Externally Validated Predictive Clinical Model For Untreated Del(17p13.1) Chronic Lymphocytic Leukemia Patients

Abstract CLL patients (pts) with del(17p13.1) (17p-) karyotype are typically refractory to therapy. There are limited data on clinical outcomes of large groups of these pts treated at a single institution. We aimed to develop a risk score to classify pts with de novo 17p- CLL at high risk of early treatment or death. We retrospectively reviewed records of 114 CLL pts with 17p- and no prior therapy seen at OSU from 2002-2012. Treatment free survival (TFS) was calculated from date of 1st visit until date of 1st treatment or death, censoring pts alive and treatment-free at last follow-up. Overall survival (OS) was calculated from date of 1st visit until date of death or last follow-up. TFS/OS estimates were calculated using the Kaplan-Meier method. Proportional hazards models were fit using backwards selection to identify variables significantly associated with TFS & OS. A risk score (RS) was calculated based on the variables and regression coefficients of the model. A simplified risk score (SRS) to be used in clinical practice was based on the strength of associations with clinical outcome when all variables had been categorized. To externally validate the SRS, a dataset of 129 de novo 17p- pts was obtained from MD Anderson Cancer Center (MDA). Consistency in model coefficients used to derive the SRS and predictive power of the SRS using Harrell’s c-index (c) were compared between the sets. In the OSU set, median age was 62 yrs, 33% had Rai Stage 0, 61% had ECOG performance status (PS) 0 and 11% had ECOG PS >2. Around 35% and 10% of pts had white blood cell count (WBC) >50 x109/L and lactate dehydrogenase at least 2 x the upper limit of normal (LDH x2 ULN), respectively. Only 14% had concomitant 11q- and 36% had complex karyotype with >3 aberrations. None of these variables were significantly different between the OSU and MDA sets (p>0.15), nor were TFS and OS (p>0.10). Median TFS estimates were 16 mos (95%CI 6-27) and 6 mos (95%CI 3-12) for the OSU and MDA sets, respectively, while median OS estimates were 5.2 yrs (95%CI 3.4-7.8) and 6.4 yrs (95%CI 4.7-not reached). Using the OSU set, a multivariable model for TFS included ECOG PS, Rai Stage, WBC and 11q- (all p<0.017, c=0.84). A RS used the formula: 0.794 x (ECOG PS1, no=0,1=yes) + 1.686 x (ECOG PS≥2, no=0,1=yes) + 1.485 x (Rai I/II/III/IV, no=0,1=yes) + 0.053 x (age in yrs) + 0.0045 x (WBC) + 0.881 x (11q-, no=0,1=yes). A SRS used the formula: 1 x (ECOG PS1, no=0,1=yes) + 2 x (ECOG PS≥2, no=0,1=yes) + 2 x (Rai Stage I/II/III/IV, no=0,1=yes) + 1 x (age≥65yrs) + 1 x (WBC>50) + 1 x (11q-, no=0,1=yes), with possible scores ranging from 0 to 7. TFS estimates at 2 yrs for SRS=0/1, 2/3, and >4 were 85% (95%CI=0.60-0.95), 51% (95%CI=0.32-0.67), and 0%, respectively (Figure 1A). In the MDA set, Rai Stage and WBC contributed significantly to the SRS, followed by ECOG PS, with little consistency in the impact of age or 11q- compared with the OSU set, leading to a loss in predictive power (c=0.66). Still, the SRS was significantly associated with TFS (p<0.0001), with 2-yr estimates of 63% (95%CI=0.39-0.79), 26% (95%CI=0.15-0.39), and 16% (0.06-0.29) for SRS=0/1,2/3, and >4 (Figure 1B). Using the OSU set, a multivariable model for OS included ECOG PS, age, and LDH (all p<0.025, c=0.76). A RS used the formula: 0.783 x (ECOG PS1, no=0,1=yes) + 1.637 x (ECOG PS≥2, no=0,1=yes) + 0.042 x (age in yrs) + 0.445 x (LDH relative to ULN). A SRS used the formula: 1 x (ECOG PS1, no=0,1=yes) + 2 x (ECOG PS≥2, no=0,1=yes) + 1 x (age≥65yrs) + 1 (LDH x2ULN, no=0,1=yes), with possible scores ranging from 0 to 4. The SRS was associated with OS (p<0.0001, c=0.73), with 2-yr estimates of 89% (95%CI=0.74-0.96), 64% (95%CI=0.39-0.81) and 0% for those with SRS=0, 2, and 4, respectively (Figure 2A). In the MDA set, with the exception of ECOG PS 1, the strength in association of all variables with OS was similar to what had been observed in the OSU set. The predictive ability of the SRS decreased in the MDA set (c=0.68), but remained associated with OS, with the highest score showing early, inferior OS (Figure 2B). Estimates at 2 yrs ranged from 95% (95%CI=0.83-0.99), to 80% (95%CI=0.55-0.92) to 20% (95%CI=0.01-0.58) with an SRS of 0, 2, and 3, respectively; no one had a SRS=4. In conclusion, pretreatment clinical characteristics can be used in a simplified score for de novo CLL pts with 17p- to predict TFS and OS. These scores, particularly the very highest, can be utilized to identify high-risk pts for expedient enrollment on clinical trials. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

ASXL1 Mutations in AML: Molecular Biomarker for Secondary AML?

