External Validation of the Impede VTE Risk Score in Newly Diagnosed Multiple Myeloma (MM) Patients

Background: Venous thromboembolism (VTE) is a prevalent cause of morbidity in MM patients. The IMPEDE VTE score was recently proposed by Sanfilippo KM et al. in 2018 ASH annual meeting to predict VTE in MM. Herein, we report on the external validation of this score. Methods: We reviewed consecutive newly diagnosed MM patients who were treated at the Cleveland Clinic between 2010 and 2012. All treatment variables were collected as time-varying variables. Poor cytogenetic features were defined as monosomy 13 or 17, t(4;14), or t(4;16). We calculated the total IMPEDE VTE score for each patient as previously defined; immunomodulatory drug (IMiD) use (+3), BMI >25 kg/m2 (+1), pathologic pelvis/femur fracture (+2), erythropoiesis-stimulating agent use (+1), low/high dexamethasone use (+2/+4), doxorubicin use (+2), Asian race (-3), history of VTE (+3), central venous catheter use (+2), prophylactic aspirin or enoxaparin (-2), therapeutic anticoagulation (-5). Patients with IMPEDE VTE score of <3, 3 to 6, and >6 were defined as low-, intermediate-, and high-risk groups, respectively. Cumulative incidence of symptomatic VTE after initiation of systemic treatment was calculated with death as competing risk and compared with the Gray's test. Overall survival (OS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox analysis was used to identify independent predictors of OS. Results: We identified 210 MM patients, 102 (49%) were female, 31 (15%) were black, and median age at diagnosis was 63 years (range: 30 - 91). Fifteen (7%) patients had VTE prior to MM diagnosis and 30 (14%) patients had pathologic pelvic or femur fracture at or after MM diagnosis. Poor cytogenetic features were seen in 65 (31%) patients. ECOG performance status at diagnosis was ≥2 for 33 (16%) patients. Sixty-seven (32%), 65 (31%), and 57 (27%) patients had ISS stage I, II, and III disease, respectively. MM subtypes were IgG, IgA, and light-chain disease for 109 (52%), 46 (22%), and 52 (25%) patients, respectively. IMiDs and low-dose dexamethasone were given to 145 (69%) and 205 (98%) patients, respectively. Seventy-seven (37%) patients underwent autologous hematopoietic cell transplant. Patient and treatment characteristics were compared between patients with and without VTE after MM diagnosis in Table 1. Twenty-two (10%) patients had symptomatic VTE within 6 months after initiation of systemic treatment for MM. When IMPEDE VTE score was calculated based on the risk factors during this time period, 37 (18%), 157 (75%), and 16 (8%) patients were in low-, intermediate- and high-risk groups, respectively. Six-months cumulative incidence of VTE in low-, intermediate- and high-risk groups were 2.7% (95% CI: 0 - 7.9), 10.8% (95% CI: 6.0 - 15.7), and 25% (95% CI: 3.8 - 46.2), respectively (p=0.011) (Figure 1A). Whereas, 39 (19%) patients were diagnosed with symptomatic VTE during median follow-up of 86 months. When the highest IMPEDE VTE score for each patient was calculated based on the risk factors at any time after initiation of treatment, 16 (8%), 151 (72%), and 43 (20%) patients were in low-, intermediate-, and high-risk groups, respectively. Seven-year cumulative incidence of VTE in low-, intermediate- and high-risk groups were 9.0% (95% CI: 0 - 25.7), 16.3% (95% CI: 10.3 - 22.3), and 29.3 (95% CI: 15.2 - 43.3), respectively (p=0.014) (Figure 1B). Seven-year OS of patients with and without VTE within 6 months after initiation of treatment was 50% (95% CI: 32% - 79%) and 46% (95% CI: 39% - 55%), respectively (p=0.4). On multivariable analysis, VTE vs no VTE within 6 months after initiation of treatment did not predict OS (HR 1.10, 95% CI: 0.46 - 2.66, p=0.8), whereas each 1-year increase in age (HR 0.99, 95% CI: 0.96 - 1.02, p=0.61), each 1 increase in ECOG performance status (HR 1.77, 95% CI: 1.24 - 2.53, p=0.002) and ISS stage (HR 1.50, 95% CI: 1.06 - 1.14, p=0.024), poor vs non-poor cytogenetics features (HR 4.38, 95% CI: 2.25 - 8.57, p<0.0001), high vs normal LDH (HR 1.94, 95% CI: 1.05 - 3.60, p=0.035), IMiD use vs non-use at first induction (HR 0.52, 95% CI: 0.29 - 0.43, p=0.026), and transplant vs no transplant (HR 0.40, 95% CI: 0.20 - 0.79, p=0.008) were statistically significant predictors of OS (Table 2). Conclusion: In this cohort of MM patients, we showed that IMPEDE VTE score was able to stratify patients into distinct risk groups and can be a helpful tool to provide personalized strategies for thromboprophylaxis. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Valent:Takeda pharmaceuticals: Speakers Bureau; Amgen corporation: Speakers Bureau; Celgene corporation: Speakers Bureau.

