Increasing The Dose Of AraC In Consolidation Therapy Does Not Lead To Higher Overall Survival Or Improved Relapse Incidence In Patients With AML Over The Age Of 60 Years

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2645-2645
Author(s):  
Dietger Niederwieser ◽  
Rainer Krahl ◽  
Christian Jakob ◽  
Thomas Heinicke ◽  
Christoph Kahl ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Research Funding ◽  
Cox Regression ◽  
De Novo ◽  
Patient Characteristics ◽  
Consolidation Therapy ◽  
Consolidation Chemotherapy ◽  
De Novo Aml ◽  
Wbc Count

Abstract The optimal consolidation chemotherapy in AML patients >60 years has yet to be defined in detail. Although age-adjusted induction chemotherapy results in CR rates comparable to those in younger patients, relapse remains the major hurdle to successful treatment. While the role of stem cell transplantation (HSCT) in elderly patients is currently being evaluated in randomized studies, we focus here on the intensity of consolidation chemotherapy. Patients data from the elderly AML trials OSHO 1997 (n=410) and OSHO 2004 (n=733) were pooled and analyzed. These protocols have identical inclusion/exclusion criteria and induction chemotherapy, but differ in the intensity of consolidation therapy. In the OSHO 1997 trial, Ara-C 120 mg/m2 bid was given from day 1-5 and mitoxantrone 10 mg/m2 from day 1-2 as consolidation. In the OSHO 2004 an intensified consolidation using Ara-C 500 mg/m2 bid on day 1/3/5 was applied together with mitoxantrone as used in the OSHO 1997 study. Of the 1143 patients, 689 entered CR (60% in the OSHO 1997 and 61% in the OSHO 2004) and 536 (OSHO 1997, n=242, OSHO 2004, n=294) did not receive HSCT as consolidation. The analysis concentrated on the dose of AraC used in the consolidation for this elderly population and on the cycles of consolidation applied. Patient characteristics were compared using chi-square test for categorical data and Wilcoxon rank sum test for continuous data. OS was analyzed using the Kaplan-Meier method, and univariate comparisons were made by means of the log-rank test. Cox regression was used to find any association between consolidation chemotherapy considered as a time-dependent covariate on Overall Survival (OS) or Relapse Incidence (RI). RI and Non Relapse Mortality (NRM) were calculated using the competing risk method, and the Gray test was applied to compare differences. Multivariate modeling was performed by Cox regression analyses with a forward selection method. Median ages in the AML studies were 66 (60-81) years and 69 (60-85) years for the OSHO 1997 and OSHO 2004, respectively. Patients characteristics were balanced except for age and Karnofsky score (p< .0005) and a trend towards more intermediate and high risk karyotypes, more female and less WBC in the OSHO 2004 compared to the OSHO 1997 study (p=0.06). OS at 15 years was 14±2% in all patients with no difference between the two consolidations, but strong dependence on cytogenetic risk factors. In multivariate analyses risk factors for survival were high/intermediate risk karyotypes, male gender, non de-novo AML and less than two consolidations. Patients with two consolidations had better OS than patients with one or no consolidations in the pooled group and in each of the two protocols with no difference between OSHO 1997 and OSHO 2004. Relapse incidence amounted to 79±2% and NRM 10±04% at 15 years with no difference between the two protocols. Relapse incidence was dependent upon cytogenetic risk and the number of consolidations applied in a multivariate model. There were no risk factors predicting TRM in multivariate analysis. Our analysis of patient characteristics according to the number of consolidations showed the distribution of consolidation therapies to be 15.2%, 28.0%, 56.6% and 14.2%, 32.3% and 53.4% for 0, 1 and 2 consolidations in the OSHO 1997 and OSHO 2004 respectively (n.s.). Higher age, higher risk cytogenetics, non-de novo AML type, less CR after one induction cycle and lower WBC count at diagnosis were characteristic of patients receiving none or one as compared to two consolidation therapies. The multivariate analysis revealed cytogenetics and gender as independent risk factors, but not the application of one as opposed to two consolidation treatments. The increase of AraC dose in the OSHO 2004 was unable to either increase survival or improve relapse incidence in the cohort of elderly patients. TRM was not different between the OSHO 1997 and 2004 studies. However, the application of one or two consolidation cycles had a significant impact on survival that was not due to decreased relapse incidence after normalization for risk factors. Interestingly, just above 50% of patients received 2 consolidations as proposed in the protocol with no statistically significant difference between OSHO 1997 and OSHO 2004. Patients receiving fewer consolidation therapy cycles are older, have more non-de novo AML and lower WBC count. Disclosures: Hochhaus: Novartis: Consultancy, Honoraria, Research Funding, Travel Other; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Ariad: Consultancy, Honoraria.

