Secondary AML After a History of Myelodysplastic Syndrome Is An Independent Adverse Prognostic Factor for Achievement of Complete Remission, Relapse-Free and Overall Survival. An Analysis of 2,819 Adult Patients with Newly Diagnosed AML Enrolled On Seven AMLSG Treatment Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2621-2621
Author(s):  
Sabine Kayser ◽  
Konstanze Doehner ◽  
Juergen Krauter ◽  
Heinz A. Horst ◽  
Marie von Lilienfeld-Toal ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
De Novo ◽  
Adult Patients ◽  
Prior History ◽  
Newly Diagnosed ◽  
Adverse Prognostic Factor ◽  
Time Period ◽  
History Of ◽  
Multivariable Analyses ◽  
De Novo Aml

Abstract Abstract 2621 Poster Board II-597 Background: AML patients with a prior history of a myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN) (in the following referred to as secondary AML [s-AML]) in the new WHO classification are listed in the category “AML with myelodysplasia-related changes”. Patients with s-AML are considered to have an inferior outcome compared with de novo AML. Even after accounting for clinical and cytogenetic risk factors, s-AML is believed to remain an important predictor of poor outcome although mechanisms for this effect remain elusive. The minimal time period between diagnosis of MDS and occurrence of s-AML has been defined differently, 3 months by Cheson et al. (J Clin Oncol 1990) versus 6 months according to the WHO 2001 classification. Aims: To study the clinical impact of s-AML in a large cohort of patients with newly diagnosed AML, in the context of clinical characteristics as well as cytogenetics and mutational status of the NPM1, CEBPA and FLT3 genes. Methods: The study included 3,139 adult patients (median age, 53.5 years; range, 16-85 years) with newly diagnosed AML entered on 7 protocols of the German-Austrian AML Study Group (AMLSG) between 1993 and 2008. In all protocols intensive induction and consolidation therapy was used. Information on type of AML, karyotype and molecular marker status of NPM1 and FLT3 (internal tandem duplication [ITD]) was available in 2,858 of 3,139 (91%) and 2,126 of 3,139 (68%) patients, respectively. Since this report focuses on the comparison of s-AML versus de novo AML, patients with therapy-related AML (t-AML) and those lacking information on type of AML were excluded (n=200, n=120, respectively). Results: 151 of the 2,819 patients (5.4%) were classified as s-AML, 122 with at least a 6-month (s-AML-6), and 29 with a 3- to 6-month (s-AML-3) time period of a preceding MDS or MDS/MPN. Compared with patients with de novo AML, those with s-AML-6 and s-AML-3 were significantly older (62 and 58 years vs 53 years; p<0.0001), and they had significantly lower median white blood counts (WBC) (6.9 and 4.6 vs 12.5 ×109/L; p=0.005), lower percentage of bone marrow blast (50 and 52 vs 75%; p<0.0001) and of peripheral blast counts (22 and 20 vs 55%; p=0.004). Compared to patients with de novo AML, those with s-AML-6 or s-AML-3 showed more frequently MDS-related cytogenetic changes (as defined by WHO 2008) (22% and 31% vs 16%, p=0.02), whereas the frequency of cytogenetically normal AML was equally distributed (48% and 52% vs 49%). However, the distribution of molecularly defined subgroups in cytogenetically normal AML was significantly different (p<0.0001) with a lower frequency of the subgroups CEBPAmut, NPM1mut/FLT3-ITDneg and FLT3-ITDpos in s-AML-6 and s-AML-3 and a higher frequency of the triple-negative genotype (75% and 45% vs 28%). In univariable analyses for the clinical endpoints achievement of complete remission (CR), relapse-free (RFS) and overall survival (OS), s-AML-6 and s-AML-3 showed a significant inferior outcome (p<0.0001, equivalent for all endpoints). Therefore s-AML-6 and s-AML-3 were combined as s-AML for further multivariable analyses. In multivariable analyses, s-AML was consistently an independent adverse prognostic factor for the endpoints achievement of CR (OR, 0.48, p=0.0001), RFS (HR, 1.38, p=0.0005) and OS (HR, 1.27, p=0.02). In cytogenetic subgroup analyses, s-AML was an unfavorable factor for OS particularly in patients with cytogenetically normal karyotype AML (p=0.01) and in patients with the molecularly defined genotype NPM1neg, FLT3-ITDneg as well as CEBPAneg (p=0.04). In as treated analysis, younger adult patients (age <61 years) with s-AML had a beneficial effect from allogeneic hematopoietic stem cell transplantation (HSCT) on OS (p=0.008). Conclusions: In this large cohort of adult patients with newly diagnosed AML, s-AML showed consistent features irrespective of duration of prior history of MDS (>6 months versus 3 to 6 months) and was an adverse prognostic factor for achievement of CR, RFS and OS. Younger adult patients with s-AML appear to benefit from allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

