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In: Transplantation and Cellular Therapy, Elsevier BV, Vol. 28, No. 10 ( 2022-10), p. 712.e1-712.e8

Type of Medium: Online Resource

ISSN: 2666-6367

URL: Article

DOI: 10.1016/j.jtct.2022.07.014

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 3056525-X

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4719-4719

Abstract: Introduction: Budd-Chiari Syndrome (BCS) is a consequence of obstruction of hepatic venous outflow tract leading to increased sinusoidal pressure, portal hypertension and hepatic necrosis. The true incidence and ideal management strategy including the duration of anticoagulation is not fully clear due to the rarity of the event in general population. Many associations like hypercoagulablestates, tumors, infections, and auto immune diseases are described. We intend to describe the patient population diagnosed with BCS and following up in our thrombosis clinic. Methods: We identified 9 patients diagnosed with from 2010-2015. We evaluated various demographics, laboratory data, identifiable etiology of BCS, Child-Pugh score (CP), Model of End stage Liver Disease score (MELD), presence of esophageal varices, anticoagulation used and duration of therapy. Results: Characteristics of the study population included a median age of 36 years (28-58 y), 55% females and 77% whites (Table 1). Following anticoagulants used: Warfarin (n=7), Heparin switched to Bivalirudin due to heparin induced thrombocytopenia (n=1), None (n=1) and those 7 remained on indefinite anticoagulation. The one treated with Heparin-Bivalirudin died soon from diagnosis and the one with no identifiable thrombophilia was non compliant and did not receive anticoagulation. Of those 7 on Warfarin only one experienced anticoagulation failure with recurrence of thrombosis needing a change in anticoagulant. At diagnosis median INR was 1.5 (1-2.4), median Anti thrombin (AT) activity of 68% (39-111%) (Ref range 80-120%) in 8 evaluated patients, Protein C was 62% (65-145%) in 3 patients tested, Protein S was 90% (71-170%) in 3 tested patients. Other tests were positive for heterozygous factor V Leiden (FVL) mutation (11%) and Antiphospholipid antibody syndrome (APS) (11%) but not for Prothrombin G20210A mutation. Median Creatinine was 1.04 mg/dL (0.5-2.2 mg/dL), bilirubin 2.8 mg/dL (0.3-6.4 mg/dL), Albumin 3.3 gm/dL (2.3-3.4 gm/dL), Alkaline phosphatase 163 U/L (86-275 U/L), AST 135 U/L (14-1037 U/L), ALT 236 U/L (18-1694 U/L), Hemoglobin 15.8 gm/dL (9.9-20 gm/dL), Platelet count of 335 x 10E3/cmm (70-971 x 10E3/cmm). 2 of the 5 women were on OC pills (One 〉 6 month and one patient 〈 6 months duration). 8 of 9 had ascites, 2 of 9 had alcohol abuse, 4 of 9 had cirrhosis. Median MELD score was 11 (6-28) and Child-Pugh score of 9 (8-13), 3 of 9 patients did not have varices, 3 of 9 had smoking history. Median BMI is 30 (18-38), 3 of 9 underwent liver transplant and 1 of 9 underwent TIPS but died before liver transplant. Etiologies include Myeloproliferative Neoplasms (67%), APS (11%), Sarcoidosis(11%) and none (11%). Conclusions: The incidence of Myeloprolifeartive neoplasms was very high (67%) in our cohort and indicates that such disorders be ruled out in patients with BCS at diagnosis. The most common familial thrombophilia including Factor V Leiden and Prothrombingene mutations appear to be less frequent than reported previously. Acquired AT deficiency is not uncommon. Proper evaluation of the underlying etiology may help identify important disorders and may guide anticoagulant management. APS-Antiphospholipid antibody syndrome, AT-Antithrombin activity, ET-Essential thrombocythemia, MPN-MyeloprolifeativeNeoplasms, NA-Not available, PV-Polycythemia Vera Table.Age/SexAT%FVLPT G20210AMELDCP scoreThrombophilia/etiologySmokingBMI30/F70NANA89JAK2+ETNo1828/F59NANA119APSNo2440/F111NN66SarcoidosisNo3036/M63NN1612JAK2+PVNo3029/M66NN118JAK2+ETYes3750/FNANANA2813JAK2+PVNo3846/F39NN1611JAK2+PVYes2858/M90HeteroN88CALR+MPNYes3829/M89NN98NoneNo26 Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.4719.4719

