Personalizing Cancer Supportive Care: Predicting Neutropenic Complications in Patients Receiving Intermediate Risk Cancer Chemotherapy

Abstract Abstract 1022 Background: Neutropenic complications represent important dose-limiting toxicities of cancer chemotherapy. We recently developed and validated a risk model for neutropenic complications in patients with solid tumors or lymphoma receiving cancer chemotherapy (Lyman et al. Cancer 2011). While practice guidelines recommend primary colony-stimulating factor (CSF) prophylaxis for patients at >20% risk of febrile neutropenia (FN), many patients receive chemotherapy regimens associated with an intermediate risk (10–20%) of FN. For these patients, the decision to give or withhold primary CSF prophylaxis is based on clinical judgment. We report here the ability of the risk model to identify patients with individual characteristics placing them at high risk for neutropenic complications among patients receiving intermediate risk chemotherapy regimens. Methods: A prospective cohort study was conducted of consenting patients initiating a new chemotherapy regimen at 115 randomly selected US oncology practices between 2002–2006. The risk of cycle 1 severe or febrile neutropenia was estimated [95% CI] utilizing logistic regression analysis adjusting for key clinical factors including: planned chemotherapy, prior chemotherapy, age, abnormal hepatic or renal function, low pretreatment white blood count, and immunosuppressive medications. The cumulative incidence of severe neutropenia and FN across 4 cycles was estimated by the product limit method of Kaplan and Meier. Results: Among 3,760 patients with cancers of breast, lung, ovary, colon, or lymphoma, 2,270 received an intermediate risk chemotherapy regimen based on NCCN guidelines. Overall, in the subpopulation receiving intermediate risk regimens, severe or febrile neutropenia occurred in cycle 1 in 21.4% while FN over 4 cycles was observed in 11%, and primary CSF prophylaxis was utilized in 16.4%. The performance of the risk model was good in this subgroup with a c-statistic of 0.82 [0.80–0.84]. Among the half of patients classified as high risk based on the model despite receiving an intermediate risk chemotherapy regimen, cycle 1 severe or febrile neutropenia occurred in 38% [35%–41%] compared to 5% [4%–6%] of patients classified as low risk based on the model receiving such regimens. Model sensitivity and specificity were 89% and 61%, respectively. The cumulative risk of FN over 4 cycles of chemotherapy was 20% in predicted high risk group versus 5% in the low risk group (Figure). The majority of severe or febrile neutropenia events (67%) and FN events (55%) were observed in cycle 1. One-half of high risk patients who did not receive primary CSF prophylaxis in cycle 1 received CSF during subsequent cycles following a neutropenic event. Conclusions: Our model for predicting neutropenic complications can identify patients at high individual risk for severe neutropenia in cycle 1 or FN in the first 4 cycles of chemotherapy when receiving intermediate risk chemotherapy. This analysis emphasizes the potential value of determining an individual patient's risk of chemotherapy complications based on a validated risk model. Disclosures: Lyman: Amgen: Research Funding. Crawford:Amgen: Consultancy, Honoraria, Research Funding. Dale:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kuderer:Amgen: Research Funding.

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Application of a Validated Predictive Model for Venous Thromboembolism in Cancer to Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.534.534 ◽

2016 ◽

Vol 128 (22) ◽

pp. 534-534

Author(s):

Natasha Catherine Edwin ◽

Jesse Keller ◽

Suhong Luo ◽

Kenneth R Carson ◽

Brian F. Gage ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Risk Group ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Discriminative Ability ◽

