bluuebunny/crossref_metadata_2025_split huggingface dataset:
Financial toxicity and quality of life in patients undergoing bone marrow transplant evaluation: A single center analysis.
Authors: Hussaini S. M. Qasim , Ren Yi , Racioppi Alessandro , Lew Meagan , Bohannon Lauren M. , Johnson Ernaya , Thompson Jillian , Henshall Bethany , Darby Maurisa , Choi Taewoong , Lopez Richard D , Sarantopoulos Stefanie , Gasparetto Cristina J. , Long Gwynn Douglas , Horwitz Mitchell , Chao Nelson Jen An , Zafar Yousuf , Sung Anthony Derek 
Published: June 2023

7052 Background: The impact of pre-transplant financial toxicity on quality of life (QOL) outcomes following bone marrow transplant (BMT) is unknown. We investigated the prevalence of financial toxicity in a population undergoing evaluation for BMT and its impact on post-transplant clinical and health-related QOL outcomes. Methods: This is a cross-sectional study in patients undergoing evaluation for allogeneic BMT between 1/1/2018 and 9/23/2020 at a large academic medical center. Financial health at baseline was measured via the comprehensive score for financial toxicity (COST) survey. The cohort was divided into three groups: none, mild, and moderate-high financial toxicity. QOL was measured using Functional Assessment of Cancer Therapy (FACT)-based questionnaires at multiple timepoints. Multivariate logistic regression analysis evaluated factors associated with financial toxicity. Kaplan-Meier curves and log-rank tests evaluated overall survival and non-relapse survival. Results: Of 245 patients evaluated for BMT, 176 (71.8%) completed both questionnaires with 63.1% male, 72.2% white, and median age 57 years. Common diagnoses were myelodysplastic syndrome (39.2%), leukemia (38.1%), and lymphoma (13.6%). Overall, 83 (47.2%) patients reported no financial toxicity, 51 (29.0%) mild, and 42 (23.9%) with moderate-high financial toxicity at initial evaluation for BMT. Compared to those with no financial toxicity, those with mild or moderate-high financial toxicity reported significantly reduced spending on leisure, food/clothing, used all or a portion of savings, borrowed money or accumulated debt using a credit card, and did not fill a prescription due to costs (p < 0.0001 for all). In patients with baseline moderate-high financial toxicity, FACT-BMT scores were lower at 6 months (126 none vs 122 mild vs 92 moderate-high; p = 0.0007) and 1 year (133 none vs 117 mild vs 112 moderate-high; p = 0.0075) following BMT. Older age (>62) (OR 0.4; 95% CI [0.17 – 0.94], p = 0.03) and income equal or greater than $60,000 (OR 0.16; 95% CI [0.07 – 0.36], p = < 0.001) were associated with lower odds of financial toxicity. No association was noted between financial toxicity and selection for BMT, overall survival, or non-relapse mortality. Conclusions: Financial toxicity was highly correlated with patient-reported changes in behavior affecting their daily activities and transplant care, with notable impact on QOL following transplant for up to 1 year. Early interventions by physician and social work-led teams may benefit patients who are at risk for financial toxicity. [Table: see text]
Report of a chronic myeloid leukemia registry in a low-and middle-income setting.