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5949-5949

Abstract: Introduction : DLBCL is a heterogeneous disease with increasingly complex treatment selection. Prior studies demonstrated improved outcomes of hematologic malignancies managed in academic centers and based on socioeconomic factors. We aimed to compare OS of patients with DLBCL based on the type of treatment facility and other factors. Methods: This retrospective study utilized the National Cancer Data Base (NCDB) to identify patients with DLBCL diagnosed between 1998 and 2012. Health care facilities were categorized as either academic (academic/research program) or non-academic (comprehensive community cancer program, community cancer program, and other programs). Patients with complete data for sex, age, race, education, income, distance traveled for health care, hospital type, facility location, urban/rural, insurance, Charlson co-morbidity score, chemotherapy use, time from diagnosis to treatment initiation, use of hematopoietic stem cell transplant, last contact, and vital status were included. OS of patients who received first course treatment at academic centers, was compared to those treated at non-academic centers. Kaplan Meier curves for OS were compared using log-rank test. Multivariate Cox proportional hazard model was performed to identify determinants of OS. Results: Of 264,697 patients with DLBCL, 33% were treated at academic centers. Patients treated at academic centers differed from non-academic centers in mean age (65 vs. 68 years; p 〈 0.0001), gender (45 vs. 47% females, p 〈 0.0001), race (85 vs. 91% whites, p 〈 0.001), income (38 vs. 31% with annual income 〉 $63,000, p 〈 0.001), education (17 vs. 15% residing in locality with ≥21% population without high school graduates, p 〈 0.001), and insurance status (40 vs. 35% with private insurance, p 〈 0.001), Charlson comorbidity score (79 vs. 76% with score 0, p 〈 0.001) and AJCC stage (40 vs. 33% stage IV, p 〈 0.001). Because of missing data, only 167,458 patients were used for OS analysis. Receipt of first course treatment at academic versus non-academic centers was associated with a higher median OS (95 months vs. 78 months, p 〈 0.0001) (Figure 1). After adjusting for other co-variates, treatment at non-academic centers was associated with an increased risk of death (hazard ratio 1.05, 95% confidence interval 1.03-1.07). Other factors associated with improved OS include younger age, female sex, white race, private insurance, higher income and educational status, lower stage, lower comorbidity score, early initiation of chemotherapy, and use of radiation therapy (Table 1). Conclusion : Our study demonstrated differences in the characteristics of patients with DLBCL based on the facility type. Academic centers were more likely to treat patients who were younger, females, of ethnic minorities, with less education, higher income levels, private insurance, less comorbidities and higher stage disease. The receipt of frontline therapy at academic centers was associated with increased OS in patients with DLBCL. Some of the possible reasons for this difference may include provider experience, increased access to resources and clinical trials. Our study also demonstrated cancer health disparities based on other socioeconomic factors such as gender, race, income and insurance status. Further investigations into the factors contributing to such disparities should be a research priority to help standardize care and improve outcomes. Figure 1 Kaplan-Meier curves Figure 1. Kaplan-Meier curves Disclosures Armitage: Conatus - IDMC: Consultancy; Roche: Consultancy; Spectrum Pharmaceuticals: Consultancy; GlaxoSmithKline IDMC: Consultancy; ZiopharmOncology: Consultancy; Tesaro bio Inc: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.5949.5949

