Dynamics and Prognostic Impact of Peripheral Blood Blast Clearance in Patients with Acute Myeloid Leukemia (AML) Receiving FLT3 Inhibitor Therapy in Combination with Induction Chemotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1417-1417
Author(s):  
Christopher B. Benton ◽  
Peng Qiu ◽  
Farhad Ravandi ◽  
Hagop M. Kantarjian ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Group ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Patient Characteristics ◽  
P Value ◽  
Prognostic Impact ◽  
Sorafenib Group ◽  
The Difference ◽  
Acute Myeloid

Abstract Abstract 1417 Background: We have previously shown that for patients with acute myeloid leukemia (AML) treated with induction chemotherapy with cytarabine (ara-C) plus an anthracycline, the day of blast clearance from peripheral blood (PB) is a powerful prognostic marker. Earlier PB blast (but not white blood cell [WBC]) clearance portends improved overall survival (OS). We expanded our investigation to include patients with AML undergoing induction chemotherapy with ara-C (1.5g/m2 ×3 days) plus idarubicin (12mg/m2×3 days) that is, the AI regimen, plus sorafenib (400mg orally twice daily). Patients and Methods: We reviewed the clearance of PB blast and WBC (PB blasts = 0%, WBC≤0.1×109/dL), for patients with AML (except APL) undergoing AI alone (n=168) or AI+sorafenib (n=75). Patient characteristics for the AI alone group (n=168) were as follows: median age 55 years (range, 19–72), diploid cytogenetics (n=57, 34%), poor cytogenetics (n=61, 36%), FLT3-ITD positive (n=15, 9%), FLT3-negative (n=122, 73%), median WBC 5.0×109/dL (range, 0.3–132.3), median platelets 37×109/dL (range, 1–581), median hemoglobin 9.1g/dL (range, 4.0–13.2), median PB blasts 15% (range, 1–96), median BM blasts 42% (range, 1–96). Patient characteristics for the AI+sorafenib group (n=75) were as follows: median age 52 years (range, 18–66), diploid cytogenetics (n=38, 51%), poor cytogenetics (n=10, 13%), FLT3-ITD (n=25, 33%), FLT3-negative (n=48, 64%) median WBC 5.9×109/dL (range, 0.6–228.5), median platelets 51×109/dL (range 7–306), median hemoglobin 9.2g/dL (range, 7.4–12.6), median PB blasts 21% (range 0–98), median BM blasts 56% (range 6–98). Results: The overall response rate (ORR=CR+CRp) in the AI group was 63% (58%+5%) and 50 patients (30%) were resistant to therapy. The ORR in the AI+sorafenib group was 79% (72%+7%) and 11 patients (15%) were resistant. We analyzed OS by dividing patients based on the day of PB blast clearance: group 1 (0–1 days), 2 (2–3 days), 3 (4–5 days), 4 (6–8 days), and 5 (>8 days). For the patients receiving AI induction therapy, a total of 32, 59, 38, 18, and 2 patients were included in groups 1–5, and median OS for groups 1–4 were 167, 48, 67, and 25 weeks respectively. A logrank test comparison revealed these four OS curves were significantly different (p-value=0.0015). For the AI treatment group, earlier blast disappearance corresponded with better OS. In contrast, for patients in the AI+sorafenib group, the correlation between day of PB blast clearance and OS was less clear. A total of 10, 23, 25, 6, and 3 patients were included in groups 1–5. The median OS for groups 1, 3, and 4 were 101, 74, and 66 weeks respectively, and the median survival for group 2 could not be estimated because the curve did not fall below 0.5. The difference between these four survival curves was not significantly different (p-value=0.35). Survival differences for the AI group were more clearly demarcated when patients were divided based on blast disappearance within 0–5 days or >5 days (p-value=0.0004). A similar analysis in the AI+sorafenib group revealed no significantly different OS (p-value=0.13). Among patients in the AI+sorafenib treatment group, the mean day of blast disappearance for FLT3-ITD versus FLT3-negative patients was 5.2 vs. 4.5 days, and this difference was not statistically significant (p-value=0.33). While FLT3-ITD patients who cleared their blasts within 0–3 days (n=10) tended to have better OS survival than FLT3-ITD patients who cleared their blasts after 3 days (n=13), the difference in OS curves did not reach significance (p-value=0.18). Conclusion: The day of PB blast clearance is prognostic among patients receiving classic induction chemotherapy, where early clearance predicts better long-term outcomes. The addition of a targeted agent to a standard induction regimen limits the prognostic power of early PB blast clearance. We are currently investigating a novel mathematical approach to evaluate the prognostic value of clearance of peripheral blasts compared to WBC after initiation of therapy in patients receiving targeted agents during induction therapy; the approach aims to integrate the prognostic impact of FLT3 and NPM1 in combination with cytoreduction kinetics to better identify prognostically distinct groups. Disclosures: Off Label Use: Plerixafor plus G-CSF as a part of conditioning in allogenic transplant for AML/MDS.

