tbuckley/cabot-search huggingface dataset:
The role of MDSCs in the development of bone marrow fibrosis.
Authors: Qiutian Feng, Jian Huang
Journal: Journal of Clinical Oncology (2024)

e18532 Background: Myelofibrosis is a type of myeloproliferative disorder, and research indicates that the immunosuppressive tumor microenvironment plays a significant role in the pathogenesis of myelofibrosis, with myeloid-derived suppressor cells (MDSC) being the primary inhibitory cells involved in shaping the tumor immune microenvironment. In this study, we used flow cytometry to detect the number of MDSC in the bone marrow of myelofibrosis patients, and the concentration of CCL2 in the supernatant of bone marrow MDSC cells of patients with myelofibrosis was detected by Elisa technique. Methods: In this study, we utilized flow cytometry to identify the number of Lin-HLA-DR-CD33+ labeled MDSC in the bone marrow of 109 myelofibrosis patients and 20 healthy individuals. Subsequently, we detected the CCL2 concentration in the cell culture supernatant of bone marrow MDSC cells from 42 patients with bone marrow fibrosis after stable culture using ELISA technique. Results: The results of flow cytometry revealed a significant increase in the percentage of MDSC in the bone marrow of myelofibrosis patients (15.16±6.25%) compared to healthy individuals (1.72±0.88%) (p&lt;0.0001). Among them, the MDSC counts were 20.86±6.17% in PMF patients, 18.10±4.77% in post-ET MF patients, and 15.58±3.65% in post-PV MF patients, with no significant statistical difference in MDSC counts among the three groups.And them, the CCL2 concentration in the supernatant was 13.67±1.68 pg/ml for patients with MDSC count &lt;5% (n=6), 36.36±11.88 pg/ml for patients with MDSC count between 5% and 10% (n=16), 55.12±9.71 pg/ml for patients with MDSC count between 10% and 20% (n=14), and 83.19±14.01 pg/ml for patients with MDSC count &gt;20% (n=6). Conclusions: Research has shown that the number of MDSCs is elevated in patients with myelofibrosis compared to healthy individuals. We also found that as the MDSC count increased, the CCL2 concentration in the cell culture supernatant increased accordingly, suggesting that CCL2 may be involved in the proliferation and activation of MDSCs.
Analyzing the characteristics and prognostic outcomes for patients with myelodysplastic syndrome with Q-gene deletion.
Authors: Kingsley Chinonyerem Nnawuba, Matthew Blake Lockwood, Tochukwu Nzeako, Zeytun Guyo, Mohammad Al Fazal, Hanna Jensen
Journal: Journal of Clinical Oncology (2024)

e18526 Background: Myelodysplastic syndromes (MDS) are a group of hemopoietic disorders in which the bone marrow is deficient in producing healthy mature blood cells. MDS associated with a deletion in the long arm of chromosome 5Q is a rare occurrence, but considered a good prognosis in comparison to other subgroups of MDS. There has been limited focus directed towards this variant of the disease, especially concerning outcomes among different demographics. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End-Result (SEER) registry research database 17 (2000 -2020) was used to assess &amp; compare the outcomes for this variant of MDS in adult &amp; AYA pts. Univariate &amp; multivariate analyses was performed and cox proportional hazards regression was used to assess prognostic outcomes. A two-sided pvalue ≤0.05 was considered significant. Results: Analysing (table) 2,323 pts identified, 98.92% (n= 2298) were adults ≥40yrs, and 1.08% (n= 25) were AYAs. AYAs comprised 32% Hispanic, 4% Non-Hispanic Asian or Pacific Islander (NHAPI), 16% Non-Hispanic Black (NHB), and 48% Non-Hispanic White (NHW). Compared to adults, AYAs had higher proportions of Hispanics and NHBs but fewer NHWs. AYAs showed longer average survival (57.7 vs 33 months) than older adults. Females generally had longer survival periods than males in both AYA (64.4 vs 49.1 months) &amp; adult (37.2 vs 26.4 months) groups. Among adult racial groups, Non-Hispanic Black females had the poorest prognosis (29.6 months), while Hispanic males had the worst prognosis overall (21 months). Among AYAs, Hispanic females had the worst prognosis (4 months), followed by Hispanic males (24.2 months). Conclusions: Our study shows AYAs are less likely to die from MDS compared to adults ≥40. Hispanic females appear to have a worse outcome than males in both age groups &amp; is independent of other analysed prognostic factors. More research is needed to examine other prognostic factors with the aim of improving survival outcomes. [Table: see text]
Health disparities in acute myeloid leukemia: A decade-long analysis of Afro-Caribbean patients in a safety net New York City hospital.
