bluuebunny/crossref_metadata_2025_split huggingface dataset:
10-year real-world data on acute myeloid leukemia: The paradigm of a public health center in Brazil.
Authors: Campos Camilla Correia de A P , Teixeira Lais , Salvino Marco Aurelio 
Published: June 2023

e19022 Background: Acute myeloid leukemia (AML) is a heterogeneous disease with different predominant molecular pathways. The last few years have witnessed great advances in targeted therapy. There are several trials in developed countries evaluating clinical outcomes. Nevertheless, data from low and middle-income (LMIC) countries frequently describe inferior results. Methods: This was a retrospective single-center cohort conducted in a university hospital in Northeast Brazil. We have analyzed the outcomes of all 62 patients diagnosed with AML between 2007 and 2017. Patients were classified using the European LeukemiaNet 2017 model into favorable (n=8), intermediate (n=18), and adverse risk (n= 7). 29 were not otherwise classified because of the absence of cytogenetic and/or molecular tests. We used logistic regression for data analysis assessing death as the outcome. Survival measures were estimated using the Kaplan-Meier method. The impact of bone marrow transplant (BMT) on patients eligible for intensive treatment on overall survival (OS) was assessed using a Cox proportional hazards model. Results: The median OS (mOS) of the entire cohort was 7 months (CI: 3.14-10.85). Stratifying by the risk, the mOS was shorter in patients with unknown and adverse risk (3 and 5 months, respectively) than in favorable and intermediate risk (22 and 11 months, respectively, P = 0.05). 16 (38%) patients were submitted to allogeneic BMT. We found a survival advantage (hazard ratio, HR: 0.32, 95% CI: 0.15-0.71) – p=0.005) in transplant patients, with superior median overall survival (mOS) (49 months) when compared with the chemotherapy group (6 months) ( P = 0.003). A total of 48 (77%) patients died during the follow-up and most deaths (n=39, 81%) occurred during the first year of diagnosis. Univariate analysis of clinical and laboratory characteristics found no association with death. A multivariate model including AML origin, risk stratification, and alloBMT as predictor variables demonstrated the protective power of alloBMT (table). Conclusions: Inferior outcomes found in LMIC are the result of a multifactorial scenario that reflects the absence of proper diagnostic tools, hospital infrastructure, and the lack of more effective and less toxic therapies. We suggest that patients with inadequate risk assessment should undergo consolidation with alloBMT as this remains the primary curative intervention in the real-world setting of LMIC. [Table: see text]
Why adult patients with acute leukemias are dying in the developing world: The other side of the coin.
Authors: Voskanyan Astghik , Ivanyan Arusyak , Harutyunyan Lusine , Movsisyan Alisa , Ghahramanyan Nerses , Sahakyan Lusine , Danielyan Samvel , Tamamyan Gevorg 
Published: June 2023

e19035 Background: Majority of the patients with acute leukemias can reach complete remission (CR) in case of appropriate therapy and many of those in CR are expected to remain in remission for several years, which could be considered a cure. Because of progress in recent decades, less and less patients in the developed world are dying. In the developing world the situation is different and with the current work we would like to report the state of leukemias in Armenia and significant disparities, which affect the treatment outcomes of those patients. Methods: We analyzed the medical records of all expired adult patients diagnosed with acute leukemia at the Hematology Center of Armenia from 01/01/2016 until 12/31/2020. Hematology Center is the only institution in Armenia treating leukemias, meaning the data is a countrywide report. Death dates were taken from the United Information System of Electronic Healthcare in the Republic of Armenia. Results: Over the five-year period, 431 patients were diagnosed with AL, of which 310 (71.9%) died. 244 medical records were available for further analysis. The median age of patients at the time of diagnosis was 59 (18-85), 45.9% (112) were female. 23.8% (58) of patients died before starting chemotherapy, of which 44.8% (26) refused the treatment, the others died from different complications due to disease progression. 33.6% (82) patients reached CR of which 29.3% (24) died in first remission: 3 pts from acute heart failure, 1 from COVID-19, 3 from septic shock, 1 from pulmonary aspergillosis, 2 from acute respiratory failure, in 14 patients the causes of death were unknown. 58(70.7%) of those patients, who developed relapse, only 12% (7) of them reached 2nd remission. In 82.8% (48) of patients the death was because of disease progression. One patient died from acute kidney failure, 1 from acute respiratory failure, 1 from COVID-19,1 from septic shock. 50 patients died during induction therapy, form which 58% (29) was due to disease progression, the other reasons were: septic shock, acute heart failure, brain hemorrhage, acute respiratory failure, mesenteric venous thrombosis, multiple organ failure. 30 patients were resistant to the first line therapy and refused further therapy. In 24 patients it was not possible to clarify if they have developed remission and what were the death causes. Conclusions: In our analyzed cohort 23% of all patients refused the treatment, almost half of which did not even start the treatment. It should also be mentioned that because of stigma about cancer, some of those patients did not know their diagnosis and the decisions were made by the relatives. Other reasons for such high abandonment rates are mostly financial and social.