Treatment-Related AML Is An Independent Adverse Prognostic Factor for Relapse-Free and Overall Survival. An Analysis of 2,868 Adult Patients with Newly Diagnosed AML Enrolled On Seven AMLSG Treatment Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 578-578
Author(s):  
Sabine Kayser ◽  
Konstanze Doehner ◽  
Juergen Krauter ◽  
Heinz A. Horst ◽  
Marie von Lilienfeld-Toal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
De Novo ◽  
Negative Impact ◽  
Adult Patients ◽  
Newly Diagnosed ◽  
Primary Malignancy ◽  
Adverse Prognostic Factor ◽  
De Novo Aml ◽  
Independent Adverse Prognostic Factor

Abstract Abstract 578 Background: Therapy-related AML (t-AML) is a recognized clinical syndrome occurring as a complication following cytotoxic and/or radiation therapy. The etiology and specific factors that predispose to t-AML largely remain unknown. Survival of t-AML patients has been poor compared with that of patients with de novo AML. However, there is a paucity of studies evaluating the impact of t-AML as a risk factor, in particular in the context of other clinical and biological prognostic markers. Aims: To study the clinical impact of t-AML in a large cohort of patients with newly diagnosed AML, in the context of clinical characteristics as well as cytogenetics and mutational status of the NPM1 and FLT3 genes. Methods: The study included 3,139 adult patients (median age, 53.5 years; range, 16-85 years) with newly diagnosed AML entered on 7 protocols of the German-Austrian AML Study Group (AMLSG) between 1993 and 2008. In all protocols intensive induction and consolidation therapy was used. Information on type of AML, karyotype and molecular marker status of NPM1 and FLT3 (internal tandem duplication [ITD] and tyrosine kinase domain mutation [TKD]) was availabel in 2,858 of 3,139 (91%) and 2,126 of 3,139 (68%) patients, respectively. Since this report focuses on the comparison of t-AML versus de novo AML, patients with secondary AML following myelodysplastic syndrome (s-AML) and those lacking information on type of AML were excluded (n=151, n=120, respectively). Results: Two hundred of the 2,868 patients (7%) were classified as t-AML. In more than two thirds of t-AML cases, a solid cancer was the primary malignancy with breast cancer being the most common (55%), followed by gastrointestinal (7.5%), prostate (7%) and testicular cancer (7%). In 27% of the cases, a hematologic neoplasm was the primary malignancy with non-Hodgkin (43%) and Hodgkin lymphoma (35%) being the most common. Three patients received cytotoxic treatment for autoimmune diseases. The median latency period between diagnosis of primary malignancy and occurrence of t-AML was 4 years (range, 4 months to 44 years). Patients with t-AML were significantly older compared to patients with de novo AML (58 versus 53 years; p<0.0001), and they had significantly lower median white blood counts (WBC) (7.4 vs 12.5 ×109/L; p=0.002). The frequencies of cytogenetic risk groups in t-AML versus de novo AML were as follows: favorable [t(8;21), t(15;17), inv(16) or t(16;16)] (16% vs. 16%), intermediate [all cytogenetic abnormalities not classified as favorable or adverse] (46% vs. 66%), and adverse [t(v;11q23), inv(3) or t(3;3), t(9;22), -5 or 5q-, -7 or 7q-, abn(17p), complex karyotype] (38% vs. 18%, respectively). Response to induction therapy was not significantly different between t-AML (64%) and de novo AML (69%) in uni- (p=0.18) and multivariable (p=0.58) analysis. In contrast, for the clinical endpoints relapse-free (RFS) and overall survival (OS), t-AML was an adverse prognostic factor in univariable (p<0.00001, p<0.00001, respectively) and multivariable analyses (HR, 1.69, p=0.001; HR, 1.3, p=0.004, respectively). The negative prognostic impact of t-AML on RFS was due to both a higher cumulative incidence of relapse (p=0.01) and death in complete remission (CR) (p=0.0001). In cytogenetic subgroup analyses, t-AML was an unfavorable factor for OS in particular in patients with inv(16) or t(16;16) (p=0.008), whereas this was not the case in t(8;21) and t(15;17). In cytogentically normal AML, OS was significantly inferior in t-AML patients (p=0.009), and this negative impact was due to a significant inferior OS in the molecularly defined subgroups NPM1mut/FLT3-ITDneg (p=0.05) and the triple negative group (p=0.004), whereas there was no difference in the subgroup FLT3-ITD and CEBPAmut. In as treated analyses in patients younger than 61 years with t-AML, allogeneic hematopoietic stem cell transplantation (HSCT) in first CR had a beneficial effect in cytogenetic intermediate- and adverse-risk (OS, p=0.008), but not favorable-risk patients. Conclusions: In this large cohort of adult patients with newly diagnosed AML, t-AML was an independent adverse prognostic factor for RFS and OS. The negative impact on RFS was not only due to an increased relapse rate but also to a higher rate of deaths in CR, possibly reflecting cumulative toxicity of primary and secondary cancer therapy. Allogeneic HSCT appears to have a beneficial impact in younger adults with t-AML. Disclosures: No relevant conflicts of interest to declare.

