bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluconazole vs. voriconazole prophylaxis for prevention of invasive fungal infections post haploidentical stem cell transplant.
Authors: Hamadeh Issam , Shahid Zainab , Chhabra Saurabh , Mendez Anjeanette , He Jiaxian , Butler Candace , Dodd Brandy 
Published: May 2020

e19504 Background: IFIs are one of the most detrimental complications of profound and prolonged neutropenia post-allogeneic SCT. Prophylaxis with broad spectrum azole antifungals has become standard of care given favorable outcomes associated with their use in this setting. Nonetheless, the choice of antifungal agent varies between institutions due to absence of consensus guidelines in patients undergoing haploidentical SCT. Methods: Non-interventional retrospective study seeking to compare efficacy of fluconazole vs. voriconazole for prevention of IFI post haploidentical SCT for hematologic malignancies. SCT databases at two academic insitutions (one uses fluconazole and other uses voriconazole) were queried to identify patients who underwent allogeneic SCT from April 2012 until March 2018, and received prophlaxis with either voriconazole (group I) or fluconazole (group II). Patients with intent to start prophylaxis with fluconazole or voriconazole were included, even if antifungal agent was changed later. Primary endpoint was cumulative incidence of breakthrough IFIs (based on MSG criteria) on day +100 and +180. Fisher exact test was used to compare rates of breakthrough IFIs between two cohorts. Secondary endpoint was overal survival (OS). Kaplan Meiers analysis was performed to compare OS on day +180 and 1-year post SCT. Results: The cohort included 141 patients (group I: 75 and group II: 66). Percentage of patients who underwent transplant for leukemia was higher in group I compared to group II (77.3% vs. 56.1%, p < 0.001). A haploidentical SCT was performed in 62.7% of patients in group I compared to 100% in group II (p < 0.001). All patients received non-myeloablative conditioning. There was no statistically significant difference in rates of IFIs between two groups on day +100 (0% in I vs. 4.5% in II, p = 0.9) and +180 (1.4% vs. 4.6%, p = 0.2). A significant difference in OS was noted on day +180 and at 1-year in univariate analysis (Table). Conclusions: Our findings suggest that prophylactic use of either voriconazole or fluconazole after haploidentical SCT is associated with low rates of IFIs. However, survival data favored voriconazole over fluconazole. [Table: see text]
An ultrasensitive amplicon-based sequencing panel for noninvasive molecular testing of hematological malignancies using blood.
Authors: Cher Chae Yin , Lim Zi Yi , Tan Daryl , Mya Hae Tha , Mongkonsritragoon Wichean , Tan Min-Han , Choudhury Yukti 
Published: May 2020

e19511 Background: Hematological malignancies, especially acute myeloid leukemia, myeloproliferative neoplasms, and myelodysplastic syndromes (MDS), present with distinct genomic alterations relevant to prognosis. Bone marrow (BM) is the primary sample source for genetic testing, but is obtained by an invasive biopsy procedure which carries risk of infection. An alternative non-invasive sample type to profile disease-relevant genomic alterations at diagnosis and subsequently, is desired for clinical decision making. An ultrasensitive sequencing panel was applied to peripheral blood (PB) as an alternative to BM, to demonstrate its utility for disease profiling and monitoring. Methods: A total of 27 pairs of matched PB and BM samples were obtained from patients with hematological malignancies including leukemia (n = 21), lymphoma (n = 4), multiple myeloma (n = 1) and MDS (n = 1). The sequencing panel covers 45 genes commonly mutated in myeloid and lymphoid malignancies. The panel is based on amplicon-sequencing and includes error correction for variant detection with allele frequency (VAF) as low as 0.1%. Optimized bioinformatics pipeline and in-house sequencing noise removal was used for variant selection and clonal analysis. Results: Complete concordance was seen for mutations detected in 23 of 27 patient-matched BM and PB paired samples. The likely cause of discordance in the other 4 pairs is attributable to mutations with low VAF ( < 0.5%). Overall, 91% of detected variants were concordant between PB and BM with strong correlation of VAFs (R = 0.9617). Serial testing trends correlated with stable disease with limited changes in VAFs (n = 2), and successful treatment response with rapidly falling VAFs (n = 5). In particular, 2 patients with FLT3-ITD and BCR-ABL1, respectively, identified at diagnosis had dramatic decrease in VAFs with respective targeted treatment. Conclusions: We report the utility of an ultrasensitive sequencing assay in PB with excellent concordance of mutations with BM, suggesting PB is a reliable alternative source for testing. In serial samples, the assay demonstrated value in treatment selection and response evaluation.
