Red Blood Cell Transfusion ◽

Rank Test ◽

Intermediate Risk ◽

Prognostic Information ◽

Clin Pathol ◽

Risk Patients

Background: The myelodysplastic syndromes (MDS) represent heterogeneous disorders with varied clinical courses. The major prognostic tool in MDS is the IPSS-R, which helps estimate survival outcome and estimate risk for AML transformation. In low or intermediate risk pts, the IPSS-R has shortcomings; in these pts, the development of transfusion dependent anemia is the major disease associated complication, and this is not addressed by IPSS-R stratification. Previous studies have indicated that aberrancies detected by flow cytometry can risk stratify pts with MDS. The purpose of this study was to determine whether detection of neoplastic-specific blast aberrancies in pts diagnosed with low or intermediate risk MDS can identify pts at higher risk for transfusion dependent anemia after MDS diagnosis. Methods: We performed a retrospective chart review on MDS patients initially diagnosed at our institution between 1/2010 and 12/31/2017. Patients with low/intermediate risk by IPSS-R were identified. Flow cytometry findings on initial diagnostic BM biopsies performed at our institution only were reviewed. Flow cytometry (4- and 8-color) was performed on bone marrow aspirates for the following antigens: CD3, CD7, CD11b, CD13, CD14, CD15, CD19, CD20, CD33, CD34, CD36, CD38, CD45, CD56, CD64, CD117, and HLA-DR using FACS Calibur or FACSCanto II flow cytometers. Myeloblasts were identified by cluster analysis, as previously described (Am J Clin Pathol. 2010 Nov; 134(5):749-61), and compared to 20 control cases. Blast aberrancies were defined as an immunophenotypic difference of > ¼ log compared to the blasts in the controls. Neoplasia-specific blast aberrancies were defined as: expression of CD7, CD11b, CD15, and/or CD56 and/or under expression of CD38 and CD45. We estimated probability of transfusion dependent anemia using Kaplan Meier product limit method and compared survival curves using log-rank test. Analyses were performed using Stata v12.0. Results: A total of 63 patients were identified, with median age of 68 years (range 31-89 years). Median hemoglobin (Hg) at diagnosis was 9.8 (range 5.2-15.3). Cytogenetic risk categories were very good, good, intermediate and poor in 3%, 71% 16%, and 10% respectively. IPSS-R category was very low or low in 70% (44 pts), and intermediate in 30% (19 pts). The presence of blast aberrancies was similar in proportion among low risk patients (61%, n=27) compared to intermediate risk patients (68%, n=13). Overall, the presence of only one blast aberrancy, whether neoplasia-specific or not, did not significantly segregate patients at greater risk for transfusion dependence. However, the presence of 2 or more aberrancies statistically defined two populations. Those possessing 0-1 blast aberrancy did not reach a median time to transfusion dependence, whereas those possessing 2+ aberrancies had a median time to transfusion dependence of 1.2 years (p=0.02). Additionally, when looking at neoplasia-specific blast aberrancies, pts with 0-1 aberrancy had a median time to transfusion of 4.7 years, compared to 2+ aberrancies, at 0.8 years (p=0.02). Figure 1 illustrates this finding. Conclusion: The determination of blast aberrancies by flow at time of MDS diagnosis may provide prognostic information in low/intermediate risk MDS patient and could help predict risk for early red blood cell transfusion dependence. Upfront risk stratification would be valuable information to plan follow-up for these patients, as well as treatment decision making including early initiation of ESAs. Disclosures Michaelis: Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; JAZZ: Other: Data Safety Monitoring Board, uncompensated, Research Funding; BMS: Research Funding; Bioline: Research Funding; ASTEX: Research Funding; Janssen: Research Funding; Millenium: Research Funding; Macrogeneics: Research Funding; Pfizer: Equity Ownership, Research Funding; Incyte: Consultancy, Research Funding. Runaas:Agios: Honoraria; Blueprint Medicine: Honoraria. Atallah:Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy; Jazz: Consultancy; Novartis: Consultancy; Helsinn: Consultancy. Abedin:Actinium Pharmaceuticals: Research Funding; Pfizer Inc: Research Funding; Helsinn Healthcare: Research Funding; Agios: Honoraria; Jazz Pharmaceuticals: Honoraria.