Blood Institute ◽

C Statistic

Abstract Background Patients with multiple myeloma (MM) have a 9-fold increased risk of developing venous thromboembolism (VTE). Current guidelines recommend pharmacologic thromboprophylaxis in patients with MM receiving an immunomodulatory agent in the presence of additional VTE risk factors (NCCN 2015, ASCO 2014, ACCP 2012). However, putative risk factors vary across guidelines and no validated VTE risk tool exists for MM. Khorana et al. developed a VTE risk score in patients with solid organ malignancies and lymphoma (Blood, 2008). We sought to apply the Khorana et al. score in a population with MM. Methods We identified patients diagnosed with MM within the Veterans Health Administration (VHA) between September 1, 1999 and December 31, 2009 using the International Classification of Diseases (ICD)-03 code 9732/3. We followed the cohort through October 2014. To eliminate patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, we excluded patients who did not receive MM-directed therapy within 6 months of diagnosis. We also excluded patients who did not have data for hemoglobin (HGB), platelet (PLT) count, white blood count (WBC), height and weight, as these are all variables included in the Khorana et al. risk model. Height and weight were assessed within one month of diagnosis and used to calculate body mass index (BMI). We measured HGB, PLT count, and WBC count prior to treatment initiation: within two months of MM diagnosis. A previously validated algorithm, using a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement, identified patients with incident VTE after MM diagnosis (Thromb Res, 2015). The study was approved by the Saint Louis VHA Medical Center and Washington University School of Medicine institutional review boards. We calculated VTE risk using the Khorana et al. score: We assigned 1 point each for: PLT ≥ 350,000/μl, HGB < 10 g/dl, WBC > 11,000/μl, and BMI ≥ 35 kg/m2. Patients with 0 points were at low-risk, 1-2 points were considered intermediate-risk and ≥3 points were termed high-risk for VTE. We assessed the relationship between risk-group and development of VTE using logistic regression at 3- and 6-months. We tested model discrimination using the area under the receiver operating characteristic curve (concordance statistic, c) with a c-statistic range of 0.5 (no discriminative ability) to 1.0 (perfect discriminative ability). Results We identified 1,520 patients with MM: 16 were high-risk, 802 intermediate-risk, and 702 low-risk for VTE using the scoring system in the Khorana et al. score. At 3-months of follow-up, a total of 76 patients developed VTE: 27 in the low-risk group, 48 in the intermediate-risk group, and 1 in the high-risk group. At 6-months of follow-up there were 103 incident VTEs: 41 in the low-risk group, 61 in the intermediate-risk group, and 1 in the high-risk group. There was no significant difference between risk of VTE in the high- or intermediate-risk groups versus the low-risk group (Table 1). The c-statistic was 0.56 at 3-months and 0.53 at 6-months (Figure 1). Conclusion Previously, the Khorana score was developed and validated to predict VTE in patients with solid tumors. It was not a strong predictor of VTE risk in MM. There is a need for development of a risk prediction model in patients with MM. Figure 1. Figure 1. Disclosures Carson: American Cancer Society: Research Funding. Gage:National Heart, Lung and Blood Institute: Research Funding. Kuderer:Janssen Scientific Affairs, LLC: Consultancy, Honoraria. Sanfilippo:National Heart, Lung and Blood Institute: Research Funding.

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Prognostic Value of Circulating Myeloblasts in Patients with Myelodysplastic Syndromes (MDS): A Proposal for Incorporation in the Revised International Prognostic Scoring System (R-IPSS)

Blood ◽

10.1182/blood.v124.21.4650.4650 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4650-4650

Author(s):

Rami S Komrokji ◽

Eric Padron ◽

Najla H Al Ali ◽

Jeffrey E Lancet ◽

Jeff Hall ◽

...

Keyword(s):