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4512-4512

Abstract: Background: BPDCN is a rare subtype of aggressive acute leukemia that usually has an indolent clinical presentation such as isolated solitary or multiple cutaneous lesions. Despite initial clinical responses to systemic chemotherapy, BPDCN follows an aggressive course with a reported median OS of approximately 8-14 months based on single-center studies. We aimed to determine the OS of BPDCN and its predictors utilizing a US population-based database. Methods: Using International Classification of Disease for Oncology, 3rd edition (ICD-O-3) code 9727/3, SEER 18 database was analyzed to identify adult patients with BPDCN diagnosed from 2001-2012. We divided the entire cohort into 3 groups based on time periods of 4 years each (2001-2004, 2005-2008, 2008-2012) to represent early (E), middle (M) and late (L) cohorts. Age, sex, race, marital status, radiation use, and OS were compared across the three time periods. Multivariate analyses of OS were performed using Cox regression to adjust for significant covariates. A p-value of 〈 0.05 was considered statistically significant. Results: Of 417 patients, the majority were males (67%), patients aged ≤ 60 years (75%) and whites (82%). A higher proportion of patients were diagnosed in the early time period (E=43% vs. M=29% vs. L = 29%). About a sixth of the cohort (17%) received radiation therapy. Median OS was not reached for the cohort. Five-year OS was higher for patients ≤ 60 years, as compared to patients 〉 60 years (70% vs. 50%, p 〈 0.01). On a multivariate analysis, age 〉 60 years (hazard ratio, HR 2.05; 95% confidence interval, CI 1.28-3.27, p 〈 0.008) and African American ethnicity (HR 1.79; 95% CI 1.10-2.89, p=0.018) were associated with a higher hazard for death whereas OS did not differ based on sex, marital status, time period, or the use of radiation therapy. Of the 106 patients 〉 60 years, the majority were males (68%), whites (93%), married (74%), and did not receive radiation (92%). On a multivariate analysis after adjusting for age, sex, race, time of diagnosis, and radiation therapy, being single (marital status) was associated with a worse OS (HR2.24; 95% CI 1.05-4.77, p=0.034) among patients 〉 60 years. Conclusions: To our knowledge, this is the largest and most recent population-based study in BPDCN. Compared to prior single-center studies, our results demonstrate much better OS. Older age and African American ethnicity are determined to be negative prognostic factors for OS. Single older patients are at even a higher risk of mortality. The study findings may help in patient counseling and informed decision-making. Racial disparities in OS require further investigation. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.4512.4512

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 125, No. 21 ( 2015-05-21), p. 3359-3360