Outcome of Patients with Acute Myeloid Leukemia Treated with Salvage High-Dose Cytarabine Monotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2543-2543
Author(s):  
Jonathan Canaani ◽  
Marlise R. Luskin ◽  
Alison Loren ◽  
Colleen Timlin ◽  
James Mangan ◽  
...  
Keyword(s):  
Research Funding ◽  
De Novo ◽  
Residual Disease ◽  
Single Agent ◽  
Patient Characteristics ◽  
High Dose ◽  
Refractory Disease ◽  
De Novo Aml ◽  
Wbc Count ◽  
Active Disease

Abstract Introduction Cytarabine in high doses (> 1 g/m2) is commonly combined with other cytotoxic chemotherapy agents to treat acute myeloid leukemia (AML) in the initial and salvage settings. Single-agent high dose cytarabine (HiDAC) is traditionally reserved for consolidation therapy for patients in remission. At our institution we also use single agent HiDAC to treat patients with active disease. We reviewed our experience to assess the outcomes. Methods We identified patients (pts) with AML diagnosed from 2009-2014 and treated at the Hospital of The University of Pennsylvania with anthracycline plus infusional cytarabine induction (7+3) who received subsequent single agent HiDAC for active disease. Pts included were those with evidence of residual leukemia on nadir biopsy after one cycle of therapy or those with refractory disease (positive nadir after 2 cycles of therapy or disease at the time of or within 30 days of count recovery). Comparisons of categorical covariates by subgroup were evaluated using the Fisher's exact test. Patients In total, 44 pts with median age of 54 (range 23-69) years were identified. Twenty-five (56%) pts had de novo AML, and 19 (43%) had AML secondary to prior myelodysplasia (MDS) or a myeloproliferative neoplasm (MPN). Twenty-two pts (50%) had unfavorable cytogenetics, 8 (18%) were FLT3 -ITD positive, and 4 (9%) were NPM1 mutant (Table 1). Indications for HiDAC salvage included positive nadir marrow or frankly progressive disease at day 14 of 1 (n=28) or refractory disease (n=16) Outcome Six pts (14%) died during index hospital admission for HiDAC therapy (5 from sepsis, 1 from multi-organ failure). Twelve (27%) pts achieved CR following HiDAC salvage and 4 (9%) achieved CRp. Pts with de novo AML were more likely to achieve a CR/CRp (11/24; 46%) compared to those with secondary AML (antecedent myeloid disorder or prior chemotherapy/radiation therapy) (5/20, 25%; p=0.037). CR/CRp rates were higher for pts with a white blood cell (WBC) count ≤10K/µL at initial diagnosis (50% vs. 20%; p=0.039). Pts treated for residual disease at first nadir were more likely to respond to HiDAC (n=13/28, 46%) than pts treated for refractory disease (3/16, 19%; p=0.104). Cytogenetic risk, age, presence of extramedullary disease, and FLT3 -ITD/NPM1 mutation status were not associated with response in this small sample (Table 2). No features predicted early mortality. Conclusion Our data suggest that pts with AML who received HiDAC therapy for active disease after 1-2 cycles of anthracycline plus infusional cytarabine induction have CR rates of 36% with single agent HiDAC with a 14% rate of early mortality. De-novo disease, initial WBC count < 10K/µL and treatment for residual disease at first nadir predict for a better response. Pts presenting with refractory disease are less likely to respond to this approach, consistent with previously published data with HiDAC combination regimens. HiDAC monotherapy for persistent AML following initial induction is a reasonable therapeutic option. Figure 1. Patient Characteristics Figure 1. Patient Characteristics Figure 2. Response to HiDAC monotherapy Figure 2. Response to HiDAC monotherapy Disclosures Loren: Merck: Research Funding. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Frey:Novartis: Research Funding. Porter:Novartis: Patents & Royalties, Research Funding.