Authors: Othieno-Abinya Nicolas Anthony , Mwanda Walter , Mutebi Miriam Claire , Nyangasi Mary Flaviane , Mwenda Valerian , Oyiro Peter Omondi , Mcligeyo Angela Awino , Ezzi Mohammed Shabbir , Odhiambo Andrew Oluoch , Ong'ondi Matilda , Mwanzi Sitna Ali , Adamjee Ebrahim , Induli Magdalene 
Published: June 2023

7054 Background: Treatment of chronic myeloid leukaemia (CML) in Kenya has been supported since the year 2002 by a collaboration between the Max Foundation and Novartis Pharmaceuticals in the Glivec International Patient Assistance Program (GIPAP). In November 2020 this was transitioned to Max Access Solutions (MAS) that brought in the Ministry of Health as a partner. A broad range of BCR-ABL tyrosine kinase inhibitors are available. We wanted to describe epidemiology, treatment and outcome of CML in the country. Methods: Patients’ records were reviewed and data entered in a database. Key variables included age, sex, BMI, diet, disease phase at diagnosis, treatment, and outcome. Continuous variables were summarized using mean (standard deviation) or median (interquartile range). Categorical variables were summarized using counts and percentages. Bivariate comparisons of treatment outcome were done using chi-square or Fisher’s exact test. Analysis of variance (ANOVA) or Kruskal-Wallis test was used for continuous variables. Results: 1347 patients-males 748 (55.5%), females 599 (44.5%). Mean age was 44.5 years. Seventy (9.0%) were underweight, 88 (11.4%) obese. Mean body surface area (BSA) was 1.75m2. Chronic phase cases were 1177 (96.2%), accelerated phase 46 (3.8%), blastic phase 1 (0.1%). Mean bone marrow blast count was 5.25%, BCR-ABL/ABL was 63.7%, haemoglobin 10.8g/dl, total wbc count 225 x 109/litre, platelets 392.5 x 109/litre. Imatinib was administered upfront to 1319 patients (99.8%). Two hundred and six (15.3%) were switched to second line; 100 (48.8%) to dasatinib, 50 (24.4%) to bosutinib. Transformation was registered in 26 cases (1.9%) - accelerated in 13 (72.2%), blastic in 5 (27.8%), 4 (80.0%) being myeloid and 1 (20%) lymphoblastic. Those alive are 1151 (85.4%) and 185 (13.7%) lost to follow-up. Deaths were recorded in 11 (0.8%). Those with lower BSA were more likely to die (p = 0.01). Conclusions: CML in Kenya occurs at a younger age-group with a slight male preponderance. With availability of a range of BCR-ABL tyrosine kinase inhibitors, treatment outcome is close to what is documented in high-income settings.
Methylation-based prediction of myelodysplastic syndrome survival outcomes.
Authors: Shi Alvin , Ali Abdullah , Cann Gordon , Shaknovich Rita , Venn Oliver , Raza Azra , Liu Qinwen 
Published: June 2023

7058 Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid malignancies associated with a myriad of deleterious outcomes and a 5-year relative survival of 37%. MDS risk stratification is key for optimal treatment decisions. DNA methylation is associated with MDS biology due to frequent somatic mutations in genes (i.e. TET2, DNMT3A, IDH1, IDH2, and WT1) that affect DNA methylation. We hypothesized that methylation-based markers may help stratify risk and improve IPSS-R (the Revised International Prognostic Scoring System). Here, we evaluated the potential of both Bone Marrow (BM) Whole-genome Bisulfite Sequencing (WGBS) and Serum-based Targeted Methylation (TM) Sequencing to predict survival of MDS patients. Methods: We conducted paired BM WGBS and Serum-based TM sequencing on a cohort of 127 patients with MDS (N = 104) and secondary AML (N = 23) treated at the Columbia University Medical Center. We categorized patients based on an overall survival of > 3 (“long”, N = 50) or < 3 years (“short”, N = 77). We then identified differentially methylated regions (DMRs) differing between long and short survivor groups, and analyzed the biological pathways and functions enriched in these regions. To assess survival association, we trained a random forest classifier on principal components (“methylation classifier”) on the methylation fractions from a subset of 96 Serum and 98 BM MDS patient samples to predict long vs. short survival, and compared this against a logistic regression IPSS-R model. We optimized the hyperparameters and assessed classifier performance using six-fold nested cross-validation. Finally, we conducted a multivariable cox regression with predicted scores from the methylation classifier, IPSS-R scores (recalculated at sample collection), age, and gender. Results: We identified a total of 7,742 DMRs in the BM WGBS and 14,093 DMRs in the Serum TM as significantly different between long and short survivor groups. Signaling pathways for calcium, cAMP, MAPK, Rap1, and PI3K-Akt were significantly enriched in DMRs. We also identified a previously-reported CpG island hypermethylation signature associated with AML progression in BM and Serum. The methylation classifier achieved a comparable AUROC compared to IPSS-R logistic regression for both BM WGBS (0.80 vs 0.78) and Serum TM (0.77 vs 0.73) samples. Multivariable Cox regression demonstrated that both predicted scores from the methylation classifier (Serum p =0.002; BM p =0.016) and IPSS-R scores (Serum p =0.003; BM p =0.004) are significant predictors of survival. Conclusions: We demonstrated methylation-based sequencing represents a promising new tool for MDS patient risk stratification. As IPSS-R relies on bone marrow aspirates, the Serum-based TM assay offers a less-invasive method for MDS risk stratification.
