bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II trial of ponatinib and blinatumomab in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL).
Authors: Short Nicholas James , Jabbour Elias , Jain Nitin , Macaron Walid , Huang Xuelin , Montalban-Bravo Guillermo , Kadia Tapan M. , Daver Naval Guastad , Haddad Fadi , Zoghbi Marianne , Nasnas Cedric Christophe , Nasr Lewis Fady , Mayor Ejiroghene , Deen Wuliamatu , Thankachan Jennifer , Loiselle Christopher , Garris Rebecca , Konopleva Marina , Ravandi Farhad , Kantarjian Hagop M. 
Published: June 2023

e19013 Background: Ponatinib and blinatumomab are both active in Ph+ ALL. A combination of these agents may lead to durable remissions when given in the frontline setting and may eliminate the need for chemotherapy or stem cell transplant (SCT). Methods: In this phase II study, patients (pts) with newly diagnosed Ph+ ALL received up to 5 cycles of blinatumomab in combination with ponatinib, followed by ponatinib maintenance for at least 5 years. Ponatinib 30mg daily was given during cycle 1 and decreased to 15mg daily once a complete molecular response (CMR) was achieved. Pts also received 12 doses of prophylactic IT chemotherapy. Results: Between 2/2018 and 1/2023, 54 pts were with newly diagnosed Ph+ ALL were treated. Baseline characteristics are shown in the table. Among 35 pts evaluable for hematologic response, 23 (97%) achieved CR/CRi; 1 pt had early death. Among 48 pts evaluable for molecular response, 34 (71%) achieved CMR after 1 cycle, and 43 (90%) achieved CMR at any time. After 2 weeks of therapy, 18/35 tested pts (51%) achieved CMR in the peripheral blood. 34/38 tested pts (89%) achieved MRD negativity by next-generation sequencing at a level of 10-6. Four of these pts who were MRD-negative by NGS had detectable low-level BCR:ABL1 transcripts by PCR at the same time (ranging from 0.01% to 0.05%). The median follow-up is 16 months (range, 1-55 months). Three patients relapsed after a median of 9 months of remission (range, 8-23 months), 1 in bone marrow with new E225V mutation and 2 extramedullary-only. Three pts have died (1 from intracranial hemorrhage, 1 from post-procedural hemorrhage, and 1 from brain aneurysm). There have been no leukemia-related deaths, the estimated 2-year EFS and OS are both 90%. Only 1 pt underwent SCT in first remission; this pt was transplanted due to persistently low-level BCR:ABL1 positivity. Among the 47 pts in ongoing remission without SCT, the median duration of response is 15 months. Most side effects were grade 1-2 and were consistent with the known toxicity profile of the two agents. Ponatinib was discontinued in 2 patients due to possibly related adverse events (CVA and coronary stenosis in 1 pt each). Conclusions: The chemotherapy-free combination of ponatinib and blinatumomab is safe and effective in newly diagnosed Ph+ ALL, with high rates of MRD negativity. Encouraging duration of remission and OS has been observed without the need for SCT. Clinical trial information: NCT03263572 . [Table: see text]
Optical genome mapping for cytogenomic analysis of hematological neoplasms.