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2015-01-625764

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 2155-2155

Abstract: Introduction: Whether adults aged ≥60 years with AML benefit from multiagent (or intensive) chemotherapy is a matter of controversy. Prior studies have demonstrated conflicting results. We performed analysis of a large National Cancer Data Base (NCDB) to determine the value of multiagent vs. single agent chemotherapy. Methods: NCDB captures approximately 70% of all cancer diagnoses in US, and undergoes rigorous quality monitoring. We utilized NCDB to identify patients aged 60-79 years, who were newly diagnosed with AML (other than APL) between the years 2004-2014. Logistic regression model was used to determine factors associated with the use of multiagent chemotherapy. Kaplan-Meier curves were generated and compared using the log rank test. Logistic regression model and Cox Proportional Hazard model were used for one-month mortality and OS analyses, respectively. In a separate analysis, patients who received single agent (n=6743) vs. multiagent chemotherapy (n=6743) were matched based on the variables age, Charlson comorbidity score, and AML subtypes (good-risk AML, therapy-related AML/AML with myelodysplasia related changes, and other intermediate/high-risk AML). A Cox Proportional Hazard model was used for OS analysis of the matched cohort. Results: Of a total of 25,621 patients, 70% received multiagent chemotherapy. The receipt of multiagent chemotherapy declined with increasing age, Charlson comorbidity score, AML subtypes other than good-risk, female, non-academic center, shorter distance traveled to receive care, lower rate of high school graduation, and more recent year of diagnosis. Patients treated with multiagent chemotherapy had higher likelihood of receiving hematopoietic cell transplant (HCT) (9% vs. 1%); lower one-month mortality (11% vs. 19%); and greater 1-year OS (43% vs. 28%) (Figure 1). The use of multiagent chemotherapy had particularly higher 1-year OS in patients aged 60-64 and 65-69 years, in good-risk AML, patients with Charlson comorbidity score of 0-1 and those who did not receive upfront HCT consolidation (Table 1). One-month mortality (odds ratio 1.64, 95% confidence interval, CI 1.51-1.78) and OS (hazard ratio, HR 1.32, 95% CI 1.28-1.36) remained more favorable for multiagent chemotherapy group in multivariable analyses. Other factors that affected OS included age, comorbidity, AML subtypes, median household income, insurance, use of HCT, academic status of facility, distance traveled to receive care, sex and year of diagnosis. In a matched analysis of 13,486 patients, the use of single agent vs. multiagent chemotherapy resulted in a higher risk of mortality (HR 1.28, 95% CI 1.23-1.32). Conclusions: In one of the largest real-world studies, we demonstrate an association between factors such as age, comorbidity and AML subtypes and the use of multiagent chemotherapy. After adjusting for covariates, the use of multiagent chemotherapy among older adults was associated with higher receipt of HCT, and improved one-month mortality and OS. Improved OS was confirmed in a matched analysis. Certain groups such as patients younger than 70 years, good-risk AML and those with low Charlson comorbidity score had the greater OS benefit with the use of multiagent chemotherapy. Further studies to determine the role of multiagent or intensive chemotherapy are particularly important with approvals of several new drugs in the recent years and integration of many novel drugs in both low-intensity and intensive chemotherapy regimens. Disclosures Bhatt: Tolero Pharmaceuticals: Research Funding; Incyte: Consultancy, Research Funding; Partner therapeutics: Consultancy; Abbvie: Consultancy; Agios: Consultancy; CSL Behring: Consultancy; National Marrow Donor Program: Consultancy; Pfizer: Consultancy. Holstein:Celgene: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sorrento: Consultancy. Al-Kadhimi:Celldex Biotech: Other: Stocks; Seattle Genetics: Other: Stocks. Armitage:Union Pacific: Consultancy; Tesaro bio: Membership on an entity's Board of Directors or advisory committees; Ascentage: Consultancy; Samus Therapeutics: Consultancy; Oncology Analytics: Consultancy; Partner Therapeutics: Consultancy. Gundabolu:Pfizer: Consultancy; Novartis: Consultancy; Jazz pharmaceuticals: Consultancy; Samus Therapeutics: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-122679