Changes in the Hierarchy of Risk Factors with Older Age in De-Novo Acute Myeloid Leukemia (AML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1977-1977
Author(s):  
Thomas Buchner ◽  
Wolfgang E. Berdel ◽  
Claudia Schoch ◽  
Torsten Haferlach ◽  
Hubert L. Serve ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Complete Remission ◽  
De Novo ◽  
Older Age ◽  
High Dose ◽  
Age Group ◽  
Risk Profiles ◽  
Age Related ◽  
De Novo Aml

Abstract After recent reports addressed prognostic factors and outcome in older age AML (Burnett et al. Blood106:162a,2005; Wheatley et al. Blood106:199a,2005; Appelbaum et al. Blood107:3481–5,2006; Farag et al. Blood108:63–73,2006) we evaluated 764 patients of 60–85 (median 66) years reduced to those with de-novo AML, known karyotype, and identical consolidation-maintenance chemotherapy, who were part of the 1992 and 1999 multicenter randomized trials by the German AMLCG (Buchner et al. J Clin Oncol21:4496–504,2003;24:2480–9,2006). 521 patients were 60 -< 70 (median 64) and 243 patients were 70–85 (median 73) years of age. 64% and 50% patients respectively went into complete remission, 24% and 29% remained with persistent AML, 12% and 21% succumbed to early and hypoplastic death (p<.001). The overall survival in the younger (60- < 70y) and older (70+) patients was at a median of 13 vs 6 months and 18% vs 8% survived at 5 years (p<.001). Once in complete remission, the remission duration was 14 vs 12 months (median) and equally 18% at 5 years; the relapse-free survival is 13 vs 11 months (median) and 14% vs 13% at 5 years. While all patients were randomized up-front for 2 versions of induction either by TAD-HAM (HAM, high-dose araC 1g/m2x6 and mitox 10mg/m2x3) or by HAM-HAM, response and survival did not differ between the two arms in neither age group. In contrast to response and survival between the younger (60-<70y) and older (70+y) age group corresponding differences in the risk profiles were missing. Thus, favorable/intermediate/unfavorable karyotypes accounted for 8% vs 4% / 67% vs 73% / and 25% vs 24% of patients (p=.073); WBC > 20.000/ccm was found in 40% vs 39% (p=.52); LDH > 700U/L was remarkably 26% vs 18% (p=.014), and the day 16 b.m. blasts ≥ 10% accounted for 41% and 41% of patients. Conclusion: Approximately 50% of patients 70 years of age or older benefit from standard or intensive chemotherapy by complete remission which continues after 1 year in about 50% of responders. The inferior overall survival in the patients of 70+ versus those of 60- < 70 years is mainly explained by more frequent early and hypoplastic death (21% vs 12%) (p=.0016) and death with persistent AML (26% vs 18%) (p=.0145); while death in remission (7% vs 6%), relapse rate (50% vs 53%) and death after relapse (21% vs 26%) did not show this trend. In contrast to the important differences in outcome, established risk factors such as cytogenetic groups, WBC, and early blast clearance show concordance between the two age groups. The even lower LDH may support assumptions of older age AML as a less proliferative disease (Appelbaum et al. Blood 107:3481–5,2006). Thus, the hierarchical risk profiles cannot predict the age related outcome beyond 60 years in patients with de-novo AML.