Promising Outcome for Patients with AML-MRC Following Cord Blood Transplantation: Is Induction Chemotherapy Before Transplant Necessary?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3132-3132
Author(s):  
Naoyuki Uchida ◽  
Kazuhiro Masuoka ◽  
Hikari Ota ◽  
Aya Nishida ◽  
Kazuya Ishiwata ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Induction Chemotherapy ◽  
De Novo ◽  
Cord Blood Transplantation ◽  
Prior History ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
History Of ◽  
De Novo Aml

Abstract Abstract 3132 Introduction: In year 2008 version of WHO classification for myeloid malignancies, a category of AML with myelodysplasia-related changes (AML-MRC) was defined which included both de novo AML with dysplasia and AML secondary to MDS. It is characterized by poor chemosensitivity for which allogeneic transplantation (allo-SCT) has been a viable option to cure. Umbilical cord blood transplantation (UCBT) is a possible treatment strategy that can be performed for those who lack suitable donors due to rapid availability and less stringent HLA matching required. So far, there have been sparse reports available on UCBT for those with AML-MRC. This study was conducted to see the current update in our institute and to see whether the presence of induction chemotherapy before transplant is better for the outcome. Design and Methods: We retrospectively reviewed patients diagnosed as AML-MRC who underwent UCBT at our institute from Mar. 2002 to Mar. 2011 consecutively. Patients who lacked appropriate adult PB/BM donors underwent UCBT. Patients who had prior history of transplantation, were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. Results: Eighty-one patients were included. 52 (64%) were males, and median age was 61 years (range, 17–72). 35 (43%) were de novo AML, and 46 (57%) were AML secondary to MDS. Median time from diagnosis to transplantation was 346 days (range, 42–7997). 39 (48%) did not receive induction chemotherapy before transplant. 76 (94%) were not in remission, 29 (36%) were in high, and 52 (64%) were in very high WPSS risk group, just before transplant. 54 (67%) received reduced-intensity conditionings. 65 received GVHD prophylaxis of tacrolimus-based, while 16 did cyclosporine alone. Median observation time for survivors was 646 days (range 32–2456). Median days of neutrophil recovery (> 500/ul) was 20 days (range, 11–45), and cumulative incidence of engraftment was 76.5 % up to day 50 post-transplant. Cumulative incidences of relapse and non-relapse mortality at 2 years post-transplant were 37.8 % and 33.3 %, respectively. Higher incidence of relapse was observed in those with prior history of MDS in univariate analysis (51.8 % vs. 21.2 % at 2 years post-transplant, P = 0.004), which was the only significant factor associated with higher relapse rate in multivariate analysis (P = 0.020). More NRM was observed in those received transplant early period from 2002 to 2005 vs. those who did from 2006 to 2010 (45.1 % vs. 25.5 % at 2 years post-transplant, P = 0.001), and in those received GVHD prophylaxis using CsA alone vs. others (72.0 % vs. 24.8 % at 2 years post-transplant, P = 0.0002). In multivariate analysis, higher degree of HLA mismatch (2 antigens vs. less than 2) and GVHD prophylaxis using CsA alone were associated with higher incidence of NRM (P = 0.024 and P = 0.00047, respectively). Overall survival (OS) was estimated as 42.1 % at 2 years post-transplant. Better OS was observed in those who received conditioning containing 12.8mg/kg of iv busulfan (60.8% vs. 32.4% at 2 years post-transplant, P = 0.0337), in those received tacrolimus-based GVHD prophylaxis vs CsA alone (47.9 % vs. 17.0 % at 2 years post-transplant, P = 0.0024), and in those received transplant in recent period from 2006 to 2010 vs. those who did from 2002 to 2005 (52.1 % vs. 26.1 % at 2 years post-transplant, P = 0.0248). In multivariate analysis, GVHD prophylaxis using CsA alone and poor WPSS risk category just before transplant were the factors significantly asssociated with poor OS (P < 0.0001 and P = 0.001, respectively). There were no significant differences between presence or absence of prior induction chemotherapy in terms of cumulative incidence of neutrophil recovery (71.4 % vs. 82.1% up to day 50 post-transplant, P = 0.88), relapse (38.0 % vs. 36.1%, P = 0.94), NRM (30.7 % vs. 35.4 %, P = 0.87), and OS (47.7 % vs. 36.2%, P= 0.72) at 2 years post-transplant. Conclusions: These data indicate that CBT is a feasible and promising treatment approach for those with AML-MRC, including elderly patients. More intensive GVHD prophylaxis was beneficial in reducing NRM and improving OS for the population studied. Presence of prior induction chemotherapy before transplant was not associated with higher rate of engraftment or better OS, suggesting tumor reduction before pre-transplant conditioning may not be necessary for successful outcome in our transplant settings. Disclosures: No relevant conflicts of interest to declare.