Treatment outcomes and healthcare resource utilization (HRU) among patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy in US community oncology setting.
Authors: Lyons Roger M. , Potluri Jalaja , Bui Cat , Choi Michelle E , Ma Esprit , Svensson Anders , Davies Kalatu , Annavarapu Srinivas , Kapustyan Tatyana 
Published: May 2020

e19513 Background: Treatment options for AML patients ineligible for intensive chemotherapy are limited. This study aims to describe demographic and clinical characteristics, outcomes, and HCRU in this patient population. Methods: This was a retrospective observational study of patients aged > 60 years who received first-line (1L) treatment within 60 days of AML diagnosis between 1/1/2011 – 1/1/2018 and had > 2 visits at US Oncology Network (USON) clinics. Patients were followed until 6/30/2018, last visit, or death, whichever came first. Data were sourced from structured fields of the USON database and chart reviews. Patient characteristics and HRU were assessed using descriptive statistics while overall survival (OS), time-to-treatment failure (TTF), and progression-free survival (PFS) from 1L treatment initiation were assessed using the Kaplan-Meier method. Results: 378 patients were included with median age of 79 years; 62.7% were male, 29.3% had an ECOG score > 2, and 38.4% had poor cytogenetic risk profile. Most patients received 1L hypomethylating agent (HMA) monotherapy: azacitidine (AZA, 57.9%) or decitabine (DEC, 25.9%). Few patients received best supportive care only (7.1%) or other AML treatment (9.1%). Median (range) durations of 1L treatment among patients receiving AZA and DEC were 2.9 (0.0, 46.9) and 2.5 (0.1, 26.4) months, respectively. Median (95% CI) OS, TTF, and PFS in the AZA and DEC cohorts were 7.5 (5.7, 9.6) and 7.3 (4.8, 8.8) months, 3.4 (2.8, 4.4) and 3.7 (2.4, 5.2) months, and 6.7 (5.0, 8.0) and 5.7 (3.4, 7.4) months, respectively. Among patients receiving HMAs, 84.5% received at least one transfusion. Median number of red blood cell and platelet transfusions was 4.0. Hospitalization rates in the AZA and DEC cohorts were 79.9% and 83.7%; proportions with hospitalization > 2 days duration were 64.4% and 66.3%, respectively, with median (range) durations of 6.5 (3.0, 34.0) and 7.0 (3.0, 26.0) days, respectively. Conclusions: The low TTF and OS and high HRU in this real-world community oncology study indicates an unmet need to improve outcomes among AML patients ineligible for intensive chemotherapy. NCCN guidelines were updated since this study and future real-world studies are warranted to evaluate impact of novel therapies on treatment patterns and outcomes.
Evaluation of the differences between extramedullary and bone marrow relapse in adult acute lymphoblastic leukemia patients in terms of clinical features and survival outcomes.