Authors: Aye Mon Thida, Burak Erdinc, Sylvester Homsy, Firas Muhammad Jafri, Edwin Chiu, Jason Parker Gonsky
Journal: Journal of Clinical Oncology (2024)

e18515 Background: Acute Myeloid Leukemia (AML) in the Afro-Caribbean population is associated with poor outcomes due to disparities in health insurance and access to healthcare resources, among other factors, when compared to survival data in the national SEER database. This study reviews clinical characteristics and treatment outcomes of a cohort of 51 Afro-Caribbean patients who were diagnosed with AML and treated in the past 10 years in a urban safety net hospital in Brooklyn, New York. Methods: This is a retrospective review of patients diagnosed and treated for AML at New York City Health and Hospitals/Kings County from 2012 to 2022. Electronic Health Data was reviewed for clinicopathologic data and treatment outcomes. Analysis was performed through descriptive statistics with specific focus on insurance status and survival outcomes. Results: Our AML patient cohort had a mean age of 66, with 84% of patients identifying as Afro-Caribbean, and 51% being female. In this cohort, the AML risk stratification distribution based on 2022 European LeukemiaNet Risk classification includes 21 (41%) patients in the adverse-risk group, 23 (45%) patients in the intermediate-risk group, and 7 (14%) patients in the favorable-risk group. Of the 36 patients with molecular analysis data, 9 (25%) harbored a mutation in FLT3-ITD. Healthcare disparities are evident in insurance coverage, as 58% of patients lacked medical insurance, 19% had Medicare/Medicaid, and 23% had private insurance. At the time of this retrospective chart review, 35% of patients lacked any follow-up information, including appointments or status updates regarding their condition, vital status, or engagement with healthcare, possibly due to missed appointments, transfers, mortality, or other reasons. Of the 27 patients who were deemed transplant eligible, three (11%) successfully completed allogeneic bone marrow transplant. Reasons for non-transplantation include lack of a compatible donor, inadequate social support, insurance-related challenges, or patient refusal. Patients who completed induction and consolidation treatment with documented follow-up had a 23% survival rate at the five-year mark, compared to 31.7% overall survival rate reported in SEER data from 2013 to 2019. Conclusions: Our study highlights persistent healthcare disparities in Afro-Caribbean AML patients leading to poor survival outcomes. Despite treatment advancements, challenges related to insurance coverage, social support, follow-up care, and access to restricted, advanced care remain. Addressing these disparities calls for targeted interventions to enhance access and support systems for this vulnerable population.
Predictors of mortality among adults with acute lymphocytic leukemia in relapse with tumor lysis syndrome during chemotherapy.