High Risk ◽

Gene Mutation ◽

Risk Model ◽

Risk Group ◽

Gene Mutations ◽

High Risk Group ◽

Low Risk ◽

Medical Laboratory ◽

Intermediate Risk ◽

Prognostic Variable

Abstract Introduction The World Health organization (WHO) MDS classification proposes presence of 2-4% peripheral myeloblasts (PB) as criteria for Refractory anemia with excess blasts I (RAEB-I) and 5-19% PB for RAEB-II classification, while 1% PB persistently is recognized as MDS unclassified. The most widely used clinical prognostic models such as IPSS, R-IPSS, and MD Anderson risk model (MDAS) have not incorporated PB as a prognostic variable. We evaluated the prognostic value of PB in a large MDS cohort and provide a proposal to incorporate presence of PB in R-IPSS. Methods The MDS database at Moffitt Cancer Center (MCC) was used to identify MDS patients (pts). Pts were classified into two groups based on presence of PB (1% or more) at time of diagnosis as PB-MDS group and those without PB called BM-MDS. Kaplan-Meier curves were used to depict survivals, and the log-rank test was used to compare median overall survival (OS). We collaborated with Genoptix Medical Laboratory to assess the correlation between presence of PB and gene mutations identified by next generation sequencing (21 myeloid gene panel) in a cohort of de-identified MDS pts. Results There were 1905 pts included from MCC MDS database among whom 260 pts (14%) had evidence of PB near time of diagnosis. PB-MDS patients were younger, more likely to have trilineage cytopenia, complex karyotype, transfusion dependent and more in therapy related MDS. Among PB-MDS pts 175 (67%) received hypomethylating agent (HMA) compared to 977 (59%) in the BM-MDS group, p 0.017 According to IPSS risk stratification PB-MDS pts were more likely to be classified as higher risk (HR-MDS) 157 (63%) compared to 445 (28%) in the BM-MDS group (p<0.005). Pts with PB-MDS were also HR-MDS by MDAS (p <0.005). The rate of AML transformation was 46% (n=120) compared to 25% (n=418) in PB-MDS and BM-MDS group respectively, p <0.005. Median overall survival (OS) was 46 month (95% CI 42 to 49.6) in the absence of PB compared to 17.5 mo (95% CI 14.9-20) with PB (p < 0.005). Impact on OS was greater in IPSS lower risk MDS patients where median OS was 34 mo in PB-MDS compared to 60 mo in BM-MDS patients (p < 0.005), while in IPSS HR- MDS the median OS was 16.5 in PB-MDS compared to 18 month BM-MDS (p 0.018) We then examined prognostic discrimination of PB among each R-IPSS category. Median OS for very low risk R-IPSS was 104 mo in absence of PB compared to 37 mo in BM-MDS (p 0.032). Among low risk patients the median OS was 69 mo in absence of PB compared to 40 mo (p 0.07). In the intermediate risk group, median OS was 40 mo in absence of PB compared to 23 mo with PB (p 0.001), whereas median OS in the high risk group was 24 mo without PB compared to 20 mo with PB (p 0.11). Finally, in the very high risk R-IPSS the median OS was 15 mo compared to 13 mo respectively (p 0.44). The presence of PB upgraded pts with very low or low risk R-IPSS to intermediate risk. The outcome of intermediate risk group with PB was similar to the high risk group. In Cox regression analysis the presence of PB was an independent prognostic covariate for OS after adjusting for R-IPSS and age, HR 1.5 (95% CI 1.3-1.8). Among HR-MDS pts treated with HMA (n=470) presence of PB was independent prognostic variable for OS. (HR 1.3, p 0.027) We next created a R-IPSS+PB risk model where one additional point was awarded for presence of PB and pts categorized into risk groups based on the same lump score suggested by R-IPSS for each risk category. We applied this score for 245 pts with PB where R-IPSS score was known (Table-1). Sixty three pts (26%) were upstaged to high or very high risk group and most pts were upstaged to next risk group. Among 51 pts in Genoptix Medical Laboratory database with known PB, the rate of at least single gene mutation identification in pts with PB-MDS was 100%, (4 out of 4 with PB) compared to 81% in those without PB (38 out of 47 without PB, 12 of those were single SF3B1 gene mutation in ring sideroblasts MDS subtype). The gene mutations in PB-MDS included U2AF1 gene mutation in 2 pts, SRSF2, TET-2, ASXL-1, and RUNX-1. Two pts had two gene mutations. Conclusions Presence of PB in MDS is an adverse independent prognostic variable that refines prognostic discrimination in Low to Intermediate risk R-IPSS groups. Accounting for presence of PB particularly the intermediate risk group, prioritizes disease altering therapeutic strategies. TableRisk groupR-IPSSR-IPSS+PBNOverall survival (mo)NOverall survival (mo)Very low91low2440854intermediate51231238High63204330Very high991318115 Disclosures Hall: Genoptix Medical Laboratory: Employment. Kwok:Genoptix, Inc., a Novartis company: Employment, Equity Ownership.

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Possibility of a Risk-Adapted Treatment Strategy for Untreated Aggressive Adult T-Cell Leukemia-Lymphoma (ATL) Based on the ATL Prognostic Index: A Supplementary Analysis of the JCOG9801 Study

Blood ◽

10.1182/blood-2018-99-112734 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1645-1645

Author(s):

Kosuke Toyoda ◽

Kunihiro Tsukasaki ◽

Ryunosuke Machida ◽

Tomohiro Kadota ◽

Takuya Fukushima ◽

...