Authors: Sayınalp Nilgun , Ciftciler Rafiye , Buyukasik Yahya , Haznedaroglu IC , Aksu Salih , Demiroglu Haluk , Goker Hakan , Ozcebe Osman 
Published: May 2020

e19516 Background: Acute lymphoblastic leukemia (ALL) in adult patients is an uncommon and difficult-to-treat hematological malignancy that is characterized by excess lymphoblasts in the bone marrow (BM). Although many patients achieve remission with chemotherapy, relapse rates are high and survival outcomes in adults are worse than pediatric patients. With uncontrolled proliferation and accumulation of these lymphoblasts, normal hematopoiesis is suppressed and infiltrates various extramedullary (EM) regions. The aim of this study is to evaluate the difference between EM and BM relapse in adult ALL patients in terms of clinical features and survival outcomes. Methods: In this study, we retrospectively analyzed 108 patients who were diagnosed as ALL and treated in our tertiary care center between 2003 and 2019. Statistical analyses were performed using the SPSS software version 25. Results: The study included 108 patients, consisting of 64 males and 44 females with a median age of 30 (range: 17-79 years). The majority of cases were B-cell in origin; 87 (80.6%) patients had B-ALL and 21 (19.4%) had T-ALL. Median follow-up duration for all patients was 21.1 months (range: 0.49-158.7 months). In the follow-up, 28 patients (25.9%) were received allogeneic hematopoietic stem cell transplantation. A total of 27 (25%) patients relapsed during the follow-up period. In 15 (13.9%) of 27 patients, only BM relapse was observed. EM relapse was observed in 12 (11.1%) patients. EM localizations were identified: brain [n = 2, 1.8%], lung [n = 1, 0.92%], retroperitoneum region [n = 1, 0.92%], kidney [n = 2, 1.8%], breast [n = 1, 0.92%], vertebral column [n = 3, 2.7%], spleen [n = 1, 0.92%], and uvea [n = 1, 0.92%]. All of the patients relapsed with bone marrow were B-ALL. Five of the patients (41.7%) with EM relapse were T-ALL (p = 0.006). No significant difference was observed in terms of gender (p = 0.16) and age (p = 0.12) in patients with BM relapse and EM relapse. Median overall survival (OS) was 42.3 months (95% CI: 15.6-69.0) for patients with BM relapse and 32.8 months (95% CI: 20.0-45.5) for patients with EM relapse (p = 0.42). Conclusions: In conclusion, EM relapse is common in ALL patients. We observed that EM relapse is more frequent, especially in patients with T-ALL cell origin. no significant difference was observed in both groups in terms of OS. ALL patients should be carefully followed up in terms of EM relapses as well as bone marrow relapse.
Intestinal microbiota in patients with acute leukemia (AL) and allogeneic hematopoietics stem cell transplantation (allo-HSCT).
Authors: Acosta-Maldonado Brenda Lizeth , Vallejo-Leucona Fernando , Vaca-Paniagua Felipe , Rivera-Fong Liliana , Hernández-Urzúa Elizabeth , De La Garza Jaime G. , Valero-Saldana Luis Manuel , Venegas-Olvera Alinne , Lozano-Aguirre Luis , Velazquez Consuelo , Herrera Angel , Aguilar Jose Luis 
Published: May 2020

e19518 Background: Microbiome is a challenging study area due to its influence on the multiple host functions. The majority of human-associated microbes reside within the colon. Our understanding about the complex interplay between host and environmental factors to shaping the microbiota is evolving rapidly AL is an unfavorable prognosis disease whose only cure possibility is the allo-HSCT. This procedure uses high doses of chemotherapy and multiple drugs such as antibiotics, antiviral, antifungals, and immunosuppressants that damage the mucous membranes and alter the intestinal microbiome balance. These events have been linked to bacterial resistance, relapse risk, Graft Versus Host Disease (GVHD), and poor Overall Survival (OS). The present study’s objective was to identify the intestinal microbiome bacteria groups during allo-HSCT and to evaluate their impact on patients outcome. Methods: Observational and prospective study was