Outcome of TP53-mutated CCUS and the risk of progression to myeloid neoplasms.
Authors: Shah Syed Naseem , Li Marissa , Baranwal Anmol , Chen Dong , He Rong , Alkhateeb Hassan B. , Tefferi Ayalew , Mangaonkar Abhishek A , Al-Kali Aref , Patnaik Mrinal S , Shah Mithun Vinod 
Published: June 2023

7059 Background: TP53-mutated ( TP53mut) myeloid neoplasms (MN) are aggressive leukemia with poor survival. A subset of TP53mut MN is preceded by TP53mut CCUS that is conventionally considered to be high-risk premalignant condition, though evidence supporting the notion is lacking. We studied outcomes of TP53mut CCUS compared to TP53 wild-type ( TP53wt) CCUS. Methods: Mayo Clinic Molecular Hematology Database (N=7593) was queried to identify patients (pts) harboring pathogenic variant(s) in exons 4-11 of the TP53 gene with ≥2% variance allele frequency (VAF). CCUS was defined using the 5th edition of the WHO Classification for MN. Results: Of 457 pts with TP53mut, 29 (5.9%) had TP53mut CCUS. The median age at diagnosis was 67 years, 17 (59%) were female, and 20 (69%) had received cytotoxic therapies. One and ≥2 TP53mut were seen in 26 (89.6%) and 3 (10.3%) pts, respectively. Median TP53mut VAF was 9% (range 3-42), 3 had TP53mut VAF ≥20%, and 4 (14%) had non-MDS defining cytogenetic anomalies. Of 16 pts with available follow up evaluation (median interval 22 months, Table), 3 (10.3%) progressed to TP53mut MN at 5, 13, and 14 months from diagnosis. We next compared outcomes of TP53mut CCUS to TP53wt CCUS (n=138). The proportion of pts developing MN was not different between TP53wt and TP53mut CCUS (18.1 vs 10.3%, P= .42). Progression free survival of TP53mut CCUS was comparable to TP53wt CCUS at 1- (77 vs 83%), 2- (67 vs 67%), and 5-years (67 vs 59%, P=.9). Similarly, overall survival of TP53mut vs TP53wt CCUS at 1- (81 vs 89%), 2- (76 vs 76%), and 5-years (76 vs 67%) was comparable ( P= .94). Conclusions: In contrast to the prevalent notion, TP53mut was not associated with a higher risk of MN progression or mortality compared to TP53wt CCUS. Majority of TP53mut clones showed remarkable stability over years. [Table: see text]
Indirect treatment comparison (ITC) of momelotinib (MMB) vs fedratinib (FED) safety in patients (pts) with myelofibrosis (MF).