Olutasidenib in post-venetoclax patients with mIDH1 AML.
Authors: Cortes Jorge E. , Schiller Gary J. , Numerof Robert , Floryk Daniel , Jonas Brian Andrew 
Published: June 2023

e19041 Background: Olutasidenib is a potent, selective, oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Olutasidenib is FDA approved for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) based on the registrational cohort (n = 153) of the Phase 2 trial, which demonstrated a rate of complete remission (CR) or CR with partial hematologic recovery (CRh) of 35%, with a duration of response of 25.9 months. Venetoclax (VEN) in combination with a hypomethylating agent (HMA) is standard treatment for AML patients unfit for chemotherapy and has adequate efficacy in IDH1-mutated AML. The sequence of therapy following failure of a VEN-based regimen in IDH1-mutated AML has not been established. We evaluated the efficacy and safety of olutasidenib in a subset of 17 patients from the Phase 2 trial (NCT02719574) previously treated with VEN combination regimens. Methods: Adults with mIDH1 R/R AML received olutasidenib 150 mg twice daily alone (n = 15) or in combination with azacitadine (AZA) (n = 2). The primary endpoint was achievement of a CR/CRh. Secondary endpoints included time to and duration of CR+CRh and rate of transfusion independence (TI). Data cut-off for the analysis was 18 June 2021. Results: Of 17 patients with prior VEN treatment, 5 are ongoing and 12 discontinued due to progressive disease (6), adverse events (4), or withdrawal by subject (2). Median age was 73 (range 65-83). Median time since diagnosis was 19.5 months (1.2-41). Cytogenetic risk class was intermediate in 9, poor in 6, favorable in 1 and unknown in 1. Most patients had relapsed; 6 were refractory to prior treatment. The median number of prior regimens was 2 (range 1-6); 13 had prior HMA, 2 had prior olutasidenib. VEN was generally used for induction. Some patients received VEN in multiple regimens. VEN was used with azacytidine (AZA) in 8 patients, after AZA (1), and with decitabine (5), cytarabine +/- idarubicin (5), and dinaciclib (2). The best response to olutasidenib was CR/CRh in 5/17 (29.4%), of which 4 (23.5%) were CR. In the 8 patients who previously received the combination of VEN-AZA, 3 (37.5%) patients achieved a CR/CRh. Time to CR/CRh was median 2.1 months (actual: 1, 1.9, 2.1, 2.8 and 2.8). Duration of CR/CRh was median 18.5+ months (4.8, 9.0+, 18.5+, 22.6+, and 28.5+ months as of cut-off date). Other responses included CR with incomplete blood count recovery (CRi) in 2 patients, stable disease (SD) in 2, progressive disease (PD) in 3, not done (ND) in 2, not evaluable (NE) in 1 and not listed in 2. At baseline 14/17 were red blood cell (RBC) dependent, and 4 of the 14 (28%) had a 56-day period of RBC transfusion independence (TI). Ten were platelet dependent at baseline and 5 of the 10 (50%) had a 56-day period of platelet TI while receiving olutasidenib. Conclusions: Olutasidenib induced durable remissions in patients with mIDH1 R/R AML, including those failing prior treatment with a venetoclax-based regimen. Clinical trial information: NCT02719574 .