performed. Eleven patients with acute leukemia under alloHSCT and 11 health control (relatives) were enrolled. Gut faecal samples were collected in both groups; three for patients (at income day (ID), neutropenic period (N) and 30 days after discharge (+30D) and one in healthy donor (HD) at income day of their relatives. Bacterial 16S rRNA gene sequences were characterized by illumina and QUIIME 2. Biodiversity of microbiome was evaluated by OTUS, Shannon index and dominance. This proyect was supported by CONACyT. Results: We analyze 11 patients, 55% were male, with a median of 25 years-old at allo-HSCT. 7/10 received a HLA-identical and 4/10 an haploidentical HSCT. 82% had GVHD (I-IV), 1/11 died (two due to infections-GVHD and one of disease relapse). We analyzed 44 samples. There are no difference between healthy control group and income day patients’ samples. Statistical differences in the patients’ microbiome were identified among HSCT moments. According OTUS and Shannon Index the biodiversity decrease at neutropenia, and increase at day +30 outcome but it doesn’t represent a complete recovery. Greater bacterial dominance was observed in neutropenia period. (Table). 3/10 patients who died didn’t recovery biodiversity at day +30. Conclusions: Our results suggest that poor microbiome biodiversity recovery could be a worst prognostic [Table: see text]
Induction and maintenance for chronic myeloid leukemia-chronic phase: A novel treatment strategy.
Authors: Jain Aditi , Mahapatra Manoranjan , Seth Tulika , Irom Anil , Sazawal Sudha 
Published: May 2020

e19526 Background: Imatinib remains the standard of care for CML-CP in many countries because of its affordability and safety with long term use. Given that upfront Nilotinib has higher rates of major molecular response and early deep responses predict long term responses, we hypothesized that upfront Nilotinib as induction followed by Imatinib maintenance may help to capitalize on the efficacy of Nilotinib without sacrificing the safety and efficacy of Imatinib. Methods: CML CP patients were divided into 3 groups at the time of diagnosis. Group 1 received Imatinib 400mg OD upfront, Group 2 and 3 received Nilotinib 300 mg BD for 1st 3 and 6 months respectively then switched over to Imatinib 400 OD. Quantitative real time PCR for BCR-ABL (RQ PCR for BCR-ABL) was done at 3, 6,12, 18, 24, 30, and 36 months to assess response. 3 early molecular responses were defined for analysis. EMR 1 was defined as Bcr-abl RQPCR < 10% at 3 months, EMR 2 as < 1% at 6 months and EMR 3 as < 0.1% at 6 months. Results: Patients on Nilotinib induction had deeper responses than patients on Imatinib at 3 and 6 months. However, subsequent molecular responses were similar in all 3 groups. The rates of Early Molecular responses were significantly better in the Nilotinib group compared to the Imatinib group. Significantly lesser patients in Group 1 had EMR 1 compared to Groups 2 and 3 [80.49% vs 100% vs 95.56%, p value 0.001]. Results were similar for EMR 2 and 3 [EMR 2: 34.15% vs 42.11% vs 60%, p value 0.017, EMR 3: 25.71% vs 25.53% vs 44.44%, p value Group 1 vs Group 3: 0.030]. TKI failure/progression rates were significantly better amongst patients who achieved EMR vs those who did not achieve EMR for EMR 2 and 3 but not EMR 1. For EMR 2, 42.68% who did not achieve EMR eventually had TKI failure compared to 18.03% of those who achieved EMR (p value 0.002). Similarly, 32.95% who failed to achieve EMR 3 progressed vs 11.9% of those who achieved EMR 3 (p value 0.011). 3 patients in group 1 and 1 patient in group 2 developed T315I mutation while none did in Group 3. Conclusions: The early advantage achieved with Nilotinib Induction was not sustained after switching to Imatinib maintenance. Nevertheless, target responses were still achieved and similar failure rates were present in all 3 groups. Patients who attained an EMR < 1 % at 3 months or < 0.1% at 6 months tend to have higher EFS and lower rates of TKI failure/progression irrespective of the treatment arm.
