bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial disparities in the outcomes of allogeneic bone marrow transplant: A 5-year nationwide inpatient study.
Authors: Vikash Sindhu , Kamal Syeda Ashna Fatima , Vikash Fnu , Mehta Ansh , Palaiodimos Leonidas , Al Hamed Rama , Bazarbachi Abdul-Hamid , Thakur Rahul Kumar , Shah Nishi , Shastri Aditi , Steidl Ulrich G , Verma Amit , Sica Alejandro R. 
Published: June 2023

e19060 Background: Allogeneic bone marrow transplantation (ABMT) is a life-saving procedure in hematological malignancies and bone marrow failure disorders. Despite advances in the field, literature proposes racial disparities in the outcomes of ABMT. This study aims to investigate this difference among distinct racial cohorts. Methods: We identified patients who underwent ABMT for malignant and nonmalignant hematologic diseases from 2016-2020 using the nationwide inpatient sample (NIS) database. We compared the racial differences in outcomes during the hospitalization, including immunologic and hematologic complications, associated infections, length of stay, and mortality rate. Baseline characteristics were compared using a T-test and Chi-Square. Multivariate regression analysis was applied to estimate differences in outcomes. We used STATA Version 17.0 Software for data analysis. The p-value was set at p < 0.05 for statistical significance. Results: A retrospective study was conducted on a cohort of 14,599 adults who underwent ABMT. Out of which 30% (4,379) developed complications. The mean age for ABMT was 54, and the average length of stay was 29 days. In this cohort, 79.5% (11,325) were whites, 4.2% (610) were blacks, 8.3% (1,185) were Hispanics, and 7.8% (1,125) were others. When comparing the outcomes among racial groups, invasive fungal infections 15.5% (95), mucositis 36% (220), septic shock 9% (55), and respiratory failure 14.7% (90) were more common in blacks (p < 0.05). Neutropenia 41.3% (490) and cytomegalovirus (CMV) infection 12.2% (145) were more common in Hispanics (p < 0.05). However, no significant difference was noted in immunologic complications (graft versus host disease (GVHD), bone marrow rejection (BMR), bone marrow failure (BMF)), pancytopenia, clostridium difficile infection (CDI), and mortality (p < 0.05). Conclusions: Our study shows that blacks had a higher prevalence of invasive fungal infections, mucositis, septic shock, and respiratory failure, while Hispanics reported a higher prevalence of neutropenia and CMV infection. However, no significant differences were noted in GVHD, BMR, BMF, pancytopenia, CDI, and mortality rates. Therefore, it can be concluded that while there are some differences in post-ABMT complications among racial groups, overall, the rates of major complications and mortality do not significantly differ.
Diagnostic performance of natural language processing in detection of acute cancer VTE.
Authors: Subramanian Naveen G. , Garcia Pleitez Hector , Nguyen Daniel , Milton Denai R. , Jin Jeff , Young Elliana , Kebriaei Partow , Rojas Hernandez Cristhiam Mauricio 
Published: June 2023

e19062 Background: The annual incidence of venous thromboembolism (VTE) is roughly 50-fold increased post allogeneic hematopoietic cell transplant (HSCT). Timely detection of VTE events has a significant impact on morbidity and mortality from these events. Manual chart review is commonly used for detection of VTE events; however, this is labor intensive and often not feasible. The International Classification of Diseases, 10th revision (ICD-10) has attempted to codify VTE more easily but has high false positive and false negative rates. Natural language processing (NLP) algorithms have been designed to improve detection of VTE events in electronic medical record systems over the past several years. This study aims to compare the accuracy of our institution’s NLP algorithm to the ICD-10 in detecting extremity VTE/pulmonary embolism (PE) events in hematopoietic stem cell transplant (HSCT) patients. Methods: This study was a retrospective analysis of adult patients who had allogeneic HSCT at MD Anderson between 2016-2020. Patient charts were assessed by three different methods for acute VTE events within 100 days of HSCT (index date). ICD-10 codes and our institution’s NLP algorithm were used separately to identify these VTE events. Afterwards, manual chart review was performed for confirmation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the ICD-10, NLP, and the NLP+ICD combination. Results: A total of 1,391 patient charts were analyzed in our study. There were 129 (9.3%) VTE events detected via manual chart review. Three methodologies were used for comparison: the NLP algorithm alone, the ICD code alone, and detection by NLP or ICD. The NLP algorithm alone had the best specificity (98.9%) and PPV (89.4%) of the three methods. The ICD-10 code had a statistically significant decrease in ability to detect acute VTE events compared to the NLP (p<0.001) (Table). Of the 19 VTE events not identified by NLP, all were found in radiology or vascular laboratory reports. Conclusions: Our study shows the overall superior performance of the NLP algorithm, as it had higher sensitivity, specificity, PPV, and NPV compared to the ICD-10, as well as a better specificity and PPV compared to the combination of both methods. Future refinement of the NLP algorithm and combination with other detection methodologies will allow for more accurate detection of VTE in large cohorts. [Table: see text]
Treatment patterns and outcomes of diffuse alveolar hemorrhage: Findings from a single-center retrospective study.
Authors: Butler McKenna , Defayette Aubrey , Pleskow Jordan , Loecher Alyssa , Ross Maureen , Quinn Timothy 
Published: June 2023