Venetoclax pharmacokinetics in subjects with end-stage renal disease undergoing hemodialysis.
Authors: Noorani Behnam , Menon Rajeev , Cen Xin , Marsh Kennan , Huang Weize , Gupta Shelly , Dobkowska Edyta , Marbury Thomas , Salem Ahmed H. 
Published: June 2023

e19042 Background: Venetoclax is a first-in-class Bcl-2 inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia(AML) and is currently being investigated as a treatment for t(11;14)-positive relapsed/refractory multiple myeloma (MM). Renal insufficiency is a common comorbidity in patients with hematologic malignancies, and no clinical study has been conducted to assess how end stage renal disease might affect venetoclax pharmacokinetics. This study aimed to assess the pharmacokinetics of venetoclax after oral administration of a single 100 mg dose of venetoclax in subjects with normal renal function and end-stage renal disease, including those undergoing hemodialysis. Methods: Venetoclax was administered as a single 100 mg dose to 7 healthy female subjects with normal renal function (eGFR > 90 ml/min) and 6 female subjects with end-stage renal disease (ESRD) (eGFR < 15 ml/min) both prior to hemodialysis (Period 1) and between hemodialysis days (Period 2). Intensive PK and protein binding samples were collected from all subjects. Arterial and venous samples were collected from ESRD subjects during hemodialysis to assess the effect of hemodialysis on the pharmacokinetics of venetoclax. Pharmacokinetic parameters were estimated using non-compartmental methods. Results: There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that hemodialysis did not affect the PK of venetoclax. The fraction unbound (fu) of venetoclax increased approximately 2-fold for subjects with ESRD compared to subjects with normal renal function.The unbound Cmax and AUC0-48 of ESRD subjects, between dialysis days were comparable to unbound Cmax and AUC0-48 observed in the normal renal function subjects. The harmonic mean t1/2 between groups (normal renal function vs. ESRD) ranged from 11 and 12.2 hours, demonstrating that end-stage renal disease did not affect the half-life of venetoclax. Conclusions: End-stage renal disease does not alter unbound venetoclax plasma concentrations and no dose adjustment is neededfor patients with renal insufficiency based on pharmacokinetics. Clinical trial information: NCT04810598 .
Characteristics and survival of secondary acute myeloid leukemia arising from myelodysplastic syndrome (MDS-sAML).
Authors: Adrianzen Herrera Diego Andres , Sparks Andrew , Batra Akshee , Zakai Neil A. 
Published: June 2023

e19075 Background: sAML is a heterogenous category including therapy-related AML, AML arising from MDS or myeloproliferative neoplasm, and other biologically distinct groups. Combining these as one entity likely masks important clinical and therapeutic differences. We defined the clinical profile and survival for MDS-sAML. Methods: The population consisted of patients (pts) with MDS identified in SEER-Medicare (2007-17) by ICD-O-3 histology codes and continuous Medicare parts A+B coverage. Transformation to leukemia was confirmed by at least 2 AML codes during follow up. Established algorithms identified MDS type and risk group, Charlson comorbidity index (CCI), and transfusion dependence for red blood cells (RBC) and platelets. Logistic regression identified risk factors for transformation to MDS-sAML. Kaplan-Meier estimation and multivariable Cox regression were used to analyze overall survival (OS). Results: Of 15,227 MDS pts, 1,871 transformed to AML. MDSsAML incidence varied by MDS risk group and histology. Time to transformation was shorter with higher risk groups. Younger age (odds ratio [OR] = 1.6, 95% confidence interval [95 CI]: 1.4-1.9), lower CCI (OR = 1.6, 95 CI: 1.4-1.9), higher risk (OR = 2.3, 95 CI: 2.0-2.5), transfusion dependence for RBC (OR = 1.2, 95% CI: 1.1-1.3) or platelets (OR = 2.5, 95 CI: 2.1-3.0), were associated with transformation (all respective p < 0.05). Median OS (mOS) after transformation was 3.3 months. The 1- and 2-year OS rates for MDS-sAML were 25% and 12%. MDS-sAML survival varied by antecedent MDS histology and risk group, being longer for pts with antecedent low risk MDS (p < 0.001). Sex, race, and CCI did not affect survival after transformation. Older age (hazard ratio [HR] = 1.5, 95 CI: 1.2-2.0), higher MDS risk (HR = 1.5, 95 CI: 1.2-1.9), RBC transfusion dependence (HR = 1.4, 95 CI: 1.3-1.6), and platelet transfusion dependence (HR = 1.5, 95 CI: 1.3-1.7), were associated shorter MDS-sAML survival (all respective p < 0.05). Conclusions: Risk of MDS-sAML is substantial, with 5% AML transformation even in lower risk MDS histology. Real-world survival of MDS-sAML pts is dismal and lower than reported in clinical trials. Worse MDS risk group before transformation is associated with lower OS after developing AML. These data support a unique pathophysiology of MDS-sAML. [Table: see text]
Racial and ethnic representation in large B-cell lymphoma trials and real-world databases.