Blood ◽

10.1182/blood.v124.21.2343.2343 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2343-2343

Author(s):

Jingmei Hsu ◽

Anita J. Kumar ◽

Martin P. Carroll ◽

Noelle V. Frey ◽

Nirav N. Shah ◽

...

Keyword(s):

Overall Survival ◽

De Novo ◽

Conflicts Of Interest ◽

Prognostic Significance ◽

Myeloproliferative Neoplasm ◽

Molecular Characteristics ◽

Intermediate Risk ◽

Kaplan Meier ◽

The Impact

Abstract Background: Additional sex combs like transcription factor 1 (ASXL1) is a member of the polycomb group protein. ASXL1 mutation has been implicated in myeloid malignancy transformation. It is hypothesized that mutated ASXL1 leads to the loss of polycomb repressive complex 2 (PRC2) mediated gene repression and subsequent transforming events. Recent studies identify ASXL1 mutation as a poor prognostic marker in patients (pts) with de novo acute myeloid leukemia (AML) who present with intermediate–risk cytogenetic lesions (Patel, NEJM 2012; Schnittger, Leukemia2013). To study the impact of ASXL1 mutations in an unselected AML population, we analyzed clinical and molecular characteristics of patients with untreated AML who express ASXL1 mutation at presentation. Methods: Using next generation sequencing, 254 adult patients with AML seen at the Hospital of the University of Pennsylvania were analyzed for mutations, including ASXL1, using a 33-gene hematologic malignancy panel. Clinical characteristics were obtained from retrospective chart review. Kaplan-Meier estimates were used to calculate overall survival (OS) from time of diagnosis. Living patients were censored at date last seen. Results: ASXL1 mutations were detected in 36/254 (14%) AML pts. There were 29 known pathologic mutations, 1 benign, 1 probable pathologic, and 9 variants of unknown clinical significance (VUS). In 6/36 (16.7%) pts, ASXL1 was the sole mutation identified. Of the 30 pts with additional mutations (Figure 1), 6/30 (20%) pts harbored 2 independent ASXL1 mutations. When the 27 patients with pathologic ASCL mutations were analyzed for co-mutations, TET2 (13/27, 48%) was the most frequent ASXL1 co-mutation. FLT3 (0/27, 0%) and NPM1 (1/27, 3.7%) were notable for their absence. Median age of pts at diagnosis was 69 years (range 23-80). Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) was noted in 9/36 (25%) and 11/36 (30.6%) pts, respectively. Four pts (11.1%) had received chemotherapy and/or radiation therapy for a prior non-myeloid neoplasm. Karyotype was normal in 18/36 (50%) pts, and 7 additional pts had intermediate cytogenetic lesions. There were 7 pts (19.4%) with unfavorable cytogenetics (complex karyotype (3 pts), 7q- (3 pts), and 5q- (1 pt)). Four pts (11.1%) had a favorable karyotype, with t(8;21) in 3 pts and t(15;17) in 1 pt. At presentation, median white blood cell count (WBC) was 6.4x103/uL (1.0 x -103). In pts whose AML transformed from prior MPN, median WBC was 50 X103/uL (3.3-140). Standard induction chemotherapy with an anthracycline and cytarabine was given to 17/36 (47%) pts. An additional 3/36 (8.3%) pts underwent induction therapy with clofarabine. Complete remission (CR) was documented in 14/20 (70%) evaluable pts. Of the remaining pts, 11 received a hypomethylating agent, and 5 received other therapies. Thirty-day treatment mortality for all 36 pts and for 27 pts with known ASXL1 pathologic mutation was 13.4% and 18.5% respectively. Kaplan-Meier estimate showed a median overall survival of 349 days (median follow up of 107 days (range 15-1570)). For the 27 pts with a pathologic ASXL1 mutation, the OS was 276 days (Figure 2, median follow up of 145 days (range 18-1570)). Conclusion: ASXL1 mutations in de novo AML with intermediate-risk cytogenetics is associated with poor clinical outcome in cooperative group trials. Strikingly we demonstrate in a single institution, retrospective analysis that 66.7% of pts who present with ASXL1 mutations in the setting of previously untreated AML had documented MDS, MPN and/or prior chemotherapy/radiation. Further studies are necessary to evaluate if ASXL1 mutation has independent prognostic significance in AML or if it is primarily a marker for secondary leukemia. Figure 1: ASXL1 and co-mutations Figure 1:. ASXL1 and co-mutations Figure 2: Overall survival for AML patients with ASXL1 pathologic mutation Figure 2:. Overall survival for AML patients with ASXL1 pathologic mutation Disclosures No relevant conflicts of interest to declare.