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Validation of Kantarjian (2010) Model for Intensive Chemotherapy in Older Adults with Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2018-99-112710 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5258-5258

Author(s):

Shawn Tahata ◽

Annie Im ◽

Michael Boyiadzis ◽

Daniel Normolle

Keyword(s):

Older Adults ◽

High Risk ◽

Myeloid Leukemia ◽

Prognostic Value ◽

Historical Data ◽

Performance Status ◽

Risk Groups ◽

Intensive Chemotherapy ◽

Ecog Performance Status ◽

Acute Myeloid

Abstract Background: Acute myeloid leukemia (AML) carries a poor prognosis in older adults. Limited clinical trial data exist to support the use of conventional cytarabine-based regimens in this population, and practice standards have been extrapolated from studies in younger patients. Intensive chemotherapy in older adults is associated with high rates of treatment-related mortality and poor overall survival. In 2010, Kantarjian and colleagues developed a risk model for 8-week mortality using adverse prognostic risk factors, including age ≥80 years, complex karyotype (≥3 abnormalities), poor performance status (ECOG score ≥2), and serum creatinine >1.3 mg/dL. This study validates the Kantarjian model for progression-free survival (PFS) and overall survival (OS) in older patients with AML treated with intensive chemotherapy. Methods: Adults aged ≥70 years with AML (≥20% blasts in bone marrow or peripheral blood) who received intensive chemotherapy at UPMC Hillman Cancer Center between 2000 and 2011 were evaluated. Patients were stratified into low, intermediate, and high-risk groups according to the Kantarjian (2010) model and analyzed for PFS and OS using the Kaplan-Meier method. Differences in PFS and OS between risk groups were assessed with the log-rank test. ECOG performance status was estimated using historical data at the time of diagnosis. Additional variables, including AML type (primary vs. secondary), percent blasts at diagnosis, percent CD34-positive blasts, hemoglobin, leukocytes, platelets, LDH, AST, ALT, total bilirubin, albumin, and Charlson comorbidity index (CCI) were tested for added prognostic value when incorporated into the model, using Cox proportional-hazards regression for PFS and OS. Results: Clinical data were collected for 68 patients. Of these, 26 patients, all of whom were diagnosed prior to 2003, were excluded from the final analysis due to insufficient electronic health records. The remaining 42 patients were used for the validation study. Median age at diagnosis was 73 years (range: 70-87). Twenty-seven patients (64%) had primary AML, whereas 10 (24%) had AML evolving from another hematologic disorder and 5 (12%) developed AML after radiation or chemotherapy for another malignancy. Eleven (26%) patients had ≥3 karyotypic abnormalities and the remaining 31 (74%) had fewer than 3. Thirty-three (79%) patients had an ECOG performance status of 0 or 1, and the remaining 9 (21%) did not have sufficient historical data to estimate ECOG score and were given a score of 0. In total, there were 23, 16, and 3 patients categorized into the low, intermediate, and high-risk groups, respectively. These groups had non-overlapping PFS and OS curves (p <0.001 for both endpoints). The low, intermediate, and high-risk groups had median PFS of 9.6, 5.1, and 2.1 months and median OS of 14.0, 6.3, and 2.1 months, respectively. None of the additional variables were found to add significant prognostic value to the existing model. Discussion: The Kantarjian (2010) model is a valid method of risk-stratifying older adults with respect to PFS and OS, and may be useful when weighing the risks and benefits of intensive chemotherapy in these patients. In this study, we did not identify other disease characteristics or measures of organ function that significantly improved the model, although our analysis is limited by small sample size. We note that all patients in our study had an ECOG score of 0 or 1, implying selection of healthier patients for induction chemotherapy at our institution. Our results suggest that patients in the intermediate and high-risk groups may not derive significant PFS and OS benefit from intensive chemotherapy when the risks of morbidity and mortality from treatment are considered. Disclosures No relevant conflicts of interest to declare.