Keyword(s):

High Risk ◽

Research Funding ◽

Risk Group ◽

Prognostic Index ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Adult T Cell Leukemia ◽

Ann Arbor ◽

Ecog Ps

Abstract Introduction The JCOG9801 study, a randomized phase III trial of the Japan Clinical Oncology Group (JCOG), compared CHOP every two weeks (CHOP-14) with VCAP-AMP-VECP (mLSG15) for patients with untreated aggressive adult T-cell leukemia-lymphoma (ATL) [J Clin Oncol 2007;25:5458-64]. Based on a higher complete response (CR) rate and marginally better overall survival (OS), we concluded that mLSG15 could be a sufficiently effective regimen at the expense of higher toxicity profiles. However, there was an insufficient mLSG15 effect among patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or those aged ≥56 years, suggesting that mLSG15 is not always a definitive treatment for all patients with aggressive ATL. Thus, identifying patients who should receive mLSG15 is essential. We aimed to conduct a supplementary analysis of patients enrolled in the JCOG9801 study using the ATL prognostic index (ATL-PI) that has been recently advocated for acute- and lymphoma-types of ATL [J Clin Oncol 2012;30:1635-40]. Methods We adopted the "age-adjusted" ATL-PI that was established for ATL patients aged ≤70 years as patients aged between 15 and 69 years were eligible in the JCOG9801 study. Having eliminated "age", this index comprised 4 factors, namely Ann Arbor stage (III or IV), ECOG PS (>1), serum albumin (<3.5 g/dL), and soluble interleukin-2 receptor (sIL-2R; >20,000 U/mL). We excluded patients lacking any factors of the age-adjusted ATL-PI and those with unfavorable chronic type based on the age-adjusted ATL-PI model from patients enrolled in JCOG9801. Subsequently, we categorized the remaining patients into three groups, namely low, intermediate, and high risk, and compared mLSG15 and CHOP-14 in terms of OS, treatment CR rate, and toxicity in each risk group. Results Of 118 enrolled JCOG9801 patients, we included 105 patients in this supplementary analysis based on the above criteria, of which 51 and 54 were treated with mLSG15 and CHOP-14, respectively. According to the age-adjusted ATL-PI, these patients were classified as follows: low (n=44, 41.9%), intermediate (n=54, 51.4%), and high (n=7, 6.7%) risks. Regarding patient characteristics, between the two treatment arms, there were no remarkable differences in age, sex, ECOG PS, ATL subtypes, Ann Arbor stage, presence of B symptoms, presence of bulky mass (≥5 cm), and serum albumin, serum calcium, and sIL-2R levels. The mLSG15 arm included 21 (41.2%), 25 (49.0%), and 5 (9.8%) patients in the low-, intermediate-, and high-risk groups, respectively, whereas the CHOP-14 arm included 23 (42.6%), 29 (53.7%), and 2 (3.7%) patients, respectively. We excluded the high-risk group from our analysis due to the small number of patients. mLSG15 did not show any superior trend for OS compared to CHOP-14 in the low-risk group (hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.491-1.868) (Figure A). In contrast, in the intermediate-risk group, better prognosis for OS was observed with mLSG15 (HR: 1.538; 95% CI: 0.841-2.811) than with CHOP-14 (Figure B). Similarly, the CR rate, including the unconfirmed CR rate, did not differ between both arms of the low-risk group (mLSG15 vs. CHOP-14, 47.6% vs. 43.5%), while in the intermediate-risk group, mLSG15 showed a higher CR rate than CHOP-14 (44.0% vs. 13.8%). Regarding toxicity profiles, grade 4 thrombocytopenia was more frequently observed in the mLSG15 arm of both risk groups than in the CHOP-14 arm (66.7% vs. 4.5% in the low-risk group; 68.0% vs. 24.1% in the intermediate-risk group only). There was a higher incidence of grade 4 neutropenia in the mLSG15 arm than in the CHOP-14 arm (100.0% vs. 75.9%) only in the intermediate-risk group. All three treatment-related deaths were documented in the mLSG15 arm of the intermediate-risk group. Conclusions Given the very poor prognosis of ATL, our findings suggest that despite higher toxicities, mLSG15 is more suitable for the intermediate-risk group of age-adjusted ATL-PI, whereas its benefits appear modest in the low-risk group. This supplementary analysis is exploratory; therefore, a further prospective study of aggressive ATL is necessary to confirm these results. Disclosures Tsukasaki: Daiich-Sankyo: Consultancy; Ono Pharma: Consultancy; HUYA: Consultancy, Research Funding; Chugai Pharma: Honoraria, Research Funding; Eisai: Research Funding; Celgene: Honoraria; Mundy Pharma: Honoraria; Kyowa-hakko/Kirin: Honoraria; Seattle Genetics: Research Funding. Fukushima:NEC corporation: Research Funding. Maruyama:Bristol-Myers Squibb: Honoraria; Solasia Pharma: Research Funding; Pfizer: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Novartis: Research Funding; Otsuka: Research Funding; Astellas Pharma: Research Funding; Abbvie: Research Funding; Mundipharma International: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Biomedis International: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding; Fujifilm: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Dai-ichi-Sankyo: Honoraria; Dai-Nippon-Sumitomo: Honoraria; Asahi Kasei Pharma: Honoraria; AstraZeneca: Research Funding; Amgen Astellas BioPharma: Research Funding; Zenyaku Kogyo: Honoraria, Research Funding; GlaxoSmithKline: Research Funding. Nagai:SymBio Pharmaceuticals Limited: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Honoraria, Research Funding; Janssen Pharmaceutical K.K.: Honoraria, Research Funding; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Solasia Pharma K.K.: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer Yakuhin Ltd.: Research Funding; Abbvie G. K.: Research Funding; Celgene Corporation: Honoraria, Research Funding; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding; AstraZeneca plc.: Research Funding; Roche Ltd.: Honoraria; Esai Co., Ltd.: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; Ono Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Sanofi K. K.: Honoraria; Zenyaku Kogyo Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria, Research Funding; Gilead Sciences Inc.: Honoraria, Research Funding.

