bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stopping study in chronic myeloid leukemia: Defining a new paradigm for Ontario CML1.
Authors: Ravipati Siri , Bakheet Waffa , Hamm Caroline M. 
Published: June 2023

e19069 Background: The National Comprehensive Cancer Network (NCCN) guidelines state that in order to safely stop tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML) patients, we need access to reliable polymerase chain reaction (PCR) tests on a monthly basis (4 weeks). However, Ontario, Canada can only provide a 6-week turnaround reliably. Therefore, we aimed to test a new paradigm for safely stopping TKI treatment by monitoring molecular response every 6 weeks for 6 months instead of the recommended 4-week intervals. Methods: A prospective pilot cohort study was conducted to assess the outcome of cessation of TKI treatment in chronic-phase CML patients. Eligibility criteria includes obtaining MMR4 (4-log reduction) for 2 years and had to have been on TKI therapy for 5 years. Patients' PCR for BCR-ABL, a driver of CML, was tested every 6 weeks for 30 weeks to ensure ongoing major molecular response (MMR). The primary endpoint was successful maintenance of MMR3 (3-log reduction) or greater at 36 weeks. Secondary endpoints include incidence of withdrawal syndrome, psychological effects, and quality of life (QoL) as per the EORTC Global Quality of Life scoring system were assessed during each visit every 6 weeks for 30 weeks. The secondary endpoint was assessing whether MMR was regained once lost. Results: 18 consenting patients were enrolled, 2 were censored from data analysis as additional time is required to assess whether they regained deep molecular response after stopping, 1 patient was deemed too early to analyze. 12 of the 17 enrolled participants were able to successfully stop TKI therapy and remain in remission at 30 weeks, yielding a 71% success rate. 5 patients had relapsed and 3 successfully regained MR 3.0 with resumption of TKI therapy. Conclusions: The findings demonstrated in a small pilot study that testing at 6-week intervals is safe and effective. Most Ontario CML patients treated in large community centers and have not stopped TKI therapy based on the NCNN guidelines that recommend a 4-week testing turnaround. We plan to expand this study to other sites in Ontario and if successful, this new paradigm may enable more CML patients to stop TKI therapy in a safe manner leading to significant financial and clinical impact. Data will be updated at the time of the conference. By determining that Q6 weekly is a safe paradigm, there is potential for increased comfort in patients unable to maintain Q4 weekly testing for various reasons such as compliance or patients in rural settings. Clinical trial information: OCT1250 , CML1 .
The genetics of transformation from myelodysplastic syndrome to secondary acute myeloid leukemia.
Authors: Zhang Zhenyu , Zhang Hong , Lin Yani , Zhao Miaoqing , Ru Kun 
Published: June 2023

e19073 Background: Gene mutations play key role in the transformation from myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (s-AML). The aim of this study was to explore the clonal progression pattern from MDS to s-AML. Methods: A total of 663 patients diagnosed with MDS (n = 291), s-AML (n = 86), and primary AML (p-AML) (n = 286, M3 excluded) were enrolled in this study from May 2018 to December 2021, and the median age was 57 year-old (range 1~88). The diagnosis was established according to the WHO criteria. The MDS patients were divided into low-risk MDS ( n = 158) and high-risk MDS (n = 133) according to 2012 IPSS-R. Next generation sequencing was performed to detect the mutations of entire coding regions of 112 genes related with hematologic tumors in all patients. Results: It was found that mutations from 31 genes occurred in both MDS and AML, including DNA methylation ( DNMT3A, TET2, IDH1, IDH2, WT1), chromatin modification ( SETBP1, ASXL1, EZH2, PHF6), RNA splicing ( U2AF1, SF3B1, SRSF2, ZRSR2), transcription regulation ( TP53, CEBPA, RUNX1, ETV6, GATA2, BCOR, BCORL1), signal transduction pathways ( NRAS, KRAS, PTPN11, NOTCH1, FLT3, JAK2, KIT), and others ( NPM1, FAT, STAG2, DDX41). By enrichment analysis, those mutations were classified into two categories: type A mutations ( FLT3, IDH1, NPM1, NRAS, PTPN11, WT1, CEBPA) and type B mutations ( IDH2, KRAS, U2AF1, ZRSR2, SRSF2, STAG2, DNMT3A, EZH2, RUNX1, ETV6, TP53). The type A genes were significantly enriched in p-AML than in MDS, while some type B mutations, particularly RNA splicing, were significantly enriched in MDS than in p-AML. The VAFs of type A mutations were significantly lower than those of type B mutations. The longitudinal analysis of 10 patients with s-AML revealed two main models of clonal evolution, linear evolution and clone sweeping. Although the two models differed in the disease development, new sub-clones appeared in 9/10 patients. Interestingly, many of the new mutations were type A mutations (n = 7, 7/10), and 7 out of 10 patients carried type B mutations when they were at MDS state. The VAF data also showed that the preexisting mutations were generally higher than the newly emerging genetic alterations. Finally, an individual case was used to delineate the clone evolution. The patient was initially diagnosed with 5q syndrome and U2AF1 mutation (type B) was identified. After treatment, the patient experienced remission, and developed a new ETV6 mutation while the clonal size of U2AF1 decreased. When the patient relapsed, the clone size of ETV6 decreased while U2AF1 mutated clone size were amplified, a typical “clone sweeping” pattern. When the patient eventually transformed to s-AML, three type A mutations ( NRAS, KRAS and PTPN11) appeared simultaneously. Conclusions: This study revealed that the type A mutations are mainly responsible for the progression of MDS to AML, and the type B mutations are related to the clonal origin of MDS.