Download Full-text

Impact of t (11;14) on the outcome of autologous hematopoietic cell transplantation (Auto-HCT) in multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8040 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8040-8040

Author(s):

Koji Sasaki ◽

Gary Lu ◽

Chitra Hosing ◽

Uday R. Popat ◽

Sairah Ahmed ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Chromosomal Abnormalities ◽

Normal Karyotype ◽

Cancer Center ◽

Induction Treatment ◽

High Dose ◽

Significant Difference ◽

The Impact

8040 Background: Approximately 15-20% of patients with multiple myeloma (MM) present with t(11;14)(q13;q32) involving IgH and CCND1-XT genes. In this study, we report the impact of the t(11;14) on the outcome of patients with MM. Methods: We performed a retrospective chart review on patients with MM who underwent high-dose chemotherapy followed by auto-HCT at the M.D. Anderson Cancer Center between 2/2000 and 8/2010, and had conventional cytogenetic (CC) or fluorescent in situ hybridization (FISH) results available before transplant. The primary objective was to compare the progression free survival (PFS) and overall survival (OS) of patients with t(11;14) to patients without chromosomal abnormalities. Results: CC or FISH studies were available for 1239 patients: 863 normal, 28 with t(11;14), 348 with other abnormalities. Concurrent high-risk abnormalities on CC or FISH were seen in 15/28 patients with t(11;14): del(13q) in 11 , del(17p) in 3, and t(14;16)(q32;q23) in 1. Induction treatment in patients with t(11;14) was: bortezomib + dexamethasone +/- thalidomide/lenalidomide : 15 (53%), thalidomide or lenalidomide + dexamethasone: 11 (39%), others 2 (8%); they received auto-HCT after a median of one line (1-7) of therapy. Median follow up in surviving patients was 39 months. There was no significant difference in median time from diagnosis to auto-HCT from diagnosis (6.9 vs. 7.7 months, p=1.0), disease status at auto HCT (>PR1: 82 vs. 76%, <PR1: 7 vs. 11%, relapsed 10 vs. 13%), complete remission (CR: 21% vs. 32%; p=0.30), very good partial remission (VGPR: 29% vs. 21%; p=0.23) or overall response (75% vs. 85%; p=0.18) between patients with t(11;14) and normal karyotype. Median PFS in patients with t(11;14) and normal karyotype was 15.7 months and 35.9 months, respectively (p=0.017). Median OS in patients with t(11;14) and normal karyotype was 51.4 months and 88.4 months, respectively (p=0.03). There was no difference in PFS (p=0.25) or OS (p=0.71) in patients with t(11;14), with or without other high-risk chromosomal abnormalities. Conclusions: In this large single center study with a long follow up, we demonstrated that t(11;14) in MM is associated with a shorter PFS and OS in the context of auto-HCT.

Download Full-text

A Prognostic Score for Overall Survival (OS) with Azacitidine (AZA) In Higher Risk MDS Based on 282 Patients (pts), and Validated In 175 Pts From the AZA 001 Trial

Blood ◽

10.1182/blood.v116.21.3996.3996 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3996-3996

Author(s):

Raphael Itzykson ◽

Sylvain Thepot ◽

Bruno Quesnel ◽

Francois Dreyfus ◽

Odile Beyne-Rauzy ◽

...

Keyword(s):