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Influence of the fusion gene ETV6-RUNX1 in the prognosis of the Pediatric B- Precursor Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v118.21.2515.2515 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2515-2515

Author(s):

Alejandro Contento-Gonzalo ◽

Antonio Jimenez-Velazco ◽

Alcala-Peña Magdalena ◽

Manuel Barrios ◽

Katie Hurst ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Disease Free Survival ◽

Rank Test ◽

Prognostic Impact ◽

Excellent Outcome ◽

Log Rank Test ◽

Significant Difference

Abstract Abstract 2515 INTRODUCTION AND OBJECTIVES: The ETV6-RUNX1 (TEL-AML1) rearrangement comes from the translocation of two chromosomes t(12;21)(p12;q22), and represents one of the most frequently detected anomalies (15–30%) in the B-precursor Acute Lymphoblastic Leukemia (B-ALL). It must be identified by polymerase chain reaction (PCR) or fluorescent in situ hybridization (FISH) methods, since this translocation is not detected by conventional cytogenetic techniques. The prognostic value of ETV6-RUNX1 is still a matter of controversy. Recently, the group of the St Jude Children's Hospital reported an excellent outcome in patients carrying the translocation, whereas the BMF group did not find any significant difference in the survival of ETV6-RUNX1 positive patients when compared to ETV6-RUNX1 negative. The aim of our study has been to determine the prognostic impact of the ETV6-RUNX1 rearrangement in patients diagnosed of B-ALL in our Hospital, after a long period of follow-up and with the same Spanish treatment protocols (from PETHEMA and SHOP groups). PATIENTS AND METHODS: All patients with B-ALL diagnosis from January 1997 to May 2011 were included in the study: in total, 114 patients with a mean of age of 6 ys (0.3–14). The type of leukemia was ALL common (83 patients), pro-B (17 patients), pre-B (13 patients) and mature (1 patient). All the children over 1 yr received treatment according to PETHEMA group protocols, adjusted to the risk. Children under 1 yr were treated following SHOP group protocols. Seventeen patients received an allogeneic transplantation. The main clinical features of the positive and negative patients for ETV6-RUNX1 are detailed in table 1. ETV6-RUNX1 assay was performed in our laboratory by RT-PCR, according to the European BIOMED project methodology. RESULTS: ETV6-RUNX1 was found in 31 of the 114 patients (27.2%). These patients showed a significantly higher frequency of myeloid antigens (p<0.001), and were always positive for CD10 (p=0.006). All cases of positive ETV6-RUNX1 were over 2 years old. No significant differences between positive and negative ETV6-RUNX1 were obtained when complete remissions (100 vs 80%), relapse (16 vs 20%) or deaths (10 vs 13%) were analyzed. Furthermore, estimation of disease free survival (DSF) at 14 ys for both groups were similar: 80 ± 8% for positive vs 66 ± 7% for negative (p=0.21, log-rank test). And the same happened for overall survival (OS): 87 ± 7% for positive vs 83 ± 5% for negative (p=0.4, log-rank test). DISCUSSION: In our series, including patients with B-ALL treated with similar protocols with long periods of follow-up, we could not find differences between positive and negative ETV6-RUNX1 patients. It is well known that the intensity of the chemotherapy regimen and the age of inclusion in different protocols may influence the prognosis. Therefore, at present, it is still a matter of discussion if previous reported differences in the B-ALL ETV6-RUNX1 positive group could be explained by a different stratification in risk groups or by different chemotherapy regimens. This work has been funded by a grant from AECC, Carmen Lavigne Prize 2010 Disclosures: No relevant conflicts of interest to declare.