Authors: Masarova Lucia , Verstovsek Srdan , Palandri Francesca , Mesa Ruben A. , Harrison Claire , Sajeev Gautam , Gorsh Boris , Simpson Ryan , Cho Sang Kyu , Wang Zhaohui , Ellis Catherine Elizabeth , Conlon Seán , Signorovitch James 
Published: June 2023

7065 Background: JAK inhibitors (JAKi) are a mainstay of MF treatment, with proven ability to improve symptoms and spleen volume for most pts; although safety profiles vary, some approved JAKi have associated hematologic toxicity. The JAK1/JAK2/ACVR1 inhibitor MMB has shown consistent benefit in improving anemia, symptoms, and spleen volume in pts with MF. Clinical trials have directly compared MMB with ruxolitinib, with MMB showing a more favorable hematologic toxicity profile. However, there are limited data comparing MMB vs other JAKi such as FED. We performed an ITC of safety outcomes between MMB and FED in pts with MF. Methods: A matching-adjusted indirect comparison (MAIC) was undertaken to compare outcomes from phase 2 and/or 3 MMB and FED trials. Adverse events (AEs) occurring in > 10% of a treatment arm over 24 weeks were evaluated; primary outcomes were grade 3/4 anemia and thrombocytopenia. Separate analyses were performed in JAKi-naive (SIMPLIFY-1 [S1] vs JAKARTA) and JAKi-experienced (pooled SIMPLIFY-2 [S2], MOMENTUM vs JAKARTA2) pts. Evaluable outcomes were limited by published aggregate data, so not all were feasible to compare. MAIC involved reweighting MMB pt data by matching baseline characteristics prioritized by expert clinical input (DIPSS/IPSS, Total Symptom Score, platelet counts, spleen volume/length, and/or hemoglobin levels) between trial arms, and determining odds ratios (ORs), risk ratios, and risk differences (RDs) between outcomes in resulting balanced populations. As nonrandomized groups were compared, results may be biased due to unmeasured/residual confounding, despite adjusting for prognostic factors/effect modifiers. Results: Effective MMB sample sizes after adjustment were 151.1 JAKi-naive and 79.4 JAKi-experienced pts. Risk of any or grade 3/4 anemia, diarrhea, nausea, and serious AEs leading to dose reductions were statistically less likely with MMB vs FED in both populations; any or grade 3/4 thrombocytopenia was also less likely with MMB vs FED, significantly so in JAKi-naive pts. Odds/risk of other outcomes assessed varied in significance (key OR/RD results presented in the Table). No identified outcomes were statistically less likely with FED. Conclusions: MMB showed a favorable safety profile vs FED in both JAKi-naive and experienced pts, including a significantly lower risk of key hematologic AEs, diarrhea, and nausea over 24 weeks. Clinical trial information: NCT04173494 ; NCT01969838 ; NCT02101268 ; NCT01523171 ; NCT01437787 . [Table: see text]
Bromodomain and extra-terminal (BET) inhibitor INCB057643 (LIMBER-103) in patients (pts) with relapsed or refractory myelofibrosis (R/R MF) and other advanced myeloid neoplasms: A phase 1 study.
Authors: Watts Justin M. , Hunter Anthony , Iurlo Alessandra , Xicoy Blanca , Palandri Francesca , Reeves Brandi , Vannucchi Alessandro M. , Bose Prithviraj , Diaz Rosa Ayala , Halpern Anna B. , Chen Xuejun , Seguy Francis , Zhou Feng , Zheng Fred , Vachhani Pankit 
Published: June 2023

7069 Background: BET proteins are epigenetic readers that regulate expression of critical oncoproteins involved in the pathophysiology of hematologic malignancies, including MF. INCB057643 is a small-molecule BET inhibitor evaluated as monotherapy and in combination with ruxolitinib (RUX) in pts with advanced malignancies in 2 previous phase 1/2 clinical trials. Methods: This ongoing phase 1, 3+3 dose-escalation/expansion study (NCT04279847) evaluates safety and tolerability of INCB057643 (4 mg once daily [qd]; escalation up to 12 mg qd) in pts aged ≥18 years as (1) monotherapy (part 1) in R/R MF, myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasm (MPN) overlap syndromes (MDS/MPN) or (2) added to RUX (part 2) in pts with MF and suboptimal response to RUX. The primary endpoint is safety and tolerability, including identification of dose-limiting toxicities (DLTs). Results: 13 pts have been treated in part 1 (4 mg, n=6; 8 mg, n=4; 10 mg, n=1; 12 mg, n=2), and 3 pts received 4 mg + RUX in part 2 (overall age range, 50–79 years; men, n=9; study treatment duration range, 15–314 days). 