Authors: Saisree Reddy Adla Jala, Dhruvkumar Gadhiya, Hemamalini Sakthivel, Nayanika Tummala, Madho Mal, Kanwar Bir Singh Dhaliwal, Mehndi Dandwani, Kamleshun Ramphul, Suma Sri Chennapragada
Journal: Journal of Clinical Oncology (2024)

e18510 Background: Tumor lysis syndrome (TLS), a common complication of chemotherapy, can be an oncologic emergency involving various complications, such as electrolyte imbalance, triggering a higher risk of mortality. We aim to understand the predictors of death among Acute lymphocytic leukemia (ALL) patients in relapse who experienced TLS during their chemotherapy admission. Methods: Our study focussed on ALL adults in relapse, ages≥ 18 years, from the 2016-2020 National Inpatient Sample (NIS) undergoing chemotherapy who experienced TLS. Multivariate regression analyses helped evaluate the impact of several patient characteristics on all-cause mortality. Results: Initially, a total of 11710 patients with ALL in relapse were found who were undergoing chemotherapy. Among them, an estimated 930 (7.9%) experienced TLS. The mortality rate among TLS patients was 14.0%, as 130 deaths were reported. Higher odds of mortality were noted among Females (vs. Males, aOR 2.169, 95% CI 1.188-3.959, p=0.012), patients with events of acute kidney injury (AKI) (aOR 2.006, 95% CI 1.096-3.672, p=0.024), hypertension (aOR 5.582, 95% CI 2.969-10.494, p&lt;0.01), cirrhosis (aOR 39.119, 95% CI 16.380-93.422, p&lt;0.01), presence of hyperkalemia (aOR 3.366, 95% CI 1.605-7.063, p&lt;0.01), or cardiac dysrhythmias (aOR4.630, 95% CI 2.063-10.391, p&lt;0.01). Meanwhile, lower odds of mortality were seen among people with diabetes (aOR 0.386, 95% CI 0.157-0.951, p=0.039). No racial disparities were noted between Blacks (aOR 1.806, 95% CI 0.730-4.471,p=0.201) and Hispanics (aOR 1.870, 95% CI 0.900-3.887, p=0.094) compared to Whites. Similarly, smoking status (aOR 0.466, 95% CI 0.196-1.110, p=0.085), events of acidosis (aOR 1.012, 95% CI 0.494-2.074, p=0.974), and patients of ages ≥60 years(vs.&lt;60 years, aOR 1.230, 95% CI 0.627-2.415, p=0.547) did not show any differences in mortality. Patients who died also had a more extended hospitalization (24.27 days vs. 20.15 days, p&lt;0.01), with a more expensive stay (mean hospital charge $600779 vs. $418867, p&lt;0.01). Conclusions: Our analysis confirms the burden of TLS in the prognosis of ALL patients undergoing chemotherapy. The mortality rate was higher for women and those with pre-existing comorbidities. However, people with diabetes have a lower risk, possibly due to close monitoring and prophylactic strategies. Notably, race, smoking status, acidosis, and age over 60 years did not show significant differences in mortality rates. Scaling the study to different healthcare organizations will help augment the sample size, assess the impact of treatment plans, and overcome limitations such as lack of disease duration, post-discharge follow-up, and potential diagnostic and coding errors.
Cytogenetic and molecular features of mixed-phenotype acute leukemia in US veterans and its potential impact on therapy.
Authors: Zoe McKinnell, Seta Degann, Daniel Karel, Martha Antonio, Samah Nassereddine, Amarendra Kumar Neppalli, Maneesh Rajiv Jain
Journal: Journal of Clinical Oncology (2024)

e18535 Background: Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous subtype of acute leukemia. Per the 2022 WHO criteria, it is categorized based on its predominant immunophenotypic lineage (B vs. T) and the presence of a Philadelphia chromosome (Ph+) or a KMT2A rearrangement. While many other cytogenetic and molecular abnormalities have been described, due to the rarity of this disease, neither their incidence nor the role of targeted therapies has been well defined. We conducted a retrospective study of all veterans with MPAL diagnosed between 2000-2023 to examine the impact of different clinical, immunophenotypic, cytogenetic, molecular, and treatment strategies on overall survival (OS). Methods: Electronic medical record data from the Veterans Affairs Informatics and Computing Infrastructure database were used to identify 320 patients diagnosed with MPAL between 2000-2023 using the text utilization integration feature to query all notes. All patient charts were reviewed manually. Pathology reports and clinical notes were reviewed to collect data on diagnosis, treatment, and outcome. To date, 74 patients have been identified and included in this preliminary analysis. Cox regression analyses were used to compare OS between patients with different MPAL subtypes, cytogenetic, and molecular features as well as different treatment approaches. Multivariate analysis was performed with controls for age, race, and BMI. Results: In line with prior research, decreases in OS were seen among older patients &gt; 65 yo compared to patients &lt;30 yo and those who received an AML induction over ALL induction regimen with HR of 8.28 (p 0.04) and 2.02 (p 0.03) respectively. Patients who had a transplant had significantly improved OS with a HR of 0.19 (p &lt;0.001). Of the 32 patients who had potentially targetable mutations, 14 received targeted maintenance therapy with either Ph+ or FLT3 inhibitors. Patients who got targeted maintenance therapy (including FLT3 inhibitors) had an OS of 55 months compared to 17 months for those who did not. 50% of those patients who did not get maintenance therapy went to transplant and 31% of patients who did get maintenance therapy went to transplant yet these patients still had improved OS. Conclusions: This preliminary data demonstrate that while MPAL is a complex and heterogeneous disease, a significant portion of patients have targetable mutations. Further studies evaluating targeted therapies such as FLT3, IDH, and menin inhibitors in MPAL patients may be warranted. [Table: see text]
Relationship of body mass index and plasma imatinib levels in CML patients and mitigation of clinical impact using PK-guided dosing strategy.
