bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomic Features Prognosticates Treatment Response in CAR-T Cell Therapy
Authors: Balagurunathan Yoganand , Wei Zhouping , Qi Jin , Dean Erin A. , Thompson Zachary , Choi Jung , Jain Michael D. , Locke Frederick L. 
Published: December 2023

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common, aggressive disease form that accounts for 30% of all lymphoma cases. Recent development in chimeric antigen receptor (CAR) T-cell therapy has shown tremendous promise in providing a cure to patients with relapsed/refractory (R/R) DLBCL. We propose to develop Radiomics (quantitative image metric) based biomarker as a surrogate to tumor burden assessment and compare its ability to prognosticate treatment response to engineered cell-based treatments.
METHODS: We identified a cohort of 58 patients with R/R DLBCL, whose largest lesions on the baseline positron emission tomography /computed tomography (PET/CT) imaging were identified along with their anatomical sites related to non-lymphatics. The lesion's co-registered PET imaging was used to converge on a regional boundary to obtain the most active part of the lesion, applying Standardized Uptake Value definition with 41% regional threshold. The lesion regions were characterized using imaging metrics (radiomics) followed by principal component (PC) analysis to reduce the dimensionality in the feature categories (Size, Shape and Texture). These Radiomics metrics along with metabolic tumor volume (MTV) were used both collectively and independently to assess prognosis to disease progression measured by overall survival. We assessed and report the correlation between the principal components and the tumor burden.
RESULTS: We find that Shape-PC (Non-Lymph) were prognostic (p &lt; 0.0073) along with MTV (p &lt; 0.00026) of Overall survival (1 year after treatment), using median value of the respective metrics as a cutpoint. We find these Shape-PC metrics showed moderate to weak correlation with MTV (spearman's ρ of 0.42, p &lt; 0.01, for Shape-PC1).
CONCLUSION: We identified Non-Size based features that are prognostic to patient response to treatment. These metrics provide complementary information to MTV and may serve as a surrogate to treatment response.
Immunosuppressant Drug-Associated Non-Hodgkin Lymphoma: A Real-World Pharmacovigilance Database Analysis
Authors: Ananthaneni Anil , Heap David , Weis Francesca , Chowdary Sriram , Sam Riya , Al-Yafeai Zaki , Ramadas Poornima 
Published: December 2023

Background: The association between immunosuppressant drugs and lymphoma has been reported frequently; however, the precise relationship remains uncertain. Non-Hodgkin lymphoma (NHL) is among the most common cancers associated with long-term immunosuppressant drug use. The FDA Adverse Event Reporting System (FAERS) is a publicly available tool that collects reports of adverse events from healthcare professionals, manufacturers and consumers.
Methods: Nine immunosuppressant drugs belonging to different classes were shortlisted . The FAERS database was searched for all types of NHL as an adverse event reported between 2013 and 2022. Reporting odds ratio (ROR) was used to measure disproportionality in reporting of adverse events for these drugs.
Results: When NHL was analyzed as a percentage of all cancers reported for a particular drug,azathioprine had the highest percentage (22.14%) followed by methotrexate (18.94%), mycophenolate (14.04%), infliximab/biosimilars (11.22%), cyclosporine (10.71%), etanercept (10.44%), tacrolimus (10.13%), adalimumab/biosimilars (8.80%) and sirolimus (8.51%). Drugs with highest ROR for NHL included azathioprine (2.09, 95% CI 1.94-2.24) followed by methotrexate (1.90, 95% CI 1.82-1.98) and azathioprine (1.17, 95% CI 1.10-1.25). Drugs with lowest ROR for NHL included adalimumab/biosimilars (0.62, 95% CI 0.59-0.65) followed by sirolimus (0.66, 95% CI 0.54-0.80) and tacrolimus (0.78, 95% CI 0.73-0.84).
Conclusions: Although all immunosuppressive drugs have been associated with an increased risk of developing NHL, it is advisable to exercise caution with prescribing azathioprine, methotrexate and mycophenolate in patients with preexisting risk. While the use of adalimumab is an independent risk factor for the development of lymphoma, it had the lowest odds of NHL compared to other immunosuppressant drugs in the study. Prospective studies are needed to better understand the true incidence of NHL associated with immunosuppressant drugs.