Authors: Tang Guilin , Tang Zhenya , Kanagal-Shamanna Rashmi , Kantarjian Hagop M. , Garcia-Manero Guillermo , Cuglievan Branko , McCall David , Jain Preetesh , Robinson Melissa , Reynolds Alex , Danos Christopher P , Cardona Griselda Jazmin , Geiger Christopher P , Yang Su , Medeiros L Jeffrey , Toruner Gokce A 
Published: June 2023

e19016 Background: Optical genome mapping (OGM) provides a genome-wide analysis for structural variants and copy number changes in one-assay. Compared with conventional G-banded karyotyping (GBK), OGM provides significantly higher resolution and does not require metaphase cells. In this study, we assessed the added value of OGM for cytogenomic analysis of hematological neoplasms. Methods: OGM was performed on blood or bone marrow using Saphyr from Bionano Genomics on 63 patients diagnosed with various types of hematological malignancy (see Table). Variant calling was made by the Rare Variant Analysis pipeline on Bionano Access after applying recommended filters. Each patient had karyotype and/or fluorescence in situ hybridization (FISH) results available for comparison and confirmation. Only Tier 1 (pathogenic) and Tier 2 (likely pathologic) abnormalities were included for comparison purposes in this study. Results: The results were completely concordant between GBK/FISH and OGM in 30 (47.6%) patients, including 10 patients who showed no cytogenetic abnormality (normal). Fully discordant results were found in 8 (12.7%) patients: 2 had an abnormal karyotype but normal OGM, the discrepancy was mainly due to the clonal size (<20%) below the limitation of detection of OGM; 6 had a normal karyotype but cytogenetic abnormalities were detected by OGM, the discrepancy was mainly due to failure of tumor cells growth (n=5) or subtle cytogenetic abnormality undetectable by GBK (n=1). Partially concordant results between karyotype/FISH and OGM were observed in 25 (40%) patients, some abnormalities were detected by both, some were detected by GBK alone (n=4) or by OGM alone (n=25), the latter group included 10 cases with chromothripsis which only be detected by OGM. Overall, OGM provided clinically significant information in 14 (22%) patients regarding diagnosis, risk stratification, and/or identifying therapeutic targets. The added value was more common in lymphoid neoplasms (9 of 27 patients, 33%). Conclusions: OGM provides additional clinically relevant cytogenetic information in the workup of hematological neoplasms. This added value is more apparent in lymphoid neoplasms. These improvements are largely contributable to the higher resolution provided by OGM and analysis independent of metaphase cells. A major limitation of OGM usage is the need for a clonal size of at least 20%. [Table: see text]
Clinical spectrum and outcomes of carbapenem resistant infections in patients with acute leukaemia: A clinical study from a tertiary oncology centre in India.
Authors: Hari Vishnu , Prakash N.P. , Nath Swapna R. 
Published: June 2023

e19020 Background: The prevalence of carbapenem resistant organisms (CRO) are increasing worldwide and associated with grave implications in patients with hematological malignancies. Data on such infections in patients with acute leukemia are scarce, especially from the developing world. The aim of this study was to evaluate characteristics and outcomes of bacteremia with CRO in patients treated for acute leukemia with aggressive chemotherapy regimens. Methods: This prospective observational study was conducted in a tertiary oncology centre in South India. Data on Carbapenem resistant bloodstream infection (CRBSI) in patients with acute leukemia (ALL and AML) aged 14-60 years, from March 2017 to February 2018 were prospectively collected. The final outcome was determined as survival and all-cause death due to CRBSI. Results: Out of 334 patients treated for acute leukemia, 49 patients developed infections with CRO (14.6%). The patients included 27 males (55%) and 22 females (45%), with age ranging from 14 year to 58 years (median age: 42 years). The most common isolates were Klebsiella species (63%) and E.coli (25%). All carbapenem resistant isolates were sensitive to Colistin and 74% were sensitive to Tigecycline. The case-fatality rate was 69% (34/49) in our cohort. Acute kidney injury, shock, septicemia and an initial procalcitonin value > 1mcg/L were predictor of mortality. Disease in remission and neutrophil count recovery post chemotherapy were favorable factors associated with the outcome. There was no statistically significant difference in mortality in patients treated with single agent antibiotics versus combination antibiotics sensitive against CRO. Conclusions: Carbapenem resistant infections in patients with acute leukaemia are associated with a high mortality rate. The factors associated with improved outcome were disease in remission and neutrophil count recovery, post chemotherapy. The presence of acute kidney injury, shock, sepsis and a procalcitonin value more than 1 mcg/L were significant predictor of mortality.
A demographic study of acute megakaryoblastic leukemia using the national cancer database.