Prognostic Factors ◽

High Risk ◽

Risk Score ◽

Research Funding ◽

Missing Values ◽

De Novo ◽

Prognostic Score ◽

Continuous Variable ◽

Ecog Ps ◽

Rbc Transfusion

Abstract Abstract 3996 Background: AZA significantly improves OS in higher-risk MDS (including RAEB-t/AML) compared to conventional treatments (AZA 001 trial, Lancet Onc, 2009), but prognostic factors of response and OS to AZA remain largely unknown. We designed a prognostic score for OS in a cohort of AZA treated higher-risk MDS in a patient-named compassionate program (French ATU), and validated it in patients from the AZA 001 trial. Methods: Between Sept 2004 and Jan 2009, prior to AZA approval in Europe, IPSS int-2/high risk MDS (including RAEB-t) not previously treated with intensive chemotherapy (IC), allo SCT, or a hypomethylating agent were included in a compassionate program (ATU), and received AZA (planned schedule 75 mg/m2/d ×7 d every 28 d for ≥4 cycles). Independent prognostic factors of OS were individualized in a Cox model. A prognostic score was then developed based on those factors. After validation of the score as a continuous variable, pts were grouped in three distinct risk categories. We subsequently tried to validate this score in the 175 higher risk MDS pts treated with AZA at the same schedule in AZA 001 trial (4 of the 179 pts randomized to AZA in that trial did not start AZA). Results: The ATU cohort included 282 pts with de novo (74%) or therapy related (t) (26%) higher-risk MDS (IPSS int-2 in 54% high in 43%, at least int-2 in 2%). ECOG PS ≥2, RBC transfusion dependence ≥4 units/8 weeks and circulating blasts were present in 21%, 46% and 46% of pts respectively (resp). Cytogenetic risk was good, int, and poor in 31%, 17% and 47% (unknown in 5%). 10% pts had previously been treated with LD araC for their MDS. Multivariate analysis of survival retained PS ≥2 (HR= 2.0 [95% CI: 1.4–2.9]), RBC transfusion dependence ≥4 units/8 weeks (HR=1.9 [1.4-2.6]), presence of circulating blasts (HR=2.0 [1.5-2.7]), and IPSS cytogenetic risk (intermediate: HR=1.4 [0.8-2.3], poor: HR=3.0 [2.0-4.3]) as independent prognostic factors (all p<10-4). We designed a simple prognostic score attributing 1 and 2 points for intermediate and poor risk cytogenetics, resp, and 1 point for each other adverse prognostic factor. As a continuous variable, an increasing score was associated to poorer OS (HR=1.9 [1.6-2.1], p<10-4). Patients were grouped as “low risk” (score=0), intermediate risk (score=1-3) and high risk (score=4-5). Due to missing values, a prognostic group could be attributed to 269 of the 282 pts: 30 (11%), 191 (71%), and 48 (18%) pts were considered low, intermediate and high risk resp. With a median follow-up of 26 months, median OS were not reached, 15.0 and 6.1 months in patients with low, intermediate, and high risk score respectively (p<10-4). The validation cohort included 175 pts of the AZA-001 trial with higher-risk MDS. Apart from the presence of 5 (3%) int-1 pts in AZA-001 cohort (their removal did not affect conclusions), IPSS (int-2 in 42% high in 46%, at least int-2 in 9% vs 54%, 43%, 2% resp., p=0.15) was comparable to the ATU cohort, as well as RBC transfusion dependence ≥4 units/8 weeks (46 vs 45%, p=0.8), presence of circulating blasts (51 vs 45%, p=0.4), whereas all AZA-001 pts were de novo (vs 74% in the ATU cohort), had not been pretreated (vs 10% pretreated by LD AraC in the ATU cohort), had better PS (7% PS ≥2 vs 21% in the ATU cohort, p<10-4) and better cytogenetics (47%, 21% and 27% 5%, good, int, poor, unknown cytogenetics vs 31%, 17%, 47%, 5% resp., p<10-4). The score was validated as a continuous variable on OS (HR=1.4 [1.2-1.7], p=0.0005). Due to missing values, a prognostic group could be attributed to 166 (95%) of pts of the AZA 001 cohort: 27 (16%), 123 (74%), and 16 (10%) pts were classified in the low, intermediate and high risk respectively. Median follow-up was 21 months. Median OS were not reached, 21.4 and 14.3 months respectively in patients with low, intermediate, and high risk score (p=0.004). Conclusion: Our compassionate cohort scoring system based on conventional prognostic factors (ECOG PS, RBC transfusion requirement, circulating blasts and karyotype) was prognostic for survival. Additionally, it was successfully validated in a more selected cohort of higher-risk MDS from a prospective multicenter trial. Prognostic factors of outcome with AZA based on more refined biological studies (including gene methylation status) will probably emerge. In particular, we found in a more recent patient cohort (Itzykson, abstract also submitted to ASH 2010), that TET2 mutations may predict better response to AZA in higher risk MDS. Disclosures: Beach: Celgene: Employment. Fenaux:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding.

Download Full-text

Effects of Multiple Myeloma (MM) Therapy and Type of Thromboprophylaxis On the Incidence and Timing of Venous Thromboembolism (VTE) and Factors Predictive of VTE.

Blood ◽

10.1182/blood.v120.21.2244.2244 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2244-2244

Author(s):

Jatin J. Shah ◽

Aparna Hegde ◽

Xiao Zhou ◽

Sheeba K. Thomas ◽

Michael Wang ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Cancer Center ◽