Acute myeloid leukemia-type chemotherapy for newly diagnosed patients without antecedent cytopenias having myelodysplastic syndrome as defined by French-American-British criteria: a Cancer and Leukemia Group B Study.

1996 ◽  
Vol 14 (9) ◽  
pp. 2486-2494 ◽  
Author(s):  
S H Bernstein ◽  
V L Brunetto ◽  
F R Davey ◽  
D Wurster-Hill ◽  
R J Mayer ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Refractory Anemia ◽  
Newly Diagnosed ◽  
History Of ◽  
De Novo Aml ◽  
Group B ◽  
Leukemia Group ◽  
French American British ◽  
Acute Myeloid

PURPOSE To determine the treatment outcome of standard acute myeloid leukemia (AML)-type chemotherapy in a subset of patients with newly diagnosed myelodysplastic syndromes (MDS) compared with that of patients with de novo AML as defined using French-American-British (FAB) criteria. In addition, to determine the pretreatment variables having prognostic significance for treatment outcome in patients with MDS. PATIENTS AND METHODS Nine hundred seven newly diagnosed patients with no history of cytopenias having a local institutional de novo AML successfully karyotyped and treated on Cancer and Leukemia Group B (CALGB) protocols for AML from 1984 to 1992. Thirty-three of the 907 patients were reclassified as having MDS on central pathology review using FAB criteria and form the basis of this analysis. RESULTS The treatment outcomes for patients with MDS and AML were similar; the complete remission (CR) rate was 79% and 68%, respectively (P = .37); median CR duration was 11 and 15 months, respectively (P = .28); and median survival was 13 and 16 months, respectively (P = .72). For the MDS patients, there were no prognostic variables for CR rate identified. For CR duration, only the Sanz classification had prognostic value. The prognostic factors for survival in a univariate analysis included age, WBC count, Sanz classification, and percent blood blasts. In a proportional hazards analysis of survival, age greater than 60 years and WBC less than 2.6 x 10(9)/L were adverse prognostic factors. CONCLUSION In patients with no known history of cytopenias who are treated intensively at diagnosis, the FAB distinctions between MDS (refractory anemia with excess blasts and refractory anemia with excess blasts in transformation) and AML appear to have little therapeutic relevance.

scholarly journals Limited FISH Testing for MDS-Defining Cytogenetic Abnormalities Rapidly Identifies Patients with Newly Diagnosed AML Eligible for CPX-351

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4785-4785 ◽  
Author(s):  
Christine M. McMahon ◽  
Nya Nelson ◽  
Alex Ganetsky ◽  
James K. Mangan ◽  
Noelle V. Frey ◽  
...  
Keyword(s):  
Board Of Directors ◽  
De Novo ◽  
Clinical History ◽  
University Of Pennsylvania ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Cytogenetic Abnormalities ◽  
History Of ◽  
Cytogenetic Changes ◽  
De Novo Aml