Authors: Paul Maroselli, Raphaelle Fanciullino, Julien Colle, Laure Farnault, Pauline Rocher, Geoffroy Venton, Régis Costello, Joseph Ciccolini
Journal: Journal of Clinical Oncology (2024)

e18522 Background: Imatinib is a mainstay of treatment for patients with chronic myeloid lymphoma (CML). Exposure-response relationships have been demonstrated and trough levels between 800 and 1000 ng/ml are usually associated with Major Molecular Response (MMR), prolonged survival and acceptable safety. The extent to which body mass index (BMI) might influence drug pharmacokinetics (PK) and clinical outcome remains to be investigated. Methods: Therapeutic drug monitoring was performed in 60 adult patients (56 years, M33/27F) starting imatinib (400 mg QD) for CML, and baseline deviation from target Cmin was used to subsequently adjust dosing using Monolix software. Baseline BMI was calculated and collected along with other patient characteristics and comedications likely to alter imatinib PK. Response (MMR at 3 months) and drug-related toxicity (CTCAE grading) were recorded. Patients were divided into three subgroups: BMI&lt;18.5; 18.5&lt;BMI&lt;24.5, and BMI&gt;24.5. The association between BMI and trough imatinib levels at baseline, further differences in toxic events and response rate between cohorts, as well as differences in dosing after PK-guided dose adjustment, were all tested using appropriate statistical analysis. Results: Mean imatinib trough levels at baseline were 1172 (754-4737), 870 (276-1767) and 820 (334-2217) ng/ml for patients with BMI&lt;18.5, 18.5&lt;BMI&lt;24.5 and BMI&gt;24.5, respectively. Patients with BMI&lt;18.5 were statistically overexposed (p&lt;0.01, ANOVA). Conversely, there was a trend towards lower exposure in patients with BMI&gt;24.5, but this was not statistically significant. Multivariate analysis confirmed that low BMI was an independent factor for overexposure with imatinib. After PK-guided dosing, a statistically significant difference in dosing after correction was observed, as overexposed patients had their dose reduced to an average of 330 mg QD, whereas underexposed patients had their dose increased to an average of 500 mg QD (p&lt;0.01, paired t-test). Consequently, when comparing in the three different cohorts the incidence of both response and toxic events, no difference was observed among patients (p=0.33 and p=0.911 for efficacy and toxicity respectively, Chi-2 test). Conclusions: Low BMI (&lt;18.5) puts patients at risk of significant overexposure to imatinib, whereas there is a trend towards lower exposure in patients with high BMI (&gt;24.5). This could potentially lead to either increased toxicity or lack of efficacy is no adjustment in dosing is performed. Here, TDM with subsequent adaptive dosing helps to correct the dose according to the initial deviation from target, thus smoothing the clinical impact of the differences in exposure observed at the start of treatment.
Patient reported outcomes among U.S. Veterans living with myeloproliferative neoplasms.