12 pts had MF, and 4 had MDS/MPN. All 6 pts in the 4-mg cohort discontinued treatment (3 for progressive disease [PD]; MF, n=2; MDS/MPN, n=1); 1 pt with MF in the 12-mg cohort discontinued for thrombocytopenia. The other 9 pts remain on treatment. Thrombocytopenia was the most common treatment-emergent adverse event (TEAE; n=9; Table) and the only TEAE leading to discontinuation (n=3). Grade ≥3 TEAEs occurring in ≥1 pt were thrombocytopenia (n=4), anemia (n=3), and hypokalemia (n=2). There were 8 serious AEs across 4 pts, with only COVID-19 occurring in >1 pt (n=2); all but one (pneumonia) were considered unrelated to study treatment. There were 2 DLTs (thrombocytopenia [MDS/MPN pt] and hyperbilirubinemia [MF pt]; both 12-mg cohort) and 2 deaths (both 4-mg cohort due to PD [MF, n=1; MDS/MPN, n=1]). Conclusions: Treatment with INCB057643 monotherapy (4 and 8 mg qd) and in combination (4 mg qd) with RUX was generally well tolerated in this pt population. The 12-mg qd monotherapy dose was not tolerated and caused 2 DLTs. There were no treatment-related fatal events. Dose finding in part 1 is ongoing with 10 mg qd, after which a recommended phase 2 dose will be declared. Combination dose escalation is also ongoing. Preliminary efficacy including spleen size and symptoms will be available for presentation. Clinical trial information: NCT04279847 . [Table: see text]
Clinical outcomes by SF3B1 mutation status in patients (pts) with lower-risk myelodysplastic syndrome (LR-MDS) retreated with erythropoiesis-stimulating agents (ESAs).
Authors: Makinde Adeola Y. , Garcia-Manero Guillermo , Matsuno Rayna K. , McBride Ali , Brown Thomas D. , Idryo Danny , Broome Ronda , Herriman Autumn , Wilkinson Kristiana , Walters Sheetal , Schrag Andrew , Mohammed Hina , Izano Monika A. , Mukherjee Sudipto 
Published: June 2023

7071 Background: Pts with SF3B1-mutated LR-MDS often have a more favorable prognosis versus those with SF3B1 wildtype. A sizeable number of pts with LR-MDS undergo ESA treatment even after experiencing ESA failure in first line. This study evaluated the outcomes of pts with LR-MDS retreated with ESAs in routine clinical practice, stratified by SF3B1 status. Methods: This retrospective cohort study included pts with LR-MDS in the US community setting who initiated ESAs as first-line therapy between January 1, 2016 and June 30, 2019, and were followed through June 30, 2021. Eligible pts discontinued ESAs (treatment gap ≥ 3 wk for epoetin alfa or ≥ 6 wk for darbepoetin alfa) and subsequently reinitiated ESA therapy at least once during follow-up. Ring sideroblasts (RS) ≥ 15% served as a surrogate for pts with unknown SF3B1 mutation status. Outcomes included ESA switches, dose reductions and escalations, ESA failure, and overall survival (OS). Primary ESA failure was defined as no rise in hemoglobin (Hb) ≥ 1.5 g/dL or no decrease in RBC transfusion requirement by 8 wk of treatment. Transfusion-dependent (TD) status was evaluated for pts who were transfusion independent (TI) at baseline. Results: A total of 82 pts with LR-MDS and repeat ESA treatment were included. Median age at start of ESA treatment was 79 y (interquartile range [IQR], 72–85). Diagnosis of MDS-RS, MDS with isolated del(5q), MDS with multilineage dysplasia, and MDS with single lineage dysplasia was reported in 30 (36%), 7 (9%), 9 (11%), and 9 (11%) pts, respectively; 27 (33%) had unknown classification. Median follow-up was 26 mo (IQR, 13–38) with 65% failing ESA therapy by 8 wk. Table shows pts’ SF3B1 mutation status, median OS, pts who had an ESA switch, dose reduction or escalation, experienced ESA failure, and pts who were TI at baseline and became TD during follow-up. Results were similar when RS was not used as a surrogate, and when analyses were limited to pts who were treated with ESAs only throughout follow-up. Conclusions: In this study of pts with LR-MDS retreated with ESAs, primary ESA failure was high with nearly half of TI pts becoming TD during follow-up. OS was poor regardless of SF3B1 status – 2–4 times lower than the remaining life expectancy for a 79-y-old (108 mo for men; 125 mo for women). Although treatment options were limited during the study period, the high primary failure rate suggests that pts with LR-MDS may benefit from alternatives to ESAs. [Table: see text]
SAVE (Safe Accelerated Venetoclax Escalation): Initial results of a prospective, phase Ib study of venetoclax with an accelerated dose ramp-up in patients with CLL.