Efficacy of Single-Agent Decitabine in Relapsed and Primary Refractory (rel/ref) Acute Myeloid Leukemia (AML)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2518-2518
Author(s):  
Andrew Hantel ◽  
Niloufer Khan ◽  
Richard A. Larson ◽  
Lucy A. Godley ◽  
Michael J. Thirman ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Genetic Risk ◽  
Research Funding ◽  
De Novo ◽  
Median Number ◽  
Advisory Committees ◽  
Secondary Aml ◽  
Induction Regimen ◽  
De Novo Aml ◽  
Wbc Count

Abstract Introduction Improving therapy for rel/ref AML remains a challenge. Decitabine, a DNA methyl-transferase inhibitor, initially showed promise in AML as a 5-day, first-line induction regimen and more recently as a 10-day regimen in older and unfit patients (1). However, little is known about the activity of decitabine in the rel/ref patient population despite increased use. Therefore, we sought to analyze the outcomes of these pts treated at our institution. Methods To obtain data regarding decitabine efficacy in rel/ref AML, we performed a retrospective analysis of outcomes following decitabine treatment in 34 adult pts treated at The University of Chicago from January 2009 to June 2014. Permission to access patient charts was granted by the medical centerÕs Institutional Review Board. AML was defined by WHO criteria, genetic risk grouping and complete remission (CR) was according to ELN classification; PR was defined as >50% decrease in bone marrow blasts and normalization of blood counts. Rel/ref AML was defined as either having had a prior CR with recurrence of disease or having received a prior induction regimen (1-2 cycles) without CR. Results Median pt age was 62 yrs (range, 18-81) and 60% were male. Median Charlson comorbidity index (CCI) was 5 (range, 0-8); 29% had ECOG performance status 0-1 and 71% had >2. 21 pts (62%) had de novo AML (7 with myelodysplasia-related changes), 3 (9%) had therapy-related myeloid neoplasm (t-MN), and 10 (29%) had secondary AML after myelodysplastic syndrome. 6% were in the ELN favorable genetic group, 3% intermediate-I, 18% intermediate-II, and 67% adverse; 2 cases were unevaluable. The median number of prior treatment regimens was three. 9% had received prior azacitidine, 85% had received prior HiDAC, and 38% had a prior allogeneic stem cell transplant (SCT). 34 pts received a total of 71 cycles of decitabine, 20 mg/m2 daily, in 5 or 10-day cycles every 28 days. All patients received 10-day courses, 91% had an initial 10-day course, and 74% had only 10-day courses. The median number of cycles per pt was 2; 59% received >1 cycle. 7 (21%) achieved CR and 4 (12%) had a partial response (PR), for an overall response rate (OR) of 33%. Responses occurred in 24% of pts with de novo AML, 66% with t-MN, and 50% with secondary AML. Intermediate and adverse group pts had OR of 14% and 39%, respectively. All pts achieving CR did so after 1 cycle; PR required a median of 3 cycles. Pts who achieved CR or PR had a significantly lower pretreatment WBC count (median, 9.5 vs 49.5 x 103/µL in non-responders; p=0.015) and blast percentage (44 vs 59.4; p=0.035) than those who did not. Pts with secondary AML or t-MN had a higher probability of OR compared to those with de novo AML (54 vs 23%; p=0.042). Median overall survival (OS) of all pts was 256 days; prior SCT was associated with reduced OS (p=0.017). When comparing de novo to secondary AML & t-MN, 1-year OS was not significantly different (Figure 1). Responders had a significantly longer OS (median, 622 days vs 278 days for non-responders; p=0.012). Age, race, CCI, ECOG PS, genetic risk group, prior HiDAC, dysplasia, azacitidine, and number of prior treatments did not impact OR or OS. 16 (47%) pts proceeded to SCT. During treatment, 70% had a grade 3-4 non-hematologic toxicity (based on NCI CTACE v4.0); the most common was fatigue. The median number of hospitalizations for complications per patient was 2 (range, 0-7). Causes of hospitalization were febrile neutropenia (40%), infection (22%), cytopenias (18%), rash (6%), acute kidney injury (6%), and 8% were for other causes. Conclusion Decitabine treatment of 34 adults with rel/ref AML resulted in an OR of 33% (21% CR) and allowed nearly one-half of these pts to proceed to SCT. All pts achieving CR did so after 1 cycle. Responding pts had improved OS over those without response (p=0.012). Interestingly, secondary AML or t-MN were 7.8 times more likely to achieve a response compared to de novo AML (p=0.046); lower WBC count and marrow blast percentage also correlated with higher OR. Further delineation of molecular subsets associated with response to decitabine should be evaluated in a larger prospective trial in this high-risk AML population. Citation 1. Blum KA, et al. Phase I trial of low dose decitabine targeting DNA hypermethylation in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: dose-limiting myelosuppression without evidence of DNA hypomethylation. Br J of Haem. Jul 2010;150(2):189-195. Figure 1. Figure 1. Disclosures Off Label Use: Decitabine is indicated for treatment of MDS but is often used to treat newly diagnosed or relapsed/refractory AML. In this study we analyzed results of patients with AML who were treated with decitabine in the relapsed/refractory setting.. Thirman:AbbVie: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Gilead: Research Funding; Merck: Research Funding; AbbVie: Research Funding; Gilead: Research Funding; Merck: Research Funding. Odenike:Sunesis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Liu:Astra Zeneca/Medimmune: Consultancy; Pfizer: Consultancy; Astra Zeneca/Medimmune: Consultancy; Pfizer: Consultancy. Stock:Gilead: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Selinexor in Combination with Induction and Consolidation Therapy in Older Adults with AML Is Highly Active