e19063 Background: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication seen in patients with malignancy most commonly after a hematopoietic stem cell transplant (HSCT). Systemic therapy with corticosteroids to reduce inflammation and control bleeding is the mainstay of treatment for DAH, however ideal dosing strategies are not known. Methods: This single-center, retrospective study reviewed patients presenting to Roswell Park Comprehensive Cancer Center (RPCCC) from January 2010 through November 2022. Patients were included in this review if they were >18 years and were actively treated at RPCCC for presumed or definite DAH. The bone marrow transplant database, ICD-9, and ICD-10 codes were used to screen patients for inclusion. Upon meeting inclusion criteria, patients were stratified based on daily methylprednisolone dosing equivalents [low-dose: < 250 mg, intermediate-dose: >250 mg or < 1000 mg, high-dose: >1000 mg, or no steroid]. The primary endpoint was 30-day mortality. Secondary endpoints included ICU mortality, ICU length of stay (LOS), overall LOS, hemorrhage recurrence, steroid complications, and utilization of other DAH treatments. Steroid complications, including hyperglycemia, infection, and uremia were evaluated as safety endpoints. Results: Thirty-seven patients met inclusion criteria; 23 HSCT and 14 non-transplant patients. Analysis included 20 patients in the low-dose, 2 patients in the intermediate-dose, 12 patients in the high-dose, and 3 patients in the no steroid group. The median duration of steroids was 15, 4, and 14 days in the low, intermediate, and high groups, respectively. There was no statistically significant difference in 30-day mortality across treatment groups (p = 0.76). The overall 30-day mortality rate was 24.3%, with 25%, 50%, and 17% in the low, intermediate, and high-dose groups, respectively. A 30-day mortality rate of 33% was seen in patients who did not receive steroids. Hemorrhage recurrence occurred in 9 patients (24.3%), most commonly in the high-dose treatment group. Utilization of additional agents including aminocaproic acid, etanercept, and inhaled factor VIIa was most common in the intermediate-dose group. Conclusions: Despite variable steroid dosing, 30-day mortality was not found to be statistically significant among patients treated for DAH. Based on our findings of similar efficacy between dosing strategies, yet increased rates of steroid complications and hemorrhage recurrence in the high-dose group, lower steroid doses for the treatment of DAH can be considered. [Table: see text]
Efficacy and safety of ponatinib in management of chronic myeloid leukaemia: Experience from Kenya.
Authors: Othieno-Abinya Nicolas Anthony , Mcligeyo Angela Awino , Oyiro Peter Omondi , Odhiambo Andrew Oluoch , Ezzi Mohammed Shabbir , Mwanzi Sitna Ali , Nyangasi Mary Flaviane , Ong'ondi Matilda , Mwanda Walter , Mwenda Valerian , Mutebi Miriam Claire 
Published: June 2023

