bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response rates in acute myeloid leukemia patients treated with attenuated durations of venetoclax in combination with hypomethylating agents.
Authors: Blanding Dena , Jonathan Bakos Keegan , Rangel Christopher Andrew , Pasyar Sarah , Hill Elizabeth Goodwin , Davis James , Hess Brian T. , Baratam Praneeth , Greenwell Irl Brian 
Published: June 2021

e19008 Background: The combination of the Bcl-2 inhibitor, venetoclax, with hypomethylating agents (HMA) recently emerged as an efficacious treatment for older adults with acute myeloid leukemia (AML) who are not eligible for intensive induction therapy. In a phase III randomized controlled trial of HMA +/- venetoclax, DiNardo et al demonstrated impressive composite complete response rate and complete response with incomplete recovery (CR+CRi) of 66% in the venetoclax arm as compared to 28% in the placebo arm. Despite HMA/Venetoclax being lower intensity, 83% of patients developed grade 3 hematologic adverse events, and 42% of patients experienced febrile neutropenia in the venetoclax arm, as compared to 19% in the placebo arm. In the trial, venetoclax was given continually for 28 day cycles, with some patients receiving shortened durations of venetoclax (21 days) due to toxicity. To reduce toxicity, some institutions have further limited the duration of venetoclax in cycle 1. Here, we report response rates with attenuated durations of venetoclax with HMA. Methods: We conducted a retrospective study of AML patients who received venetoclax in combination with HMA, excluding those with prior chemotherapy for AML or MDS, or previous exposure to HMA or venetoclax. Demographic, cytogenetic, pathology, and outcome data were collected including bone marrow biopsy results at diagnosis and after cycle 1 (day +28) or cycle 2 (day +56). The primary outcome was composite response rate (CR+CRi) following cycle 1 or cycle 2 defined by 2017 ELN criteria. Results: 25 patients were identified with median age of 73 (range 63-82). 9 patients received 14 or less days of venetoclax (attenuated duration): < 8 days in 1 patient and 8-14 days in 8 patients. 16 patients received 21 days or more (standard duration): 21 days in 14 patients, and 28 days in 2 patients. Of the patients who received an attenuated duration, the median age was 74 (68-82), 22% had either a TP53 mutation or deletion, 56% had complex karyotype, and 44% had received prior cytotoxic chemotherapy. Of the patients who received standard duration therapy, the median age was 71 (63-81), 44% had either a TP53 mutation or deletion, 75% had complex karyotype, and 6% had received prior cytotoxic chemotherapy. The composite response rate was 78% in the attenuated duration group and 75% in the standard duration group (p > 0.99). Conclusions: Though a limited sample size, this data suggests high response rates can be observed with attenuated courses of venetoclax. With appropriately selected patients, the feasibility of attenuated venetoclax courses could be further explored in larger prospective studies.[Table: see text]
Associations of coping strategies with quality of life (QOL) and mood in patients with acute myeloid leukemia (AML).
Authors: Reynolds Matthew J. , Lavoie Mitchell W. , Jones Bailey T. , Nelson Ashley M. , Amonoo Hermioni L. , LeBlanc Thomas William , El-Jawahri Areej 
Published: June 2021

e19012 Background: Patients with AML who receive intensive chemotherapy experience immense physical and psychological symptoms, which can result in a substantial deterioration of QOL. As data on the relationship between AML patient coping strategies and patient-reported outcomes are lacking, we aimed to determine the associations between patients’ coping strategies and their quality of life and mood. Methods: We conducted a secondary analysis of cross-sectional data from a multi-site randomized supportive care trial for hospitalized patients diagnosed with AML and receiving intensive chemotherapy. Within 72 hours of initiating chemotherapy, patients completed baseline assessments of QOL (FACT-Leu), anxiety and depression symptoms (HADS), and symptom burden (ESAS). Patients also completed subscales from the Brief Cope to assess baseline use of coping strategies. We created high-order factors (approach-oriented coping vs. avoidant-oriented coping) from the coping subscales