Clinical Implications of Reticulin Fibrosis of Bone Marrow in De Novo Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2585-2585
Author(s):  
Tzung-Chih Tang ◽  
Hung Chang ◽  
Chien-Feng Sun ◽  
Lee-Yung Shih ◽  
Po Dunn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Recovery Duration ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Abstract 2585 Background: Microenvironment of bone marrow (BM) plays an important role to support proliferation, renewal and differentiation of hematopoietic stem cells. Whether the stroma of BM affects leukemic cells with the same manner, or impacts on the prognosis in leukemia patients, has not been fully investigated. Previous studies have described that increased reticulin content in the BM is associated with poor outcome in patients with acute lymphoblastic leukemia, chronic myeloid leukemia and primary myelofibrosis, but there is no cohort study to determine the clinical correlation between degree of reticulin fibrosis of BM and acute myeloid leukemia (AML). To investigate prognostic impact of reticulin fibrosis on de novo AML, 881 patients diagnosed between Jun 1999 to Dec 2011 in Chang Gung Memorial Hospital and treated with anthracycline-containing induction chemotherapy were retrospectively reviewed. Patients and methods: According to the grading of reticulin content in the bone marrow, we categorized the 881 patients into four groups: A. BM easily aspirated without biopsy, n = 698; B. Reticulin grade 0, n = 99; C. Reticulin grade 1–2, n = 51; D. Reticulin grade 3–4, n = 33. The induction failure (IF) rate after treatment with induction chemotherapy, the recovery duration of absolute neutrophil count (ANC) greater than 0.5 × 109/L in patients who achieved the first complete remission, the overall survival (OS) and relapse-free survival (RFS) in four groups were analyzed. Based on the cytogenetic or molecular features, 648 of the patients were stratified into unfavorable, intermediate and favorable risk groups, and the clinical significance of reticulin fibrosis of BM were also examined for various risk groups. Results: Of the 881 patients, the patients in group D had a statistically higher IF rate (P = 0.0108) and longer ANC recovery duration (P = 0.0008). But the OS and RFS between four groups were not significantly different (P = 0.5146 and 0.3853, respectively). After risk stratified by cytogenetic and molecular analysis, increased reticulin content of BM (group C or D) had an adverse impact on OS in the intermediate and favorable risk groups (P = 0.006 and 0.0215, respectively). Conclusion: Reticulin content of BM influences the IF rate and myeloid recovery for the patients of de novo AML, and affects OS in patients with intermediate or favorable risk factors. Disclosures: No relevant conflicts of interest to declare.

Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 3869-3876 ◽  
Author(s):  
Jeanne E. Anderson ◽  
Kenneth J. Kopecky ◽  
Cheryl L. Willman ◽  
David Head ◽  
Margaret R. O'Donnell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
P Value ◽  
Term Survival ◽  
Acute Myeloid

Complete remission and long-term survival rates are low for older adults treated for acute myeloid leukemia (AML). Because of favorable phase 2 data using mitoxantrone and etoposide, we conducted a phase 3 study (SWOG-9333) in which patients over 55 years of age with previously untreated AML were randomized to receive mitoxantrone (10 mg/m2 per day × 5) and etoposide (100 mg/m2per day × 5) [ME], or cytarabine (200 mg/m2 per day × 7) and daunorubicin (45 mg/m2 per day × 3) [AD] as induction therapy. The randomization was stratified by age, onset of leukemia, and multidrug resistance phenotype. Over a 4-year period, 328 eligible patients from 66 institutions were enrolled. The complete remission rate was 34% (95% confidence interval [CI] 26%-41%) for patients in the ME and 43% (CI 35%-51%) for patients in the AD treatment arm (one-tailedP value .96). The rates of resistant disease were 43% (CI 35%-51%) and 34% (CI 27%-42%), respectively, for the 2 treatment arms (one-tailed P value .95). The estimated overall survival at 2 years was 11% (CI 6%-15%) and 19% (CI 12%-25%) for patients randomized to ME and to AD induction therapy, respectively (one-tailed P value .99). After accounting for the independent prognostic factors associated with survival (karyotype, performance status, age, white blood cell count), exploratory analysis suggested there was a worse survival for patients who received ME compared with AD induction therapy (2-tailed P value .0066). We conclude that the results of our study do not demonstrate any benefit to the use of ME induction chemotherapy instead of AD in older patients with AML.