Incidence of cardiac events in patients with MDS or AML receiving azacitidine or decitabine within a large community health system.
Authors: Naffakh Noor , Williams Michael , Patel Priyam , Pedersen Rachel , Peterson Michael , DeFranco Anthony , Medlin Stephen , Sana Sherjeel , Gul Zartash 
Published: June 2023

e19074 Background: Hypomethylating agents (HMA) such as decitabine and azacitidine are frontline therapies for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Limited data exist on subsequent cardiovascular (CV) events. Johnson et al. reported 170 patients receiving HMA + venetoclax with a CV event rate of 20%. Aims: To investigate the incidence of CV events in patients receiving HMA. Methods: We analyzed adult AML and MDS patients with > 1 dose of azacitidine or decitabine from 1/2018-12/2020. New CV events were defined as new atrial fibrillation, acute coronary syndrome, cardiomyopathy, congestive heart failure, myocarditis, or pericarditis. Competing risks regression identified baseline predictors associated with time to first CV event while accounting for the competing event of death. Results: 94 patients with no CV history were evaluated which consisted of a mean age 69 +/- 12 years and 50% male. 56% had MDS and 44% AML. Patients with BMI ≥ 30 accounted for 38.3% of the sample. 44 (47%) patients had baseline echocardiogram assessments prior to initiation of HMA with EF of 61+/- 8%; 57 (61%) had a documented prescription of beta-blocker, ACE-I, or ARB at time of HMA initiation. In the 94 patients, 16 new cardiac events occurred. Median survival after therapy initiation was 14.8 months. In a competing risks univariate analysis, lower prior EF (after adjusting for no EF performed) and absence of pre-chemotherapy beta-blocker, ACE-I, or ARB were significantly associated with having a new cardiac event post chemotherapy start (hazard ratio per 5-unit decrease = 1.62 (1.33-1.99), p<0.01 and HR=2.89 (1.08-7.77), p=0.03, respectively). Baseline BMI did not affect risk of a new CV event on HMA therapy (HR per 5 units=1.08 (0.78-1.50), p=0.63). Total HMA dose did not show significance as a predictor for CV events (HR=0.99 (0.987-1.009), p=0.72). Conclusions: We observed a CV event incidence of 19% at 3 years after the start of HMAs. Among patients receiving HMA chemotherapy, those with a lower baseline EF and those not on beta-blocker, ACE-I or ARB therapy prior to initiation of HMA had a higher incidence of cardiotoxicity. Neither pre-HMA BMI nor total HMA dose received appeared to predict risk for CV events. Further research is warranted evaluating the association between HMAs and cardiotoxicity. [Table: see text]
Real-world (RW) treatment (tx) patterns of patients (pts) with higher-risk myelodysplastic syndrome (MDS) in a US RWE database (COTA).