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5086-5086

Abstract: Introduction Polypharmacy, commonly defined as taking ≥5 prescribed medications, is a major issue in adults, especially those ≥60 years of age. Drug-drug interactions can significantly increase toxicities while undergoing chemotherapy, and may affect OS in AML. Polypharmacy can also increase treatment costs. We aimed to evaluate the effects of polypharmacy on OS in AML. Methods We included adult AML patients diagnosed from 2000-2016 at University of Nebraska Medical Center. Based on the number of prescribed medications at the time of AML diagnosis, patients were divided into 2 groups: patients with (≥5 medications) versus without polypharmacy ( 〈 5 medications). Fisher's exact test was used to identify the association of polypharmacy with baseline characteristics. OS, defined as the time from diagnosis of AML to death from any cause, was determined by the Kaplan-Meier method, and comparisons of survival curves was done using the log-rank test. Cox proportional hazard model was used to determine the effect of polypharmacy on OS adjusting for other covariates for the entire cohort, and separately for 〈 60 years and ≥60 years old. Results We included a total of 399 patients in the study- 59% were ≥60 years, 52% were male, 96% were white, and 34% had adverse cytogenetics (Table 1). Median number of medications was 4 (range 0-39). Forty-nine percent of patients received ≥5 medications. In patients with polypharmacy, median number of medications was 8 (range 5-39) vs. 2 (range 0-4) among patients without polypharmacy. Patients with polypharmacy, compared to those without polypharmacy, were more likely to be ≥60 years (77% vs 42%, p 〈 0.0001), had Karnofsky performance status (KPS) of ≤80 (53% vs.26%, p 〈 0.0001) and adverse cytogenetics (41% vs 27%, p=0.01). Median hematopoietic cell transplant (HCT) comorbidity index (HCT-CI) was 2 (range 1-4) in the polypharmacy group vs 1 (range 1-4) in the group without polypharmacy (p 〈 0.0001). Patients with polypharmacy were less likely to receive intensive chemotherapy (56% vs 81%, p 〈 0.0001) and undergo HCT (17% vs 37%, p 〈 0.0001). Patients with polypharmacy had worse OS compared to those without polypharmacy (hazard ratio [HR] 2.1, (95% confidence interval [CI] 1.6-2.6], p=0.03) (Figure 1). One-year OS of patients with polypharmacy vs. those without polypharmacy was 29% vs 49% (p 〈 0.001) (Table 1). OS was significantly lower with polypharmacy in patients 〈 60 years of age (37% vs 65% at 1-year, p 〈 0.001) but similar in patients ≥60 years (26% vs 27% at 1-year, p=0.09) (Figure 2 and 3). In polypharmacy group, 1-year OS for patients ≥60 years was 26% compared to 37% for patients 〈 60 years (p=0.02). In two separate multivariate analyses, polypharmacy conferred worse OS in patients 〈 60 years of age (HR 1.9, 95% CI 1.2-3.1) but not in patients ≥60 years (HR 1.1, 95% CI 0.8-1.6). Conclusion Patients with polypharmacy were older and had greater incidence of adverse cytogenetics, and were less likely to receive intensive chemotherapy and HCT. While HCT CI was slightly greater in the polypharmacy group, the difference in HCT CI does not seem to be clinically remarkable for the degree of difference in the median number of medicines between groups. AML patients with polypharmacy, when adjusted for age, had worse OS than those without polypharmacy. In multivariate analysis based on the age cutoff of 60 years, polypharmacy had negative impact on OS of patients aged 〈 60 years but not on patients aged ≥60 years. While traditionally older adults are considered to be at a greater risk of polypharmacy, our study highlights that the effect of polypharmacy may be even more important in younger adults with AML. Given the impact of polypharmacy on OS, patients with newly diagnosed AML should be assessed for appropriateness of prescribed and over the counter medication. Disclosures Al-Kadhimi: Celldex Biotech: Other: Stocks; Seattle Genetics: Other: Stocks. Gundabolu:Pfizer: Consultancy; Novartis: Consultancy; Jazz pharmaceuticals: Consultancy; Samus Therapeutics: Research Funding. Bhatt:National Marrow Donor Program: Consultancy; Tolero Pharmaceuticals: Research Funding; Incyte: Consultancy, Research Funding; Partner therapeutics: Consultancy; Abbvie: Consultancy; Agios: Consultancy; CSL Behring: Consultancy; Pfizer: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-124000

