bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcomes in adults with newly diagnosed B-cell acute lymphoblastic leukemia: A comparison between pediatric-inspired regimens and HyperCVAD at a Hispanic-serving cancer center.
Authors: Griffin Shawn Patrick , Lee Benjamin , Pannunzio Nicholas , Doh Jean , Chan Alexandre , Ciurea Stefan , Jeyakumar Deepa , O'Brien Susan Mary , Fleischman Angela G , Naqvi Kiran , Kongtim Piyanuch 
Published: June 2023

7048 Background: It is unknown if HyperCVAD is more favorable than pediatric-inspired regimens (PIRs) among adult Hispanic patients with newly diagnosed B-cell acute lymphoblastic leukemia. This analysis aims to determine the interaction of Hispanic ethnicity and treatment regimen on outcomes. Methods: Records of adults (≥ 18 years) treated with a PIR or HyperCVAD from January 2011 to November 2022 at our institution were reviewed. Patients were excluded if they received treatment modifications in a clinical trial or were lost to follow-up prior to 6 months. The primary endpoint was event-free survival (EFS) comprised of relapse, death, secondary malignancy, or failure to achieve complete remission. Secondary endpoints included overall survival (OS). Ph+ disease was not grouped into the poor-risk category. Results: 100 patients were included. Median age was 39 years, 57% were male, and 61% self-identified as Hispanic. 48 were included in the PIR and 52 in the HyperCVAD groups. 37 in the PIR group received CALGB 10403. There was no difference in race, ethnicity, rituximab use, WBC, LDH, bone marrow blast %, presence of CNS disease at diagnosis, or poor-risk genetics (Table) between the PIR and HyperCVAD groups. However, a lower rate of Ph+ disease (8.3% vs 58%) and younger median age (31 years vs 49 years) was observed in the PIR group. Allogeneic stem cell transplantation (ASCT) was pursued in 48% of PIR and 37% of HyperCVAD-treated patients. EFS at 5-years was lower among patients receiving a PIR compared to HyperCVAD (28% vs 41%; hazard ratio [HR], 1.89; P = .022). After censoring for ASCT there was no change (P = .03). Treatment group was the only significant predictor for EFS although a treatment-by-subgroup interaction (P < .10) with Hispanic ethnicity was found. OS at 5-years was 61% in PIR and 64% in HyperCVAD-treated patients (HR, 1.54; P = .25). In multivariable Cox regression analysis, Hispanic ethnicity (HR, 2.56; P = .041) and male sex (HR, 2.62; P = .027) were predictors for worse OS. Hispanic patients demonstrated worse EFS with a PIR compared to HyperCVAD (HR, 2.52; P = .008), which remained significant when evaluating only Ph- patients (HR, 2.20; P=.048). Non-Hispanics did not experience the same difference in EFS (HR, 0.88; P=.81). Conclusions: Treatment with a PIR resulted in worse EFS over HyperCVAD in adult Hispanic ALL patients. Future studies focusing on regimen intensity, adherence, and toxicities are needed to explore potential causes for this disparity. [Table: see text]
Mortality rate and social disparity trends with tyrosine kinase inhibitory availability in chronic myelogenous leukemia: An analysis in the US from 1999 to 2020.
Authors: Varughese Tony , Koprivnikar Jamie 
Published: June 2023

7055 Background: We analyzed CML mortality from 1999 to 2020 in the US in relation to FDA approval of tyrosine kinase inhibitors (TKIs). These agents were introduced in the 2000s, revolutionizing the treatment of CML and providing a paradigm for targeted therapy in oncology. Starting with imatinib in 2001, followed by dasatinib (2006), nilotinib (2007), and bosutinib (2012). TKIs have increased tolerability and efficacy for the treatment of CML as compared to previous treatment modalities. We investigated age-adjusted mortality rates (AAMR) and annual percent change (APC) in this population in relation to TKI approval. Methods: Using the CDC WONDER database, we examined mortality trends from 1999 to 2020 for CML in the US. AAMRs were calculated per 100,000 people and stratified by sex, race/ethnicity, and census region. AAMR groups were listed as pre-TKI era and 1 year post-FDA approval of different TKI agents. We computed the APC trends for the respective stratification with Joinpoint, a regression analysis program. Results: Between 1999 and 2020 there were 35,268 deaths from CML. In 1999, overall AAMR initially was 0.8, which improved to 0.5 by 2020 with a respective APC of -2.5%. In our subgroup analysis there was a consistent and significant decrease in AAMR since the introduction of Imatinib in 2001. With additional TKI releases, AAMR continued to decline in all subgroups. APC for mortality rates was similar between all subgroups [-2.0 to -2.8%] indicating a similar benefit regardless of subgroup. Male AAMR was consistently higher than female AAMR. Black and white patients (0.5, 2020) have a 2.5x higher AAMR (0.2, 2020) compared to Asian patients. Census region did not show a significant difference between each other. Conclusions: Since the FDA approval of imatinib in 2001 and the subsequent release of TKIs there has been a significant impact on reducing AAMR for patients with CML. The decline was seen in sex, race, and census region. The APCs were similar between all subgroups indicating a consistent improvement in survival. Possible etiologies of disparities in AARM for males in comparison to females and for black and white patients in comparison to Asian patients include gender and race-associated gene polymorphisms possibly inducing differences in drug metabolism. Further gender and race specific pharmacokinetic studies would be useful to further elucidate etiology of the disparity and may lead to changes in TKI dosing strategies. [Table: see text]
External validation of the Molecular International Prognostic Scoring System (IPSS-M) for myelodysplastic syndromes.