and utilized the median split method to identify the proportions of patients with high use of approach and avoidant-oriented coping strategies, respectively. We used linear regression models adjusting for age, gender and diagnosis type (newly diagnosed vs. relapsed/refractory AML) to examine the relationships between patients’ use of coping strategies and their baseline QOL, mood and symptom burden. Results: A total of 160 patients were enrolled in the study (60.0% male; median age 64.4 years [range 19.7-80.1]). Overall, 47.5% (76/160) of patients reported high use of approach-oriented coping strategies, while 38.8% (62/160) reported high use of avoidant-oriented strategies. In regression models, the greater use of approach-oriented coping strategies at baseline was associated with higher baseline QOL (β = 1.33, SE = 0.44, P= 0.003), lower depression (β = -0.28, SE = 0.07, P< 0.001) and anxiety symptoms (β = -0.24, SE = 0.08, P= 0.002), and lower symptom burden (β = -0.96, SE = 0.34, P= 0.006). By contrast, the greater use of avoidant-oriented coping strategies at baseline was associated with lower baseline QOL (β = -4.98, SE = 0.81, P< 0.001), higher depression (β = 0.60, SE = 0.13, P< 0.001) and anxiety symptoms (β = 0.79, SE = 0.14, P< 0.001), and worse symptom burden (β = 2.30, SE = 0.64, P< 0.001). Conclusions: Newly hospitalized patients with AML who utilize approach-oriented coping strategies experience better baseline QOL and mood, and a lower symptom burden. These findings underscore the need for supportive care interventions that promote effective coping in patients with AML, to improve patients’ QOL and reduce their physical and psychological distress.
Low incidence of hepatic veno-occlusive disease (VOD) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin (INO) followed by allogeneic stem cell transplantation (allo-SCT).
Authors: Cahill Kirk , Alban Juan , Mortel Mylove , Dworkin Emily , Kosuri Satyajit , Duvall Adam , Liu Hongtao , Bishop Michael Russell , Larson Richard A. , Stock Wendy 
Published: June 2021

e19024 Background: Hepatic VOD is an uncommon, but often fatal complication of allo-SCT. The risk is increased after INO, an anti-CD22 antibody conjugated to calicheamicin with high remission rates in relapsed CD22-positive B-ALL. Previous reports have described VOD rates as high as 19% in INO-treated patients who then received allo-SCT. We report our safety experience using INO followed by allo-SCT. Methods: We identified patients >18 yrs with B-ALL treated with allo-SCT and INO in the University of Chicago IRB-approved SCT database. We reviewed the EMR for patient details, toxicities (CTCAE v5.0), and outcomes. Hepatic VOD was defined according to EBMT criteria. Overall survival (OS) was from time of allo-SCT to death or last follow-up. Results: Between 2010-2021, 72 adult patients with B-ALL received allo-SCT, and 17 also received INO as salvage therapy (Table). Median follow-up was 19 months (1-110). All received ursodiol prophylaxis and 15/17 received an azole for antifungal prophylaxis. They had median 2 cycles (1-3) of INO with median of 1.9 months (1-14) from the last dose of INO to allo-SCT. For cycle 1, 13/17 (77%) received 0.8 mg/m2 on D1 and 0.5 mg/m2 on D8 and D15. Of these, 11 had a subsequent cycle (5 with same dosing and 7 had 0.5 mg/m2 on D1, D8, and D15). 1 patient had 0.5 mg/m2 on D1, D8, and D15 for 2 cycles. 3 patients received 0.8 mg/m2 on D1 and 0.4 mg/m2 on D8 and D15 for 2 cycles. After INO, 10 patients achieved CR and 3 had CRi for ORR of 13/17 (76%). The 4 patients with persistent disease despite INO went into remission with a different salvage therapy prior to allo-SCT. Conditioning regimens are listed in Table 1. No patients developed VOD after allo-SCT. Within 2 yrs of allo-SCT, 3/17 (18%) relapsed and 7/17 (41%) died. The median OS was 21.2 months [18 - NR]. Conclusions: Limiting the number of INO cycles (median 2) prior to allo-SCT, delaying allo-SCT for 2 months after INO exposure, and avoiding dual alkylating agent conditioning may have contributed to the absence of VOD in our patients. Larger data sets will be useful to validate these important safety observations.[Table: see text]
Outcomes and predictors of hospital mortality of patients with Philadelphia-negative myeloproliferative neoplasms and sepsis: A Nationwide Inpatient Sample Database analysis.