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 41-42

Abstract: Introduction: Venetoclax (VEN) in combination with a hypomethylating agents (HMA) is associated with a high rate of composite remission (complete remission [CR] and complete remission with incomplete recovery [CRi] ) among older and unfit patients with untreated AML. However, data regarding the activity of VEN-HMA in those patients with favorable-risk AML is limited, particularly in those with core-binding factor (CBF) alterations. Although more frequent among younger patients, favorable-risk alterations are also observed among older patients, often unfit for intensive regimens. Even among the subset of older patients ( & gt;60 years) with favorable-risk AML eligible for intensive regimens, long-term outcomes are poorer in comparison to younger patients. Methods: We retrospectively analyzed outcomes of 46 patients with favorable-risk AML who underwent therapy with VEN-HMA between 2016-2020 at 4 academic cancer centers in US. Favorable-risk AML was defined by the presence of either CBF [t(8;21) and inv(16) or t(16;16)], NPM1 mutation in the absence of FLT-3 ITD mutations; or bi-allelic CEBPA mutations. Results: Forty-six patients with favorable risk AML were treated with HMA-VEN, including 26 (57%) with newly diagnosed (ND) and 20 (43%) with relapsed/refractory (R/R) AML (Table1). Ten (22%) patients had CBF, 21 (46%) had NPM1 mutations (NPM1m), and 13 (28%) had bi-allelic CEBPA mutations (CEBPAm). The median age was 70 years, and 54% were females. Patients with R/R AML were younger than ND patients (56 vs. 72 yrs, p=0.003). Twenty (44%) patients had secondary or therapy-related AML, including half of ND patients. The median lines of prior therapy were 2(1-4) in patients with R/R AML, including 6 (30%) who had failed prior allogeneic HCT. Eleven (24%) patients had received HMA prior to HMA-VEN therapy, including 1 patient in the ND cohort for prior MDS. Eleven (24%) patients received azacitidine in combination with VEN, while the rest (76%) of patients received decitabine, including 14 patients who received 10-day decitabine during the first cycle. The CR/CRi rate among the whole cohort was 80%, including 52% CR and 28% CRi. There was no statistically significant difference in CR/CRi rate between ND and R/R patients (88% vs. 70%, P =0.15). However, patients with history of prior HMA exposure had lower response rate compared to HMA-naïve patients (55% vs. 88%, p= 0.025). No difference in response was observed based on the favorable genetic alteration subgroups (80% in CBF vs. 86% in NPM1m vs. 77% in CEBPAm, p=0.44). Furthermore, no difference in response was observed according to patient age (p= 0.83), AML types (de novo vs. secondary; p= 0.47), prior transplant (p=1.00), or the type and schedule of HMA (P=0.66). Among the responders who had MRD assessment done (n= 26), 22 (85%) achieved MRD negativity by multicolor flow cytometry. Post response, 13 (35%) patients underwent allogeneic transplant consolidation. The median overall survival (OS) for the whole cohort was 18 months (12.5-NA). Median leukemia-free survival (LFS) was 13.2 months (7-20.2) for all responders, 11.2 months (1.7-NA) for ND responders, and 14.0 months (1-NA) for RR responders (p=0.986). The 30- and 60-day mortality for the whole cohort was 0% and 9%, respectively. Conclusion: In patients with favorable-risk AML, VEN-HMA combination is associated with a highly promising CR/CRi rate, with durable responses. The majority of responders achieved MRD negativity. Patients with prior use of HMA had lower response rate with VEN-HMA, nonetheless, over half of these patients responded despite most being treated in the R/R setting. Disclosures Pullarkat: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stein:Stemline: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Marcucci:Abbvie: Speakers Bureau; Merck: Other: Research Support (Investigation Initiated Clinical Trial); Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial); Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees. Yaghmour:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau. Bhatt:Omeros: Consultancy; Agios: Consultancy; Rigel: Consultancy; Tolero: Research Funding; Pfizer: Research Funding; Abbvie: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Partnership for health analytic research: Consultancy; Takeda: Consultancy; Jazz: Research Funding; National Marrow Donor Program: Research Funding; Oncoceutics: Other. Fathi:Takeda: Consultancy, Research Funding; Jazz: Consultancy; Forty Seven: Consultancy; Daiichi Sankyo: Consultancy; Amphivena: Consultancy; Blueprint: Consultancy; Kura Oncology: Consultancy; Boston Biomedical: Consultancy; Astellas: Consultancy; Trovagene: Consultancy; Novartis: Consultancy; PTC Therapeutics: Consultancy; Agios: Consultancy, Research Funding; BMS/Celgene: Consultancy, Research Funding; Kite: Consultancy; Pfizer: Consultancy; Trillium: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Abbvie: Consultancy; Newlink Genetics: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-142780