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WED 130 Designing a care pathway for high risk parkinson’s patients

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-abn.53 ◽

2018 ◽

Vol 89 (10) ◽

pp. A14.4-A15

Author(s):

Tam Lok Yee Chloe ◽

Thea Dominey ◽

Emma Pearson ◽

Fiona Murphy ◽

Camille Carroll

Keyword(s):

High Risk ◽

Adverse Outcome ◽

Care Pathway ◽

External Validation ◽

Risk Groups ◽

Prognostic Indicator ◽

List Type ◽

Newly Diagnosed ◽

Care Needs ◽

Risk Patients

ObjectiveTo inform pathway design for patients at high risk of an adverse outcome at 5 years post-Parkinson’s disease (PD) diagnosis.BackgroundIn our service, all newly diagnosed patients follow a 12 month new patient pathway, which includes assessment with PDQ-39, NMS Quest and MOCA. Use of a prognostic calculator1 allows for refinement of the pathway according to patient need. Patients are classified as low (0–0.3), medium (0.31–0.79) or high (0.8–1) risk of an adverse outcome at 5 years (postural instability, dementia, death).AimWe aim to evaluate whether assessments in the newly diagnosed pathway identify additional care needs in higher risk patients.MethodsAn evaluation was carried out of our new patient database. Individuals who had the prognostic indicator performed (n=52) were included in the evaluation.ResultsPatients in the high risk groups were found to be older and more cognitively impaired than lower risk patients (p<0.05). MOCA scores negatively correlated with NMS Quest (r=−0.44, p<0.001) and PDQ-39 (r=−0.51, p<0.001) suggesting as cognition becomes impaired, NMS burden increases, and quality of life is reduced.ConclusionsAdditional care needs were identified in high-risk patients. These findings highlight additional resources are required in this patient cohort to ensure needs are met.Reference. Velseboer DC, et al. Development and external validation of a prognostic model in newly diagnosed Parkinson disease.

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High Risk Older AML Patients May be Benefited from the Treatment of Decitabine Combined Wih CAG Regimens

Blood ◽

10.1182/blood.v124.21.4953.4953 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4953-4953

Author(s):