Authors: Munoz Javier , Mutebi Alex , Wang Tongsheng , Zhang Guihua , Yu Junhua , He Jing , Chibber Anindit , Kamalakar Rajesh , Jun Monika P. , Adejumo Kelechi , Yang Shibing , Kalsekar Anupama 
Published: June 2023

e19530 Background: In large B-cell lymphoma (LBCL) trials, racial and ethnic representation is difficult to determine due to underreporting in some regions, or because some patients may not provide data. It is difficult to understand the full extent of any underrepresentation of specific races or ethnicities in these trials relative to the prevalence of LBCL in clinical practice. The objective of this study was to characterize racial and ethnic representation in LBCL real-world databases and recently published LBCL studies. Methods: Analyses of the distribution of different racial and ethnic categories were conducted across 6 real-world clinical practice databases from the United States (US): SEER-Medicare, COTA, Medicare, Optum Market Clarity, Optum CDM, and ConcertAI RWD. In addition, a targeted review of recently published studies in patients with LBCL was conducted to identify reported race and ethnicity distributions. Distributions were described using counts and percentages for each race (Asian, Black, White, and other/unknown/not reported) and ethnicity (Hispanic, non-Hispanic, and other/unknown/not reported) category. Results: Patients with LBCL from the databases included: COTA (N=5848), SEER-Medicare (N=102,548), Medicare (N=136,466), Optum Market Clarity (N=19,649), Optum CDM (N=22,175), and ConcertAI (N=1828). Race and ethnicity distributions are reported in the table. Across databases, Asian (2–6%) and Black (5–8%) races were substantially lower than White race (69–88%). Across various lines of therapy, distributions were similar: 3–5% Asian, 3–5% Black, and 78–82% White. Hispanic ethnicity (5–22%) was substantially lower than non-Hispanic ethnicity (70–91%). In the targeted review, 14 publications of LBCL therapies were identified; of these, 10 did not report racial/ethnic composition. In 4 publications (Salles et al, 2020; Sehn et al, 2020; Bannerji et al, 2022; and a real-world study by Shenoy et al, 2011), Asian, Black, White, and other/unknown/not reported represented 2–13%, 0–7%, 71–89%, and 1–11%, respectively. Conclusions: Information on racial and ethnic distributions in LBCL studies is underreported, particularly in global trials. If this information was reported and reflective of LBCL in clinical practice in the US, the numbers of Asian and Black patients would be low at ≤8%, and most patients would be expected to be White and non-Hispanic. [Table: see text]
Cryptococcosis in non-HIV/non-transplant hematological patients: A 12-year retrospective clinical analysis in a Peruvian referral cancer center.