Authors: Juang Eric , Furtado Nikhil , Keirns Darby , Wu Xinxin , Silberstein Peter T. , Hsia Beau 
Published: June 2023

e19023 Background: Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia that, based on past studies, primarily affects children. Patients with Down syndrome (DS) have a higher risk of developing AMKL. While DS-associated AMKL has an overall survival rate of 80%, the prognosis of adult AMKL is much poorer (overall survival rate of < 40%). The prognostic heterogeneity of AMKL warrants an investigation of its diagnostic trends in order to gain epidemiological insights. In this study, demographic data of AMKL patients was obtained from the National Cancer Database (NCDB) and analyzed to determine factors that affect the outcome of AMKL patients. Methods: In this retrospective cohort study, data from the 2004-2020 NCDB was analyzed to identify cases of AMKL with ICD-O-3 code 9910. Demographic data attached to the identified cases assessed included age, sex, race, Hispanic status, insurance status, facility type, surgery status, palliative care status, and Charlson-Deyo score. Descriptive statistics were obtained, and the incidence trends of AMKL were interpreted using regression analysis. Results: A total of 765 patients diagnosed with AMKL were identified in the database between 2004 – 2020 with a decreasing incidence of patients diagnosed per year (64 cases in 2004 and 11 cases in 2020; R^2 = 0.86). The average age of diagnosis was 40.3 years (SD = 32.4, range = 0 – 90 years, median = 51 years). AMKL exhibits slight male prevalence (55.2% vs 44.8% for females). The majority of the patients were Non-Hispanic White (77.6%). Most individuals had Charlson-Deyo comorbidity scores of 0 (79.1%). The incidence rates were similar across household income quartiles. 72.8% of AMKL cases were diagnosed in urban areas with a population of > 250,000. Fewer cases were treated at community cancer programs as compared to either academic/research programs (45.1%) or integrated network cancer programs (20.6%). Private insurance (38.6%), Medicare (30.6%), and Medicaid (22.0%) were the most common insurance types. All patients received surgical intervention of the bone marrow and 3.2% of patients received palliative care. Conclusions: This NCDB-based demographic analysis on AMKL serves to improve the general understanding of AMKL. Surprisingly, the average and median ages of diagnosis are 40.3 and 51 years, respectively, which contradicts prior reports of AMKL being primarily a pediatric disease. Our analysis of the socioeconomic factors of AMKL patients showed that most AMKL patients were non-Hispanic Whites and diagnosed and treated in urban settings. In addition, the majority of AMKL patients had government insurance (54.6%; Medicare, Medicaid, and others). While this study provides initial insight into the role demographics play in the diagnosis and treatment of AMKL patients, further studies on how these factors contribute to their outcome would provide great value in understanding the social disparity in AMKL.
Mini-hyper-CVD plus inotuzumab ozogamicin (InO), with or without blinatumomab (Blina), in older patients with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (ALL): Updates from a phase II trial.
Authors: Nasnas Cedric Christophe , Jabbour Elias , Haddad Fadi , Short Nicholas James , Nasr Lewis Fady , Macaron Walid , Zoghbi Marianne , Ravandi Farhad , Jain Nitin , Kadia Tapan M. , Daver Naval Guastad , Borthakur Gautam , Dinardo Courtney Denton , Jacob Jovitta , Roy Edith , Loiselle Christopher , Milton Anna , Rivera Juan , Garris Rebecca , Kantarjian Hagop M. 
Published: June 2023

e19025 Background: The overall survival (OS) of patients (pts) with relapsed/refractory B-ALL has improved with the introduction of InO and Blina. Compared to conventional chemotherapy, the incorporation of these agents into the frontline setting of older pts with ALL may allow the use of less chemotherapy and potentially improve outcomes. Methods: Adults ≥60 yrs with newly diagnosed Ph-negative B-ALL received mini-Hyper-CVD (mini-HCVD) for up to 8 cycles. Initially, InO was given at 1.3-1.8mg/m2 on Day (D) 3 of Cycle (C) 1 and 0.8-1.3mg/m2 on D3 of C2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. Responders received POMP maintenance for up to 3 yrs. Beginning with pt #50, InO was given in fractionated doses each cycle (0.6 mg/m2 on D2 and 0.3 mg/m2 on D8 of C1; 0.3 mg/m2 on D2 and 8 of C2-4) and 4 cycles of Blina were given following 4 cycles of mini-HCVD plus InO. Maintenance was with 12 cycles of POMP and 4 cycles of Blina (1 cycle of Blina after 3 cycles of POMP). Results: 83 pts were treated, of whom 6 were in complete remission (CR) at enrollment(Table 1). Among 77 evaluable pts, 76 (99%) responded (CR, 90%). Among responders, the rates of MRD negativity by flow cytometry were 79% and 94% after C1 and overall, respectively. No early death was observed. Among 82 pts in remission, 11 (13%) relapsed, 4 (5%) underwent ASCT, 34 (41%) remain in ongoing continuous remission, 33 (41%) died in remission, of whom 9 died after developing MDS/AML. Three pts (4%) developed veno-occlusive disease, 2 after subsequent ASCT. After a median follow-up of 65 months (range, 6-126), the 5-yr continuous remission duration and OS rates were 78% and 48%, respectively. Age ≥70 and adverse cytogenetics were associated with worse outcomes. The inferior outcome in pts ≥70 yrs was primarily attributed to higher rates of death in CR. The 5-yr OS for pts age 60-69 yrs without adverse cytogenetics (n=40), age 60-69 with adverse cytogenetics (n=15), age ≥70 without adverse cytogenetics (n=24) and age ≥70 with adverse cytogenetics (n=4) were 72%, 27%, 38% and 0%, respectively. Conclusions: Favorable outcomes were observed in older pts with newly diagnosed Ph-negative ALL treated with mini-HCVD plus InO, with or without Blina. The 5-yr OS was 48%. Clinical trial information: NCT01371630 . [Table: see text]
Demographic factors affecting patients with AML with myelodysplasia-related changes.