Influence of High Expression of p73 and p53 Proteins on Clinical Outcome in Acute Myeloid Leukemia Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4306-4306
Author(s):  
Agnieszka Pluta ◽  
Piotr Smolewski ◽  
Agnieszka Wierzbowska ◽  
Barbara Cebula ◽  
Krzysztof Jamroziak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
High Expression ◽  
Leukemic Cells ◽  
Prognostic Impact ◽  
Spontaneous Apoptosis ◽  
Acute Myeloid

Abstract Background: Prognostic significance of apoptosis-regulating proteins, especially p73, is not clearly determined in acute myeloid leukemia (AML). The p73 protein is a member of p53 family implicated in the regulation of cell cycle, apoptosis and development. Overexpression of p73 protein, with prevalence of short TAp73 isoforms, has recently been described in patients with AML. Aims: The main objective of this study was to verify whether expression of p73 and p53 proteins has a prognostic impact on response to induction chemotherapy and overall survival (OS) of adult patients with AML. Additionally, we aimed to correlate the expression of p73 and p53 proteins with spontaneous apoptosis of leukemic cells. Material and Methods: Intracellular expression of p73 protein in leukemic blasts isolated from bone marrow or peripheral blood was examined in 73 AML patients (59 de novo, 14 refractory/relapsed) of median age 54 years (range 28–78 years). In parallel, analysis of cell cycle in leukemic blasts was performed to assess the subG1 fraction as a marker of spontaneous apoptosis. The control constituted leukemic cells incubated with isotype antibodies. All measurements were performed using multi-colour flow cytometry. Protein expression was expressed by both percentage of positive cells and mean fluorescence intensity. Results: Fifty six patients received intensive induction chemotherapy. Twenty four (43%) patients achieved complete response (CR), 26 (46%) patients did not respond and 6 (11%) patients died in the early post-induction period. The median time of follow up reached 5.6 months (range 0.1–99 months). High expression of p73 showed a trend towards probability of CR achievement after induction regimen (p=0.08). Higher expression of p53 did not correlate with response to the treatment (p=0.28). In univariate analysis we found significantly better OS in patients less than 60 years old, with good or intermediate risk of kariotype and treated with intensive chemotherapy (p=0.00001; p=0.04; p=0.00001, respectively). Probability of better OS in AML patients with high p73 and p53 protein expression was p=0.1 and p=0.95, respectively. Simultaneous high expression of both p73 and p53 proteins on AML cell showed a trend toward longer OS (p=0.09). Moreover, a strong trend to better OS was observed in patients with high subG1 fraction. Importantly, high subG1 fraction correlated with high expression of p53 but not with p73 protein expression (p=0.03; p=0.15, respectively). Conclusions: These data indicate that p73 protein may be implicated in apoptosis of AML in response to chemotherapy, especially when p53 pathway is abrogated. Further studies are needed to establish exact role of p73 and p53 proteins in this process and its influence on OS of AML patients.

Impact of Transporter Genes Polymorphisms in Standard Induction of Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4842-4842 ◽  
Author(s):  
Juan Eduardo Megías ◽  
Pau Montesinos ◽  
María José Herrero ◽  
Federico Moscardó ◽  
Virginia Bosó ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Platelet Count ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Multivariable Analysis ◽  
Hepatic Function ◽  
Hematologic Toxicity ◽  
Prognostic Impact ◽  
Ocular Toxicity ◽  
Acute Myeloid