Xia Xiao ◽

Mingfeng Zhao ◽

Qi Deng ◽

Qing Li ◽

Juan Mu ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Adverse Events ◽

Older Patients ◽

Median Overall Survival ◽

Performance Status ◽

Newly Diagnosed ◽

Ecog Performance Status ◽

Secondary Aml ◽

Number Of Patients

Abstract Patients over age 60 maked up more than 50% of newly diagnosed patients with acute myeloid leukemia (AML). Futhermore, with an aging population, more and more older AML patients were diagnosed in China. But the treatment approaches of this disease were variable, with many uncertainties and controversies. Treatment options for older patients with adverse prognostic features, such as poor performance status, unfavorable cytogenetics or an antecedent hematologic disorder were limited, and outcomes were poor. Aggressive induction chemotherapy had a high mortality and relatively low efficacy in this population. There were several new therapeutic schemes for older patients with AML. CAG regimens consisting of low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor for the treatment of older patients with AML showed higher rates of CR (42-68%). Decitabine, a DNA-hypomethylating agent induces differentiation and apoptosis of leukemic cells. The current National Comprehensive Cancer Care guidelines suggested decitabine as alterative options for older patients with AML. Previous studies have shown that decitabine demonstrated efficacy in a phase II multicenter study of older patients with AML, with a CR rate of 25%, 30-day mortality of 7%, median overall survival 7.7 months and little extramedullary toxicity. In our study, decitabine(15 mg/m2/d, d1-5) combined with CAG regimens (aclarubicin 20 mg/d, d3-6, Ara-C 10 mg/m2, q12h, d3-9, G-CSF 300ug, qd, d1-9) treated 27 older patients with AML, repeated every 4 weeks. Effectiveness and safety were assessed. 27 older patients with newly diagnosed AML who were in Tianjin First Central Hospital of China from January 2011 to December 2013 were enrolled in our study. They were all treated with decitabine combined with CAG regimens. The characteristics of the 27 patients were described in Table I. The study population included 15 males and 12 females, with a median age of 68 years (range 60-79 years). All patients had Eastern Cooperative Oncology Group (ECOG) performance status of <3. Cytogenetics were classified according to criteria of the Cancer and Leukemia Group B(CALGB), and were adverse in 11 patients (40.7%) and intermediate in 16 patients (59.3%). No patient had favorable cytogenetics. 12 patients (44.4%) had secondary AML or an antecedent MDS or myeloproliferative disorder. Molecular diagnostics with mutations of FLT3-ITD in 6 patients (22.2%), NPM1 in 7 patients (25.9%) patients and JAK-2 in 4 patients (14.8%). Clinical responses, survival and adverse events of all 27 patients were analyzed. The median treatment cycle was 4 cycles. Rate of complete remission, overall response rate and a 30-day mortality rate were 40.1%, 66.7%, 7.4%, respectively. The median overall survival and median recurrence-free survival were 13.0months (95%CI, 7.0-18.0 months ) and 7.0 months (95%CI, 3.0-11.0 months), respectively. Adverse events in the regimens were mainly included myelosuppression, infection, nausea, vomiting and liver dysfunction. The adverse events could be well tolerated after managements. In conclusion, the treatment of decitabine combined with CAG regimens was found to be feasible and useful in high-risk older patients with AML. This regimen was a well-tolerated therapeutic alternative, was effective in producing remissions lasting several months or disease stabilization in high-risk older patients with AML. Table 1. The characteristics of newly diagnosed patients with AML Total number of patients n=27 median age(range) 68 years(60-79 years) Male/female 15/12 (1.25/1) ECOG performance status, n (%) 0 5 (18.5%) 1 10 (37.0%) 2 12 (44.4%) Cytogenetics, n (%) Adverse 11 (40.7%) Intermediate 16 (59.3%) secondary AML, n (%) MDS 6 (22.2%) myeloproliferative 5 (18.5%) Other tumors 1 (3.7%) Molecular mutations, n (%) FLT3-ITD 6 (22.2%) NPM1 7 (25.9%) JAK-2 4 (14.8%) Disclosures No relevant conflicts of interest to declare.

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A New Prognostic Index (MIPI) for Patients with Advanced Stage Mantle Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.814.814 ◽

2006 ◽

Vol 108 (11) ◽

pp. 814-814 ◽

Cited By ~ 1

Author(s):

Eva Hoster ◽

Martin Dreyling ◽

Michael Unterhalt ◽

Joerg Hasford ◽

Wolfgang Hiddemann

Keyword(s):