e19067 Background: BCR-ABL tyrosine kinase inhibitors imatinib, nilotinib, bosutinib, and dasatinib, are used upfront in the management of chronic myeloid leukaemia (CML). In terms of resistance, ponatinib is the most potent tyrosine kinase inhibitor used in CML. It is however not used as first line therapy because of the fear of cardiovascular toxicity. However, because of a lot of inconsistency in the way oncology and cardiovascular trials define adverse events, this risk is not well defined. Methods: To document the efficacy and safety of ponatinib among CML patients treated at the Max Access Solutions Clinic at the Nairobi Hospital retrospectively. Results: Fourty-five patients were included between 02-10-2017 and 03-12-2022; males 23(51.1%) and females 22 (48.9%). All patients took imatinib first line. Ponatinib was taken second line by 10 (22.2%), third line by 18 (40%) and 4th line by 17 (37.8%). Of these, 25 (55.6%) were in chronic phase, 10(22.2%) accelerated and 9(20%) blastic phases. Of 22 evaluable cases in chronic phase, 1 (4.5%) died after 9 months on ponatinib, the rest are on follow-up for 1 – 60 months with a mean of 16.8 months and median of 10 months. Of 8 evaluable in accelerated phase, one (12.5%) died after 36 months. The range of follow-up is 2-36 months and mean 19.4 months. Of 9 evaluable in blastic phase, two (22.2%) are still alive after 6 and 41 months respectively. Seven (77.8%) died after follow-up ranging from 2-18 months, mean of 9.3 months. Interquartile range (IQR) for total white blood cell (wbc) count dropped from 9.08 x 109/litre to 4.82 x 109/litre on ponatinib, absolute neutrophil count dropped from 6.70 x 109/litre to 2.29 x 109/litre and platelets IQR rose from 114 x 109/litre -163 x 109/litre. Adverse events were registered in 6 (13.3 %), mainly grade 1-2, none of which was cardiovascular. Conclusions: Ponatinib is an active in all phases of CML with manageable side effect profile.
Effect of hypomethylating agent (HMA) exposure on survival of secondary acute myeloid leukemia (sAML) from myelodysplastic syndrome (MDS).
Authors: Adrianzen Herrera Diego Andres , Sparks Andrew , Batra Akshee , Zakai Neil A. 
Published: June 2023

e19076 Background: AML arising from previously treated myeloid neoplasm (tsAML) is considered a distinct category of sAML less responsive to therapy. AML from MDS (MDS-sAML) formerly treated with HMA is the most common entity in this category but has not been independently studied. We determined the impact of prior HMA therapy on MDS-sAML survival. Methods: Patients (pts) with MDS were identified in SEER-Medicare 2007-2017 by ICD-O-3 histology codes. MDS-sAML was confirmed by at least 2 AML ICD codes. Established algorithms were used to define MDS risk group, Charlson comorbid index (CCI), transfusion dependence and HMA therapy. We used logistic regression to test factors associated with HMA therapy before transformation, and multivariable Cox regression with propensity score matching (PSM) for survival analysis after transformation. Results: We included 1,871 pts with MDS-sAML, of which 1,151 (61.5%) received at least 1 HMA cycle before AML transformation and 826 (44.1%) had sustained HMA therapy (4 or more cycles). Preceding MDS was of low, intermediate, and high risk in 6.2%, 61.9%, and 31.9% pts, respectively. Younger age (odds ratio [OR] = 1.6, 95% confidence interval [95 CI]: 1.3-1.9), lower CI (OR = 1.4, 95 CI: 1.2-1.5), higher MDS risk (OR = 2.3, 95 CI: 2.3-2.8), and RBC (OR = 1.3, 95 CI: 1.2-1.5) and platelet transfusion dependence (OR = 3.4, 95 CI: 2.8-4.0), were associated with pre-AML HMA use (all respective p < 0.05). Median OS after AML transformation was 3.3 months and was longer in pts previously treated with HMA, particularly ≥4 cycles (4 vs 2 months, p < 0.01). The 1:1 matched HMA and non-HMA groups were similar for all variables listed in the table. In the PSM cohort, prior HMA therapy was associated with 22% lower hazard of death in MDS-sAML (hazard ratio [HR] = 0.78, 95 CI: 0.7-0.88, p < 0.01). Traditional Cox regression adjusted for age, sex, race, MDS risk, CCI, RBC and platelet transfusion dependence, confirmed these results (HR = 0.76, 95 CI: 0.68-0.84, p < 0.01). The point estimate of the association of HMA therapy with lower risk of death was lower in pts who received ≥4 cycles (HR = 0.62, 95 CI: 0.56-0.69, p < 0.01). Conclusions: Real-world survival of MDS-sAML pts is dismal but HMA exposure preceding AML transformation is associated with longer survival. Further studies are needed to determine whether this reflects the impact of HMA on subsequent AML biology or residual confounding. [Table: see text]
Expression of CD47 and CALR in myeloproliferative neoplasms: Potential new therapeutical targets.
Authors: Rinaldi Ciro Roberto , Boasman Kristian , Simmonds Matthew 
Published: June 2023