Authors: Stewart Laura , Keirns Darby , Wu Xinxin , Silberstein Peter T. , Hsia Beau 
Published: June 2023

e19027 Background: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a rare and aggressive form of acute myeloid leukemia (AML) that makes up about 25-34% of its annual cases. The subtype includes a varied group of tumors with clinical, genetic, and morphological characteristics that confer poor outcomes. AML-MRC is commonly treated with intensive chemotherapy, but the median survival is only 9-12 months. Given the poor outcomes, gaining a better understanding of epidemiologic factors could reveal opportunities for earlier diagnosis and improved treatment planning. Demographic characteristics of AML-MRC patients were identified and examined using the National Cancer Database (NCDB). Methods: Individuals with a confirmed diagnosis of AML-MRC (N = 14,536) were identified using the NCDB for a retrospective analysis from 2004 to 2020. Patient sex, age at diagnosis, race, household income, insurance status, urban/rural residence, and Charlson-Deyo score were examined by descriptive statistics, and diagnostic trends by year were identified and calculated with regression analysis. Results: A total of 14,536 patients diagnosed with AML-MRC between 2004 – 2020 were identified in the NCDB. Within this timeframe, there was an increasing incidence of diagnosis per year (R2 = 0.9). AML-MRC was more common in males (61.1%) than females (38.9%), and the average age at diagnosis was 68.9 years (SD = 13.0, range = 0 – 90 years). The majority of patients (87.3%) were White. Patients were most likely to be a part of the highest median household income quartile (33.6%) and least likely to be a part of the bottom quartile (13.2%). A higher percentage of patients were insured by Medicare (63.0%) compared to private insurance (25.3%). Most patients lived in counties in metro areas of 1 million population or more (51.4%). Most individuals had Charlson-Deyo comorbidity scores of zero (68.1%). The most common type of treatment facility was academic/research programs (55.1%) followed by comprehensive community cancer programs (23.3%). Conclusions: AML-MRC is a common subtype of AML with a poor prognosis. Previous studies have found that most individuals with AML-MRC are older-aged, White males. Our study corroborated this finding and examined additional demographic factors. We found that these patients were more likely to hold insurance through Medicare, likely reflecting the older average age at diagnosis. Additionally, patients were most commonly in the highest household income quartile and living in a metropolitan area with the highest population density. This could suggest that better access to healthcare improves rates of diagnosis of AML-MRC. Especially given that more people are being diagnosed each year, further research should work to understand the effects of these, and other, socioeconomic factors on the diagnosis, treatment, and prognosis of patients with AML-MRC.
Comparison of time of onset of leukemia with patients receiving adalimumab vs other TNF α inhibitors.