Abstract Introduction: CPX-351 (liposomal cytarabine and daunorubicin; VYXEOS) improves survival and complete remission rates compared to standard induction chemotherapy (7+3) in patients 60 to 75 years old with newly diagnosed myelodysplastic syndrome (MDS)-associated and therapy-related AML (Lancet et al., JCO 2018) and was approved by the U.S. Food and Drug Administration in August 2017. In addition to patients with a known history of MDS or cytotoxic and/or radiotherapy, patients with de novo AML with WHO-defined MDS-related cytogenetic changes are also eligible for CPX-351. We have implemented a diagnostic clinical pathway for patients with newly diagnosed AML which includes rapid FISH assessment for the most common MDS-defining karyotypes in patients who are potential candidates for CPX-351. We reviewed outcomes after the first year of this diagnostic pathway in our institutional cohort comparing results of chromosome metaphase analysis and rapid FISH. Methods: We performed both rapid MDS-FISH testing (turnaround time < 6 hours) and metaphase analysis on all patients who presented to the University of Pennsylvania from 9/2017 through 6/2018 with newly diagnosed AML who were potential candidates for CPX-351 induction therapy based on age and other clinical factors. Our MDS-FISH panel includes probes for EGR1(5q31)/5p15.2, D7S486(7q31)/CEP7, and TP53(17p13.1)/NF1(17q11.2) (MetaSystems). Results of the limited FISH testing were compared with metaphase chromosome analysis. Demographic and clinical information was abstracted from the electronic medical record. This study was approved by the University of Pennsylvania Institutional Review Board. Results: Twenty-nine patients with newly diagnosed AML from 9/2017 through 6/2018 had both rapid MDS-FISH and karyotype testing performed. Nineteen patients (65.5%) had de novo AML, while 7 (24.1%) had a clinical history of MDS and 3 (10.3%) had a history of prior cytotoxic and/or radiation therapy. Metaphase analysis revealed WHO-defined MDS-related cytogenetic abnormalities in 14/29 patients (48.3%). Of these 14 patients, 11 (78.6%) also had positive MDS-FISH testing in >=1 probe. Of the 3 patients with MDS-related cytogenetic abnormalities that were identified by metaphase analysis but not the FISH panel, 2 had a history of either MDS (n=1) or prior cytotoxic chemotherapy (n=1) and therefore were eligible for CPX-351 based on clinical history alone. Of the 7 patients with de novo AML and MDS-defining cytogenetic abnormalities, 6 (85.7%) were identified by the FISH screen. Conclusions: Rapid FISH testing for MDS-defining cytogenetic changes using probes for abnormalities of chromosomes 5, 7, and 17 efficiently identifies the majority of patients with newly diagnosed de novo AML who do not have a clinical history of MDS or cytotoxic therapy but are eligible for induction therapy with CPX-351 based on the presence of MDS-defining cytogenetic abnormalities. The combination of rapid FISH testing and clinical history has a high sensitivity for identifying patients with MDS-defining karyotypic abnormalities. This diagnostic clinical pathway allows for the expeditious identification of patients eligible for CPX-351. Disclosures Frey: Servier Consultancy: Consultancy; Novartis: Consultancy. Perl:Astellas: Consultancy; Daiichi Sankyo: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; NewLink Genetics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy.

Predictors Factors of Onset de Novo Heart failure after STEMI

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Abouradi ◽  
H Choukrani ◽  
A Maaroufi ◽  
A Drighil ◽  
R Habbal
Keyword(s):  
Heart Failure ◽  
De Novo ◽  
Microvascular Disease ◽  
Prior History ◽  
Killip Class ◽  
Funding Sources ◽  
Significant Difference ◽  
Primary Coronary Angioplasty ◽  
History Of ◽  
Predictor Factors

Abstract Funding Acknowledgements Type of funding sources: None. INTRODUCTION STEMI gets complicated very often by a heart failure (HF), which it is important to know associated factors. The aim of this study  was to determinate the predictor factors of onset of de novo HF after STEMI in patients with no prior history of heart failure recorded at baseline. METHODS A retrospective, descriptive study from 1 center in Morocco, including 210 patients hospitalized in a cardiology intensive care unit for STEMI from September 2019 to November 2020. The main outcomes were HF Killip class at hospital presentation and intra-hospital mortality. RESULTS The main age was 59.3 ± 7.02 and Sex ratio: 2, 86. The incidence of de novo HF at admission was higher in women (40, 4% vs. 29.5%, [OR 1, 61; 95%, [CI] 0, 83-3, 11). Forty-nine point eight percent were in Killip≥ 2. The method of early revascularization was Thrombolysis in 82, 3% compared to primary coronary angioplasty without significant difference in onset of the novo HF. There was no association of age, comorbidities, delay to hospital presentation and coronary involvement with incidence of onset of de novo HF.  Women had higher mortality than men with the novo HF (28, 6% vs. 20.5%; OR: 1, 55; 95%). CONCLUSION  Gender has appeared associated to onset of de novo HF after STEMI with a superiority of the female sex after controlling for others factors described in the literature. Anterior studies have related this to the increased prevalence of microvascular disease in women predisposing them to heart failure after STEMI.