e19079 Background: Myeloproliferative neoplasms (MPN) are myeloid malignancies characterized by overproduction of mature blood cells, hyperplastic bone marrow and tendency to evolve into acute myeloid leukaemia. In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti-phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. We Investigate the expression and cellular localisation of CALR and CD47 in untreated and treated patients with essential thrombocythemia (ET), polycythemia vera (PV) myelofibrosis (MF), in comparison with healthy controls. Methods: Mononuclear cells were collected by Ficoll separation, from peripheral blood of 30 MPN (8 PV, 16 ET, 6 MF); 18 MPN patients received cyto-reductive therapies (Hydroxyurea, Anagrelide or Ruxolitinib); and 4 controls. Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples compared with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold, respectively). CD47 showed higher expression of its overall protein on MPN cell membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR expression in all MPN subtypes when patients were treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET cell membranes however, CD47 expression is reduced after cyto-reductive treatment (22% vs 16.6%), suggesting instead a prophagocytic effect. Conclusions: CD47, but not CALR, is overexpressed on the membrane of patients with MPN, suggesting a role for CD47 as a strong antiphagocytic signal responsible for immune survival in MPN. We observed a significant difference in CD47 expression across different MPN subtypes with a significant increase in CD47 expression in PV and MF but not ET. The use of anti-CD47 antibodies could represent a new strategy to enhance the treatment response in particular in PV and MF.
Translational development of BAFF-R-specific chimeric antigen receptor T-cell therapy targeting B-cell lymphoid malignancies.
Authors: Luo Yan , Qie Yaqing , Gadd Martha E. , Manna Alak , To Tommy , Li Shuhua , Murthy Hemant S. , Dronca Roxana Stefania , Kharfan-Dabaja Mohamed , Qin Hong 
Published: June 2023

e19501 Background: Relapsed and/or refractory (R/R) disease is observed in patients who receive CD19 targeting chimeric antigen receptor (CAR)-T cells to treat B-cell lymphoid leukemias and lymphomas. We generated a novel CAR, MC10029 that targets B-cell activating factor receptor (BAFF-R) to address this unmet medical need. Methods: We engineered a second-generation BAFF-R CAR (MC10029 CAR). The construct includes the single chain variable fragment (scFv) of our newly developed BAFF-R antibody with CD28 costimulatory and CD3ζ signaling domains. We confirmed MC10029 CAR-T cell antigen-specific activation with in vitro degranulation assays and a direct cytolytic assay. We used BAFF-R positive leukemia and lymphoma cell lines in both in vitro and in vivo models to further characterize MC10029 CAR-T cells, and finally, we enriched tumor primary cells from chronic lymphocytic leukemia (CLL) patients as a target for MC10029 CAR-T cells. In preparation for our Phase I clinical trial, we have manufactured three batches of CAR-T cells using a MC10029-encoding lentiviral vector produced under GMP conditions. The production batches of MC10029 CAR-T cells were evaluated for product quality with Viability, Identity and Potency as well as Safety from adventitious viral agents. Antigen specific cytotoxicity of the MC10029 CAR-T cells was confirmed using our standard degranulation assay. Results: MC10029 CAR-T cells elicited in vitro antigen-specific cytotoxicity against Nalm-6 cells, Z138 cells, MEC-1 cells, and a CD19 knock out Nalm-6 model designed to mimic CD19-negative R/R disease. We demonstrated in vivo antitumor effects of MC10029 CAR-T cells in NSG mice challenged with these same cell lines. We showed cytotoxicity of MC10029 CAR-T cells against CLL patients’ tumors. We also showed our quality control results to highlight our clinical trial trajectory. Conclusions: Novel MC10029 CAR-T cells showed broad utility against BAFF-R positive B-cell lymphoid malignancies in a series of in vitro, in vivo, and ex vivo models. With these robust data, we have moved forward to generate clinical grade MC10029 CAR-T cells using cGMP manufacturing and quality protocols in preparation of a MC10029 CAR-T cell Phase I clinical trial.
Safety of concurrent use of radiotherapy for second primary malignancy (SPM) in patients with chronic lymphocytic leukemia (CLL) receiving novel agent therapy.
Authors: Kosydar Samuel R , Parikh Sameer Ashok , Lester Scott , Rabe Kari G. , Ding Wei , Kenderian Saad , Wang Yucai , Muchtar Eli , Koehler Amber , Schwager Susan M. , Slager Susan L. , Kay Neil E. , Call Timothy , Breen Will , Hampel Paul Joseph 
Published: June 2023