Authors: Devarkonda Vishal , Balmuri Shravya , Gaddam Shiva Jashwanth , Keerty Dinesh , Akabane Hugo 
Published: June 2023

e19034 Background: TNF α (Tumor necrosis factor alpha) inhibitors were first approved by US FDA (Food and drug administration) in the late 1990s to manage several inflammatory conditions. Theoretically, TNF α inhibitors have an elevated risk of malignancies as TNF plays a role in cell apoptosis. The development of newer human monoclonal TNF α antibodies like Adalimumab has been approved for a broader clinical spectrum of activity. However, any increase relative risk of malignancies associated with these drugs is highly debatable, with many post-marketing surveillance studies showing no significant increases in the relative risk of malignancies receiving these drugs. We hypothesize with the null hypothesis stating that there is no significant difference in the time of onset of acute leukemia in the patients receiving Adalimumab in comparison with other TNF α inhibitors. Methods: A comprehensive literature search of PubMed, Embase, and Cochrane was conducted. A total of 19 cases of acute leukemia were reported in association with TNF α inhibitors receiving it for various inflammatory conditions. Of nineteen patients, ten received Adalimumab as the last TNF α inhibitor, while nine received other TNF α inhibitors for various inflammatory etiologies. These patients received multiple lines of treatment with steroids, Thiopurines, Methotrexate, and TNF α inhibitors with varying duration of disease activity. We performed a one-way ANOVA analysis comparing the mean duration of the last TNF inhibitor with the time to diagnosis of leukemia. Results: The results indicate a significant effect [F (1, 17) = 5.652, p=0.029 < 0.05]. The comparison revealed a significant difference between the patients who took Adalimumab (M=5.650; SD=3.8733) and other TNF α inhibitors (M=23.333; SD=23.2379) as the last drug. We, therefore, reject the null hypothesis as there is a significant difference in the time of onset of acute leukemia in the patients receiving Adalimumab in comparison with other TNF α inhibitors. Conclusions: In this limited study of the cases of acute leukemia reported in the literature receiving TNF inhibitors for various inflammatory conditions, patients receiving Adalimumab would have the early time of onset of leukemia in comparison with the other TNF α inhibitors. [Table: see text]
Trajectories of physical well-being among adults with acute myeloid leukemia.
Authors: Jensen-Battaglia Marielle , Sohn Michael , Wang Ying , Consagra William , LoCastro Marissa , Davis Jenae N. , Buettner Kathryn , Mortaz Soroush , El-Jawahri Areej , Loh Kah Poh 
Published: June 2023

e19040 Background: Adults with acute myeloid leukemia (AML) commonly experience physical decline related to their disease and treatment which is associated with negative outcomes. However, physical trajectories differ among patients. Identifying distinct physical trajectories may help guide clinical decision making and supportive care interventions. In this secondary analysis, we examined physical trajectories of patients with AML and factors associated with these trajectories. Methods: We used data from patients with newly diagnosed AML in four clinical trials. Functional Assessment of Cancer Therapy Physical Well-Being sub scale (FACT-PWB, range 0-28) was measured from baseline to day 200, up to 5 timepoints per patient. We used group-based trajectory models (GBTM) weighted for mortality-related drop out to identify groups of patients with similar trajectories of change in FACT-PWB and estimate the association of baseline demographics (age, marital status, education) and clinical factors (AML risk, baseline FACT-PWB, depression, anxiety) with group membership. The number of groups was selected based on clinical interpretability and model fit statistics. Results: We included 343 patients with ≥ 1 FACT-PWB score during up to 200 days of follow-up. Mean age was 65 (SD 12.7), most had intermediate risk AML (178, 52%), received intensive treatment (244, 71%), and died during the follow up period (199, 58%). The GBTM with 4 patterns of change in FACT-PWB showed the best fit for our data (Table). The largest group (Group 2: N = 188, 55%) declined slightly in the first month, then stabilized, while those in the smallest group (Group 1: N = 16, 5%) declined steadily in the first 3 months before improving and stabilizing. Lower baseline FACT-PWB was associated with membership in Group 3: Slight improvement then stable (115, 34%) and Group 4: Steep improvement then stable (24, 7%)), relative to Group 2 (p < .001). Other variables were not associated with group membership. Conclusions: Adults newly diagnosed with AML show distinct patterns of change in their physical well-being after starting treatment. Future studies should measure self-reported and objective physical function in addition to physical well-being in patients with AML, especially with recent change in treatment landscape, to better understand their trajectories. [Table: see text]