Authors: Gonzalez Mosquera Luis F. , Tobar Pool , Cardenas Maldonado Diana D. , Moscoso Bernard , Podrumar Alida I. , Cuenca John A. 
Published: June 2021

e19038 Background: Sepsis is associated with increased mortality in patients with hematologic malignancies, especially in those receiving cytotoxic chemotherapy. The development of new therapies also increases the risk of infections in Philadelphia negative myeloproliferative neoplasms (MPN). However, the clinical implications and costs of sepsis in patients with polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF) have not been reported at a national level. Therefore, we aimed to determine the outcomes, hospitalization costs, and predictors of mortality in patients with MPN and sepsis. Methods: We retrieved adult patients with MPN from the Nationwide Inpatient Sample database from 2016-2018. We used the ICD-10 codes to identify and compare patients with and without sepsis. The main outcomes were hospital mortality and predictors of mortality. We computed the chi-squared test and the Mann-Whitney U-test. Mortality predictors are estimated using multivariate logistic regression and logistic fixed-effect methods to control for admission cohort and hospital time invariant characteristics. All analyses were performed using Stata Statistical Software version 14 (StataCorp, College Station, TX). Results: A total of 86,723 patients with MPN were identified. The majority of them were white (66.9%), female (54.3%), with a median age of 62 (IQR 47-76). The most common MPN was ET (84.3%), followed by PV (14.2%). Sepsis was diagnosed in 16,146 (18.6%) of the MPN patients. There was a significantly higher mortality in the sepsis group vs. the non-sepsis group (7.4% vs. 1.8%; p < 0.001), longer LOS (8 vs. 4 days; p < 0.001), and higher median hospitalization cost (US$74,128 vs. US$39,987; p < 0.001). In the multivariable analysis, sepsis was associated with higher mortality (OR: 4.74; CI 95%: 4.33-5.18; p < 0.001). Among the MPN, those with PMF and sepsis had a higher risk of death (OR: 2.21; CI 95%: 1.72-2.82; p < 0.001). Other significant variables associated with mortality were age > 65 (OR: 2.51; CI 95%: 2.14-2.95; p < 0.001), concomitant chronic heart failure (CHF) (OR: 1.57; CI 95%: 1.39-1.77; p < 0.001), chronic kidney disease (CKD) (OR: 1.22; CI 95%: 1.10-1.35; p < 0.001), and weight loss (OR: 2.12; CI 95%: 1.79-2.51; p < 0.001). There was no significant association with sex and race/ethinicity. Conclusions: On patients with MPN, sepsis was associated with higher mortality, hospitalization costs, and LOS. Additionally, those with increased age, CHF, CKD, weight loss, and PMF were also at increased risk of death. There should be more emphasis on assessing the risk of sepsis on MPN to prevent worse outcomes and higher costs. Further studies should focus on identifying the specific causes of sepsis in MPN and promoting early recognition.
Outcomes of CNS involvement in blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Authors: Greenwell Irl Brian , Davis James , Li Hong , Soong Deborah , Taylor Justin , Lane Andrew A. , Rizzieri David 
Published: June 2021

e19043 Background: BPDCN is rare cancer commonly involving the skin and marrow. Tagraxofusp (Tag), a CD123 targeted therapy, was the first FDA approved drug for BPDCN in 2018. CNS involvement occurs in 10-60% of patients and CNS staging and prophylactic (ppx) practices are variable. The pivotal trial of Tag in BPDCN did not require CNS staging and excluded those patients with known CNS involvement. Here, we describe one of the largest cohorts of BPDCN patients with known CNS involvement, including patients treated with Tag. Methods: We collected data from 4 centers on patients with CNS involvement defined by LP or imaging with high clinical suspicion. Survival was estimated via the Kaplan-Meier method with other analyses being descriptive. Results: CNS involvement was identified in 11 patients. Median age was 74 (range 51–83) and 10 were male. 5 patients had CNS staging at initial diagnosis. At time of CNS involvement, 6/11 patients had neuro symptoms. Prior to diagnosis of CNS involvement, 5 received Tag and none received CNS ppx. Of 9 patients treated for their known CNS involvement (table), one received CNS directed systemic therapy, with all others being treated with intrathecal (IT) chemotherapy. All patients treated with 3 or more doses of IT chemotherapy cleared their CSF, and survived at least 6 months from the diagnosis of CNS involvement, including two patients (#5 and 8) with large burden CNS disease and neuro symptoms. Median survival from time of diagnosis of BPDCN was 13.8 months (2.7-35.5) and from time of diagnosis of CNS involvement was 6.0 months (0.1-25.7). Conclusions: Asymptomatic CNS involvement by BPDCN is common; routine staging and ppx should be considered at diagnosis. Tagraxofusp did not appear to prevent the development of CNS disease. IT therapy effectively cleared and controlled CNS involvement in a majority of patients. IT therapy may be sufficient to control CNS disease and IT prophylaxis should be considered, including in patients on CD123 targeting therapies. Our results provide new insights into BPDCN with CNS involvement and include patients treated with recently developed novel systemic therapies.[Table: see text]
Chimeric antigen receptor T-cell therapy real-world assessment of total cost of care and clinical events for the treatment of relapsed or refractory lymphoma.