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Upfront Autologous Stem Cell Transplantation (SCT) Ameliorates the Prognostic Disadvantage of an Intermediate/High-Risk FLIPI Score in Patients with Advanced Follicular Lymphoma (FL): Evidence from Two Independent Data Sets.

Blood ◽

10.1182/blood.v106.11.2070.2070 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2070-2070

Author(s):

Kornacker Martin ◽

Simone Suessmilch ◽

Hilde Gulla ◽

Baerbel Seyfarth ◽

Robert Schoch ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Risk Group ◽

Low Risk ◽

Data Sets ◽

Prognostic Impact ◽

Intermediate Risk ◽

Independent Data ◽

Risk Patients ◽

First Remission

Abstract The Follicular Lymphoma International Prognostic Index (FLIPI) is a useful predictor for the prognosis of patients with FL. It relies on a score consisting of age, stage, hemoglobin, LDH, and number of nodal sites involved at diagnosis, which defines 3 risk groups with different 5-year survival (5-y OS): Low risk (0–1 factor; 5-y OS >90%); intermediate risk (2 factors; 5-y OS 78%); and high risk (>2 factors; 5-y OS 53%). We hypothesized that SCT in first remission might improve the course of patients with advanced FL and high/intermediate risk FLIPI, thereby abrogating the prognostic impact of the FLIPI. Methods: Consecutive patients from two independent data sets (Kiel/Hamburg = training sample (T); Heidelberg = validation sample (V)) who received upfront SCT for FL between 1990 and 2002 and had sufficient baseline information available to assess the FLIPI were analyzed retrospectively. SCT eligibility criteria were similar for both series and comprised first remission of advanced FL, age <60, and performance status <2. Patients were treated with sequential therapy comprising 2–8 cycles of a CHOP-like regimen for remission induction, Dexa-BEAM (T) or HAM (V) for stem cell mobilization, and TBI/CY or BEAM for myeloablation prior to SCT. Results: 49 (T) and 57 (V) patients were eligible. Time from diagnosis to transplant was 9 (5–21) and 14 (5–116) months, respectively. The FLIPI assigned 40 (82%) and 36 (63%) patients to the high/intermediate risk group. With a median follow-up from SCT of 64 (12–134) or 62 (1–132) months, respectively, outcome data were similar in both samples. 5-y OS from diagnosis was 94% (T) and 90% (V) for the high/intermediate risk group vs. 83% (T) and 87% (V) for the low-risk group (p=0.09 and p=0.4). 5-year progression-free survival (PFS) was 62% (T) and 77% (V) vs. 71% (T) and 77% (V) (p=0.35 and p=0.73). Combining all patients (n=106) allowed for examination of each prognostic group separately. Differences in 5-y OS from diagnosis (90% for high risk, 93% for intermediate risk and 85% for low risk) or in 5-y PFS (60% for high risk, 75% for intermediate risk and 78% for low risk) were not statistically significant. Conclusions: Upfront SCT abrogates the prognostic impact of the FLIPI by improving the outcome of intermediate/high-risk patients but not of low-risk patients. Therefore the FLIPI might be a useful tool to select patients for prospective trials on SCT in FL who may particularly benefit from this procedure.

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AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy

Blood ◽

10.1182/blood-2005-09-3600 ◽

2006 ◽

Vol 107 (10) ◽

pp. 3832-3840 ◽

Cited By ~ 92

Author(s):

Nicolas Mounier ◽

Michele Spina ◽

Jean Gabarre ◽

Martine Raphael ◽

Giuliano Rizzardini ◽

...