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 24-25

Abstract: Background: Clinical trial data suggest excellent short-term outcomes for younger patients and a subset of fit older patients. Translating findings of clinical trials into the real-world practice has challenges, and longer-term data are often not available. Hence, we utilized NCDB to determine age-based probability of ten-year OS of unselected cohorts of adults with AML. Methods: NCDB captures about 70% of all new diagnosis of cancer. We utilized NCDB to analyze ten-year OS of 15,646 patients aged ≥18 years, who were diagnosed with AML during the years 2004-2007. Univariate and multiple logistic regression models were used to determine factors associated with ten-year OS. Kaplan Meier curves were generated for OS analysis. Results: Ten-year OS was 12.7% for patients aged 18-59 years treated with chemotherapy without hematopoietic cell transplant (HCT) (Table 1, Fig. 1). Older age, male, Charlson-Deyo comorbidity score & gt;0, insurance other than private, subtypes other than core-binding factor AML were associated with lower ten-year OS. Ten-year OS was 24.3% for patients aged 18-59 years treated with chemotherapy and HCT (Fig 2). Older age, male, and insurance other than private were associated with lower ten-year OS. Ten-year OS was 16.1% and 2.2% for patients older than 60 years and treated with and without HCT, respectively; multivariate analysis was not performed for older patients because of low sample size (HCT group) or low survival (non-HCT group). Detailed analysis will be presented. Conclusions: Long-term OS of adults with AML is low with less than a quarter of patients being alive at ten years. Ten-year OS is particularly poor for older patients who are treated with chemotherapy alone. Whereas recent advances and approval of eight new drugs will likely improve short-term OS at 2-3 years, innovative strategies are necessary to improve long-term OS and cure. Further study to identify the cause of death will be insightful. Disclosures Bhatt: Takeda: Consultancy; Partnership for health analytic research: Consultancy; Jazz: Research Funding; National Marrow Donor Program: Research Funding; Oncoceutics: Other; Abbvie: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero: Research Funding; Rigel: Consultancy; Agios: Consultancy; Omeros: Consultancy. Chaulagain:Sanofi Genzyme: Honoraria. Gundabolu:BioMarin: Consultancy; Bristol Myers Squibb pharmaceuticals: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-134434