Factors other than sheer numbers of blood cells in circulation may be responsible for clinical presentations in chronic myeloid leukaemia.
Authors: Othieno-Abinya Nicolas Anthony , Odhiambo Andrew Oluoch , Ezzi Mohammed Shabbir , Oyiro Peter Omondi 
Published: May 2020

e19527 Background: CML commonly presents with abdominal pain and swelling, and in up to about 50% of cases it is discovered incidentally due to abnormally elevated white blood cell (wbc) counts in circulation. Some present with bleeding tendency, others nusual presentations including hearing and visual loss whose pathogenesis is poorly understood also occur. Priapism presents rarely, attributed to hyperviscosity complicating wbc counts ≥ 250x109/litre. Nonspecific symptoms also present. We wanted to interrogate the link between baseline myeloid elements in circulation, bone marrow blasts, and BCR-ABL values with clinical manifestations. Methods: Patients attending the Glivec International Patient Assistance Clinic at the Nairobi Hospital had records prospectively collected, and analyzed. These included demographic profiles, physical examination, and laboratory values. Absolute, range, median and mean counts for wbcs, absolute neutrophil counts (ANC), platelets, haemoglobin and BCR-ABL values, were tested against each of the clinical presentations. Results: There were 583 patients, males 322 (55.2%) and females 261 (44.8); mean age 39.8 years. Commonest symptom was abdominal swelling in 235 cases (40.3%); 70 (12%) experienced abdominal pain. Priapism occurred in 4 males (1.2%), blindness and deafness in 8 patients (1.4%). Splenomegaly was more common among males than females; [Pearson Chi2 (1) = 5.9545, ( Pr = 0.015)]. Patients aged ≤ 20 years were more likely to be in heart failure, [Pearson Chi2 (3) = 8.8255,( Pr = 0.032)], leg swelling more in those with high platelet counts; [Ranksum test, (p = 0.023)]. Unclear presentation was more common in those with high wbc counts; [Ranksum test, (p = 0.015)]. Total wbc counts and BCR-ABL levels were higher among younger patients; [Kruskal-Wallis test (p = 0.036, and 0.025 respectively)]. Patients with leg swelling had lower BCR-ABL levels; [Ranksum test (p = 0.005)], those in heart failure had significantly higher BCR-ABL levels at baseline compared with the rest; [Ranksum test (p = 0.037)]. Patients with lymphadenopathy were more likely to have lower ANCs; [Ranksum test (p = 0.035)]. Conclusions: Clinical manifestations of CML cannot be explained merely by haematologic values. Complex biologic factors should be interrogated further.
Superior therapy response predictions for patients with myelodysplastic syndrome (MDS) using Cellworks Singula: MyCare-009-02.