e19507 Background: Patients (pts) with CLL are at elevated risk of developing non-hematologic malignancies. Radiation therapy (RT) is a critical component of management in localized solid organ malignancies. Novel agents (NA) are widely used in CLL treatment; however, safety data are lacking to guide treatment of pts requiring concurrent RT and NA. Methods: We identified pts treated concurrently with NA for CLL and RT for second primary malignancy (SPM) at Mayo Clinic from 2014-2022. Adverse events within 3 months of RT were evaluated using the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematological toxicity and the Common Terminology Criteria for Adverse Events (CTCAE) version 5 for non-hematological toxicity. Patients without seamless, concurrent treatment with NA and RT were excluded. Results: Twenty-six pts were included. NA therapy consisted of ibrutinib (n = 23), acalabrutinib (n = 2), and venetoclax (n = 1). Median follow up time since RT completion was 1.5 years. The median age at NA initiation was 67 years (range:46-85) and at RT start was 68 years (range: 51-85); 92% of pts were male. NA was first treatment in 23% of pts; the median number of prior lines of therapy was 1 (range: 0-4). IGHV was unmutated in 82% and TP53 aberration was present in 24% of evaluable patients. SPM sites included prostate (n = 9), head/neck (n = 8), lung (n = 3), and brain, breast, bone, skin, kidney, and thymus (n = 1 each). The most common conventionally fractionated prescriptions (cGy/fx) were 6000/30 (n = 6) and > 6000-7020/20-33 (n = 7). SBRT ranged from 3300/5 to 5400/3 (n = 8). Five pts received other, varied RT prescriptions. Overall, 3 (12%) pts experienced at least one grade 3/4 toxicity. Grade 3/4 thrombocytopenia was observed in 2 (8%) pts and grade 3/4 neutropenia was observed in 2 pts per iwCLL criteria. Grade ≥3 non-hematological toxicities occurred in two pts that required hospitalization for critical illness, including 1 pt with grade 5 respiratory failure within 6 weeks after RT. Dose de-escalation of ibrutinib was reported in one case for pancytopenia attributed to use of a radiosensitizing agent. There were no cases of RT dose modification. Conclusions: Continuing NA CLL therapy during RT did not result in unexpected toxicities. This approach may maintain CLL disease control without compromising management of the SPM. [Table: see text]
Real-world treatment outcomes in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were treated with first-line single-agent ibrutinib vs. chemoimmunotherapy.
Authors: Wang Ruibin , Ding Zhijie , Lu Xiaoxiao , Mavani Heena , He Jinghua , Qureshi Zaina P. , Pinilla-Ibarz Javier 
Published: June 2023

e19509 Background: Real-world evidence on Bruton Tyrosine Kinase Inhibitor treatment vs chemoimmunotherapy (CIT) for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) has been limited to certain practice settings; research using a large and more comprehensive data source is warranted. Methods: This retrospective cohort study evaluated treatment outcomes among patients with CLL/SLL treated with first-line (1L) ibrutinib (IBR) or CIT using the US claims data from the Komodo Health payer-complete dataset, derived from >150 private insurers and >140 million insured individuals from 2015 to 2022. This study included adult patients with CLL/SLL who initiated 1L single-agent IBR or CIT (defined as no prior CLL/SLL treatment for ≥12 months in the baseline period) on or after March 2016. Time to next treatment (TTNT) was defined as the time from initiation (index date) of 1L treatment to treatment add-on or switch to a next line of therapy ≥29 days post-index and was compared using Cox proportional hazards models. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Results: A total of 3570 1L IBR- and 2391 CIT-treated patients were included, with the mean age 68 vs 64 years, 63% vs 66% male, and mean Quan-Charlson Comorbidity Index score 2.87 vs 3.05, respectively. Median follow-up was 26 vs 31 months, and 13% vs 26% of patients recorded a next treatment during the study period for IBR and CIT, respectively. At 1-, 3-, and 5-year post-index, the probabilities (95% confidence interval [CI]) of not initiating a new treatment were 92% (91%-93%), 83% (81%-84%) and 76% (73%-78%) vs 88% (87%-89%), 70% (68%-73%) and 56% (53%-60%) for the IBR and CIT cohorts, respectively. After controlling for baseline characteristics, 1L IBR patients were significantly less likely to initiate the next line of therapy during the study period (hazard ratio 0.61, 95% CI 0.54-0.69, p<0.001). Conclusions: 1L single-agent IBR was associated with a significantly lower risk of advancing to next line of treatment compared to CIT in this large claims-based data set, reinforcing real-world effectiveness of 1L IBR for CLL in an insured US patient population. [Table: see text]