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Clinical Relevance of Somatic Mutations in Chronic Myelomonocytic Leukemia Undergoing Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood-2019-121969 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1713-1713 ◽

Cited By ~ 2

Author(s):

Nico Gagelmann ◽

Anita Badbaran ◽

Rashit Bogdanov ◽

Olivier Nibourel ◽

Friedrich Stoelzel ◽

...

Keyword(s):

High Risk ◽

Genetic Risk ◽

Research Funding ◽

Risk Group ◽

Performance Status ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Research Support ◽

Total Cohort

Current risk stratification for newly diagnosed patients with chronic myelomonocytic leukemia (CMML) includes clinical and genetic features accounting for its variable disease course. Allogeneic stem cell transplantation still remains the only curative treatment option, and prognostication of posttransplant outcome may be improved using molecular information. Here, we aim to evaluate the molecular profile and its role on posttransplant outcome in a multicenter CMML cohort. Mutation analysis was performed on DNA from bone marrow mononuclear cells or peripheral granulocytes collected prior to transplant and included previously published CMML-associated genes (i.a. SETBP1, ASXL1, RUNX1, NRAS, KRAS, TET2, CBL, IDH1/2, SF3B1, DNMT3A, EZH2, ZRSR2, U2AF1). Current prognostic models were calculated at time of transplant. Patients with transformation to acute leukemia were excluded. Top predictors of posttransplant outcome were identified using the Random Forest algorithm. Main end points were overall survival (OS) and non-relapse mortality (NRM). The total cohort consisted of 185 patients of whom seven had CMML-0, 100 CMML-1, and 78 CMML-2 at time of transplant. The median follow-up was 74 months and 6-year OS was 37% for the total cohort and differed for CMML-0 (57%), CMML-1 (43%), and CMML-2 (29%). Relapse and NRM were 27% and 44% for the total cohort being 17% and 31% for CMML-0, 23% and 40% for CMML-1, and 34% and 40% for CMML-2. Most frequently mutated genes were: TET2 (55%), ASXL1 (41%), SF3B1 (38%), DNMT3A (27%), ZRSR2 (22%), NRAS (21%), EZH2 (21%), RUNX1 (17%), and SETBP1 (17%). Ninety-two percent of patients showed at least one somatic mutation. More than three mutations were present in 49% of all patients and in 29% of CMML-0, 50% of CMML-1, and 49% of CMML-2 patients. Frequencies according to CMML-specific prognostic scoring system (CPSS) and its molecular refinement (CPSS-mol) were 8% and 6% (low risk), 31% and 18% (intermediate-1 risk), 43% and 40% (intermediate-2 risk), and 18% and 36% (high risk). Transplants were received from matched unrelated (51%), mismatched unrelated (25%), matched related (21%), or mismatched related donors (3%). Conditioning intensity was reduced (49%), myeloablative (43%), or non-myeloablative (8%). Median age of patients was 60 years, 29% were female, 30% had a Karnofsky performance status <90%, and 15% had a comorbidity index >3. In the first step of the OS analysis, the algorithm identified mutations in ASXL1, KRAS, SF3B1, ZRSR2 as high-risk mutations (HRM) predicting worse OS. In addition, the number of the HRMs was associated with worse OS. In the next step, the algorithm automatically stratified