Patterns of Disease, Risk Factors and Treatment in Chronic Lymphocytic Leukemia (CLL). a retrospective Report of Real World Patient Cohort from United Arab Emirates
Authors: Alam Arif , Al Qawasmeh Khaled , Alam Nida , McCarthy Philip L. 
Published: December 2023

Introduction:
Chronic Lymphocytic Leukemia (CLL) is an indolent B cell Malignancy. It is the most common type of leukemia in Western Hemisphere (35% of all leukemia (American Cancer Society. Cancer Facts & Figures 2023) but is rare in East Asia. Data about CLL in Middle Eastern countries is scarce. Here we report a retrospective analysis of the patients with CLL seen in a real world setting at the largest cancer center in UAE.
Methods:
This is a retrospective analysis of patients diagnosed with CLL between January 2018 to September 2022. Data was collected from Electronic Medical Records (EMR) regarding patient demographics, risk profile (genetics) and treatment patterns.
Results:
Thirty-seven patients with CLL were seen in the study period. They accounted for approximately 3 % of all leukemia patients (Al-Shamsi HO. The State of Cancer Care in the United Arab Emirates in 2022. Clin Pract. 2022 Nov 23;12(6):955-985). The median age was 59 years (range 30 to 88 years.) Sixteen percent of the patients were under the age of 50 years. The majority of the patients were male (5:1). The median WBC at presentation was 30000/μl, Hemoglobin was 112 grams/liter and platelet count was 140000/μl.
Approximately one third of the patients (35%, 13 out of 37) have not required any therapy due to early-stage disease and/or comorbidities. Twenty-four patients (65 %) had advanced stage disease and required therapy at the time of diagnosis.
FISH results are available for 19/24 patients on therapy. The most common was deletion 13q (8/24) followed by Trisomy 12 (7/24). 17p/TP 53 deletion was seen in3/24 and 1/24 had ATM gene deletion. IGHV mutational analysis is not available for most patients
Treatment patterns showed chemoimmunotherapy (CIT) in 10/24 patients (Bendamustine rituximab N=8 and FCR N= 2), BTK inhibitors as single agent 9/24 while 5/24 patients receive Venetoclax R in combination with Anti CD 20 antibody.
Conclusion:
This is the first report on CLL seen in a large tertiary care center in UAE over a period of 5 years. The number of patients is significantly less (3%) as compared to incidence in western hemisphere (35%) of all leukemia cases. Median age (59 years) is at least a decade earlier than western hemisphere with a preponderance in males.
Treatment patterns are being rapidly revised with the availability of BTK inhibitors, Venetoclax R and anti-CD 20 monoclonal antibodies to conform with current guidelines. More epidemiologic investigation is needed to understand the low numbers of patients with CLL reported in this UAE cancer center.
Development and Validation of an Individualized and Weighted Prognostic Model in Patients with Newly Diagnosed Multiple Myeloma
Authors: Yan Wenqiang , Mao Xuehan , Mery David E. , Xu Yan , Sui Weiwei , Deng Shuhui , Zou Dehui , Shaughnessy, Jr John D , Anderson Kenneth C. , Zhan Fenghuang , Qiu Lugui , An Gang 
Published: December 2023

Introduction
Multiple myeloma (MM) is a malignancy of terminally differentiated antibody-secreting plasma cells in the bone marrow with highly variable survival outcomes. Precise risk stratification not only plays a vital role in predicting patient prognoses, but critically can be used to develop risk-adapted treatment regimens. However, current risk stratification models do not adequately account for the heterogeneity of patients with new-diagnosed multiple myeloma (NDMM).
Methods
In this retrospective, multicohort study, we collected clinical data from 1792 NDMM patients and formulated a weighted Myeloma Prognostic Score System (MPSS) risk model to predict overall survival (OS). Construction of the MPSS model was carried out based on the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199) cohort, external validation cohort was created using TT2, TT3a, and TT3b cohorts from a series of randomized prospective studies from the University of Arkansas for Medical Sciences (UAMS).