Prognostic Factors ◽

Performance Status ◽

International Prognostic Index ◽

External Validation ◽

Prognostic Index ◽

Risk Groups ◽

Intermediate Risk ◽

Advanced Stage ◽

Ecog Performance Status ◽

Wbc Count

Abstract On behalf of the German Low Grade Lymphoma Study Group (GLSG) and the European MCL Network. Background: There is no generally established prognostic classification system for patients with mantle cell lymphoma (MCL), as the International Prognostic Index (IPI) and the Follicular Lymphoma International Prognostic Index (FLIPI) have been developed based on data of patients with diffuse large cell and follicular lymphoma, respectively. Methods: The data of 455 patients with advanced stage MCL treated first-line within three clinical trials of GLSG and European MCL Network have been analyzed to clarify the prognostic relevance of IPI and FLIPI and to derive a new prognostic index of overall survival (OS). Age, sex, ECOG performance status, Ann Arbor stage, B-symptoms, number of extranodal sites, number of involved nodal areas, tumor size, serum LDH activity, WBC count, platelet count, hemoglobin, albumin, β2-microglobulin and cell proliferation (Ki-67) were considered as candidate prognostic factors. Statistical methods included Kaplan-Meier estimates and logrank test for the validation of IPI and FLIPI and multiple Cox regression with backward variable selection for the derivation of the new prognostic index. Results: IPI showed a significant impact on OS, but low-intermediate and high-intermediate risk groups comprised more than two thirds of the patients and were not well separated. According to the FLIPI, only 6% of the patients were classified as low risk and almost two thirds of the patients as high risk, and low and intermediate risk groups were not separated. Four of the candidate prognostic factors were independently associated with OS, namely age, ECOG performance status, LDH and WBC count. The relative risk was 1.42 (95% confidence interval 1.18 to 1.72, p = 0.0002) for an increased age by ten years, 2.01 (1.19 to 3.39, p = 0.0088) for an ECOG greater than one, 1.51 (1.13 to 2.02, p = 0.0059) for a 2 fold elevation of LDH and 2.56 (1.66 to 3.95, p < 0.0001) for a 10 fold increase of WBC count. According to these four parameters, patients could be classified into a low risk (44% of the patients, median OS not reached), an intermediate risk (35%, median OS 51 months), and a high risk group (21%, median OS 29 months). Discussion: IPI and FLIPI showed only modest prognostic discrimination in our external validation data set of patients with advanced stage MCL. In contrast, age, ECOG performance status, LDH and WBC were identified as independent prognostic factors of OS, and three reasonably sized and well separated risk groups were defined. With four clinical prognostic factors readily determined in clinical routine, our new prognostic index (MIPI) is superior to the IPI. Bootstrap validation confirmed the separation of three risk groups, but external validation is still needed. The MIPI may prove to be an important tool to facilitate risk-adapted treatment decisions for patients with advanced stage MCL.

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External validation of a prognostic model for overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5022 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5022-5022

Author(s):

Susan Halabi ◽

Sandipan Dutta ◽

John C. Araujo ◽

Christopher Logothetis ◽

Cora N. Sternberg ◽

...

Keyword(s):

Prognostic Model ◽

Characteristic Curve ◽

Opioid Analgesic ◽

Performance Status ◽

External Validation ◽

Age Groups ◽

Risk Groups ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Ecog Performance Status

5022 Background: We have previously developed and externally validated a prognostic model of OS in men with mCRPC treated with docetaxel (D), which included eight predictors: opioid analgesic use, ECOG performance status, albumin, disease site, LDH, hemoglobin, PSA, and alkaline phosphatase. We have used this model to develop prognostic risk groups. We sought to externally validate this model in a broader group of men with mCRPC and in specific subgroups (White, Black, Asian patients, different age groups) and to validate the two and three prognostic risk groups in this large dataset. Methods: Data from 5,790 mCRPC men randomized on 5 phase III trials were utilized to validate the prognostic model of OS: D +/- zibotentan (ENTHUSE), D +/- lenalidomide (MAINSAIL), D +/- dasatinib (READY), D+/- custirsen (SYNERGY), and tasquinimod/placebo)). We applied the estimated parameters from the prognostic model to each of the five data sets and computed a risk score. We assessed the predictive performance of the model by computing the time-dependent area under the receiver operating characteristic curve (tAUC) and validated the two-risk (low, high) and three-risk prognostic risk groups (low, intermediate, high) that were defined by the model. Results: The tAUC for the different groups is presented in the table. Race, age, and treatment subsets had similar results. For the two prognostic risk groups, the median OS in the low and high groups were 27.6 months (95% CI = 26.6-28.7) and 13.8 months (95% CI = 13.3-14.4). For the three prognostic risk group, median OS in the low, intermediate and high groups were 29.7 months (95% CI = 28.3-31.4), 19.0 month (95% CI = 18.3-20.4) and 12.1 months (95% CI = 11.5-12.9), respectively. Conclusions: This prognostic model for OS in men with mCRPC has been validated in a larger dataset, yields similar results across race, age and treatment groups. The model is robust and can be used to identify prognostic risk groups of patients for stratification and enrichment trials. Clinical trial information: NCT00626548. [Table: see text]