this information into three distinct risk groups: the absence of HRMs (reference; low risk), presence of 1-2 HRMs (HR, 1.81; intermediate-risk), and 3-4 HRMs (HR, 2.93; high-risk). Corresponding 6-year OS was 59% for the low-risk, 34% for the intermediate-risk, and 14% for the high-risk group (P<.001; Figure 1A). Furthermore, the absence of HRMs was associated with lower NRM (15%) compared with present HRMs (46%; P=.01). In contrast, the CPSS-mol genetic risk classification including ASXL1, RUNX1, NRAS, and SETBP1 mutations showed no distinct 6-year OS or NRM (P=.15, respectively). Next, we adjusted the impact on OS of the proposed genetic risk for other factors included in the CPSS-mol. Higher genetic risk was independently associated with increased hazard for death (with the low-risk group as reference) showing HRs of 1.70 for the intermediate-risk and 2.83 for the high-risk group (P<.001). This model showed a concordance index of 0.633 versus CPSS-mol (0.597) or the CPSS (0.572) suggesting utility of transplant-specific prognostication. Therefore, we evaluated the multivariable effect on posttransplant outcome including the following independent clinical and molecular predictors: genetic risk, % of peripheral and bone marrow blasts, leukocyte count, and performance status. This model was predictive of OS and NRM (P<.001, respectively), and showed increased prognostic precision for OS, reflected in a concordance index of 0.684. In conclusion, mutations in ASXL1, KRAS, SF3B1, ZRSR2, and the number of these mutations predict OS and NRM in CMML undergoing transplantation. Accounting for these genetic lesions may improve the prognostic precision and patient counseling in the transplant setting. Figure 1 Disclosures Bogdanov: Jazz Pharmaceuticals, MSD.: Other: Travel subsidies. Stoelzel:Neovii: Other: Travel funding; JAZZ Pharmaceuticals: Consultancy; Shire: Consultancy, Other: Travel funding. Rautenberg:Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Dreger:Neovii, Riemser: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau. Finke:Riemser: Honoraria, Other: research support, Speakers Bureau; Neovii: Honoraria, Other: research support, Speakers Bureau; Medac: Honoraria, Other: research support, Speakers Bureau. Kobbe:Pfizer: Honoraria, Other: Travel support; Takeda: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Jazz: Honoraria, Other: Travel support; Amgen: Honoraria, Other: Travel support, Research Funding; Biotest: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Neovii: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support. Platzbecker:Celgene: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Robin:Novartis Neovii: Research Funding. Beelen:Medac GmbH Wedel Germany: Consultancy, Honoraria. Kroeger:JAZZ: Honoraria; Neovii: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi-Aventis: Honoraria; Novartis: Honoraria, Research Funding; Medac: Honoraria; DKMS: Research Funding; Riemser: Research Funding.

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SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094540 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4540

Author(s):

Johannes Korth ◽

Benjamin Wilde ◽

Sebastian Dolff ◽

Jasmin Frisch ◽

Michael Jahn ◽

...