Results
Each risk factor was defined as its weighted value respectively according to their hazard ratio for OS (thrombocytopenia 2, elevated LDH 1, ISS III 2, one high-risk cytogenetic aberration [HRA] 1, and ≥2 HRA 2 points). In the training cohort, patients were furtherly stratified into four risk groups: MPSS I (22.5%, 0 points), II (17.6%, 1 points), III (38.6%, 2-3 points), and IV (21.3%, 4-7 points). MPSS risk stratification showed optimal discrimination, as well as calibration, of four risk groups with median OS of 91.0, 69.8, 45.0, and 28.0 months, for patients in MPSS I to IV groups (P&lt; 0.001), respectively. Importantly, the MPSS model retained its prognostic value in the internal validation cohort and an independent external validation cohort, and exhibited significant risk distribution compared with conventional prognostic models (R-ISS, R2-ISS, and MASS).
Conclusions
In conclusion, we formulated and validated the MPSS risk model to predict the prognosis of patients with MM using readily available standard clinical and genetic test data. The established MPSS profile shows a better performance in risk discrimination than the current R-ISS, R2-ISS, and MASS. A score-based risk stratification is derived, and identifies patients with high and ultra-high risk of death after diagnosis and may therefore aid the development of more personalized treatment strategies, especially for patients for whom current therapies are likely to fail.
Deletion 1p at Time of Diagnosis of Multiple Myeloma Portends Inferior Outcomes
Authors: Vaishnav Arti , Khan Abdullah , Zhao Qiuhong , Bumma Naresh , Cottini Francesca , Umyarova Elvira , Sharma Nidhi , Rosko Ashley E , Benson Don , Devarakonda Srinivas 
Published: December 2023

Background: Multiple myeloma (MM) is associated with several cytogenetic abnormalities (CA) that influence the disease course, response to treatment and survival. Trisomies and immunoglobulin H chain translocations are primary CA while del(17p), gain(1q), del(1p) and others are secondary CA. Gain (3 copies) and amplification (&gt;3 copies) 1q have been recognized as adverse prognostic markers and incorporated into the second revision of the International Staging System (R2-ISS). However, the role of del(1p) is less well defined, especially in the era of modern myeloma therapeutics. We aimed to analyze the outcomes of newly diagnosed MM (NDMM) patients (pts) with chromosome 1 abnormalities, mainly del 1p, treated with autologous hematopoietic cell transplant (AHCT) consolidation at The Ohio State University.
Methods: We identified and reviewed the medical records of all NDMM pts who were treated with AHCT from 1/1/2015-2/13/2019 (n=511). High-risk cytogenetics (HRC) was defined by the presence of del(17p), t(4;14), or t(14;16) similar to R-ISS; standard-risk cytogenetics (SRC) were defined as the absence of HRC. Modified HR cytogenetics (mHRC) included gain/amp 1q and/or t(14;20) in addition to HRC, while ultra high-risk (uHRC) included 2 or more mHRC risk factors.
Results: The baseline pt characteristics are presented in Table 1. Of 511 pts transplanted, 453 had cytogenetic data from diagnosis. SRC were seen in 353 pts (77.9%), while 100 (22.1%) had HRC, 156 (34.4%) had mHRC, and 43 (9.5%) had uHRC. Thirty-two (7.1%) pts had del(1p) while 105 (23.2%) had gain 1q and 30 (6.6%) had amp 1q. As expected, compared to SRC pts, pts with HRC, mHRC and uHRC had higher risk of relapse or death. Patients with gain and amp 1q had inferior outcomes in terms of PFS (HR 1.35; 95% CI 1.06-1.73, p=0.016), TTNT (HR 1.84; 95% CI 1.40-2.42, p&lt;0.001) and OS (HR 1.47; 95% CI 1.06-2.02, p=0.02), consistent with published literature. The median PFS, TTNT and OS from AHCT in pts with gain/amp 1q was 3.17 years (y), 3.95y and 7.13y, respectively, compared to 4.01y, 7.60y and 8.21y in pts without gain/amp 1q. Pts with del(1p) had inferior PFS (median 2.43y versus 3.98y; HR 1.75; 95% CI 1.16-2.64, p=0.008), TTNT (median 2.72y versus 6.17y; HR 1.96; 95% CI 1.22-3.14, p=0.005) and OS (median 4.11y versus 8.38y; HR 2.19; 95% CI 1.34-3.58, p=0.002) from AHCT compared to those without del(1p). (Figure 1).
Conclusions: In this cohort of NDMM pts that underwent AHCT, del(1p) at diagnosis was an independent predictor of shorter PFS, TTNT and OS. Despite advances in induction regimens, AHCT consolidation and maintenance therapy, del(1p) continues to portend inferior outcomes. Larger analyses are needed to validate the prognostic value of del(1p) and investigate its role in predicting outcomes in MM.