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Association of disease prognostic model (PM) with baseline quality of life (QOL) in metastatic castration resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16579 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16579-e16579

Author(s):

Anna Prizment ◽

Susan Halabi ◽

Sean McSweeney ◽

Amy Eisenberg ◽

Arpit Rao ◽

...

Keyword(s):

High Risk ◽

Performance Status ◽

Risk Groups ◽

Castration Resistant Prostate Cancer ◽

Opioid Use ◽

Ecog Performance Status ◽

Unit Increase ◽

General Linear Regression Model ◽

Pre Treatment ◽

Ecog Ps

e16579 Background: PM’s in mCRPC accurately predict survival, but little is known about their association with QOL. We hypothesize that pre-treatment QOL is inversely correlated with PM derived scores. Our study explored associations between baseline Halabi PM derived risk score (including metastatic site, opioid use, ECOG performance status (ECOG PS), Alk phos, albumin, hemoglobin, LDH, and PSA) and multiple QOL domains at treatment initiation with docetaxel and prednisone (DP). Methods: The DP arm of MAINSAIL, a multicenter, randomized Phase 3 study of DP +/- lenalidomide in mCRPC, was analyzed via ProjectDataSphere. Halabi PM score was computed as continuous with higher score reflecting worse survival and classified as low- ( < 140 points), intermediate- (140-194.96) or high-risk groups ( > 194.96 points). QOL tests included FACT-P (higher score = better QOL), BPI-SF Severity score (BPI-SFSS; higher score = higher pain severity); and BPI-SF Interference score (BPI-SFIS, higher score = worse pain). General linear regression model was used to calculate beta estimates and 95% confidence intervals. Results: The sample included 526 mCPRC pts (median 68 years, White: 91.9%, Black: 5.3%, median PSA 75.95 ng/ml). Median [range] for FACT-P, BPI-SFSS and BPI-SFIS were 111 [0-152], 1.8 [0-9.3], and 1.4 [0-10], respectively. PM score was correlated with BPI-SFIS and BPI-SFSS and inversely correlated with FACT-P with correlation of 0.36, 0.31 and -0.33, respectively (all p < 0.0001). For each unit increase in the PM score, BPI-SFIS increased by 2.1 points), BPI-SFSS increased by 1.5 points, and FACT-P decreased by 16.4 points. Using the three-risk groups, pts in the intermediate and high-risk groups had worse FACT-P QOL and higher BPI-SFIS and BPI-SFSS than pts in the low-risk group. In multivariate analysis, factors negatively impacting FACT-P QOL, BPI-SFSS and BPI-SFIS were higher ECOG PS, visceral metastases and opioid use. Declining hemoglobin levels were associated with increased BPI-SFSS and BPS-SFIS. Conclusions: Higher PM scores are associated with a lower baseline QOL overall, higher pain and higher pain interference. These results should be validated prospectively.

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Death In Complete Remission Among Patients with Acute Myeloid Leukemia: A Preventable Problem?

Blood ◽

10.1182/blood.v116.21.2710.2710 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2710-2710

Author(s):