Real world treatment patterns in chronic myeloid leukemia patients newly initiated on tyrosine kinase inhibitors in an U.S. integrated healthcare system

2017 ◽  
Vol 24 (4) ◽  
pp. 253-263
Author(s):  
Nazia Rashid ◽  
Han A Koh ◽  
Kathy J Lin ◽  
Brian Stwalley ◽  
Eugene Felber
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Index Date ◽  
Stem Cell Transplant ◽  
Study Time ◽  
Myelogenous Leukemia ◽  
Prior History ◽  
Cell Transplant ◽  
Time Period ◽  
History Of

Purpose To evaluate treatment patterns in patients diagnosed with incident chronic myelogenous leukemia (CML) newly initiating therapy with imatinib, dasatinib, or nilotinib. Patients were followed to determine switching and discontinuation rates. Factors associated with switching or discontinuation from index TKI therapy, reasons for discontinuation based on electronic chart notes, and frequency of laboratory monitoring were assessed during the follow-up period. Methods A retrospective cohort study was conducted in chronic myelogenous leukemia patients aged ≥ 18 years who were identified from the Kaiser Permanente Southern California (KPSC) Cancer Registry database during the study time period of 1 January 2007 to 12 December 2013. The index date was defined as the date of the first TKI prescription (imatinib, dasatinib, or nilotinib) identified during the study time period with no prior history of TKI use within 12 months. Patients had to have continuous membership with drug benefit eligibility and no prior history of stem cell transplant (SCT) or other cancers during the 12 months prior to the index date. Baseline characteristics were identified during 12 months prior to the index date and outcomes were identified during the follow-up period after the index date. All patients were followed from index TKI therapy until end of study time period (12 December 2014), death, stem cell transplant, or disenrollment from the health plan unless one of the following occurred first: a patient switched their index therapy, or a patient discontinued their index therapy. Forward stepwise selection multivariable logistic regression models were used to evaluate factors associated with patients who continued therapy compared to those who switched or discontinued therapy with the index TKI. Chart notes were reviewed 30 days prior and 30 days post index TKI discontinuation to evaluate reasons for discontinuation. Molecular and cytogenetic testing frequency was also assessed during the follow-up period among the different patient groups. Results Two hundred sixteen patients were identified with incident chronic myelogenous leukemia and use of TKI therapy: 189 (87.5%) received imatinib, 19 (8.8%) received dasatinib, and 8 (3.7%) received nilotinib. The mean age on index date was 53 years and 63% were male; 103 patients (48%) continued on their index therapy, while 62 patients (28%) switched, and 51 patients (24%) discontinued.

Efficacy and safety of aspacytarabine (BST-236) as a single-agent, first-line therapy for patients with acute myeloid leukemia unfit for standard chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7007-7007
Author(s):  
Jessica K. Altman ◽  
Jamie Koprivnikar ◽  
James K. McCloskey ◽  
Vamsi Kota ◽  
Olga Frankfurt ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Single Agent ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
First Line ◽  
Standard Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
De Novo Aml