Authors: Crombie Jennifer Leigh , Ahn Inhye E , Tyekucheva Svitlana , Merryman Reid , Fisher David Christopher , Armand Philippe , Montegaard Josie , Kilcommons Marykate , Carey Celeste , Black Robert , Brown Jennifer R. , Davids Matthew Steven 
Published: June 2023

7512 Background: Venetoclax (VEN)-based regimens are highly effective for patients (pts) with treatment naïve (TN) and relapsed/refractory (R/R) CLL. Despite high rates of undetectable minimal residual disease (uMRD) and durable responses even with time-limited therapy, uptake of VEN in routine clinical practice has been relatively low, in part due to the inconvenient 5-week dose ramp-up used to reduce the risk of tumor lysis syndrome (TLS). Accelerated ramp-up schedules have been evaluated in retrospective studies (Davids et al., AJH, 2022), but prospective studies are lacking. Here we present initial results of SAVE: Safe Accelerated Venetoclax Escalation, a phase Ib study of VEN with an accelerated dose ramp-up in pts with CLL. Methods: This is an ongoing phase Ib investigator-sponsored trial for pts with TN and R/R CLL (NCT04843904). Key eligibility include CLL requiring therapy per 2018 iwCLL criteria and adequate renal function. The primary endpoint is the highest risk TLS group that can safely tolerate an accelerated VEN ramp-up. Secondary endpoints include safety and tolerability and rates of ORR/CR/uMRD after 3 months of VEN-based therapy. Patients are treated inpatient with a 5-day daily VEN ramp-up schedule (20-50-100-200-400 mg). TLS labs are monitored pre-dose and at 4, 8, 12, and 24 hours following each dose. Anti-CD20 antibody is given per SOC. At least 5 pts from cohort A (low TLS risk using standard assessment) were required to enroll prior to opening cohort B (medium and high TLS risk). Efficacy is assessed using 2018 iwCLL criteria, toxicity using iwCLL and CTCAE v5, and MRD using central 8-color flow at 10-4. Results: As of 2/2/2023, 20 pts have been treated (10 each from cohort A and B) (Table). 19 pts received obinutuzumab with VEN, and 1 pt received VEN monotherapy. All pts completed an accelerated VEN ramp-up without any clinical TLS. One pt with medium TLS risk had lab TLS (phos and uric acid peaked at 8.7 mg/dL) after the first VEN 400 mg dose, which resolved with sevelamer and rasburicase, thereby prolonging the ramp-up to 6 days. Median inpatient time was 6 days (range 5-8). All grade heme tox: neutropenia (45%; 20% G3/4), thrombocytopenia (35%; 10% G3/4). One pt died 2 months into treatment due to complications of a bowel obstruction unrelated to study treatment. ORR after 3 mo. was 89% in 19 evaluable pts including 2 CRs. Among 19 evaluable patients after 3 mo., 74% and 42% had uMRD in PB and BM, respectively. Conclusions: Our early data suggest that an inpatient, accelerated 5-day VEN ramp-up is feasible in CLL, with a low rate of TLS, even among patients with medium or high risk of TLS. The study is currently ongoing. Clinical trial information: NCT04843904 . [Table: see text]