Abstract Background: The intake of anthracyclines in blast cells could be affected by several transporters, including influx transporters (SLC22A16 and SLCO1B1) and efflux pumps of ABC family. Previous studies suggested that single nucleotide polymorphisms (SNPs) of genes coding for anthracyclines transporters may influence their effectiveness or toxicity, although their impact in acute myeloid leukemia (AML) induction therapy remains undetermined Methods: SNPs of anthracycline transporter genes (ABCB1: rs1128503, rs1045642, rs2032582 and haplotype; ABCC1: rs4148350; ABCC2: rs8187710; ABCG2: rs2231142, rs2231137; SLCO1B1: rs4149056; SLC22A16: rs12210538, rs714368) were evaluated in 225 adult patients at initial diagnosis from AML using a Sequenom (iPLEX) mass spectrometry-based multiplex genotyping assay (Sequenom, San Diego, CA). All patients received induction chemotherapy consisting of idarubicin plus cytarabine (PETHEMA-LMA 99, 2007 and 2010 trials). Efficacy of first induction cycle was evaluated comparing complete remission (CR) vs. partial remission or resistance. Patients dying during induction were considered as no evaluable for efficacy. Based on WHO grading scale, toxicities were grouped as binary variables (grade 0-1 vs. grade 2-4). The grade of toxicity assigned to an organ group was the maximum grade of all the specific toxicities within that group. Renal and hepatic toxicities were also evaluated with analytic markers (renal function with urea and creatinine; hepatic function with bilirubin, AST, ALT, FA and GGT). Hematologic toxicity was measured with the time to neutropenia and thrombocytopenia recovery since first day of chemotherapy. Genotypes were studied with co-dominant model. Association between variables was assessed using linear and logistic regression adjusting for age, gender, ECOG, leukocyte and platelet count at diagnosis (R® version 3.1.2). Results: The median age of patients was 51.1 years (16-78 years). There were no statistically significant differences in CR or hematologic toxicities. Nevertheless, several associations were obtained between transporter genes polymorphisms and toxicities (significant toxicities were summarized in table 1 and 2). Variant allele of ABCB1 SNPs was previously related with lower activity of ABCB1 pump in kidney cells and lower anthracycline clearance. Accordingly, we obtained nephrotoxicity associated with these SNPs. Association between cardiac toxicity and ABCG2 polymorphisms was found in agreement with previously published works. The ocular toxicity associated with SLCO1B1 was also correlated with low platelet count at diagnosis in multivariable analysis. Table 1. Significant association between SNPs in gene transporters and different toxicities Toxicity Gene/SNP Genotypes Grade 0-1 n (%) Grade 2-4 n (%) OR (95%IC) P Cardiotoxicity ABCG2 rs2231142 CC CA 171 (83.0) 9 (47.4) 35 (17.0) 10 (52.6) 5.64 (1.86-17.80) 0.002 Lung toxicity ABCG2 rs2231142 CC CA 174 (84.5) 12 (63.2) 32 (15.5) 7 (36.8) 3.37 (1.09-10.40) 0.031 Skin toxicity SLCO1B1 rs4149056 TT TC 112 (71.8) 21 (48.8) 44 (28.2) 22 (51.2) 2.43 (1.17-5.06) 0.015 Nephrotoxicity ABCB1 haplotype Other genotypes TT/TT/TT 175 (89.3) 21 (72.4) 21 (10.7) 8 (27.6) 3.74 (1.24-10.85) 0.002 Ocular toxicity ABCC1 rs4148350 GG GT/TT 205 (99.0) 16 (88.9) 2 (1.0) 2 (11.1) 13.7 (2.08-90.47) <0.001 Ocular toxicity SLCO1B1 rs4149056 TT CC 155 (99.4) 23 (92.0) 1 (0.6) 2 (8.0) 9.97 (1.39-71.39) 0.019 Table 2. Significant association between SNPs in gene transporters and analytic markers of renal and hepatic function Hematologic toxicity Gene/SNP Genotypes Mean values (mg or U/dL) Logarithm of the difference (95%IC) P Urea ABCB1 rs1045642 CC TT 57.98 70.89 0.20 (0.01 to 0.40) 0.044 Urea ABCB1 rs2032582 GG TT 56.34 72.07 0.23 (0.03 to 0.42) 0.021 Urea ABCB1 haplotype Other genotypes TT/TT/TT 59.29 78.14 0.24 (0.04 to 0.43) 0.019 Bilirubin ABCB1 rs1045642 CC CT TT 1.77 2.59 2.91 0.021 (0.01 to 0.40) 0.39 (0.12 to 0.65) 0.036 0.004 ALT SLCO1B1 rs4149056 TT TC 90.92 161.02 0.30 (0.01 to 0.60) 0.049 Conclusions: This study shows a prognostic impact of transporter genes polymorphisms in adult AML patients regarding induction chemotherapy efficacy and toxicity. Further studies with larger population are needed to validate these associations, which could be useful biomarkers in clinical practice. Disclosures No relevant conflicts of interest to declare.