Keyword(s):

High Risk ◽

Healthcare Workers ◽

Risk Group ◽

Close Contact ◽

Virus Transmission ◽

High Risk Group ◽

Low Risk ◽

University Hospital ◽

Intermediate Risk ◽

Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

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A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

10.21203/rs.3.rs-57306/v1 ◽

2020 ◽

Author(s):

Yi Ding ◽

Tian Li ◽

Min Li ◽

Tuersong Tayier ◽

MeiLin Zhang ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Risk Model ◽

Risk Group ◽

Clinical Information ◽

Low Risk ◽

Gene Set Enrichment Analysis ◽

Positive Regulation ◽

Risk Patients ◽

Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

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A Novel Risk Classification Model Predicts Overall Survival and Locoregional Surgery Benefit in Colorectal Patients with Distant Metastasis at the Initial Diagnosis

10.21203/rs.3.rs-117490/v1 ◽

2020 ◽

Author(s):

Mo Chen ◽

Tian-en Li ◽

Pei-zhun Du ◽

Junjie Pan ◽

Zheng Wang ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Distant Metastasis ◽

Cox Regression ◽

Risk Group ◽

Risk Groups ◽

Risk Classification ◽

Low Risk ◽

Classification Model ◽

Intermediate Risk

Abstract Background and aims: In this research, we aimed to construct a risk classification model to predict overall survival (OS) and locoregional surgery benefit in colorectal cancer (CRC) patients with distant metastasis.Methods: We selected a cohort consisting of 12741 CRC patients diagnosed with distant metastasis between 2010 and 2014, from the Surveillance, Epidemiology and End Results (SEER) database. Patients were randomly assigned into training group and validation group at the ratio of 2:1. Univariable and multivariable Cox regression models were applied to screen independent prognostic factors. A nomogram was constructed and assessed by the Harrell’s concordance index (C-index) and calibration plots. A novel risk classification model was further established based on the nomogram.Results: Ultimately 12 independent risk factors including race, age, marriage, tumor site, tumor size, grade, T stage, N stage, bone metastasis, brain metastasis, lung metastasis and liver metastasis were identified and adopted in the nomogram. The C-indexes of training and validation groups were 0.77 (95% confidence interval [CI] 0.73-0.81) and 0.75 (95% CI 0.72-0.78), respectively. The risk classification model stratified patients into three risk groups (low-, intermediate- and high-risk) with divergent median OS (low-risk: 36.0 months, 95% CI 34.1-37.9; intermediate-risk: 18.0 months, 95% CI 17.4-18.6; high-risk: 6.0 months, 95% CI 5.3-6.7). Locoregional therapies including surgery and radiotherapy could prognostically benefit patients in the low-risk group (surgery: hazard ratio [HR] 0.59, 95% CI 0.50-0.71; radiotherapy: HR 0.84, 95% CI 0.72-0.98) and intermediate risk group (surgery: HR 0.61, 95% CI 0.54-0.68; radiotherapy: HR 0.86, 95% CI 0.77-0.95), but not in the high-risk group (surgery: HR 1.03, 95% CI 0.82-1.29; radiotherapy: HR 1.03, 95% CI 0.81-1.31). And all risk groups could benefit from systemic therapy (low-risk: HR 0.68, 95% CI 0.58-0.80; intermediate-risk: HR 0.50, 95% CI 0.47-0.54; high-risk: HR 0.46, 95% CI 0.40-0.53).Conclusion: A novel risk classification model predicting prognosis and locoregional surgery benefit of CRC patients with distant metastasis was established and validated. This predictive model could be further utilized by physicians and be of great significance for medical practice.

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P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

European Heart Journal ◽

10.1093/eurheartj/ehz745.0468 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Grinberg ◽

T Bental ◽

Y Hammer ◽

A R Assali ◽

H Vaknin-Assa ◽

...