Gloria Mattiuzzi ◽

Hagop Kantarjian ◽

Farhad Ravandi ◽

Guillermo Garcia-Manero ◽

Gautam Borthakur ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

High Risk ◽

Causes Of Death ◽

Performance Status ◽

Poor Performance ◽

Poor Performance Status ◽

Newly Diagnosed ◽

History Of ◽

Prior Malignancy

Abstract Abstract 2710 Background: Significant advances in the treatment of patients with acute myelogenous leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS) have improved their outcome. Mortality among patients with newly diagnosed AML and HR-MDS is mainly attributed to persistent disease (i.e., failure to achieve or loss of complete remission [CR]), infectious and other complications during induction chemotherapy. However, a small but significant proportion of patients die in CR. The aim of this study was to investigate the cause of death in AML and HR-MDS patients in CR and to analyze the associated risk factors. Methods: Retrospective review of medical records of patients with newly diagnosed AML, APL and HR-MDS who received induction chemotherapy at the Department of Leukemia at MD Anderson from January 2000 to December 2009. Results: During the study period, 2156 patients were treated. One thousand one hundred fifty patients achieved CR for an overall CR rate of 53%. Among them, 114 patients (10%) died in CR. The median time from achievement of CR to death was 5.3 months (range, 0.2 – 79). There was a decline in the rate of death in CR over the 10 years of analysis reported (p=0.010). [Table 1] Information about the causes of death in 35 patients (31%) was not available. The most frequent causes of death in the remaining 79 patients were infections (27%); SCT-related complications (19%); relapse of prior malignancy (8%); hemorrhage (4%); multi-organ failure (4%); and others (9%). Among patients who died in CR, 105 (92%) had AML and 9 high-risk MDS, 60% were female, and the median age was 64 years (range 21–86). Forty-two patients (37%) had history of a prior malignancy, 22% had received previous chemotherapy (for other malignancies), and 20% prior radiotherapy. Sixty-eight percent received high-dose cytarabine-containing regimen for induction therapy, 92% achieved CR after one cycle of chemotherapy, with a median of 33 days (range 21–152) to achievement of CR. Nineteen percent underwent stem cell transplantation while in CR. In comparison to patients who did not die in CR, patients who died in remission were significantly older at the time of diagnosis [64 vs. 57 years, p <.001]; were more likely to have history of prior malignancy, chemotherapy or radiotherapy [37% vs.21%, p<0.001; 22% vs.11%, p<0.001; 20% vs. 9%, p<0.001, respectively]; had worse performance status at the time of diagnosis [26% vs. 14%, p = 0.004]; and were more likely to have undergone stem cell transplantation (SCT) while in CR [19% vs. 8%, p<0.001]. Sixty-three percent of the patients who died in CR were 60 years or older. Among patients age 60 years or older, the probability of death in CR was 14% compared to 7% for patients younger than 60 (p<0.001). Multivariate logistic regression analysis confirmed that older age (p<0.000), prior malignancy (p<0.001), poor performance status (p<0.001) and SCT while in CR (p<0.000) were independently associated with the probability of dying in CR. Risk factors for dying from infections included only older age (p<0.003) and poor performance status (p, 0.05). Conclusion: Death in CR affects a significant number of patients with AML, with older patients with poor performance status having the highest probability of dying in CR, particularly from infections. Special attention should be put to these patients to minimize their risk of death in CR to improve their long term outcome. Disclosures: No relevant conflicts of interest to declare.

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A Phase II Study Of Tosedostat (TST) In Combination With Either Cytarabine Or Decitabine In Newly Diagnosed Older Patients With Acute Myeloid Leukemia (AML) Or High-Risk Myelodysplastic Syndrome (MDS)

Blood ◽

10.1182/blood.v122.21.3926.3926 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3926-3926

Author(s):

Raya Mawad ◽

Pamela S. Becker ◽

Paul C. Hendrie ◽

Bart L Scott ◽

Brent L. Wood ◽

...

Keyword(s):