Hematopoietic Stem ◽

Vein Thrombosis ◽

Increased Risk ◽

Multivariate Proportional Hazard ◽

The Impact

Abstract Abstract 2244 Background: Patients (pts) with MM are at increased risk for VTE due to various risk factors related to the host, disease, and treatment. Immunomodulatory drugs (IMiDs) such as thalidomide and lenalidomide have further increased the risk of VTE. Several studies have shown the VTE risk can be reduced with the use of low molecular weight heparin (LMWH) or aspirin thromboprophylaxis. Based on these findings, VTE thromboprophylaxis has been recommended in pts receiving IMiDs + Dexamethasone (Dex), but the impact of these guidelines on patient outcomes in clinical practice is unclear. The objective of this observational study was to evaluate the incidence, timing and risk factors of VTE and the impact of different types of thromboprophylaxis on the incidence of VTE. Methods: This was a retrospective cohort study, and included all MM pts newly referred to the M.D. Anderson Cancer Center in 2006. Medical records of these pts were reviewed for the type and site of VTE, the incidence and timing of VTE during the five-year period from the referral date, and the risk factors, including pt demographics, co-morbidities, baseline laboratory values, types of MM and treatment, and types of thromboprophylaxis. Univariate and multivariate proportional hazard models were fitted to find the independent risk factors predictive of VTE. The stepwise selection method was employed to build a multivariate model using variables with p<0.15 in univariate analysis. Results: The cumulative incidence of VTE was 24% (38/159 pts) during the 5-year follow up period. Of the 38 pts with VTE, 25 (66%) had deep vein thrombosis (DVT), 11 (29%) had pulmonary embolus (PE), and 2 had concurrent DVT and PE. Most of the pts (32/38, 84%) had VTE within 1 year from the referral date. The incidence of recurrent VTE among these pts was 27.5% (11/38 pts), for a total of 52 episodes. Since the majority of VTEs and recurrences were within one year, we examined the risk factors for VTE during this period. Treatment with IMiDs + Dex and thromboprophylaxis with LMWH or Coumadin were independent predictive factors as shown below. The incidence of VTE was highest in pts exposed to IMiDs + Dex (30/38 pts), even after discontinuation of treatment, with most episodes (17/30) occurring during the preparation (7/30) or within 30 days (10/30) following hematopoietic stem cell transplantation (HSCT), when most (16/17) pts were not receiving anti-coagulants. Conclusions: These findings suggest that patients treated with IMiDs + Dex are at high risk for VTE, even after discontinuation of this treatment, especially, during and after the HSCT period. Future studies are needed to investigate VTE prevention strategies for this high-risk pt population. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Multiple Myeloma In Patients Under 40 Years Old Is Associated With High-Risk Features and Worse Outcomes

Blood ◽

10.1182/blood.v122.21.5359.5359 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5359-5359 ◽

Cited By ~ 7

Author(s):

Caitlin L. Costello

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

High Risk ◽

Conflicts Of Interest ◽

Young Patients ◽

Age At Diagnosis ◽

Cancer Center ◽

Common Disease ◽

High Dose

Background The median age of patients diagnosed with multiple myeloma (MM) is approximately 70 years old. It is an uncommon malignancy in persons younger than 40 years, representing only 2% of all patients diagnosed with MM. It has been suggested that young patients may present with more aggressive and less common disease features, frequently delaying the initial diagnosis and thereby affecting outcomes. With this background, we explored the outcome of young MM patients presenting to our institution over the past thirteen years. Methods We performed a retrospective review of a cohort of 236 patients with MM who received treatment for active MM at the University of California, San Diego Moores Cancer Center between January 2000 and July 2013. The demographics and disease features of patients up to 40 years of age at diagnosis were analyzed using descriptive statistics. The survival outcomes of these young patients were compared with the remainder of the cohort using the Kaplan-Meier method. Results Nineteen (6.5%) out of the 236 patients with MM were ²40 years of age at diagnosis, with a median age of 35.5 years old. The median follow-up of this group of young patients was 42 months (range 5-92). The patient and disease characteristics are outlined in Table 1. Seven young patients (37%) had MM with no heavy chain component, including light chain only secreting or non-secretory disease. Seven patients (37%) had a non-IgG paraprotein. Nine (56%) patients presented with extramedullary plasmacytomas. Two (10%) patients had plasma cell leukemia. All patients received at least one treatment regimen that included a novel agent. Fifteen patients (79%) had received high-dose therapy, and four patients (21%) underwent allogeneic stem cell transplantation (SCT) after at least one prior autologous SCT. The 5-year and 7-year overall survival (OS) from diagnosis was 51.7% and 28%, respectively, and the median OS was 60.7 months. In contrast, the median OS of patients ≥41 years old at diagnosis was 78.6 months (p=0.15, figure 1). Conclusion In this single center study with long follow up, we demonstrate that patients diagnosed with MM ²40 years of age exhibit several high-risk features and frequently present with advanced stage disease. Despite the use of novel agents in this population, there is a statistical trend towards a worse outcome with an 18-month difference in median overall survival when compared to older patients with MM. More aggressive treatment strategies are needed to improve survival in this young patient population. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Relapses of Diffuse Large B Cell Lymphoma in Rituximab Era Are Limited to the First Two Years after Frontline Therapy

Blood ◽

10.1182/blood.v124.21.1307.1307 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1307-1307 ◽

Cited By ~ 1

Author(s):

Tatyana Feldman ◽

Larysa Gromko ◽

Ewelina A Protomastro ◽

Lina Starovoitova ◽

Anthony R. Mato ◽

...