Authors: Komrokji Rami S. , Hernandez Donoso Leyla , Hodzic Sejla , Owusu Henry F , Nolan Kevin , Nourry Claire , Diez-Campelo Maria 
Published: June 2023

e19077 Background: Pts with higher-risk MDS have poor outcomes. To understand current tx patterns/identify unmet needs, the COTA database, using pt-level curated electronic health record (EHR) data from centers across the US, was analyzed. Methods: This was a retrospective, descriptive analysis of deidentified secondary data from the COTA MDS RWE database. Data were abstracted from EHRs using these criteria: inclusion of adults with IPSS-R intermediate (I)/high (H)/very high-risk (vHR) MDS on/after 1/1/2012, exclusion of pts with no diagnosis date/clinician notes or pts with concurrent malignancies. Follow-up was until the last recorded event (last visit/other cancer/death; data cutoff 06/2022). Results: Data from 640 pts were included in this analysis. See Table for baseline demographic data. Most pts with IR- (225/281, 80%) and HR-MDS (162/239, 68%) were treated at community centers; pts with vHR-MDS were equally treated at academic (59/120, 49%) and community centers (61/120, 51%). Genetic/molecular data were limited; among pts with data available, the most common genetic mutation was TP53 (75/215, 35%). Of 640 pts, 108 (17%) did not receive tx and 110 (17%) received allogeneic stem cell transplant (alloSCT). Of those given systemic tx, hypomethylating agents (HMAs) were the most common first-line tx (444/532, 83%). Venetoclax was given to 35/640 pts (5%; as first line: 10/532, 2%; as second line: 20/170, 12%; as third line: 4/66, 6%). Median time to start tx from diagnosis was 2.2, 1.1, and 0.9 mo for IR-, HR-, and vHR-MDS, respectively. Of 512 pts assessed for first-line tx with duration data, tx duration was 7.4, 5.4, and 4.2 mo for IR-, HR-, and vHR-MDS, respectively. In 340 pts—including pts who underwent alloSCT—with response data, pts with IR-, HR-, and vHR-MDS had RW response rates (any response) of 73%, 72%, and 58%, respectively. Median OS (mOS) from start of tx was 29.0, 20.3, and 11.9 mo for IR-, HR-, and vHR-MDS, respectively. mOS (from tx start) according to tx: alloSCT 31.4 mo, chemotherapy 19.1 mo, HMAs 23.1 mo, investigational 22.1 mo, venetoclax 10.1 mo, and others 23.8 mo. About 20% of pts transformed into acute myeloid leukemia, chronic myeloid leukemia, chronic myelomonocytic leukemia, or chronic lymphocytic leukemia. Conclusions: This RW study showed that available tx for pts with higher-risk MDS in the US is limited and remains a high unmet need. [Table: see text]
Predictors of survival outcomes in patients with MECOM EVI1 rearrangement aberrations in AML or MDS.
Authors: Kusne Yael , McGary Alyssa , Kelemen Katalin , Litzow Mark Robert , Al-Kali Aref , Foran James M. , Badar Talha , Patnaik Mrinal S , Mangaonkar Abhishek A , Sproat Lisa Ostrosky , Palmer Jeanne M. , Greipp Patricia T. , Arana Yi Cecilia Ysabel 
Published: June 2023

e19078 Background: MECOM (EVI1) rearrangements in MDS/AML are rare and carry an unfavorable prognosis. Although allogeneic stem cell transplantation (allo-HSCT) may prolong survival, factors impacting outcomes are not known. We conducted a retrospective analysis of patients with MECOM (EVI1) to associate clinicopathologic variables with prognosis. Methods: This study was approved by the Mayo Clinic IRB. Patients >18 years of age with MDS or AML and MECOM EVI1 at Mayo Clinic between 01/2012 and 12/2022 were included. Response was defined by ELN criteria. Intensive chemotherapy was defined as 7+3 or high dose cytarabine. Non-intensive chemotherapy included hypomethylating agents with or without venetoclax. Median overall survival (OS) and median leukemia free survival (LFS) were estimated using the Kaplan-Meier method. Outcome differences between sub-groups and univariate analyses were assessed with Cox regression. Results: Sixty patients met criteria for inclusion. Sixty-three percent (n = 38) were male and the median age at diagnosis was 67.8 yrs (range, 56 – 75). Eighty percent had AML (n = 48) and 18% had MDS (n = 11). Sixty-seven percent of patients had secondary AML/MDS (n = 40). Inv(3)/t(3;3) was present in 65% (n = 39) and t(3;21) was present in 12% (n = 7). Thirty-eight percent (n = 23) of patients had cooccurring monosomy 7 or 7q deletion and 5% had complex karyotype (n = 3). SF3B1 was the most common cooccurring mutation in 31% (n = 10), followed by KRAS in 19% (n = 6). Thirty-eight percent of patients (n = 23) received intensive chemotherapy. Complete response (CR) rates were 36% with intensive treatment (n = 8) and 4% with non-intensive treatment (n = 1; p = 0.007). Thirty percent (n = 18) underwent SCT (78% in CR1 and 22% in CR2) and of those, myeloablative conditioning (MAC) was used in 38% while 61% received reduced intensity conditioning (RIC). The mOS in the entire cohort was 11 months (95% CI 6.2, 17). Patients who received a SCT had longer mOS compared to patients who did not (19 vs 6.2 months, HR = 0.31, 95% CI 0.16,0.64; p = 0.001). AML-MRC was a poor prognostic factor in the HCST group for OS (HR = 4.23, 95% CI 1.02, 17.5, p = 0.047). Intensive vs. non-intensive chemotherapy, response prior to transplant (CR vs. no CR), or having 2 or more mutations on NGS did not significantly impact OS or LFS. Conclusions: In line with previous reports, allo-HSCT was associated with improved survival outcomes. Our results showed a high frequency of secondary AML/MDS, but only AML-MRC was associated with decreased survival outcomes. Regardless of therapy type, outcomes were poor. Novel therapies are urgently needed for these patients.