High Risk ◽

Phase Ii ◽

Older Patients ◽

Hematopoietic Cell Transplantation ◽

Controlled Trial ◽

Performance Status ◽

Newly Diagnosed ◽

Open Label ◽

Ecog Performance Status ◽

To Receive

Abstract Background Treatment outcomes for older patients with newly diagnosed AML remain poor. TST is an oral aminopeptidase inhibitor that has anti-neoplastic activity in a variety of malignancies, including AML. Phase I/II monotherapy studies in patients with relapsed AML and MDS have shown TST to have adequate safety and promising efficacy. Pre-clinical AML blast proliferation assays have demonstrated synergy between TST and both cytarabine and hypomethylating agents. For this reason, we performed a randomized, open-label Phase II trial using TST in combination with intermediate-dose cytarabine or decitabine in patients with untreated AML or high-risk MDS (i.e. RAEB-2). Methods Patients ≥60 years old with untreated AML or high risk MDS were randomized to receive TST 120 mg daily by mouth days 1-21 with 5 days of either cytarabine 1 g/m2/day IV or decitabine 20 mg/m2/day IV delivered every 35 days. Patients received up to three 35-day cycles if they had at least stable disease with an acceptable toxicity profile following the initial course. Patients who did not achieve a complete remission (CR) or CR with incomplete blood count recovery (CRi) after 3 cycles of therapy were taken off study; patients who obtained CR/CRi were eligible to receive up to 2 additional cycles (maximum of 5). The primary objective was to determine the rates of CR and 4 month survival using TST in combination with either cytarabine or decitabine for older patients with untreated AML or high-risk MDS. Results A total of 26 patients have been treated, with 14 receiving TST/cytarabine and 12 receiving TST/decitabine. The median age was 69 (range, 60-83), and 22 patients (85%) presented with an ECOG performance status of 1. Nineteen patients (73%) had AML and 7 (27%) had MDS RAEB-2. Nineteen patients (73%) had intermediate-risk and 7 (27%) had adverse-risk disease by European Leukemia Net criteria. Fourteen patients (54%) had secondary AML/MDS or antecedent hematologic disorder. The median duration of treatment was 3 months. The overall CR/CRi rate was 54%, with 10 patients (39%) achieving a CR and 4 patients (15%) achieving a CRi. Five patients required 3 cycles, four patients required 2 cycles and five patients required 1 cycle of therapy to achieve maximal disease response. CR/CRi was attained in 3 patients with adverse cytogenetics and 4 additional patients with FLT3 mutations. Of the 14 patients who achieved a CR/CRi (54%), 7 were treated on each of two study arms. Nine of the 14 patients who achieved a CR/CRi were referred for allogeneic hematopoietic cell transplantation (HCT), 3 patients deferred HCT, and 1 patient died of sepsis in CRi 133 days after starting induction. Ten patients were taken off study after a median of 2 cycles due to lack of response or disease progression. With a median follow-up of 5.7 months (range, 0.5-13.4), 21 patients (81%) lived longer than 4 months. Five (19%) of the 26 patients died within 4 months of starting therapy. Of these five patients, three died of sepsis on subsequent salvage protocols, one with a history of myeloproliferative disorder died of splenic infarct within 15 days of starting therapy and a fifth patient died at age 83 during cycle 2 of unknown cause. Eight patients (31%) were treated completely as outpatients without requiring hospitalization, and 15 patients (58%) were hospitalized at some point during treatment for febrile neutropenia. There were no Grade 3-4 non-hematologic toxicities requiring withdrawal from the study. Conclusions These results demonstrate that TST at 120 mg daily in combination with cytarabine or decitabine resulted in a 54% CR/CRi rate in 26 older patients with untreated AML or high-risk MDS. This approach was well tolerated as predominantly outpatient therapy and may warrant further study in a controlled trial. Disclosures: Wang: Cell Therapeutics, Inc.: Employment. Myint:Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment, Equity Ownership.

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The Prognostic Value of the New Combined Hemo-Eosinophil Inflammation Index (HEI Index): A Multicenter Analysis of Anal Cancer Patients Treated with Concurrent Chemo-Radiation

Cancers ◽

10.3390/cancers13040671 ◽

2021 ◽

Vol 13 (4) ◽

pp. 671

Author(s):

Margherita Rimini ◽

Pierfrancesco Franco ◽

Berardino De Bari ◽

Maria Giulia Zampino ◽

Stefano Vagge ◽

...

Keyword(s):

High Risk ◽

Cancer Patients ◽

Anal Cancer ◽

Prognostic Score ◽

Univariate Analysis ◽

External Validation ◽

Risk Groups ◽

Anal Squamous Cell Carcinoma ◽

Predictors Of Response ◽

Risk Patients

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox’s proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04–5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

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