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1388-1388
Author(s):  
Timothy S. Pardee ◽  
Kris C Wood ◽  
Kevin H Lin ◽  
Justine Rutter ◽  
Mariaelena Pierobon ◽  
...  
Keyword(s):  
Older Adults ◽  
Nuclear Export ◽  
Research Funding ◽  
De Novo ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Blood Samples ◽  
Highly Active ◽  
De Novo Aml ◽  
Activation Mapping

Background: Acute myeloid leukemia (AML) is an aggressive myeloid cancer of the hematopoietic system that primarily affects older adults and is characterized by therapy resistance and dismal outcomes. Novel approaches to treat AML are desperately needed. Selinexor is a small-molecule inhibitor of the nuclear export protein XPO1. Treatment of AML cells with selinexor was shown to sensitize them to chemotherapy in part by blocking the nuclear export of topoisomerase II, resulting in increased DNA strand breaks when an anthracycline is present. Furthermore, selinexor has shown encouraging results when combined with chemotherapy in the relapsed setting. This abstract reports on the initial results of a randomized phase II study of induction and consolidation with or without selinexor in newly diagnosed patients with AML 60 years of age or older. Methods: Patients 60 years of age or older with newly diagnosed de novo AML were randomized between 7+3 or 7+3+selinexor induction. Responding patients could then go on to high dose cytarabine consolidation with or without selinexor as per their initial treatment assignment. Patients in the selinexor arm who completed all planned consolidation could then move to maintenance therapy with selinexor alone. During induction cytarabine was dosed at 100 mg/m2 by continuous infusion for 7 days and daunorubicin was dosed at 60 mg/m2 on days 1-3. In consolidation cytarabine was dosed at 1.5 gm/m2 given Q12 hours on days 1, 3 and 5. Selinexor was dosed at 60 mg PO on days 1, 3, 8, 10, 15 and 17 during induction and consolidation and on days 1 and 8 every 21 days in maintenance. Optional blood samples were collected just prior to and at several time points after selinexor during induction. Mononuclear cells were isolated from these samples, lysed and lysates evaluated for protein pathway drug target activation mapping by reverse phase phosphoprotein array (RPPA). Results: Thirteen patients have been enrolled to date with 12 available for evaluation. Of the 12 evaluable patients 6 were randomized to each arm. Baseline demographics are listed in Table 1. Overall the combination was well tolerated with no patients discontinuing selinexor secondary to treatment related adverse events. In the standard arm 3 of 6 patients achieved a complete remission. Of the 3 responders 1 has relapsed, 1 has gone on to transplant and one has completed consolidation chemotherapy. In the selinexor arm 5 of 6 patients achieved a complete remission and 1 patient achieved a morphologic leukemia free state. All patients given selinexor achieved a response. Of the 5 responders 3 have gone on to transplant, 1 is on maintenance therapy (completed 14 cycles) and one is completing consolidation therapy. In the standard arm no patients died during induction and 3 of 6 patients have died from progressive disease. In the selinexor arm 1 patient died during induction and none of the remaining patients have progressed (Figure 1 and Table 2). No difference in the AE profile was noted between arms and no unexpected side effects were observed. The patient on long term maintenance selinexor is tolerating it without significant AEs to date. Blood samples were available from 3 patients from the selinexor arm. RPPA based protein pathway activation mapping analysis of PBMCs revealed a significant increase in phosphorylation of AMPK, BAD and LC3B at one-hour post treatment that returned to baseline by 2 hours suggesting a transient increase in these pathways that was subsequently suppressed (Figure 2). Conclusions: Selinexor in combination with standard induction and consolidation therapy appears highly active in older de novo AML patients. Selinexor may increase response by modulation of AMPK, autophagy and BAD phosphorylation. Enrollment is ongoing. Disclosures Pardee: Spherix Intellectual Property: Research Funding; CBM Bipharma: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Pharmacyclics/Janssen: Speakers Bureau; Karyopharm: Research Funding; Rafael Pharmaceuticals: Consultancy, Research Funding. Manuel:Novartis: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. Powell:Pfizer: Consultancy, Research Funding; Rafael Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Janssen: Research Funding. OffLabel Disclosure: Selinexor is not approved for the treatment of AML