Keyword(s):

De Novo ◽

Conflicts Of Interest ◽

Cohort Analysis ◽

Community Setting ◽

B Cell Lymphoma ◽

Cancer Center ◽

Cell Transplant ◽

Ki 67 ◽

Frontline Therapy

Abstract Background: Rituximab has increased the CR rate, improved both PFS and OS and changed the pattern of relapse of DLBCL pts treated with R-CHOP (leading to a > 50% cure). In contrast to the pre rituximab era, the majority of failures occur early (80% of failures occur in the 1st 18 months). The observation made that few relapses (7-8%) occur after 24 months of pts enrolled in clinical trials needs validation in the community setting. We report here a large cohort of pts treated at our institution over a period of 7 years with rituximab-containing chemotherapy regimens. Methods:We performed a retrospective cohort analysis to describe the survival experiences of adult patients with de novo DLBCL treated at our institution between 2007 and 2013. Patients were identified using Hematopathology and John Theurer Cancer Center outcomes databases. Patients who didn’t receive rituximab as part of their initial combination chemotherapy were excluded, as well as transformed DLBCL, primary CNS DLBCL, HIV-related DLBCL pts, those lacking follow up data. Results: A total of 245 patients with DLBCL treated at our institution were identified. Baseline characteristics were as follows: median age was 63 (20-92), 53% males, 75% stage III-IV and 24% stage I-II; IPI score was high in 25% of pts, high-int in 22%, low-int in 45% and low in 7%. Most patients received R-CHOP (66%), while 34% were treated with dose intense regimens based on high risk features such as high IPI, Ki-67 over 80% (R-HyperCVAD, DA-R-EPOCH, R-Magrath), only two patients had frontline planned stem cell transplant. 91% of the patients achieved a CR, 7% were primary refractory (progressed during therapy), 2% PR/SD ). With a median follow up time of 32.5 months, the median OS and PFS have not been reached (75% of patients are alive at 55.9 months). In contrast, the median OS of relapsed patients was only 14.4 months No gender-specific differences in survival were observed. No differences in PFS and OS were observed based on frontline chemotherapy regimen. Achieving CR significantly determines survival (p.<05, LR test). Relapses occurred within first 24 months in 54 out of total of 60 patients who relapsed after frontline therapy. Conclusion: Our series confirm outside clinical trial setting that in contrast to the pre-rituximab era, late relapses are rarely observed in patients treated with rituximab–containing induction therapy. The majority of relapses occur within the first two years of the initial therapy. Our findings validate the data from the Mayo clinic experience (Maurer et al, JCO 2014). This observation not only provides reassurance to patients but also support the current imaging guidelines with no longer a need for routine imaging surveillance for relapse in DLBCL beyond 2 years after frontline therapy. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Impact Of Revised-International Prognostic Scoring System (R-IPSS) Cytogenetic-Risk Stratification In Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v122.21.5234.5234 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5234-5234

Author(s):

Maria Otazo ◽

Sarvari Venkata Yellapragada ◽

Matthew Zheng ◽

Ang Li ◽

Ruben Hernandez Perez ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Risk Stratification ◽

Median Survival ◽

Predictive Power ◽

Conflicts Of Interest ◽

Biological Behavior ◽

The Impact ◽

Very High ◽

Risk Categories

Abstract Background MDS encompasses a heterogeneous group of clonal marrow disorders resulting in various degree of ineffective hematopoiesis and risk of Acute Myelogenous (AML) transformation. Intuitively, the original IPSS (4-categories) lacked predictive power to dissect subgroups with more aggressive biological behavior suitable for MDS disease modifying strategies. The new coalesced R-IPPS discriminates biological subgroups and enhances predictive power based on redefined cytogenetic [5-categories-very good: -Y, del(11q); Good: e.g., normal karyotype, del(5q), del (20q); intermediate: e.g., +8,+19, del(7q); poor: e.g., -7 inv 3/del(3q), complex 3 abnormalities (abn); very poor: complex > 3 abn], depth of cytopenias and revised blast count subcategories at disease initiation, therefore allows more precise risk adapted intervention. Here, we aimed at validating the impact of cytogenetic subcategories on survival and initiated exploration of applicability of R-IPSS in our cohort of veterans diagnosed with MDS. This strategy allowed gaining insight into intrinsic disease characteristics and survival of our population. Methods From 2000-2012, 124 patients (pts) with confirmed diagnosis MDS were identified from the Michael E. Medical Center Cancer Registry. Long rank test was used to compare median Overall Survival (OS) in all generated cytogenetic and R-IPSS subgroups. Given the known effect of patient age on survival, all scored pts had survival age- adjusted using previously described formula (Greenberg. Blood. 2012). Results Among pts studied, median age was 72 years (range, 53-91). With a median survival for the all cohort of MDS pts of 17.6 months (mo), the 3-years overall survival (OS) was 55%. In our cohort, cytogenetic classification revealed discriminative parameter from variables contained in R-IPSS with OS for very good of 32 mo (N= 10 [9.4%]), good of 26.2 mo (N=64 [59.8 %]), intermediate of 16.8 mo (N=10 [12.8%]), poor of 12.1 mo (N=14 [16.7%]) and very poor of 4.2 mo (N=9 [7%]) (P=0.5; P=0.11; P= 0.13,P =0.08; P=0.02, respectively) (Fig.1). R-IPSS was calculated as reported. Median OS for patients in low, very low, intermediate, high and very high-risk categories were 34, 35.5, 14.5, 15, 7.8 mo, respectively (Fig.2). Age adjusted median survival estimation allowed more robust discrimination of survival with median survival of 35.5 months (mo) (P=0.8; HR=1), 18.2 mo (P=0.49; HR=1.9), 15 mo (P=0.008; HR=2.1) and 8.5mo (P=0.00; HR=4.1) for low, intermediate, high and very high-risk subgroups (Fig.3). No statistical significance difference in survival was observed between very low and low risk categories. Conclusions Our results validate the predictive value of the newly developed cytogenetic risk stratification groups contained in R-IPSS. For cytogenetic risks, clinical trends were observed across very low, low, intermediate and poor risk with significant different survival seen between poor and very poor cytogenetic groups. When taking in consideration all variables included in R-IPSS, a more precise discrimination of biological subgroups was observed after cohort age-adjustment. Larger pts samples are needed to refine difference in survival between very low and low categories. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Role of long-term continuous cardiac monitoring in oral anticoagulation management of patients with known atrial fibrillation