Authors: Natasha Mathur, Andrew Chua Tiu, Ann Brazeau, Natalie Giocondo, Puneet Gill, Shanshan Liu, Guoqing Diao, Ramesh Subrahmanyam, Craig M Kessler, Maneesh Rajiv Jain
Journal: Journal of Clinical Oncology (2024)

e18528 Background: Myeloproliferative Neoplasms (MPNs) profoundly affect patients' well-being, necessitating effective symptom relief. Patient-reported outcomes are pivotal for care improvement, aligning with Centers for Medicare and Medicaid Services priorities. This study aims to assess MPN symptom burden among U.S. Veterans, examining risk levels, thrombo-hemorrhagic complications, medication use, information access, care, and service-connected benefits. Methods: Conducted as a cross-sectional survey from December 1, 2023, - January 22, 2024, all Veterans in the MPN Advocacy Education &amp; International database were recruited. Symptom burden was assessed using the validated MPN Symptom Assessment Form Total Symptom Score (MPN SAF TSS), with descriptive statistics and T-tests employed for analysis. Results: Of 61 respondents, 88% were male, 92% Caucasian, 88% served during the Vietnam war. The mean age was 73±7, with MPN diagnosis at 64±9 and a mean duration of 44±10 years from service-connected exposure. Key findings included 56% Polycythemia Vera, 26% Essential Thrombocythemia, 16% Primary Myelofibrosis, 70% JAK2, 10% CALR, 3% MPL, 14% unaware of their mutation status, and 34% unaware of MPN risk status. Seventeen (28%) underwent phlebotomy, 64% used Hydroxyurea, 29% Ruxolitinib, and 3% Interferon. Fatigue and itching were the predominant and severe symptoms (Table), with 43% reporting no symptom improvement. Mean MPN SAF TSS of all respondents was higher than prior study by Emanuel et.al. which adjusted for MPN subtype (36.4 vs. 21.6, p&lt;0.0001). Twelve (20%) reported bleeding and 10% reported venous thrombosis after MPN diagnosis, while 13% reported arterial thrombosis before MPN diagnosis. Twenty-two (36%) are not seeing an MPN specialist and 61% are not seeing a hematologist at their local Veterans Affairs Medical Centers. Twenty-three (38%) did not seek a second opinion while 43% do not have a caregiver. Respondents turn to MPN organizations (75%), physician offices (74%), Google Search (49%), Webinars (41%), and Facebook (23%) for information. Five (8%) received service-connected disability benefits. Conclusions: Veterans with MPNs endure a substantial symptom burden, surpassing previous studies, signifying suboptimal management. Limited access to care persists, necessitating enhanced support. However, self-reporting bias and potential limitations in activity assessment must be acknowledged. Efforts to enhance MPN awareness, specialized care, and support mechanisms are imperative for comprehensive management. [Table: see text]
A nationwide analysis of inpatient mortality for patients with leukemia with iron deficiency anemia.
Authors: Benjamin Olufemi Adegbite, Lawrence Cytryn
Journal: Journal of Clinical Oncology (2024)

e18521 Background: Leukemia consists of multiple diverse disorders which confer varying morbidities and an increased risk of mortality. Iron deficiency anemia (IDA) is much more common, and while non-malignant, has also been shown to have an association with increased mortality. Despite the probability of these two hematological conditions coexisting, the interaction between them has yet to be closely studied. This retrospective cohort study aims to help elucidate how IDA affects mortality in patients with leukemia. Methods: Data was obtained from the 2017 – 2019 versions of the National Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) using ICD-10 codes. Patients with all forms of leukemia were identified and then placed into 4 categories: acute myeloid leukemia (AML), acute lymphocytic anemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Lastly, a multivariate regression model was used (adjusted for age, sex, race, median household income based on patient ZIP code, Charleston Comorbidity Index score, hospital region, hospital teaching status based on rural/urban setting) to calculate the adjusted odds ratio (aOR) for the association between the presence of IDA and inpatient mortality. A significance level of p &lt; 0.05 was used throughout. Results: The sample population consisted of leukemia patients with or without IDA. In total, there were 162,873 patients with all ICD-10 coded forms of leukemia, with 5,710 (3.51%) having IDA. Furthermore, this cohort was found to be older than non-IDA leukemia patients (71.1 ± 0.45 years and 59.2 ± 0.71 years with p &lt; 0.05, respectively). With inpatient mortality as the outcome, the multivariate regression analysis performed for the entire sample showed that the odds of mortality while having IDA was 0.65 times that of not having IDA (95% CI 0.56 – 0.76, p &lt; 0.001). When the analysis was then applied to each of the 4 leukemia categories, the IDA cohort still had lower odds of mortality with CLL (aOR 0.73, 95% CI 0.56 – 0.96; p = 0.024). Conclusions: The analyses show that iron deficiency anemia was generally not associated with increased mortality among leukemia patients, particularly those with CLL. This seemingly counterintuitive result warrants further research to confirm these findings and explore possible underlying mechanisms.