Authors: Sahli Brett , Eckwright David , Darling Eric , Gleason Patrick P. , Leach Joseph W. 
Published: June 2021

e19500 Background: Axicabtagene ciloleucel and tisagenlecleucel are FDA approved to treat relapsed or refractory B-cell lymphoma. CAR-T therapy involves a complex process of extraction, transfection, administration and management of adverse reactions such as cytokine release syndrome. Little has been established using real world evidence identifying CAR-T episode total cost of care (TCC) and post administration clinical events (CE) among the commercially insured population. Methods: Integrated pharmacy and medical claims were queried among a population of 15 million commercially insured members from Jan 2018 to June 2020 to identify members 18 years and older with a CAR-T drug claim cost of > $250,000, lymphoma dx, no leukemia dx, and continuously enrolled through a CAR-T episode of 30 days prior to and 56 days post the CAR-T administration date. The TCC and CAR-T specific costs were calculated for the episode. Inpatient (IP) days pursuant to CAR-T administration were calculated using admission and discharge dates. Post CAR-T administration date CEs defined as subsequent chemotherapy, bone marrow transplant (BMT), and death or hospice, as well as time to event (TTE) were identified. Subsequent chemotherapy post CAR-T administration was identified. Results: 74 members, 59% male and mean age 55 years (min 18, max 76), met inclusion criteria. Mean CAR-T episode TCC was $711,884 (median $610,999) with mean CAR-T drug cost $527,547 (median $411,278). Mean IP days per episode were 17.3 (standard deviation [SD]) 9.6). 29 members (39%) experienced any CE with a mean 228 (SD 217) TTE. No CE identified among 21 (28%) members who disenrolled or ceased claim activity after a mean 253 days (SD 167). 24 (32%) remained enrolled with no CEs with a mean follow-up of a 390 days (SD 264), as of Oct 2020. Non-mutually exclusive CEs include: 22 (30%) members received subsequent chemotherapy, mean TTE 263 days (SD 238); 4 (7%) had a BMT, mean TTE 245 days (SD 108); and 13 (18%) had an identified death or hospice, mean TTE 297 days (SD 143). The most common non-mutually exclusive subsequent chemotherapy observed in 22 members were: rituximab (9 members), bendamustine (8), lenalidomide (8), obinutuzumab (5), pembrolizumab (4), polatuzumab vedotin (4), cyclophosphamide (3), ibrutinib (2), and venetoclax (2). 14 additional subsequent therapies with 1 unique utilizer were also observed. Conclusions: These 74 members show substantial variation in CAR-T episode TCC and clinical experience. 29 (39%) members did not have a durable response to CAR-T with providers initiating subsequent chemotherapy in 22 of 29 cases in the absence of clear guidelines. These data inform managed care activities such as performance metrics, case rates, and value based arrangements. Additionally, these data are important in actuarial forecasting for given the potential future volume of treated patients and spend.
Clinical and morphological characteristics or immunohostochemical factors determine the results of treatment for diffuse large B-cell lymphoma?
Authors: Kushtova Luiza B. , Frantsiyants Elena M. , Bandovkina Valeria A. , Nikolaeva Nadezhda V. , Kapuza Elena A. , Kozel Yuliya Yu. , Kozyuk Olga V. , Dmitrieva Viktoria V. 