The Efficacy of Obinutuzumab Combined with Pomalidomide and Covalent Btki for the Treatment of TP53 Mutated Mantle Cell Lymphoma (MCL): A Prospective, Open-Label, Single-Arm Study
Authors: Yang Ping , Liu Shuozi , Zhang Weilong , Wang Jing , Chen Yingtong , Jing Hongmei 
Published: December 2023

Background
TP53 mutated MCL lacks effective treatment options and has a poor prognosis, posing challenges in management. The guidelines recommend clinical trials as the first choice, pomalidomide as a new generation of immunomodulators (IMiDs), which have immunomodulatory effects and modulates the tumor microenvironment. Individual cases have been reported about pomalidomide be used for relapsed and refractory MCL. In this study, we investigated the application of Pomalidomide combined with Obinutuzumab and covalent BTKi (Ibrutinib and Zanubrutinib) for the treatment of TP53 mutated MCL to provide a new treatment evidence for clinical practice.
Methods
This was a prospective, single-center, clinical study. The key inclusion criteria include: confirmed diagnosis of MCL, age≥18 years, appropriate organ function, etc, both previously untreated and relapsed patients are eligible for inclusion. All patients receive Obinutuzumab (1000 mg d1) combined with Pomalidomide (4 mg d1-21) and covalent BTKi (Ibrutinib 560mg qd or Zanubrutinib 160mg bid)for 4 cycles, every 28 days as a cycle; If the treatment is effective, patients receive Obinutuzumab (1000 mg d1, every 3 months/time) combined with Pomalidomide (4 mg d1-14/28 days) and covalent BTKi triplet combination maintenance therapy until disease progression. The primary endpoint was overall response (Lugano 2004 criteria). Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. Minimal residual disease was assessed by NGS in peripheral blood.
Results
The study included 14 patients with relapsed or refractory mantle-cell lymphoma (12 patients) or previously untreated mantle-cell lymphoma (2 patient). Patients median age 59(44 to 74) with a male-to-female ratio of 6:1, and the lines of previous treatments ranged from none to three. 85.7%（12/14）of patients had mutation of TP53, 28.6%(4/14) had mutation of CCND1, 21.4%(3/14)had mutation of SMARCA4/SAMHD1. 64.3% had a higher Ki-67≥30% and 50% had a high-risk prognostic score of MIPI-c. The complete response rate at 4 course was 64.3% and the overall response rate was 85.7%. 9 patients underwent MRD testing after 4 cycles of treatment, and MRD negative was confirmed in 100% of the patients by NGS. The most common grade 3-4 adverse events were neutropenia (in 5 [35.7%] of 14 patients), thrombocytopenia (in 3 [21.4%] of 14 patients), infections (in 2[14.3%] patients), severe Covid-19 infection was in 2[14.3%] patients.
Conclusions
Our results provide preliminary evidence that the triplet combination of Obinutuzumab, pomalidomide, and covalent BTKi is an active regimen in MCL patients with the mutation of TP53, and should be evaluated in a prospective randomized controlled trial.
Risk Factors for Severe Infection and Unfavorable Outcomes in Hematologic Malignancy Patients with COVID-19 Inflection during the Omicron Era: A Chinese Single-Center Retrospective Study
Authors: Ye Li , Yang Ye , Zhang Xuewu , Wang Lu , Zhu Li , Li Xia , Zhou Yile , Zheng Xiaolong , Zhou Xinping , Ren Yanling , Ma Liya , Xu Gaixiang , Yang Chunmei , Wang Huafeng , Zhou De , Yang Min , Ye Xingnong , Wei Juying , Yu Wen-Juan , Qian Jiejing , Lou Yinjun , Xie Wanzhuo , Huang Jian , Meng Haitao , Jin Jie , Tong Hongyan 
Published: December 2023

Purpose: The objective of this study was to evaluate the potential risk factors associated with severe infection and unfavorable outcomes among individuals with hematologic malignancies who contracted the coronavirus infectious disease (COVID-19) during the Omicron era.
Methods: This retrospective analysis included adult patients with hematologic malignancies who were diagnosed with COVID-19 during the period from November 2022 to February 2023. A comparison was made between the clinical characteristics of patients who experienced persistent COVID-19 infection or succumbed to death within 30 days and those of the remaining patients.