Authors: Stein Anthony Selwyn , Watson Drew , Kapoor Shweta , Ghosh Roy Kunal Ghosh , Alam Aftab , Sahu Diwyanshu , Basu Kabya , Prakash Annapoorna , Ullal Yashaswini , Raju Karthik Sundara , Suseela Rakhi Purushothaman , Joseph Vishwas , Basu Sayani , Kumar Chandan , Mohapatra Subrat , Kumari Pallavi , Birajdar Shivgonda , Gopi Reshma , Mitra Upasana , Marcucci Guido 
Published: May 2020

e19528 Background: Despite using cytogenetic and molecular-risk stratification and precision medicine, the current overall outcome of MDS patients remains relatively poor. Therapy selection is often based on information considering only cytogenetics and single molecular aberrations and ignoring other patient-specific omics data that could potentially enable more effective treatments. The Cellworks Singula™ report predicts response for physician prescribed therapies (PPT) using the novel Cellworks Omics Biology Model (CBM) to simulate downstream molecular effects of cell signaling, drugs, and radiation on patient-specific in silico diseased cells. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response than PPT. Methods: Singula’s ability to predict response was evaluated in an independent, randomly selected, retrospective cohort of 146 MDS patients aged 28 to 89 years (median 69) treated with PPT. Patient omics data was available from PubMed and TCGA. The accuracy of Singula was compared to that of PPT using McNemar’s test to account for the correlation between Singula and PPT. Multivariate logistic regression modeled complete response (CR) as a function of patient age, PPT, and Singula against any non-response (NR). Likelihood ratio tests were performed to further validate if Singula provides predictive information beyond PPT or patient age. Similar analyses were performed for overall survival (OS) using proportional hazards regression. Results: Singula was a better predictor for CR than PPT (McNemar’s χ2 = 42.0, p-value < 0.0001), with an overall accuracy of 73.3% (Exact 95% CI: 65.3%, 80.2%) compared to 37.7% (95% CI: 30.0%, 46.1%) for PPT. Singula exhibited a sensitivity and specificity of 90.9% (95% CI: 80.0%, 97.0%) and 62.6% (95% CI: 51.8%, 72.6%), respectively. In multivariate regression analysis, Singula (p < 0.0001) remained an independent predictor for CR after adjusting for patient age (p = 0.0759) and PPT (p = 0.0496). Singula provided alternative therapy selections for 17 of 53 true negative detected by Cellworks. Conclusions: Singula is a superior independent predictor for CR compared to PPT in MDS patients. The Singula report can also validate therapy selection, correctly identify non-responders to PPT and further provide alternative therapy selections.
Secondary myelodysplastic syndrome identified via next-generation sequencing in non-small cell lung cancer patients.
Authors: Feng Yongzhi , Tao Feng , Jiang Libin , Ni Dan , Zhang Jun , Wu Linxin , Shi Lin , Yu Genhua 
Published: May 2020

e19531 Background: Chemotherapy and radiotherapy used in cancer treatment are associated with increased risk of secondary myelodysplastic syndrome (MDS). MDS is characterized with specific chromosomal abnormalities and genomic alterations in JAK2, KRAS, CBL, DNMT3A, TET2, IDH1/2, EVI1, RUNX1, GATA2, EZH2, ASXL1, SF3B1, U2AF1, SRSF2 and ZRSR2. Since next generation sequencing (NGS) techniques have been widely used for the detection of actionable genomic variation in solid tumor patients, analysis of NGS data for chromosomal abnormalities and gene mutations may be supplementary for diagnosis of secondary MDS. Methods: We retrospectively analyzed targeted NGS data of paired tumor and blood samples from patients with non-small cell lung cancer (NSCLC) for chromosomal abnormalities and gene mutations. Sequence panel covered whole exons of 381 genes associated with cancers. Sequence data were processed using a customized analysis pipeline designed to accurately detect multiple classes of genomic alterations in routine clinical specimens. All testing was done in a CLIA-certified, CAP-accredited laboratory. Clinical information of cases with chromosomal abnormalities was reviewed, including treatment for previous cancer, blood and bone marrow tests. Results: We found 4 cases carrying MDS associated chromosome abnormalities among 3523 NSCLC patients with the prevalence of0.1%. They were old (from 66 to 71 years old), and were more likely to be male (3 males and 1 females). All of 4 cases included common abnormalities associated with MDS like 5q-, 7q-, -7, +21. 3 cases had complex (≥3) abnormalities and 1 case had double abnormalities. Point mutations were identified in blood samples of 3 cases. Mutations in TP53 occurred in 3 cases, mutations in ASXL1, DNMT3A, FLT3 and CBL occurred in one case respectively. Among the 4 cases, 2 cases were confirmed as MDS by blood and bone marrow tests. Conclusions: We identified 4 MDS associated chromosomal abnormalities from 3523 NSCLC patients through analyzing NGS data. NGS techniques could serve as supplementary for diagnosis of secondary MDS. [Table: see text]