Keyword(s):

Risk Group ◽

Cox Model ◽

International Prognostic Index ◽

Prognostic Index ◽

Intermediate Risk ◽

Intensive Chemotherapy ◽

Poor Risk ◽

Cell Counts ◽

Risk Patients ◽

Good Risk

We aimed to compare AIDS risk–adapted intensive chemotherapy in AIDS-related lymphoma (ARL) patients before and after the advent of highly active antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years were randomly assigned to chemotherapy after stratification according to an HIV score based on performance status, prior AIDS, and CD4+ cell counts below 0.10 × 109/L (100/mm3). A total of 218 good-risk patients (HIV score 0) received ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177 intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90 poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The 5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47% for CHOP (P = .85); in the intermediate-risk group, 28% for CHOP versus 24% for Ld-CHOP (P = .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS (P = .14). The time-dependent Cox model demonstrated that the only significant factors for OS were HAART (relative risk [RR] 1.6, P < .001), HIV score (RR 1.7, P < .001), and the International Prognostic Index (IPI) score (RR 1.5, P < .001) but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV score, IPI score, and HAART affect survival but not the intensity of the CHOP-based chemotherapy.

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The MRD-Negativity Rate Measured By Flow Cytometry after the 1st and the 2nd Induction Course Among CR AML Patients from Different Cytogenetic Subgroups Does Not Differ Though the Morphological CR Achievement Does

Blood ◽

10.1182/blood-2018-99-116581 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1495-1495

Author(s):

Elena Parovichnikova ◽

Vera V. Troitskaya ◽

Irina V. Galtseva ◽

Tatiana I. Lobanova ◽

Yuliya O. Davydova ◽

...

Keyword(s):

Flow Cytometry ◽

Low Dose ◽

Conflicts Of Interest ◽

Risk Group ◽

Early Death ◽

Dose Schedule ◽

Long Term Results ◽

Intermediate Risk ◽

Color Flow ◽

Poor Risk

Abstract Background. The recent ELN recommendations (2017) have introduced new criteria of response in AML - complete remission with MRD-negativity (CR/MRD-neg). It's a well-known fact that AML with different cytogenetics has different chemosensitivity, and so - CR rate in patients with favorable, intermediate or poor cytogenetic markers substantially differs. MRD negativity corresponds to more favorable long-term results in CR patients, but it's not clear whether the MRD-negativity rate is the same in favorable, intermediate or poor risk AML pts. As it is still poorly understood whether the high risk AML patients need classical «7+3» induction, we introduced a new approach for this cohort of patients - prolonged low-dose cytostatic exposure after hypomethylating priming. Aim. To evaluate the MRD-negativity in CR AML patients from different cytogenetic subgroups after the first classical non-intensive induction: «7+3», «Aza+7+3», «Aza-Ida-Ara-C», and the second induction differed by intensity. Materials and patients. 83 AML patients with a median age of 37 y.o. (17-59), m/f 31/52, after achieving CR (69 pts) were included in the MRD study in the National Research Center for Hematology. From March 2016 till Dec 2017, 49 pts disregarding cytogenetic risk were treated with «7+3» as the first induction course (Dauno 60 mg/m2 1-3 days, Ara-C 100 mg/m2 bid 1-7 days). The second induction course for these pts was «7+3» with continuous Ara-C infusion (200 mg/m2 1-7 days). Since Dec 2017 till July 2018 in all patients epigenetic priming with 3 days of Azacitidine (75 mg/m2) was applied additionally in order to obtain the cytogenetic results prior to cytostatic exposure. All patients were tested by molecular markers (FLT3, CEBPa, mNPM1) but this data did not influence the treatment choice. 8 pts from favorable/intermediate cytogenetic risk group after Aza-prephase have got «7+3» (Dauno 60 mg/m2 4-6 days, Ara-C 200 mg/m2 by continuous infusion, 4-10 days), and 13 pts from poor cytogenetic risk group (complex, -7,-5, inv3, monosomy) after Aza-priming received prolonged low-dose schedule (Ida 3 mg/m2 4-10 days, Ara-C 10 mg/m2 bid sc 4-17 days). The second induction course for favorable/intermediate risk group was FLAG-Ida, for poor risk group - the same as the 1st induction. MRD testing was performed by 6-color flow cуtometry with FACS Canto II (BD) machine after 1st and 2nd chemotherapy courses. The rate of MRD-negativity was calculated among CR patients. Results. Totally among 83 patients CR was achieved in 83%, early death was registered in 6% and refractory AML was diagnosed in 11%. The induction and MRD testing results after the 1st and the 2nd induction course according to prognostic group and treatment arm are demonstrated in the Table.1. Morphological CR rate differs substantially in patients from favorable/intermediate and poor risk by any treatment approach (p=0,04). The prolonged low-dose induction with Aza-prephase induced the same numbers of CRs as the classical «7+3»: 69% vs 46% (p=0,42). Epigenetic priming provided identical MRD-negative CRs in all treatment and cytogenetic groups: 75% vs 62% in favorable/intermediate risk group (p=0,29), 67% vs 50% in poor risk (p=0,62). The second intensive induction with Flag-Ida in favorable/intermediate risk group did not increase the portion of MRD-neg CR pts in comparison with «7+3»: 88% vs 71% (р=0,14). Early relapse rate through all groups showed comparable results. Conclusion. Though the morphological CR achievement is highly influenced by cytogenetic subgroup in AML, the MRD-negativity rate among CR pts by flow cytometry after the 1st and the 2nd induction course is similar. The de-intensification of induction for poor risk group did not lead to the deterioration of therapy efficacy and provided the same rate of MRD-negativity. The 2nd intensified induction after «7+3» did not increase the MRD-negativity in CR pts. Disclosures No relevant conflicts of interest to declare.