7007 Background: Aspacytarabine (BST-236) is a prodrug of cytarabine, the backbone of acute myeloid leukemia (AML) standard of care chemotherapy, associated with toxicity which precludes its administration in older patients and patients with comorbidities. Aspacytarabine is inactive in its intact prodrug form until cytarabine is gradually released at pharmacokinetics which decrease the systemic exposure to peak toxic cytarabine levels, resulting in reduced systemic toxicity and relative sparing of normal tissues, enabling therapy with high cytarabine doses to patients otherwise unfit to receive it. Methods: A phase 2b open-label, single-arm study to evaluate the efficacy and safety of aspacytarabine as a first-line single-agent therapy in newly-diagnosed AML patients unfit for standard chemotherapy (NCT03435848). Aspacytarabine is administrated at 4.5 g/m2/d (containing 3 g/m2/d cytarabine) in 1-2 induction and 1-3 consolidation courses, each consisting of 6 daily 1-hour infusions. Patients with secondary AML, prior hypomethylating agent (HMA) therapy, and therapy-related AML, are eligible. Results: To date, in the ongoing study, 46 newly-diagnosed AML patients unfit for standard chemotherapy (median age 75 years) were treated with aspacytarabine and completed 1-4 courses of 4.5 g/m2/d aspacytarabine, including 26 patients (63%) with de novo AML and 17 (37%) with secondary AML. Six patients (13%) were previously treated with HMA (median 12 courses). The baseline median bone marrow blasts was 52%, and 54% and 29% of patients had adverse or intermediate European LeukemiaNet (ELN) score, respectively. Twenty (43%) patients had ECOG 2. Aspacytarabine is safe and well-tolerated in repeated-course administration. Grade > 2 drug-related adverse events include mainly hematological events and infections. The 30-day mortality rate is 11%. Of 43 patients evaluable for efficacy analysis to date, 15 patients (35%) reached a complete remission (CR) following 1 (13 patients) or 2 (2 patients) induction courses, all with complete hematological recovery (median 27.5 days, range 22-39 days). The CR rates in de novo AML patients and patients with adverse ELN score are 46% and 33%, respectively. Of the 11 patients evaluable to date for minimal residual disease (MRD) flow cytometry test, 8 are MRD negative (73%). While aspacytarabine treatment consists of a limited number of courses, median duration of response and median overall survival for responders are not reached at 12 and 24 months, respectively (end of follow up). Updated results will be presented at the meeting. Conclusions: The cumulative clinical data suggest that aspacytarabine, a time-limited single-agent treatment, is safe and efficacious as a first-line therapy for patients who are unfit for intensive chemotherapy, which may establish it as a new tolerable AML chemotherapy backbone. Clinical trial information: NCT03435848.

scholarly journals EPID-21. THE NATIONAL SPECTRUM OF NEWLY-DIAGNOSED BRAIN TUMORS IN ADULT PATIENTS VARIES SIGNIFICANTLY BY PATIENT DEMOGRAPHICS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi79-vi79
Author(s):  
Matthew Torre ◽  
Mustafa Ascha ◽  
Maya Harary ◽  
Timothy Smith ◽  
Ayal Aizer ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Patient Characteristics ◽  
Intracranial Tumor ◽  
Adult Patients ◽  
Intracranial Tumors ◽  
Newly Diagnosed ◽  
Patient Demographics ◽  
Common Diagnosis ◽  
History Of ◽  
Tumor Types

Abstract INTRODUCTION Herein we examine the epidemiology and outcomes of the entire spectrum of intracranial tumors in the contemporary era. METHODS Adult patients (≥20yo) presenting between 2010–2015 where the first evidence of cancer involves an intracranial tumor were queried from the National Cancer Database, which comprises >70% of cancers newly-diagnosed in the U.S. Tumor types were classified by WHO2016 ICD-O3, and stratified by patient characteristics. RESULTS 361,841 adults without a history of cancer presented with intracranial tumors between 2010–2015. Across all ages, these were comprised of 1) brain metastases (BMs; 25%: 29% in males vs. 23% in females); 2) meningiomas (25%: 15% in males, but 34% in females) including atypical (n=4,565) and anaplastic (n=833); 3) diffuse infiltrative gliomas (21%: 26% in males vs. 17% in females), mostly GBMs (14%); followed by 4) sellar (14%), 5) cranial nerve (6%), and PCNSL (3%) tumors. The remaining types each comprised ≤2 % of brain tumors, including mesenchymal non-meningothelial tumors (2%), intracranial ependymal (0.8%), mixed neuronal-glial (0.7%), circumscribed “other astrocytomas” (0.6%, mostly pilocytic astrocytomas n=1,307 and PXAs n=272), CNS embryonal (0.3%), pineal (0.2%), GCTs (0.1%), and choroid plexus (0.1%) tumors. In the 91,686 patients presenting with a BM, the most common primaries were lung adenocarcinoma (39%), lung SmallCC (14%), lung SqCC (8%), breast (8% of females), melanoma (3%), kidney (3%), colorectal (2%), and esophageal (1%). The distributions of brain tumor types differed significantly by age, sex, race/ethnicity, and insurance status. CONCLUSIONS In adult patients where the first manifestation of cancer includes an intracranial tumor, the most common diagnosis is either metastatic disease (predominantly from NSCLC) in males or benign meningiomas in females; but varies substantially by age group. Notably, our results adjust the traditional teaching that half of all new brain masses are BMs, which in fact represent only ~25% of new intracranial masses.

Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid leukemia blasts identifies a group of patients with poor response to intensive chemotherapy.