Clostridium Difficile Infection in Patients with Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5181-5181
Author(s):  
Amy L Morris ◽  
Mohammed Athar Naeem ◽  
Anjali Bal ◽  
Tanya Thomas ◽  
Alfadel Alshaibani ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Clostridium Difficile ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Toxic Megacolon ◽  
Hematologic Malignancies ◽  
P Value ◽  
Disease Characteristics ◽  
Acute Myeloid

Abstract BACKGROUND: Clostridium difficile infection (CDI) is the most important cause of nosocomial infectious diarrhea and has been not well studied in patients with neutropenia who have hematologic malignancies in the United States. Previous studies suggest patients undergoing induction chemotherapy for acute myeloid leukemia (AML) are at a high risk of contracting CDI, but these patient's clinical and disease characteristics are not described. This study reports CDI rates and disease characteristics in AML patients at the University of Virginia (UVA). METHODS: A retrospective chart review of 126 consecutive patients undergoing induction or re-induction chemotherapy for AML at UVA from July 2011 to December 2015 was conducted. The primary endpoint was to determine the rate of CDI within ninety days of chemotherapy initiation. CDI was defined by a Clostridium difficile positive PCR in the presence of diarrhea. Secondary endpoints include patient characteristics, comorbidities, risk factors, and disease specific indices associated with CDI. Statistical methods include nonparametric Wilcoxon test, Fisher's exact test, and Holm's sequential Bonferroni procedure as appropriate. Statistical significance was defined as p-value <0.05. RESULTS: Of 126 patients, 31 patients (24.6%) with AML had CDI. 8 patients (25.8%) had one recurrent episode of CDI, 2 patients (6.4%) had two recurrences, and 2 patients (6.4%) had more than two recurrences. 25 patients (80.6%) underwent CT abdominal imaging specifically for the CDI episode, revealing 2 patients (8%) with typhilitis. 2 patients (6.4%) developed toxic megacolon, but no patients underwent colectomy. There was no CDI specific mortality in these 31 patients. During the same 4 year timespan, an additional 27 patients with hematologic malignancies other than AML were identified. These two cohorts (AML and non-AML CDI patients) were not statistically different in terms of patient demographics (age, gender, BMI), medical comorbidities (tobacco use, asthma, COPD, cardiac disorders, CKD, and rheumatologic conditions), and CDI characteristics (recurrences, prior antibiotics prophylactic and treatment regimens, PPI medication usage, CDI treatment regimen and treatment duration, development of typhilitis and toxic megacolon, and mortality). The only statistically significant difference is the presence and increased duration of neutropenia in the AML CDI patient cohort (p-value < 0.001). DISCUSSION: The study concludes that the incidence of CDI in patients with AML undergoing induction chemotherapy is greater than hospitalized patients without AML as reported in the literature. However, when compared to a matched cohort of hospitalized patients with non-AML hematologic malignancies, the incidence of CDI is similar between these two groups. This result is striking as AML induction chemotherapy regimens are typically more intense, resulting in more profound and longer neutropenia. Even with increased cytopenias, the CDI rate and disease characteristics are not affected when AML CDI patients are compared to non-AML CDI patients. This suggests that cytopenias should not be the focus for CDI patients, rather hematologic malignancies as whole lead to increased CDIs and heightened awareness is warranted when caring for patients with hematologic malignancies and complaints of diarrhea. Patients in both AML and non-AML CDI cohorts have relatively favorable outcome, with no patient mortality attributable to CDI. Further studies are needed to evaluate what, if any, predictive risk factors can increase CDI in the setting of AML. Disclosures No relevant conflicts of interest to declare.

FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1262-1270 ◽  
Author(s):  
Adam J. Mead ◽  
David C. Linch ◽  
Robert K. Hills ◽  
Keith Wheatley ◽  
Alan K. Burnett ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
White Cell Count ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Prognostic Impact ◽  
The Difference ◽  
High Level ◽  
Acute Myeloid

Abstract The prognostic impact of tyrosine kinase domain (TKD) mutations of the fms-like tyrosine kinase-3 (FLT3) gene in acute myeloid leukemia (AML) is currently uncertain. To resolve this issue we screened 1107 young adult nonacute promyelocytic leukemia AML patients with known FLT3 internal tandem duplication (ITD) status for FLT3/TKDs; they were detected in 127 (11%) cases. Mutations were associated with a high white cell count (P =.006) and patients with inv(16) (P = .005) but were infrequent in patients with adverse cytogenetics and secondary AML. Overall survival (OS) at 5 years was 53% and 37% for FLT3/TKD mutant and wild-type patients respectively (odds ratio, 0.72; 95% confidence interval, 0.58 to 0.89; P = .002). For both the cumulative incidence of relapse and OS the difference in outcome between FLT3/ITDs and FLT3/TKDs was highly significant (P < .001). In multivariate analysis, impact of FLT3/TKDs on OS when including all mutant-positive patients was not significant, but patients with high-level mutations (more than 25% mutant) had a significantly improved outcome (P = .004). The novel finding that biologically distinct activating mutations of the same gene can be associated with markedly different clinical outcomes has implications for risk stratification and therapy and is significant to the understanding of chemoresistance in AML.

scholarly journals Early Blast Clearance Evaluation after Induction Chemotherapy for Acute Myeloid Leukemia By Multiparameter Flow Cytometry and WT1-RNA Quantification: A Single Center Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5333-5333
Author(s):  
Carlo Messina ◽  
Matteo G Carrabba ◽  
Elisa Sala ◽  
Michela Tassara ◽  
Raffaella Milani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Predictive Value ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Prognostic Impact ◽  
Induction Regimen ◽  
Blast Count ◽  
Acute Myeloid

Abstract Introduction: in acute myeloid leukemia (AML) the response to treatment is evaluated upon full recovery of peripheral blood counts by bone marrow (BM) assessment using morphology and cytogenetics, if appropriate number of metaphases is obtained. Real time quantitative PCR (RQ-PCR) and multiparametric flow citometry (MFC) are sensitive techniques to assess minimal residual disease (MRD) mostly used to refine risk stratification and to guide therapy. Evaluation of response to induction chemotherapy (CT) during aplasia (around day 14 from start of induction) has shown a significant prognostic impact, the presence of residual disease predicting a worse prognosis. All reported studies on early BM blast clearance evaluation rely on morphology as a single technique. Unfortunately, at day 14 BM is often not evaluable for cytology and morphologyc blast count. Unpredictability and intra-observer variability must also be considered when assessing blast count by morphology alone. No studies analysing early BM blast clearance by means of MFC and/or PCR have been published and the correlation between the two assays is unknown in this setting. Moreover, it is to be established if early intensification (around day 15 from start of induction) with a second cycle of CT could increase the CR rate in pts with disease persistence in the BM evaluated at day 14. Matherial and methods: we retrospectively evaluated data of 23 newly diagnosed AML pts who received induction CT at our center between 02/2009 and 05/2014, and for whom analysis of BM both at day 14 and after hematologic recovery (around day 28) was performed. The aim of our study was to define the prognostic value of early MRD quantification by MFC (d14-LAIP) and WT1 quantification by PCR (d14-WT1) in predicting the response to induction. Firstly we compared d14-LAIP and d14-WT1 to identify the more sensitive and specific assay in predicting the response to induction, in particular for cases not evaluable for morphologic blast count. Then we compared the outcome of pts who received or did not receive an early intensification for persistence of disease at d14 BM evaluation. Results: 20 pts received the 3+7 induction regimen, 3 pts the ICE induction regimen. After BM evaluation at day 14, 7 pts received early reinduction CT (FLAG-IDA regimen) starting at day 16 (median), 16 pts did not receive further therapy before BM evaluation at day 28. Overall CR rate was 70% (16 pts), PR/NR 30% (7 pts), TRM 4% (1 pt). At day 14, leukemic blast percentage was not evaluable by morphology in 8 (35%) cases due to marrow aplasia, in 1 (4%) case blasts were <5%, in 14 (61%) cases blasts were ≥5%; by MFC (23 cases), in 9 (39%) cases blasts were ≤2%, in 14 (61%) were >2%; by PCR (17 cases), in 4 (24%) cases WT1 was <250 cp/10e4 ABL, in 13 (76%) WT1 was ≥250 cp/10e4 ABL. At day 28 BM evaluation, of the 8 pts with aplastic marrow at day 14, 6 (75%) were in CR and 2 (25%) in PR/NR, of the 14 pts with blasts ≥5% at day 14, 9 (64%) were in CR and 5 (36%) in PR/NR. Analysis of the paired results from nadir to recovery revealed that d14-LAIP 2% had a positive predictive value (PPV) of CR at day 28 of 71% and negative predictive value (NPV) of 89%, with a sensitivity of 83% and a specificity of 80%, d14-WT1 250 had a PPV of 50% and NPV of 25%, with a sensitivity of 57% and a specificity of 20%. The d14-LAIP analysis was strongly associated with CR after induction (p 0.034). Considering the 14 pts with blasts ≥5% at day 14, 6/7 (86%) who received early reinduction CT and 3/7 (43%) who did not, obtained the CR at day 28 (p ns). Discussion: in our series d14-LAIP proved to be more predictive of response after induction CT than d14-WT1. Although one-third of pts had an early morphologic response not evaluable due to marrow aplasia MFC proved to be a useful assessment tool with a 100% applicability. Moreover, correlation between D14-LAIP and d14-WT1 was > 90%. Our data confirm the prognostic value of day 14 BM evaluation and suggest that MRD detection, also in aplasia, could drive early reinduction CT which probably could increase the CR rate, without significantly clinical complications. Anyway, this last point must be confirmed with a larger study. Disclosures Bordignon: MolMed S.p.A: Chairman and CEO Other.