Authors: Chernak Brian , Ali Abdullah , Jan Amna , Mukherjee Sanjay , Jurcic Joseph G. , Raza Azra 
Published: June 2023

7056 Background: Myelodysplastic Syndromes (MDS) comprise of a group of clonal diseases characterized by dysplastic hematopoietic progenitor cells, leading to cytopenias and in select cases transformation to acute myeloid leukemia (AML). In June 2022 the Molecular International Prognostic Scoring System (IPSS-M) was developed to build on the traditional IPSS-R and is reported to be prognostic even with incomplete molecular data. We aimed to validate this scoring system with an external dataset, and utilize a patient population which typically does not contain complete molecular testing at diagnosis. Methods: This single center study at a tertiary medical center in New York, NY was conducted as an external validation of the IPSS-M. Patients with MDS who had documented peripheral blood counts, bone marrow biopsies, and cytogenetic data were identified in the institutional tissue bank. After eliminating repetitive patient samples, 405 patient entries, collected between July 7, 2010 and March 29, 2022 were included in this study. 392 patients had previously been categorized by IPSS-R score. 332 patients had at least one subsequent follow-up event. 94 patients had bone marrow biopsies that were peri-diagnostic (within 12 months of diagnosis). Results: Patients in the entire cohort had a median age of 74 years (range, 30-96). The median follow-up duration was 1.5 years (range 0.0-9.9 years). Nearly all patients had at least partial molecular diagnostic data. Other than PRPF8 mutations (0%), all other mutations included in the IPSS-M scoring system were tested in a subset of the study population. The most common mutations in the patient population were SF3B1 (20.4%), ASXL1 (17.6%), and SRSF2 (15.9%); 12.2% of patients had the del5q cytogenetic abnormality, and 5.6% were found to have at least one TP53 mutation; 2.7% were TP53 (multi-hit). 29% of all patients were up-staged from IPSS-R to IPSS-M score, while 12% were down-staged. At the time of study evaluation, there were 84 events; 61.3% of patients were alive at the time of analysis. The median overall survival was 3.6 years (25-75% range: 2.75-5.50 years). When limited to patients with peri-diagnostic bone marrow biopsies, there were statistically significant differences in overall survival between IPSS-M categories (p<0.000001) as well as IPSS-R categories (p<0.00001). There was no statistical difference in survival between IPSS-M categories (p=0.6) or IPSS-R categories (p = 0.2) if scores were calculated at any time point in the patient’s disease course. Conclusions: This study validates the utility of both the IPSS-M and the IPSS-R scoring systems, and notably retains important risk stratification with incomplete diagnostic data. Importantly, the scoring systems are not effectively prognostic as the disease progresses, and thus should only be utilized at or near the time of diagnosis.
Hematologic and transfusion outcomes in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) receiving luspatercept: Real-world assessment in the community practice setting.