scholarly journals RDW Is a Prognostic Marker for Patients with Aggressive Peripheral T-Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5364-5364
Author(s):  
Brady E. Beltrán ◽  
Denisse A. Castro ◽  
Yesenia M. Huerta- Collado ◽  
Eduardo Sotomayor ◽  
Jorge J. Castillo
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Research Funding ◽  
Cox Regression ◽  
De Novo ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Curative Intent ◽  
The Impact

Abstract Introduction: Red blood cell distribution width (RDW) has emerged as a potential prognostic factor in solid tumors and lymphomas. Previous studies have shown an association between increased levels of RDW and inflammatory diseases, being a surrogate marker of inflammation and a predictor of poor outcome. Data on the impact of RDW in outcomes of patients with aggressive peripheral T-cell lymphoma (PTCL) are scarce. Methods: We performed a retrospective study on consecutive patients with a de novo diagnosis of aggressive PTCL diagnosed and treated at our institution between 2010 to 2016. All patients included were treated with chemotherapy with a curative intent. The RDW was collected from the hemogram of PTCL patients at diagnosis. RDW-CV >14% and RDW-SD >49 fL were our cut-offs for the categorical analysis. We fitted univariate and multivariate Cox proportional hazard regression models for overall survival (OS). P<0.05 were considered statistically significant. Results: A total of 101 patients with de novo aggressive PTCL were included. This study included 53 patients (52%) with PTCL, not otherwise specified, 16 patients (16%) with extranodal natural killer/T-cell lymphoma,15 (15%) with adult T-cell lymphoma/leukemia,14 patients (14%) with anaplastic large cell lymphoma, 2 patients (2%) with angioimmunoblastic T-cell lymphoma, and 1 patient (1%) with enteropathy-associated T-cell lymphoma. Median age was 57 with a male predominance (69%). Clinically, 45 patients (45%) were 60 years or older, 41 patients (34%) had ECOG ≥2, 63 patients (65%) had increased LDH levels, 68 patients (67%) had > 1 extranodal site, 65 patients (64%) had stage III/IV disease, and 55 patients (54%) had B symptoms. RDW-CV was >14% in 64 patients (64%). RDW-SD was >49 fL in 35 patients (35%). 38% of patients received CHOEP, 29% received CHOP, and 33% received other regimens. The overall response rate was 68%; 50% had a complete response and 18% had a partial response. At 5 years, median overall survival (OS) was 46%. In the univariate Cox regression analysis, ECOG ≥2 (p<0.001), high RDW-CV >14% (p<0.001), high RDW-SD >49 fL (p=0.007) and high neutrophil-lymphocyte ratio (NLR >4) (p=0.002) were associated with a worse survival. In the multivariate Cox regression analyses, ECOG ≥2 (HR 3.1 CI 1.6-6.0; p=0.001) and high RDW-CV >14% (HR 2.7, 95% CI 1.2-6.0; p=0.01) were independent predictors of poor survival. RDW-CV was an independent factor of survival when was compared with IPI and NCCN-IPI score. Conclusions: RDW is an independent marker for adverse prognosis in aggressive patients with aggressive PTCL treated with curative intent. Figure. Figure. Disclosures Castillo: Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Millennium: Research Funding.