Juvenile myelomonocytic leukemia: A national analysis of demographic features.
Authors: Whooley Maximillian , Hsia Beau , Keirns Darby , Luker Andrew , Silberstein Peter T. , Wu Xinxin 
Published: June 2023

e19086 Background: Juvenile Myelomonocytic Leukemia (JMML) is a rare hematological cancer originating in the bone marrow. It is a type of myelodysplastic syndrome (MDS) characterized by abnormal production of myeloid progenitor cells and monocytes. This malignancy is predominant in males, has a median age of diagnosis of 2 years, and carries a poor prognosis. It only accounts for 1% of all pediatric leukemias but constitutes 20-40% of pediatric MDS cases, making it the most common MDS subtype in children. Hematopoietic stem cell transplant (HSCT) is the only known cure for JMML, but its efficacy is just 50%. Without treatment, patients survive for a median of 10-12 months. Given the rarity of JMML, an analysis of demographic trends could offer valuable epidemiological insight. The National Cancer Database (NCDB) database was used to examine major demographic features of JMML. Methods: A retrospective analysis of all patients diagnosed with JMML between 2004 – 2020 in the NCDB (N = 242) was performed. Demographic factors including sex, race, Hispanic ethnicity, household income status, insurance status, urban/rural status, and Charlson-Deyo score were examined by descriptive statistics. Treatment statistics were also analyzed. Linear regression was used to determine incidence trends. Results: A total of 242 patients were identified with a histologically-confirmed diagnosis of JMML. Most patients were male (67.4%). The average age of diagnosis was 2 years (SD = 3.69, range = 0-33). The average incidence was 14.2 patients diagnosed per year (SD = 3.7, range = 9 – 21, R2 = 0.131). 93.8% had a Charlson-Deyo comorbidity score of 0. The majority of patients were White (74.4%), followed by Black (11.6%). 16.1% of patients were of Hispanic ethnicity. The distribution of median household income was 27.4% in the top quartile, 26.9% in the second, 26.9% in the third, and 18.7% in the fourth. Most patients were either privately insured (49.6%) or insured by Medicaid (42.6%). 75.5% of patients lived in a county with 250,000 people or more. Most patients received treatment (84.6%), while some only received active surveillance (8.7%) or no treatment (6.7%). Conclusions: This is the first NCDB analysis describing the demographic trends of JMML. Patients were twice as likely to be male than female. They were most likely to be White, with an average age of 2 years. This data reflects the expected age group and sex/race predominance described in the literature. The proportion of Hispanic JMML patients was comparable to Hispanics in the general US population. JMML appeared to be nearly evenly distributed among the top three household income quartiles. The lowest income quartile and rural inhabitants were least affected by this disease, which may indicate underdiagnosis in these populations. Further studies are needed to better define the relevance of these individual factors in the diagnosis, treatment, and survival of patients with JMML.
Influence of modified Lugano criteria by pre-infusion tumor kinetics on early survival prediction for patients with lymphoma under chimeric antigen receptor T-cell therapy.