EP Europace ◽

10.1093/europace/euab116.270 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

A Natale ◽

SE Kasner ◽

HC Diener ◽

A Verma ◽

A Amin ◽

...

Keyword(s):

Atrial Fibrillation ◽

High Risk ◽

Risk Score ◽

Oral Anticoagulation ◽

Individual Risk ◽

Private Company ◽

Atrial Ablation ◽

History Of ◽

The Impact

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic OnBehalf Reveal LINQ Registry Investigators Background Monitoring atrial fibrillation (AF) with an insertable cardiac monitor (ICM) provides objective data for clinicians to make decisions on oral anticoagulation (OAC) management, based on individual risk profiles. Whether ICM data is being used for that purpose has not been widely explored. Purpose To show the impact of AF burden measured by an ICM on OAC treatment initiation and discontinuation in patients with known AF. Methods Patients from the prospective, ongoing, multi-center Reveal LINQ Registry monitored for AF management, or pre- or post-ablation monitoring were eligible. Follow-up was scheduled every 6 months for up to 3 years. Patients were excluded if they had no AF data available within the last 6 months of follow-up (FU), or less than 6 months of FU and no change to their OAC treatment compared to baseline. AF burden was defined as the percentage of time in AF 6 months prior to last FU, excluding the first 3 months post-ablation for patients who had an ablation. Results The analysis included 225 patients (65 ± 10 years, 72% male, mean CHA2DS2-VASc score 2.1 ± 1.4) monitored with an ICM for 21.8 ± 7.9 months. At baseline, 164 (73%) were taking OAC therapy, 147 (65%) had a history of paroxysmal AF and 79 (35%) had persistent AF. Forty percent of patients had a history of atrial ablation prior to ICM insertion and 37% had ≥1 AF ablation procedure after ICM. Patients were grouped according to OAC status at baseline, CHA2DS2-VASc score and AF burden (Figure: bars show percentage of patients with a change in OAC status during monitoring). Patients at high risk of stroke and AF burden >0.5% were more likely to initiate OAC therapy, whereas patients with higher AF burden were less likely to discontinue OAC, regardless of their risk score. Among those with no AF burden detected during the last 6 months of follow-up and on OAC at baseline, approximately half discontinued OAC, whereas 1/3 of patients with high risk score had initiated OAC, despite having no AF detected. Conclusion Our results derived from real-world practice show that AF detected and quantified by an ICM influences OAC therapy management in patients with known AF. Many patients with a low CHA2DS2-VASc score and no AF or low AF burden have had OAC therapy discontinuation, whereas a high proportion of patients with high AF burden have initiated OAC, regardless of their risk score. Abstract Figure. OAC according to risk and AF burden

Download Full-text

Partnering for Success: Expanding Breast and Cancer Screening in Rural Honduras One Clinic at a Time

Journal of Global Oncology ◽

10.1200/jgo.2016.003848 ◽

2016 ◽

Vol 2 (3_suppl) ◽

pp. 24s-25s

Author(s):