Authors: Mukherjee Sudipto , Brown-Bickerstaff Cherrishe , Falkenstein Angelica , Makinde Adeola Y. , Bland Emily , Laney JaLyna , Garretson Marné , McBride Ali 
Published: June 2023

7057 Background: Erythropoiesis-stimulating agents (ESAs) are used as first-line (1L) treatment (tx) for the management of symptomatic anemia in LR-MDS. Luspatercept is approved for pts with LR-MDS with ring sideroblasts (RS) who experience ESA failure and are transfusion dependent. We assessed clinical outcomes of pts with LR-MDS with RS, or MDS/myeloproliferative neoplasms with RS and thrombocytosis, treated with luspatercept in US community practices. Methods: This retrospective, observational cohort study used physician-abstracted chart data from community oncology clinics and included adults diagnosed with LR-MDS (including Very low- to Intermediate-risk IPSS-R status) on/after Jan 1, 2015 who received luspatercept for ≥ 3 months (mos) with ≥ 3 mos of follow-up. Transfusion burden (TB) was defined by number of sessions (ses) received in the 8 weeks (wks) prior to luspatercept tx (baseline) and the lowest number for any consecutive period ≥ 8 wks during wks 1–24 of tx: transfusion independent (TI); low TB (LTB), 1–3 ses; and moderate TB (MTB), 4–5 ses. Results: Of 253 pts, 219 (87%) had 1 tx prior to luspatercept tx and 31 (12%) received ≥ 2. ESAs were used as 1L tx in 210 pts (83%). Median follow-up was 5.7 mos. The most common reason for discontinuing initial MDS tx among patients who received ≥ 1 tx prior to luspatercept was lack of anemia improvement (133/250). At baseline, 21 (8%) pts were TI, 208 (82%) had LTB, and 24 (10%) MTB. Median duration of luspatercept tx was 10.8 mos. During wks 1–24, 20/21 (95%) pts remained TI and 201/232 (87%) pts with LTB/MTB at baseline achieved TI for ≥ 8 wks. The Table shows changes in median hemoglobin (Hb), absolute neutrophil count (ANC), and platelet (plt) count. Conclusions: Most pts with LR-MDS received 1L ESAs and over half discontinued the first tx prior to luspatercept due to lack of anemia improvement, highlighting the need for alternative options to improve clinical outcomes. Consistent with data from the MEDALIST trial, 87% of pts with LTB/MTB who received luspatercept achieved TI for ≥ 8 wks, supporting its clinical benefit in routine clinical practice. [Table: see text]
Selinexor (SEL) plus ruxolitinib (RUX) in JAK inhibitor (JAKi) treatment-naïve patients with myelofibrosis: Updated results from XPORT-MF-034.
Authors: Ali Haris , Kishtagari Ashwin , Maher Keri Renee , Mohan Sanjay , Prchal Josef T. , Wang Xulong , Chamoun Kamal , Tantravahi Srinivas Kiran 
Published: June 2023

7063 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with splenomegaly, high symptom burden, and poor prognosis. Activity has been shown with the combination of SEL + the JAKi RUX in preclinical studies. Specific subgroups with lower response rates to RUX monotherapy, such as males vs females (25% vs 59%) and those with a lower (≤15 mg vs 20 mg) RUX starting dose (22-27% vs 43%), highlight unmet need in specific groups (grps). Methods: XPORT-MF-034 is a Phase 1/2, open-label study evaluating safety and efficacy of SEL at 40 mg and 60 mg once-weekly plus RUX per standard of care in 28-day cycles. Assessments included safety, spleen/symptom response, survival, and hemoglobin levels. The primary analysis population included those who had baseline assessment and were treated to at least Week 24 (W24) or discontinued before W24. Two pts with baseline total symptom score (TSS) = 0 were excluded from analysis of TSS reduction of ≥50% (TSS50). Results: As of Dec 21, 2022, 10 participants received 40 mg and 14 participants received 60 mg SEL; 22 of the 24 pts enrolled had reached at least W24 and were included in the efficacy analysis. The median duration of treatment was 28 wks overall, 33 wks for 60 mg and 22.5 wks for 40 mg grps. Most common adverse events (AEs) by dose (60/40 mg) were nausea (79%/70%; majority grade 1-2), anemia (79%/50%), and fatigue (57%/60%). Most common Grade ≥3 AEs were anemia (50%/40%), thrombocytopenia (29%/10%), and neutropenia (7%/20%). AEs were reversible with dose modifications. Two patients discontinued treatment due to treatment-related AEs (thrombocytopenia and neuropathy); 3 deaths have occurred in the study, none related to SEL. Overall, 64% (14/22) achieved SVR35 at W24, with 79% [11/14] vs 38% [3/8], in the 60 mg vs 40 mg grp, respectively. The 60 mg grp achieved a deeper median SVR response vs the 40 mg grp at W24 (49% vs 31%). At W24, TSS50 was achieved by 45% (9/20) overall, 58% [7/12] of the 60 mg, and 25% [2/8] of the 40 mg grp. Among 11 pts with baseline hemoglobin < 10 g/dL, median hemoglobin decreased by 0.5 g/dL from baseline to W12 and increased by 0.8 g/dL from baseline to W24. Similar efficacy was observed across all subgrps with 60 mg. Reduction of variant allele frequency from baseline to W24 was > 10% in 50% (4/8) and > 20% in 25% (2/8) of evaluable pts for 60 mg grp. Conclusions: Encouraging activity with 60mg SEL + RUX combination were observed in TSS50, SVR and hemoglobin levels overall, as well as in key subgroups including males, in pts started on low dose RUX (≤15 mg), and pts with larger baselines spleen size. Updated data will be available for presentation. Clinical trial information: NCT04562389 . [Table: see text]
Impact of transfusion burden on health-related quality of life (HRQOL) and functioning in patients (pts) with myelofibrosis (MF): Post hoc analysis of SIMPLIFY-1 (S1) and -2 (S2).