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1069-1069

Abstract: Background: Acute Lymphoblastic Leukemia (ALL) outcomes have significantly improved over time with multi-agent chemotherapy, and the addition of asparaginase (ASP) has demonstrated the ability to prolong overall survival. ASP has multiple toxicities, and it remains a challenge to manage them safely, particularly coagulopathy and thrombosis (30-40% based on historical studies). The best prophylactic anticoagulation strategy in patients with acute leukemias, particularly ALL with asparaginase use, remains unclear due to severe coexisting thrombocytopenia and coagulopathy. Though the current guidelines recommend using Antithrombin (AT) replacement or low molecular weight heparin (LMWH) for thrombosis prophylaxis, the evidence is weak with concerns of thrombosis (Blood (2020) 136 (3): 328-338) with the use of fibrinogen concentrates(cryoprecipitate) and limited efficacy data with AT replacement and unfractionated heparin (UFH) for thrombosis prophylaxis. Due to potential "resistance" to LMWH and UFH from acquired AT deficiency with ASP use, our institution in 2017 has adopted the use of the direct Xa inhibitor, Apixaban for thrombosis prophyalxis. We report the safety and effectiveness of Apixaban for thrombosis prophylaxis with ASP. Methods: In this retrospective study, we reviewed the data on 20 patients treated with ASP between 2017-2020. Thrombosis prophylaxis was instituted with Apixaban 2.5 mg PO Q 12 hourly for three weeks along with cryoprecipitate as needed for bleeding or fibrinogen levels & lt;100 mg/dL (normal 160-450 mg/dL) to balance the risk of bleeding. Apixaban was held if platelet count & lt;20,000/µL and for invasive procedures or clinically significant bleeding events. We evaluated demographic data, ALL risk category, type of ASP use, laboratory data (Table 1 & 2) for four weeks following ASP, amount of cryoprecipitate used, major bleeding, clinically relevant non-major bleeding (CRNMB), and thrombosis incidence. The medians of pertinent laboratory data were plotted on a graph. Descriptive statistics with medians, quartiles, frequencies, and percentages are reported. Results: Among the 20 patients treated during this period, 18 (90%) had ALL, and 2(10%) had NK/T cell lymphoma. Of the patients with ALL, 67% had high risk and 33% with standard-risk ALL. The median age of this cohort was 29.5 years (range: 19-63 years), 80% were males, 70% white, 30% were Latino or Hispanic, median body mass index-BMI of 30.2 kg/m 2(19.4-40.7 kg/m 2) and 65% were non-smokers. The median baseline AT activity was 107% (79-221%), 95% used concurrent corticosteroids (65%- Prednisone, and 30% used Dexamethasone). The most common induction treatment was CALGB 10403 (55%). Of the total, 95% received pegylated ASP, and only one patient received Erwinia ASP due to prior history of anaphylaxis. The major toxicities attributed to ASP included 5% grade II and 15% grade III-IV aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, 20% had bilirubin elevation, 10% developed grade III-IV acute pancreatitis, and 5% developed severe hypertriglyceridemia needing aphaeresis. Two patients (10%) developed thrombosis [catheter associated deep venous thrombosis (DVT) and one patient with lower extremity proximal DVT] within 4 weeks of use of ASP, with one of the two patients (5%) developing (lower extremity proximal DVT) while on being off anticoagulation due to bleeding. Major bleeding or CRNMB developed in 5% (spontaneous splenic rupture from ALL leading to hemorrhagic shock). The median number of cryoprecipitate units used per patient during weeks 1,2,3, and 4 was 5(0-35), 5(0-40), 5(0-15), 7.5(0-15), respectively; No patients received fresh frozen plasma or AT concentrates. Conclusions: With the use of Apixaban prophylaxis, the incidence of thrombosis was 10% within four weeks from ASP and 5% while on anticoagulation. The incidence of major bleeding or CRNMB was 5%. Hypofibrinogenemia, acquired AT deficiency due to ASP, was seen between days 7-21 after using ASP (figure 1 & 2) and recovered subsequently. This study demonstrates initial evidence of the safety and efficacy of Apixaban for thrombosis prophylaxis and cryoprecipitate infusions in patients treated with ASP. Figure 1 Figure 1. Disclosures Gundabolu: Samus Therapeutics: Research Funding; Pfizer: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy. Bhatt: Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Lunning: Myeloid Therapeutics: Consultancy; Janssen: Consultancy; Kyowa Kirin: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Novartis: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy; Daiichi-Sankyo: Consultancy; Legend: Consultancy; Kite, a Gilead Company: Consultancy; Verastem: Consultancy; Acrotech: Consultancy; Karyopharm: Consultancy; Spectrum: Consultancy; Beigene: Consultancy; Morphosys: Consultancy. Baljevic: BMS/Celgene: Consultancy; Oncopeptides: Other: Advisory Board; Janssen Research: Other: Advisory Board; Karyopharm: Other: Advisory Board; BMS/Celgene: Other: Advisory Board; Amgen: Research Funding; Exelixis: Research Funding. Ganti: Merck: Research Funding; Apexigen: Research Funding; Nektar: Research Funding; Top Alliance Biosceinces: Research Funding; Lovance: Research Funding; Novartis: Research Funding; WindMil Therapeitucs: Research Funding; Takeda: Research Funding; Flagship Biosciences: Consultancy; AstraZeneca: Consultancy, Other: Advisory Board; Mirati Therapeutics: Consultancy, Other: Advisory Board; G1 Therapeutics: Consultancy, Other: Advisory Board; Blueprint Medicines: Consultancy, Other: Advisory Board; Cardinal Health: Consultancy, Other: Advisory Board; Roche: Consultancy, Other: Advisory Board; YMabS Therapeutics: Other: DSMC Chair.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-148945

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

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detail.hit.zdb_id: 80069-7