Keyword(s):

Myocardial Infarction ◽

High Risk ◽

Cardiovascular Events ◽

Risk Group ◽

Temporal Trends ◽

High Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

High Risk Patients ◽

Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

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Recurrence and progression of non-muscle invasive bladder cancer following trans-urethral resection of bladder tumour with adjuvant intravesical chemo-immunotherapy

Journal of Chitwan Medical College ◽

10.3126/jcmc.v10i3.32035 ◽

2020 ◽

Vol 10 (3) ◽

pp. 34-38

Author(s):

Ashok Kumar Kunwar ◽

Kabir Tiwari ◽

Sanjesh Bhakta Shrestha ◽

Srijana Thapa ◽

Ashish Kumar Panthee ◽

...

Keyword(s):

Bladder Cancer ◽

High Risk ◽

Effective Treatment ◽

Risk Group ◽

Bladder Tumour ◽

Low Risk ◽

Invasive Bladder Cancer ◽

Intermediate Risk ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Background: Trans-urethral resection of bladder tumor is an essential diagnostic tool as well as effective treatment modality for non-muscle invasive bladder cancer. We aimed to evaluate the recurrence and progression of the non-muscle invasive bladder cancer in Nepalese patients. Methods: This was a retrospective study of 43 patients with non-muscle invasive bladder cancer, who underwent trans-urethral resection of bladder tumour followed by adjuvant intravesical instillation of chemo or immunotherapy between January, 2013 to December, 2018. Patients were divided into low, intermediate and high-risk groups according to the clinical and pathological factors used by the European Organization for Research and Treatment of Cancer scoring system. Outcomes were calculated in terms of recurrence and progression in each group. Results: Out of 43 patients, 11 (25.58%) patients had low risk, 18 (41.86%) patients had intermediate risk and 14 (32.56%) patients had high risk of recurrence categories. No recurrence and progression of the disease noted in low risk group. In the intermediate risk group, out of 18 patients, 4 (22.2%) patients developed recurrence and 2 (11.1%) patients had progression of disease. In high risk group, out of 14 patients, 4 (26.8%) patients developed recurrence and 2 (14%) patients developed progression of the disease. Conclusions: Even in a low volume centre of bladder cancer, effective treatment for non-muscle invasive bladder cancer with trans-urethral resection of bladder tumour followed by adjuvant intravesical chemo or immunotherapy can be given safely to reduce recurrence and progression of the disease.

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Application of Risk-Adapted Therapy for Acute Myeloid Leukemia to a Population. Effects of Stem Cell Transplantation on Outcome.

Blood ◽

10.1182/blood.v104.11.4449.4449 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4449-4449

Author(s):

Anders Wahlin ◽

Mats L. Brune ◽

Rolf Billstrom

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Risk Group ◽

Low Risk ◽

Intermediate Risk ◽

Relapse Free Survival ◽

Free Survival ◽

First Remission

Abstract We introduced a risk-adapted treatment program for non-APL AML in four Swedish health regions. The aim was to optimise treatment results by the use of risk group stratification, mainly based on cytogenetic findings at diagnosis. All patients received induction therapy with idarubicin-cytarabine 3+7 and consolidation cycles containing high-dose cytarabine. Stem cell transplantation was done in CR1 in selected patients, sparing patients with low/intermediate risk of relapse the risks associated with transplantation. 279 patients, 77% of all AML patients 18–60 years (median 51 yrs), in the population were included in the program. Cytogenetics was performed in 98%. Excluding APL, 19 patients had low-risk. The intermediate-risk group consisted of 165 patients, 96 with a normal karyotype. 95 patients were allocated to the high-risk group. 6% died < 30 days after diagnosis. CR rate was 80%. 111 transplants, 78 allogeneic/URD and 33 autologous, were performed in CR1. 40% of all patients were alive after five years. Median overall survival time was 887 days in low-risk, 611 days in intermediate risk, 345 days in high-risk patients. Relapse-free survival times were also significantly (p<0.001) different between the three risk groups. 43% of responding patients were alive in first remission after four years. 4-year relapse-free survival was significantly better for both intermediate risk (67%) and high-risk (41%) with allogeneic/URD transplantation than with autologous transplant or chemotherapy alone. Relapse was observed more often among patients treated with chemotherapy alone (42%, p=0.03) or with autologous transplants (42%, p=0.09) than among patients receiving allogeneic/URD transplants in CR1, 22%. Our results do not support the use of autologous transplantation in AML in first remission.

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