Authors: Mesa Ruben A. , Palandri Francesca , Verstovsek Srdan , Masarova Lucia , Harrison Claire , Mazerolle Flora , Gorsh Boris , M'Hari Manal , Wang Zhaohui , Ellis Catherine Elizabeth , Deheshi Samineh , Kawashima Jun , Von Maltzahn Robyn , Regnault Antoine 
Published: June 2023

7066 Background: MF is associated with substantial symptom burden that can negatively impact pt quality of life (QOL). Transfusions may reduce anemia-associated symptoms, but can be burdensome and carry complications that may affect social, emotional, and general health; thus, QOL may be further negatively affected in transfusion-dependent (TD) pts. To characterize the relationship between transfusion burden and pt-reported outcomes (PROs), we report an exploratory post hoc analysis of the phase 3 S1 and S2 trials of the JAK1/JAK2/ACVR1 inhibitor momelotinib (MMB) in pts with MF. Methods: The pooled analysis set comprised both arms of the intent-to-treat populations of S1 (JAK inhibitor naive, MMB vs ruxolitinib [RUX]; N = 432) and S2 (JAK inhibitor exposed, MMB vs best available therapy [88% RUX]; N = 156). Transfusion independent (TI): no transfusions and hemoglobin (Hb) ≥8 g/dL in 12 wk; TD: ≥4 units transfused or Hb < 8 g/dL in 8 wk; transfusion requiring (TR): not meeting TI or TD criteria. PRO assessment: SF-36v2 (physical functioning [PF], role-physical [RP], general health [GH], vitality [VT], social functioning [SF], and mental health [MH] domains; norm-based scores [NBS] range from 11.6 to 70.4 based on domain). PROs by transfusion status were described over the 24-wk randomized period. Results: SF-36v2 NBS were available from 503/588 pts in the pooled analysis set at baseline (BL); mean NBS in all domains were lower than the general population mean per the SF-36v2 Manual (50; SD, 10): PF, 39.6; RP, 39.0; GH, 39.8; VT, 43.6; SF, 43.2; MH, 46.3. Within the pooled analysis set, mean NBS in all domains at BL and week 24 (W24) were lower in TD vs TI pts. Among BL TD pts (n = 150) at W24, 75 remained TD (TD-TD), 40 became TI (TD-TI), 21 became TR, and 14 had no data. Pts who became TI experienced greater improvement (positive mean change from BL) in most domains vs pts who remained TD (Table). Conclusions: Among pts with MF in S1 and S2, TD pts had lower functioning and HRQOL than TI pts across SF-36v2 domains, suggesting that transfusion dependence has detrimental effects on multiple aspects of QOL. Among BL TD pts, those who became TI at W24 had greater improvement across most domains than those who remained TD, with mean changes for TD-TI pts near or above the minimally important difference (2 or 3, based on domain) for groups with low BL NBS. These analyses highlight transfusion dependence as a key pt-centered outcome and support further research into the impact of transfusions on QOL in MF. Clinical trial information: NCT01969838 ; NCT02101268 . [Table: see text]
Longitudinal assessment of cardiac involvement in Erdheim-Chester disease using cardiac magnetic resonance imaging.