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The Effect of Hyperglycemia On the Outcome of Patients with Acute Myelogenous Leukemia

Blood ◽

10.1182/blood.v120.21.4323.4323 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4323-4323

Author(s):

Shannon Leah Schmidt ◽

Linda Blust ◽

Paul Knudson ◽

Emily Richter ◽

Timothy S. Fenske ◽

...

Keyword(s):

Induction Chemotherapy ◽

Acute Myelogenous Leukemia ◽

Conflicts Of Interest ◽

Disease Free Survival ◽

Complete Response ◽

Lymphocytic Leukemia ◽

Myelogenous Leukemia ◽

Rank Test ◽

Glucose Levels ◽

Acute Myelogenous

Abstract Abstract 4323 Introduction: Hyperglycemia (HyG) has been shown to be detrimental in acute leukemia. In patients with acute myelogenous leukemia, hyG was associated with increased hospital mortality (Ali, et. al. Cancer 2007) while in patients with acute lymphocytic leukemia, hyG was associated with a shorter duration of complete response (CR) (Weiser et. al. Cancer 2004.) Our aim is to evaluate the effects of hyperglycemia on achievement of CR, disease free survival (DFS) and overall survival (OS) in patients with AML in our institution. Patients and Methods: We retrospectively reviewed all patients diagnosed with AML from 1/1/2005 to 1/1/2012 who underwent initial induction chemotherapy with 7+3 at our institution. Responses were defined according to the 2003 International Working Group criteria as CR within 6 weeks or no response. HyG was defined as 2 or more serum blood glucose levels ≥ 200 in the 30 days following induction chemotherapy. OS was determined using the Kaplan Meier method and compared using the log rank test. Results: Of the 91 patients identified, 43 (47%) were female. The median age at diagnosis was 53 years old. The cytogenetic categories were good (15 patients, 17%), intermediate (44 patients, 50%), and poor (29 patients, 33%). The median OS for all patients was 321 days. Median OS in the good, intermediate and poor cytogentics group was 423 days, 314 days and 314 days respectively. HyG, as previously defined, was seen in 39 (43%) of patients. CR was achieved in 40 (44%) of patients within 6 weeks of induction. Of the 40 patients achieving CR within 6 weeks, 19 (48%) were HyG and 21 (52%) were normoglycemic (p=0.67). Median OS was 375 days in the normoglycemic group and 210 days in the HyG group (p=0.74). Of the patients achieving CR in 6 weeks, median DFS was 290 days in the normoglycemic group and 243 days in the HyG group (p=0.54). Conclusions: Hyperglycemia in the post-induction period does not appear to have an impact on achievement of CR, DFS, or OS in the AML population. Disclosures: No relevant conflicts of interest to declare.

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