Derek S. Stenquist ◽

Suyapa Bejarano ◽

Linda S. Kennedy ◽

Silvia Portillo ◽

Ana Barrientos ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

High Risk ◽

Rural Communities ◽

Cervical Cancer Screening ◽

Conflicts Of Interest ◽

Cancer Education ◽

Cancer Center ◽

Breast And Cervical Cancer

Abstract 36 Background: Women in rural Honduras have limited access to cancer education, screening, and care. With village leaders, we piloted breast and cervical cancer screening in El Rosario, Honduras. Our objectives were to improve awareness and access, mitigate barriers, connect community and Honduran providers, and link patients with abnormal findings to cancer treatment. In 2013, health professionals and staff from Norris Cotton Cancer Center at Dartmouth- Hitchcock joined Honduran clinicians and medical students from La Liga Contra el Cáncer for two days of rural cancer screening. Peer educators taught 475 participants from 31 rural communities how to conduct self-breast exams. Of these participants, 238 chose clinical breast exams; 5% were clinically abnormal and 2.9% were referred for services at La Liga with 100% compliance. 34% reported barriers to cervical cancer screening due to distance and lack of transportation. 14.5% tested positive for HPV and 8% were positive for high risk HPV genotypes including 11 of 13 known high risk types. This group has been retested periodically by Pap. The collaborators will return in April 2016 to repeat the study, adding oral and thyroid screening. Genotyping for hrHPV will be onsite with a novel assay for PCR developed at Dartmouth-Hitchcock. Reflex testing with Pap will follow as needed. Follow up will be at La Liga where care is offered for free or at a reduced cost. A similar project for 400 urban factory-workers will also take place in April 2016. Methods: 2-day, multi-modal education and screening outreach run brigade-style combining low-tech primary screening with onsite molecular pathology. Conclusions: Partnerships between local leaders and clinicians are predicted to be essential to project implementation. Targeting populations with education and screening plus building connections to follow up care will provide earlier detection of breast and cervical cancer. We predict that community leadership will be critical to preventing loss to follow-up. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Derek S. Stenquist No relationship to disclose Suyapa Bejarano No relationship to disclose Linda S. Kennedy No relationship to disclose Silvia Portillo No relationship to disclose Ana Barrientos No relationship to disclose Suzanne P. Burgos No relationship to disclose Roberto Armando Elvir Zelaya No relationship to disclose Christine Averill No relationship to disclose Emmeline Liu No relationship to disclose Francine de Abreau No relationship to disclose Paul Burchard No relationship to disclose Torrey Gallagher No relationship to disclose Martha Goodrich No relationship to disclose Scottie Eliassen No relationship to disclose Julie Weiss No relationship to disclose Camilo Mandujano No relationship to disclose Jennifer Alford-Teaster No relationship to disclose Gregory J. Tsongalis Research Funding: Illumina, Qiagen, Thermofisher Tracy Onega No relationship to disclose Mary D. Chamberlin No relationship to disclose

Download Full-text

Community-based aftercare following an emergency department presentation for attempted suicide or high risk for suicide: study protocol for a non-randomised controlled trial

BMC Public Health ◽

10.1186/s12889-019-7751-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Vida V. Bliokas ◽

Alex R. Hains ◽

Jonathan A. Allan ◽

Luise Lago ◽

Rebecca Sng

Keyword(s):

Emergency Department ◽

High Risk ◽

Suicide Attempt ◽

Repeated Measures ◽

Hospital Emergency Department ◽

Hospital Emergency ◽

Community Based ◽

Treatment As Usual ◽

The Impact

Abstract Background Suicide is a major public health issue worldwide. Those who have made a recent suicide attempt are at high risk for dying by suicide in the future, particularly during the period immediately following departure from a hospital emergency department. As such the transition from hospital-based care to the community is an important area of focus in the attempt to reduce suicide rates. There is a need for evaluation studies to test the effectiveness of interventions directed to this stage (termed ‘aftercare’ interventions). Methods A controlled non-randomised two group (intervention vs treatment-as-usual control) design, using an intention-to-treat model, will evaluate the effectiveness of a suicide prevention aftercare intervention providing follow-up after presentations to a hospital emergency department as a result of a suicide attempt or high risk for suicide. The intervention is a community-based service, utilising two meetings with a mental health clinician and follow-up contacts by peer workers via a combination of face-to-face and telephone for four weeks, with the option of extension to 12 weeks. Seventy-five participants of the intervention service will be recruited to the study and compared to 1265 treatment-as-usual controls. The primary hypotheses are that over 12 months, those who participate in the aftercare follow-up intervention are less likely than controls to present to a hospital emergency department for a repeat suicide attempt or because of high risk for suicide, will have fewer re-presentations during this period and will have lower all-cause mortality. As a secondary aim, the impact of the intervention on suicide risk factors for those who participate in the service will be evaluated using pre- and post-intervention repeated measures of depression, anxiety, stress, hopelessness, belongingness, burdensomeness, and psychological distress. Enrolments into the study commenced on 1 November 2017 and are anticipated to cease in November 2019. Discussion The study aims to contribute to the understanding of effective interventions for individuals who have presented to a hospital emergency department as a result of a suicide attempt or at high risk for suicide and provide evidence in relation to interventions that incorporate peer-workers. Trial registration ACTRN12618001701213. Registered on 16 October 2018. Retrospectively registered.

Download Full-text