scholarly journals Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2844
Author(s):  
Christopher J. D. Wallis ◽  
Bobby Shayegan ◽  
Scott C. Morgan ◽  
Robert J. Hamilton ◽  
Ilias Cagiannos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
De Novo ◽  
Population Based ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

scholarly journals Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3433-3433
Author(s):  
Caitlin Siebenaller ◽  
Madeline Waldron ◽  
Kelly Gaffney ◽  
Brian P. Hobbs ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Smoking Status ◽  
Consolidation Therapy ◽  
Peripheral Vascular ◽  
Consolidation Chemotherapy ◽  
Advisory Committees ◽  
History Of ◽  
Acute Myeloid

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Surgical Resection Significantly Promotes the Overall Survival of Patients with Hepatocellular Carcinoma: A Propensity Score Matching Analysis

2021 ◽  
Author(s):  
Pei-Min Hsieh ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Gin-Ho Lo ◽  
I-Cheng Lu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Cox Regression ◽  
Survival Rates ◽  
Hbv Infection ◽  
Cox Regression Analysis

Abstract Background: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.Methods: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.Results: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were 1) SR and cirrhosis; 2) SR, cirrhosis, and Child-Pugh (C-P) class; 3) SR, hepatitis B virus (HBV) infection, and C-P class; and 4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs non-SR were 44.0% vs 28.7%, 72.2% vs 42.6%, 42.6% vs 36.2, 44.6% vs 23.5%, and 41.4% vs 15.3% (all p-values<0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.Conclusion: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

scholarly journals The Prognostic Impact of the Diagnostic CD34+/CD38- Cell Burden and Expression of the Stem Cell Marker GPR56 after Stem Cell Transplantation Depends on the AML Origin

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 323-323
Author(s):  
Madlen Jentzsch ◽  
Marius Bill ◽  
Juliane Grimm ◽  
Dominic Brauer ◽  
Julia Schulz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Solid Tumors ◽  
Cell Transplantation ◽  
Research Funding ◽  
De Novo ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Rheumatologic Diseases ◽  
De Novo Aml