Authors: Kunz Wolfgang G. , Blumenberg Viktoria , Rejeski Kai , Buecklein Veit , Schmidt Christian , Dekorsy Franziska , Bartenstein Peter , Ricke Jens , von Bergwelt Michael , Subklewe Marion , Winkelmann Michael 
Published: June 2023

e19500 Background: Chimeric antigen receptor T-cell therapy (CART) is effective for patients with refractory or relapsed (r/r) lymphoma with prolongation of survival. We aimed to improve the prediction of Lugano criteria for overall survival (OS) at 30-day follow-up (FU1) by including the pre-infusion tumor growth rate (TGRpre-BL) and its early change to 30-day FU1 imaging (TGRpost-BL). Methods: Consecutive patients with pre-baseline (pre-BL), baseline (BL) and FU imaging around day 30 with CT or PET/CT before CART were included. TGR was defined as change of Lugano criteria-based tumor burden between pre-BL, BL and FU examinations in relation to days between imaging exams. Overall response and PFS were determined based on Lugano criteria. Proportional Cox regression analysis studied association of TGR with OS. For survival analysis, OS was analyzed using Kaplan-Meier survival curves. Results: 59 out of 81 patients met the inclusion criteria. At 30-day FU 8 patients (16%) had a CR, 25 patients (42%) a PR, 15 patients (25%) a SD, and 11 patients (19%) a PD according to Lugano criteria. The Median TGRpre-BL was -0.6 mm2/d, 24.4 mm2/d, -5.1 mm2/d, and 18.6 mm2/d and the median TGRpost-BL was -16.7 mm2/d, -102.0 mm2/d, -19.8 mm2/d and 8.5 mm2/d in CR, PR, SD, and PD patients, respectively. PD patients could be subclassified into a cohort with an increase in TGR (7 of 11 patients [64%], PD TGRpre-to-post-BL INCR) and a cohort with a decrease in TGR (4 of 11 patients [36%], PD TGRpre-to-post-BL DECR) from pre- to post-BL. PD TGRpre-to-post-BL DECR patients exhibited similar OS to patients classified as SD, while PD TGRpre-to-post-BL INCR patients had significantly shorter OS (65 days vs 471 days, p < 0.001). Conclusions: In the context of CART, the additional use of TGRpre-BL and its change to TGRpost-BL determined at 30-day FU1 showed better OS prognostication for patients with overall progressive disease according to Lugano criteria. Therefore, this modification of the Lugano classification should be explored as a potential novel imaging biomarker of early response. [Table: see text]
Chronic lymphocytic leukemia/small lymphocytic lymphoma nationwide analysis: Comparing sociodemographic and survival outcomes among Hispanics and non-Hispanics in the United States.
Authors: Toro-Vélez Esteban , Rosas Daniel , Velez-Mejia Carolina , Liu Qianqian , Michalek Joel , Diaz Duque Adolfo Enrique 
Published: June 2023

e19505 Background: In essence, chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are the same , CLL being the most common leukemia in Western countries. (Blood PMID 29540348, CA Cancer J Clin PMID 35020204) Survival outcomes in CLL/SLL among Hispanics (HI) and Non-Hispanics (NH) have been controversial. (Cancer Causes Control PMID 34677741, Cold Spring Harb Mol Case Stud PMID 33593728) This analysis attempts to clarify if sociodemographic characteristics influence survival of HI diagnosed with CLL/SLL in the United States (US). Methods: Retrospective data analysis on CLL/SLL patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) 18 database from 2000-2018. Demographics, disease characteristics, and survival patterns were analyzed across ethnic groups, HI vs NH. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS). Multivariate analysis and propensity score matching was performed, adjusting for age, stage, and B-symptoms. Results: 98884 CLL/SLL patients were included, 5012 HI. Males predominated in both HI and NH. HI compared to NH, were diagnosed at a younger median age, 68 years vs 70 years, respectively [p<0.001]. Majority of patients belonged to the age bracket of 60-80 years; favoring a younger age distribution in HI. Most patients were white, and NH had greater heterogeneity [p<0.001]. Unknown stage at diagnosis followed by advance stage (III/IV) prevailed for both ethnicities [p=0.075]. B-symptoms were mostly unknown in both groups. The tendency was towards not receiving radiation as part of the treatment. Survival probability at 2, 5 and 10 years for HI (0.829, 0.677, and 0.474) was similar compared to NH (0.831, 0.664 and 0.437), respectively. The median survival time was 9.3 years for HI vs 8.5 years for NH, with a statistically significant difference in OS favoring HI [p=0.0045] On multivariate analysis, patients older than 80 years and between 60-80, had worse OS than those less than 60, with hazard ratio (HR) 7.5 [95% CI: 7 – 8.1] and 2.5 [95% CI: 2.4-2.7], respectively. Also, stage III and IV, had inferior OS than those at early stages, with HR 1.4 [95% CI: 1.1 – 1.6] and HR 1.2 [95% CI: 1 – 1.4], respectively. Conclusions: In this analysis, HI with CLL/SLL have a superior OS, which was noted to be statistically significant. Also, multivariate analysis showed correlation of better OS when CLL/SLL was identified at a younger age and early stages. Although demographic differences may be driving the survival effect in HI as they were noted to be younger; identification and better understanding of intrinsic disease characteristics, treatment patterns, and biological variables; may aid in the understanding on how these factors contribute and impact the survival advantage in this ethnic group.