Authors: Azoulay Levi-Dan , Bravetti Marine , Cohen-Aubart Fleur , Amoura Zahir , Spano Jean-Philippe , Cluzel Philippe , Haroche Julien 
Published: June 2023

7067 Background: Erdheim-Chester disease (ECD) is a rare multi-systemic non-Langerhans cell histiocytosis that affects the heart in nearly half of patients. Atrial infiltration and pericardial effusion are the hallmarks of cardiac involvement and can lead to clinical complications (conduction disorders, coronary artery stenosis, tamponade, constrictive pericarditis). Evolution under treatment is poorly studied. We aimed to investigate the evolution of cardiac involvement in ECD using cardiac magnetic resonance (CMR) imaging. Methods: All ECD patients with a CMR imaging disclosing a cardiac involvement and who underwent at least one follow-up CMR imaging between 2005 and 2020 at a French tertiary center were retrospectively included. First and last CMR imaging were compared. Multivariable analysis was performed to search for independent predictors of cardiac involvement resolution. Variables were included in the model if their P-value was < 0.1 on univariable analysis. Results: Overall, 46 patients were included. Median age at first imaging was 63 years [53-69]. Median delay between the first and the last imaging was 4 years [2-7]. BRAFV600E mutation was present in 43 patients (94%). Patients received a median of 2 [1-3] treatments. All patients (100%) had cardiac involvement at baseline. Right atrio-ventricular sulcus (RAVS) was infiltrated in 38 patients (83%) and was the main cardiac feature.Overall, complete regression was observed in 6 patients (13%), partial regression in 26 patients (56%), stable imaging in 12 patients (26%), and worsening in 2 patients (5%). In patients with RAVS infiltration, complete regression was observed in 5 patients (16%) and partial regression was seen 22 patients (58%) regression. On univariable analysis, patients with regression of their infiltration had a lower rate of death (16% versus 64%, P= 0.002), a higher rate of atrial infiltration late gadolinium enhancement (LGE) (97% versus 71%, P= 0.01), a higher rate of hydronephrosis (50% versus 14%, P= 0.03) and a lower rate of interferon prescription (69% versus 100%, P= 0.02). A similar rate of vemurafenib use was observed in both groups (69% versus 54%, P= 0.3). On multivariable analysis, death remained significantly associated with follow-up imaging status (ß = -2.3 P= 0.01), while atrial infiltration LGE (ß = 2.7, P= 0.06), hydronephrosis (ß = 1.6, P= 0.1) and treatment with interferon (ß = -16, P= 1) were no longer significantly associated with imaging status. Conclusions: Partial or complete resolution of cardiac involvement was observed in 69% of patients with ECD and was significantly associated with a lower rate of death on multivariable analysis.
Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias.
Authors: Bose Prithviraj , Gagelmann Nico , Gupta Vikas , McLornan Donal P. , Vachhani Pankit , Al-Ali Haifa Kathrin , Ali Haris , Treskes Philipp , Buckley Sarah , Roman-Torres Karisse , Scott Bart L. 
Published: June 2023

7068 Background: In patients with myelofibrosis (MF), JAK inhibitor therapy can improve both splenomegaly and disease symptoms. Unfortunately, dosing – and thus efficacy – of available current JAK1/2 inhibitors is frequently limited in patients with cytopenic MF due to drug-induced exacerbation of cytopenias. Pacritinib is a novel JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 that has been studied at full dose in patients with MF regardless of cytopenias. Here, we present data on spleen and symptom benefit in pacritinib-treated patients across the cytopenic spectrum, stratified by both baseline platelet (PLT) count and hemoglobin (HB) level. Methods: Evaluable patients treated with pacritinib in the PERSIST-1 and PERSIST-2 studies were analyzed, stratified by baseline PLT (<100, ≥100x109/L) and HB (<8, 8 to <10, ≥10 g/dL). Groups were analyzed for depth of spleen volume response (SVR), modified total symptom score (TSS) response, patient global impression of change (PGIC), and dose intensity. Results: Of 276 patients evaluable for spleen response, median age was 67 years, 51.5% had grade 3 fibrosis, 70% had primary MF, and 16% had prior JAK2 inhibitor exposure. Median dose intensity was >99.7% for the duration of the study across PLT and HB subgroups. Overall, 80% of patients had ≥10% SVR (SVR-10), 75.5% had TSS-10, and 78% reported that their symptoms were improved at week 24. Week 24 spleen reduction occurred consistently across PLT and HB strata, with 84-93% and 86-90% of patients respectively (Table). SVR-35 occurred in 23-25% of patients across PLT strata and in 21-28% of patients across HB strata. Symptom response was also consistent across strata, though TSS-50 occurred at highest rates (62.5%) in patients with HB <8 g/dL. There was no diminution in symptom burden reduction in patients with thrombocytopenia (Table). Across all subgroups, at least three-quarters of patients reported symptoms were “improved” at week 24. Conclusions: Pacritinib demonstrates consistent efficacy for spleen and symptom response in patients with MF regardless of blood counts. This consistent effect may be related to pacritinib’s unique kinome profile and its ability to be delivered at full dose in patients regardless of cytopenias. Clinical trial information: NCT01773187 , NCT02055781 . [Table: see text]