1997 ◽  
Vol 15 (6) ◽  
pp. 2262-2268 ◽  
Author(s):  
M Wetzler ◽  
M R Baer ◽  
S H Bernstein ◽  
L Blumenson ◽  
C Stewart ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Prognostic Significance ◽  
Poor Response ◽  
Significant Difference ◽  
De Novo Aml ◽  
Cd34 Expression ◽  
Acute Myeloid

PURPOSE c-mpl, the human homolog of v-mpl, is the receptor for thrombopoietin. Given that c-mpl expression carries an adverse prognosis in myelodysplastic syndrome and given the prognostic significance of expression of other growth factor receptors in other diseases, we attempted to determine whether c-mp/mRNA expression is a prognostic factor in acute myeloid leukemia (AML). PATIENTS AND METHODS We analyzed bone marrow samples from 45 newly diagnosed AML patients by reverse-transcription polymerase chain reaction. RESULTS Samples from 27 patients (60%) expressed c-mpl mRNA (c-mpl+); their clinical and laboratory features were compared with those of the 18 patients without detectable levels of c-mpl(c-mpl-). No significant differences in age, sex, leukocyte count, French-American-British subtype, or karyotype group were found. c-mpl+ patients more commonly had secondary AML (41% v 11%; P = .046) and more commonly expressed CD34 (67% v 12%; P = .0004). There was no significant difference in complete remission (CR) rate. However, c-mpl+ patients had shorter CR durations (P = .008; median, 6.0 v > 17.0 months). This was true when only de novo AML patients were considered and when controlling for age, cytogenetics, or CD34 expression. There was a trend toward shorter survival in c-mpl+ patients (P = .058; median, 7.8 v 9.0 months). CONCLUSION These data suggest that c-mpl expression is an adverse prognostic factor for treatment outcome in adult AML that must be considered in the analysis of clinical studies using thrombopoietin in AML.

scholarly journals OTHR-10. THE NATIONAL DISTRIBUTION OF NEWLY-DIAGNOSED BRAIN METASTASES IN ADULTS VARIES WIDELY BY PATIENT DEMOGRAPHICS

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i20-i20
Author(s):  
Vasileios Kavouridis ◽  
Matthew Torre ◽  
Maya Harary ◽  
Timothy Smith ◽  
Bryan Iorgulescu
Keyword(s):  
Brain Metastases ◽  
Pacific Islanders ◽  
Prior History ◽  
National Cancer Database ◽  
Newly Diagnosed ◽  
Patient Demographics ◽  
Asian Pacific Islanders ◽  
History Of ◽  
Asian Pacific ◽  
History Of Cancer

Abstract INTRODUCTION: Metastases are oft-cited as comprising approximately half of all adult intracranial neoplasms, and their national composition remains unclear. METHODS: The patient demographics and histologic distribution of newly-diagnosed brain metastasis (BM) patients aged &gt; 18yo without a prior history of cancer (2010–2015) were evaluated using the National Cancer Database, which comprises &gt; 70% of all newly-diagnosed cancers in the U.S. RESULTS: 91,686 adults presented with a newly-diagnosed BM between 2010–2015. The most common sites of brain metastases overall were lung (82% of metastatic cases), breast (4.1%), melanoma (3.2%), kidney (2.9%), and colorectal (1.8%). The overall 1-year and 5-year OS rates for all BMs were 27.0% (95% CI [26.7%-27.3%]) and 5.3% (95% CI [5.1%-5.5%]), respectively. The distribution of primary sites for newly-diagnosed BMs varied by sex, age, and race. Compared to males, more females had BMs from breast (8.4% versus 0.8%) and fewer had BMs from kidney (1.9% versus 3.8%), melanoma (1.9% versus 4.5%), and esophagus (0.3% versus 2.0%). In young adults, particularly those 20-29yo, BMs were more likely from melanoma, genitourinary (in males), and soft tissue than adults in middle and advanced age. Lung carcinomas comprised fewer BMs in Hispanics (66%) compared to Whites (82%), Blacks (83%), and Asian/Pacific Islanders (85%). BMs from kidney and genitourinary primaries were higher in Hispanics (7.3% and 2.4% of BMs, respectively) than in Whites (2.8% and 0.3%, respectively), Blacks (1.8% and 0.1%, respectively), and Asian/Pacific Islanders (2.6% and 0.2%, respectively). Melanoma was more frequent in Whites (3.8% of BMs) and Hispanics (2.5%) compared to Blacks (0.3%) and Asian/Pacific Islanders (0.6%). CONCLUSION: Our results illustrate the national distribution of newly-diagnosed BMs and investigates how the distribution varies by patient demographics.

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