Introduction: Acute myeloid leukemia (AML) developing secondary after other hematologic diseases, or therapy related after cytotoxic treatment for solid tumors or rheumatologic diseases (s/tAML) is clinically, genetically & prognostically distinct from de novo diseases. Data indicate that s/tAML patients (pts) have inferior outcome compared to de novo cases after chemotherapy & therefore often require consolidation therapy using allogeneic stem cell transplantation (HSCT). Leukemic stem cells (LSC) initiate & maintain AML. They are also believed to exist within the CD34+/CD38- &/or high GPR56 expressing bone marrow (BM) population, which have been shown to impact adversely on outcome. The prognostic impact of LSC markers in de novovs s/tAML after HSCT with non-myeloablative conditioning intensity - where the therapeutic approach also relies on immunological graft-versus-leukemia effects - is unknown. Methods: We analyzed 379 AML pts who received an allogeneic peripheral blood HSCT in complete remission (CR, 82%) or CR with incomplete peripheral recovery (CRi, 18%) between 1999 & 2018 after non-myeloablative (3x30 mg/m2 Fludarabine & 2 Gy total body irradiation) conditioning. At diagnosis, cytogenetic & flow cytometric analyses were performed centrally. For pts with pre-treatment BM available the mutation status of CEBPA, NPM1 & presence of FLT3-ITD by fragment analyses as well as expression levels of GPR56 by qPCR were assessed. Using a next-generation targeted amplicon sequencing approach we analyzed a panel comprising 54 recurrently mutated (mut) genes in myeloid malignancies on the MiSeq platform (Illumina). Median follow up after HSCT was 3.7 years. Results: 229 pts (60%) had de novo & 150 pts (40%) had AML secondary to myelodysplastic syndrome (MDS, n=82), myeloproliferative neoplasm (MPN, n=22) or MDS/MPN (n=10), or therapy related after Non-Hodgkin lymphoma (n=9), solid tumors (n=25) or rheumatologic diseases (n=2). At diagnosis, s/tAML pts had lower white blood counts (P=.03), lower blasts in BM (P&lt;.001) or blood (P=.007) & a higher BM CD34+/CD38- cell burden (P=.01) & GPR56 expression (P=.04). They also had worse European LeukemiaNet risk (P=.007), were less likely to have a normal karyotype by trend (P=.06), to have a core binding factor AML (P=.02), to be NPM1mut (P=.003), DNMT3Amut (P=.03) & to harbor a FLT3-ITD (P=.002) but more likely to be JAK2mut (P&lt;.001). Comparing pts with s/tAML vsde novo AML, there was no significant different cumulative incidence of relapse (CIR, P=.85) or overall survival (OS, P=.29). Next, we evaluated the prognostic impact of the LSC-associated populations in pts with de novo or s/tAML separately. In pts with de novo AML, we observed a significantly higher CIR & shorter OS for pts harboring a high CD34+/CD38- cell burden (high vs low, 6% cut, P=.006 [Fig. 1A] & P=.003) & a higher CIR but not significantly different OS for pts with a low GPR56 expression (high vs low, median cut, P=.03 [Fig. 1B] & P=.95). Combining both parameters, we observed a stepwise higher CIR & shorter OS for pts with low expression of both variables vs pts with a low CD34+/CD38- cell burden but high GPR56 expression vs pts with a high CD34+/CD38-cell burden (P=.003 [Fig. 1C] & P=.05). In contrast, in pts with s/tAML, there was no prognostic significance of the CD34+/CD38- cell burden (CIR P=.38 [Fig. 1D] & OS P=.95), the GPR56 expression (CIR P=.64 [Fig. 1E] & OS P=.82) & both markers combined (CIR P=.57 [Fig. 1F] & OS P=.98). Also in multivariate analyses, the combination of both markers significantly impacted CIR (Hazard ratio 2.49, P&lt;.001 after adjustment for donor type) & was the only significant factor for OS (Odds Ratio 0.68, P=.04) in de novo AML but not in s/tAML. Conclusion: While there was no significantly different CIR or OS in s/tAML compared to de novo AML pts undergoing non-myeloablative HSCT we observed a significant impact on outcome for the known LSC-associated prognosticators CD34+/CD38- cell burden & GPR56 expression levels at diagnosis only in de novo AML pts. Different underlying disease biology & possibly different LSC-associated populations may be relevant for disease reoccurrence in s/tAML. Figure Disclosures Jentzsch: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria. Niederwieser:Daichii: Speakers Bureau; Cellectis: Consultancy. Platzbecker:Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Schwind:Daiichi Sankyo: Honoraria; Novartis: Honoraria, Research Funding.

scholarly journals Incidence, Survival, and Associated Factors Estimation in Osteosarcoma Patients with Lung Metastasis: A Single-center Experience of 11 Years in Tianjin, China

2021 ◽  
Author(s):  
Chao Zhang ◽  
Haixiao Wu ◽  
Guijun Xu ◽  
Wenjuan Ma ◽  
Lisha Qi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Factors ◽  
Lung Metastasis ◽  
Associated Factors ◽  
Cox Regression ◽  
Cancer Center ◽  
Single Center ◽  
Cox Regression Analysis

Abstract Background: Osteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis. Methods: From February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. Prognostic factors of patients with osteosarcoma were identified by the Cox proportional hazard regression analysis. Risk factor of lung metastasis in osteosarcoma were investigated by the logistic regression model. Results: A total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteo-sarcoma patients was 70.0%. Surgery, bone and lung metastasis were the significant prognostic factors in multivariable Cox regression analysis. Twenty-one (10.3%) patients showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) lung metastases during the later course. T3 stage (OR=11.415, 95%CI 1.362-95.677, P=0.025) and synchronous bone metastasis (OR=6.437, 95%CI 1.69-24.51, P=0.006) were risk factors of synchronous lung metastasis occurrence. Good necrosis (≥90%, OR=0.097, 95%CI 0.028-0.332, P=0.000) and elevated Ki-67 (≥50%, OR=4.529, 95%CI 1.241-16.524, P=0.022) were proved to be significantly associated with metachronous lung metastasis occurrence. Conclusion: The overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.

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