Decitabine Combined with Haag Regimen Is an Effective Salvage Treatment for Advanced Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5205-5205
Author(s):  
XiaoWen Tang ◽  
Wei Cui ◽  
Zhengming Jin ◽  
Xiaming Zhu ◽  
Aining Sun ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Side Effects ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Salvage Treatment ◽  
Long Time ◽  
The Difference ◽  
Acute Myeloid

Abstract Objective To evaluate the clinical efficacy and safety of decitabine (DAC) in combination with HAAG regimen [homoharringtonine (HHT), cytarabine (Ara-C), doxorubicin (Acla) and recombinant human granulocyte colony stimulating factor (G-CSF)] for advanced patients with acute myeloid leukemia (AML). Methods Thirty-six patients with advanced AML receiving DAC combined with HAAG chemotherapy in our center from December 2012 to August 2015 were enrolled in this study. Eighteen of them were refractory or relapsed AML, and another 18 patients were those who didn't achieve complete remission (CR) after a course of induction chemotherapy. The therapeutic responses, side effects and long-time survival were retrospectively analyzed. Results After a course of treatment, the rate of CR and partial response (PR) was 58.3% (21/36) and 22.2% (8/36) respectively, while the overall response rate (ORR) was 80.6% (29/36) in the cohort. For the patients with refractory or relapse AML, CR was 61.0% (11/18), PR was 22.2% (4/18), and ORR was 83.3% (15/18). While for the other not getting CR after a course of induction chemotherapy, CR was 55.6% (10/18), PR was 22.2% (4/18), and ORR was 77.8% (14/18). Grade 4 hematological toxicities were observed in all patients, and 72.2% cases experienced infection. And all non hematological side effects were mild and well-tolerated. With a median follow-up of 7.5 (0.5~33.3) months, the 1-year overall survival (OS) rate was 43.3%, 24.2% for the refractory or relapsed AML patients, and 61.6% for those not achieving CR after a course of induction chemotherapy. The difference was significantly (P=0.01). Conclusion DAC combined with HAAG regimen is safe and effective salvage treatment for advanced stage AML patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Open-Label Phase II Prospective, Randomized, Controlled Study of Romyelocel-L Myeloid Progenitor Cells to Reduce Infection During Induction Chemotherapy for Acute Myeloid Leukemia

2021 ◽  
pp. JCO.20.01739
Author(s):  
Pinkal M. Desai ◽  
Janice Brown ◽  
Saar Gill ◽  
Melham M. Solh ◽  
Luke P. Akard ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Group ◽  
Induction Chemotherapy ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Myeloid Leukemia ◽  
Febrile Episode ◽  
Myeloid Progenitor ◽  
Acute Myeloid ◽  
Count Recovery

PURPOSE Standard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy. PATIENTS AND METHODS One hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital. RESULTS Mean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed. CONCLUSION Subjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

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