Published: June 2021

e19539 Background: Diffuse large B-cell lymphoma (DLBCL) is and aggressive heterogeneous tumor. The treatment is ineffective in more than 30% cases: primary resistance is observed in 20%, and relapses in 10%. Clinical prognostic indices do not allow assessing the DLBCL course and treatment outcomes. The purpose of the study was to evaluate the results of treatment of DLBCL patients depending on clinical and immunohistochemical factors of the disease prognosis. Methods: Patients with DLBCL (n = 48): men – 25 (52.1%, mean age 52±3.8 years), women – 23 (47.9%, mean age 60±4.3 years) received standard treatment R-CHOP, R-CHOEP, R-EPOCH. Results: After the treatment, 27 (56.2%) patients were in remission for 3 years, 10 (20.8%) patients developed relapses, and 11 (23%) patients were refractory to the therapy. All groups demonstrated Ki-67 > 80%, overexpression of Bcl2, Bcl6, CD10, MUM-1 on tumor cells, C-MYC gene rearrangements. Patients with stage I and II nodal spread were more likely to be in remission; refractory patients and those with early relapses had stages III and IV. Relapses were detected at different periods after treatment: early relapses (n = 5) within 6 months and late relapses (n = 5) after 12 months or later. Among patients with early relapses, 2 (40%) had extranodal disease and 3 (60%) nodal disease; high/medium IPI was noted in 3 patients, low/medium and low IPI – 1 patient each. Among patients with late relapses, 3 patients had nodal disease and 2 – primary extranodal disease; high/medium IPI was noted in 2 patients, low/medium – in 3 patients. Among recurrent patients, 9 had non-germ cell DLBCL and 1 - germ cell DLBCL. Among refractory patients, 8 (73%) had nodal disease and 3 (27%) - extranodal disease; low/medium IPI was registered in 4 patients, high/medium IPI in 2, low IPI in 5 patients; germ cell tumors in 2 patients, non-germ cell tumors in 9 patients. Conclusions: 33% of DLBCL patients did not benefit from the treatment. Molecular markers such as Ki-67, Bcl2, Bcl6 and CD10 were not prognostically significant. The tumor type had a prognostic value only in the group of patients with relapses - non-germ cell tumors were found in 90% of cases.
Survival outcomes of post-transplant lymphoproliferative disorder: A 12-year analysis.
Authors: Shaikh Hira Ghazal , Khan Rafiullah , Grabel Michael , Jandarov Roman , Charif Mahmoud , Latif Tahir 
Published: June 2021

e19543 Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially fatal complication of chronic immunosuppression in solid organ transplant (SOT) and hematopoietic stem cell transplant recipients. With an overall incidence of ̃ 1 percent in the transplant recipients, it is the most common malignancy, with the exception of skin cancer, after SOT in adults. There is a paucity of information concerning the outcomes and prognostic indicators of PTLD. Methods: We queried the National Cancer Database (NCDB) from 2004 – 2015 for patients with diagnosis of PTLD. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier curves to present the cumulative probability of survival. Additionally, Poisson regression was used to test the association between baseline variables and days to event. All statistical analyses were performed using R 4.0.3. Results: Total number of patients identified by inclusion criteria was 425. 1-year OS was 73% (CI 0.684, 0.776), 3-year OS 63% (CI 0.581, 0.683), and 5-year OS 56% (CI 0.502, 0.619) in patients with survival data available (n = 365). 263 patients were excluded due to incomplete data, yielding a final cohort of 192 patients for correlational analysis. The median age was 59 years. Majority were males (60%), < 65 year old (75.5%), Hispanics (91%), and had Charlson-Deyo Comorbidity score of 0 (63.5%). 77% were Caucasians while 15.6% were African Americans. OS was longer in males, Caucasians, patients who received radiation (versus no radiation), those treated at academic or comprehensive cancer center (versus community cancer center), had annual income > $63000 (versus < $63000) by Poisson regression analysis, however the difference was not statistically significant. Conclusions: Our data demonstrates a trend toward poor survival with socioeconomic and treatment variables including gender, race, annual income, treatment center expertise and radiation treatment. Randomized trials are needed to further assess the outcomes of PTLD.