Results: A total of 134 patients were included in the analysis, with 23.9% (n=32) presenting as asymptomatic/mild and 29.1% (n=39) classified as severe cases. Among the patients, 54.4% (n=73) had received at least two doses of vaccines. In the subgroup of asymptomatic/mild patients, 50% had received at least three doses of vaccines, while among the severe patients, 56.4% remained unvaccinated. The multivariate analysis examining risk factors for severe infection in COVID-19 and hematologic malignancy patients identified the number of vaccine doses as an independent prognostic factor. Less than two doses of vaccines were found to be associated with severe COVID-19 infection (odds ratio [OR]: 4.213, 95% confidence interval [CI] 1.433-12.392; p=0.009). In this study, patients with persistent COVID-19 infection or succumbed to death within 30 days were categorized as the unfavorable group (n=57), while the remaining patients were classified as the favorable group (n=77). A significant difference was observed between the two groups in terms of median age (p=0.015), malignancy status (p=0.001), number of vaccine doses received (p=0.001), neutrophil count (p=0.011), immunoglobulin G levels (p=0.038), and interleukin-6 levels (p=0.025). In the multivariable analysis of risk factors for unfavorable outcomes in patients with both COVID-19 and hematologic malignancies, it was found that the number of vaccine doses and the level of immunoglobulin G were independent prognostic factors. Specifically, receiving less than two doses of vaccines (OR: 233, 95%CI 0.068-0.798; p=0.020) and having an immunoglobulin G level below 1000 (OR: 220, 95%CI 0.066-0.753; p=0.014) were associated with unfavorable outcomes.
Conclusions: Receiving multiple doses of vaccines and having higher levels of immunoglobulin G were found to improve the clinical outcome of COVID-19 in patients with hematologic malignancies.
Adolescents and Young Adults with Multiple Myeloma, Kuwait Experience
Authors: Alhuraiji Ahmad , Ghonema Rasha Galal , Hasaneen Mahmoud , Ram Mohan , Alshemmari Salem , Khadadah Fatima , Hamadah Abdulaziz , Kunhikrishnan Anitha , Shah Abdul Rashid , Pandita Ramesh 
Published: December 2023

Background
Multiple myeloma MM is an incurable plasma cell malignancy with a median age of 65 years at diagnosis worldwide, a small number of publications were focused on young adult Multiple myeloma MM with special characteristics and clinical outcomes.
Objectives
To evaluate the incidence of MM among adolescent and young adults (AYA) in Kuwait aged 40 and below. Also, to describe the clinical characteristics, high risk features and treatment outcomes at the Kuwait Cancer Control Centre (KCCC).
Materials & Methods
We collected data retrospectively from the hematological malignancy registry at KCCC and looked at AYA patients (pts) with a confirmed diagnosis of Multiple myeloma at our center from 2015 till 2022, we looked at age of onset, gender, nationality, year of myeloma diagnosis, presence of extramedullary disease, International Staging System score (ISS score), cytogenetic aberrations, induction therapy, receipts of auto-transplant and maintenance therapy.
Results
From 2015 till 2022, 340 patients were diagnosed with MM in Kuwait, eleven patients were found 40 years old or younger, only one was female patients, the median age was 35 years old, around a third were Kuwaiti, 73% were non-Kuwaiti of middle eastern background, 4 patients were found to have extramedullary disease at diagnosis, with advanced stage ISS III found in 3/9 pts. One patient was found with 1Q gain and the rest of the 10 patients were with negative del17p, t (4,14), t(14,16), gain1q and t(11,14). Of note, interphase FISH cytogenetic is not done with CD138 selection. Six patients were treated with RVD induction (Lenalidomide, Bortizomib, Dexamethasone), two patients treated by CTD (Cyclophosphamide, Thalidomide, Dexamethasone), one pt treated by VCD (Bortizomib,Cyclophosphamide,Dexamethasone), one patient treated by Daratumumab RVD, and one patient treated by VTD. Overall response rate (ORR) was 90.9%, (10/11) responded patients proceeded to HDCT/ASCT and all these patients went on maintenance post-transplant, two patients were lost to follow up while 9 patients still under follow up, median follow up 33 months, one pt had a relapse after transplant.
Conclusion
MM is an uncommon disease among AYA in Kuwait (3.2%) of all myeloma patients, with favorable durable responses in this group of patients.