Authors: Meza Kelly , Holguin Alexis , Velarde Juan , Intimayta-Escalante Claudio , Sulca-Huamani Oliver , Poquioma Ebert , Vidal Jose Ernesto , Cuellar Luis E 
Published: June 2023

e19536 Background: Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in non-HIV/non-transplant oncohematological patients. Methods: We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2018. We exclude HIV and transplant recipients patients. Results: During the 12-year study period, among 14908 individuals with hematological malignancies (HM), a total of 21 cases of cryptococcosis were identified, representing an incidence rate of 1.41 per 1000 HM diagnosed in our center. Non-Hodgkin lymphoma (NHL) (47.6%), acute leukemias (23.8%), multiple myeloma (19.1%), and Hodgkin lymphoma (9.5%). Three cases of adult T-cell leukemia/lymphoma were identified. The sub-group analysis showed that NHL (7.35 per 1000 NHL) and Multiple myeloma (4.59 per 1000 MM) had the highest incidence rates. Regarding the clinical presentation, the time between the diagnosis of cryptococcosis and HM was 42 (18–161) days. Cryptococcal fungemia and antigenemia was the most frequent diagnosis (85.7%), followed by pulmonary (52.4%) and central nervous system (38.1%) involvement. At the time of the diagnosis of cryptococcosis, 61.5% were receiving chemotherapy, 53.9% were in the induction phase, and 7.7% were on maintenance therapy. The use of immunosuppressants and chemotherapy within a month of the diagnosis of cryptococcosis was the most common risk factor (90.5%). Regarding the subanalysis performed between the different types of malignancies (NHL versus other HM), age at admission (p = 0.02), site of cryptococcosis presentation (p = 0.01), and lymphocyte count at admission (p = 0.01) were statistically different between these groups. In the NHL subgroup, there was less involvement of the lungs and higher fungemia (p = 0.01). The overall survival (OS) of our cohort at 15 and 120 days was 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other HM was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions: Our cohort characterized the distinct clinical presentation, risk factors, and outcomes of cryptococcal infection in hematologic malignancies subgroups. NHL was the HM with the worst prognosis and the highest incidence rate. [Table: see text]
Effect on hospital outcomes of hematopoietic stem cell transplant recipients with Clostridium difficile infection.
Authors: Dhaliwal Armaan , Sohal Aalam , Chaudhry Hunza , Bains Kanwal , Singh Ishandeep , Kalra Shivam , Dukovic Dino , Patel Jay , Somasundar Ponnandai Sadasivan 
Published: June 2023

e20003 Background: Hematopoietic stem cell transplant (HSCT) recipients are at increased risk of Clostidium difficile infection (CDI) due to use of cytotoxic chemotherapy, broad-spectrum antibiotics, and sustained neutropenia. Because of the immunocompromised nature of these patients, the prevalence rates of CDI in HSCT recipients are high. In this study we evaluate the impact of CDI on in-hospital outcomes. Methods: We included all patients with a prior diagnosis or a procedure code for HSCT using ICD-10 codes from National Inpatient Sample. We excluded patients admitted for less than 14 days to exclude admissions for elective chemotherapy or catheter placement. Patients were stratified into two groups based on the presence of CDI. Information was collected regarding patient demographics, Charlson comorbidities, underlying hematologic disease, resource utilization (LOS and total hospitalization charges), and outcomes. The outcomes included sepsis, shock, acute kidney injury, ICU admission, and in-hospital mortality. The association between CDI and outcomes was studied using multivariate analysis. Results: 62,415 patients were included in the study. Of them, 5,275 (8.5%) patients developed CDI. The majority of the patients with CDI were White (70.4%), men (57.1%), and aged between 45-64 years (52.5%). Patients with CDI had a higher incidence of sepsis (21.1% vs. 16.5%), shock (8.1% vs. 5.8%), AKI (23.8% vs. 19.4%), ICU admission (9.6% vs. 7.6%) and in-hospital mortality (5.8% vs. 4%). After adjusting for confounding factors, CDI was associated with a 32% higher odds of in-hospital mortality (aOR-1.32, 95% CI-1.01-1.74, p-0.046). CDI was also associated with 26% higher odds of developing shock (aOR-1.26, 95% CI-1.01-1.72, p-0.013) and 27% higher odds of developing AKI (aOR-1.27, 95% CI-1.09-1.49,p-0.002). No statistically significant difference was noted in the risk of ICU admission between the two groups. Patients with CDI had a longer length of stay (29.5 days vs. 24.8 days, p < 0.001) and higher hospitalization charges ($400,017 vs. $508,090, p < 0.001). Conclusions: Our study suggested a relationship between CDI and worse outcomes in HSCT recipients. Physicians should be aware of this association and promptly recognize and initiate treatment in these patients to improve outcomes. [Table: see text]