bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of acute graft versus host disease clinical outcomes and the Ann Arbor Biomarker Risk Probability Using the Commercial Assay.
Authors: Mountjoy Luke , McNally Hannah , Buras Matthew , McCallen Margaret , Rogers Jaime , Sproat Lisa Ostrosky , Slack James L. , Palmer Jeanne , Leis Jose Francisco , Khera Nandita 
Published: June 2021

e19023 Background: Acute GVHD (aGVHD) is a major cause of mortality and morbidity following stem cell transplantation (HCT). In effort to prognostic patients with aGVHD, the Mount Sinai Acute GVHD International Consortium (MAGIC) combined two biomarkers, ST2 and REG3α to generate an algorithm known as the Ann Arbor (AA) biomarker risk. This is now available as a commercial test to help predict risk for severe acute GVHD and non-relapse mortality when done at the onset of symptomatic aGVHD. Our institution began utilizing these lab values and here we report our “real world” experience. The primary aim was to correlate AA risk probabilities with recently defined endpoints including day 28 overall response rate (ORR) and 6 month freedom from treatment failure (6mFFTF) and overall survival (OS). Methods: 58 HCT patients who underwent HCT between October 2018 and November 2019 and had the biomarker assay at the onset of aGVHD were identified from the institutional database and clinical information about disease, transplant and outcomes was obtained from the medical records. Clinical staging of aGVHD was documented per standardized published guidelines. Day 28 ORR was defined as complete response by day 28. 6mFFTF was defined as a patient being alive, without relapse of underlying disease or addition of new systemic therapy for aGVHD, and prior to the development of cGVHD. Results: When comparing low (n = 39), intermediate (n = 11), and high (n = 8) AA risk, there was no difference in age ( p =0.254), primary disease ( p =0.10), DRI ( p =0.994), donor source ( p =0.193), conditioning regimen intent ( p =0.537), GVHD prophylaxis ( p =0.351) ATG use ( p =0.06). Low AA risk was associated with lower grades of aGVHD at onset (grade I = 15%, grade II = 80%, grade III = 5%, grade IV = 0%), whereas high AA risk was associated with higher grades of aGVHD at onset (grade I = 0%, grade II = 50%, grade III = 25%, grade IV = 25%) ( p =0.009). For low, intermediate, and high AA risk the day 28 ORR was 69%, 45% and 29% ( p = 0.083); the 6mFFTF was 82%, 82%, and 25% ( p = 0.0001); 6 month OS was 92%, 100%, and 50% ( p = 0.0006) respectively. Conclusions: Our study shows a high correlation between AA risk and outcomes. High risk AA risk was associated with inferior outcomes This study was limited by the retrospective single institutional experience with relatively small numbers. However, our findings using the commercial assay mirror that seen with the MAGIC studies. Our “real world data” can serve as a foundation and continued validation for institutional implementation of AA risk stratification for aGVHD.
Clinicopathological characteristics of CML in children and young adults.
Authors: Yaqub Sobia , Zafar Amjad , Latif M Ahmed , Ahmad Zain , Bano Kausar , Khokhar Muhammad Abbas 
Published: June 2021

e19029 Background: CML, although a disease of middle age, is not uncommon in younger age groups in developing countries like Pakistan. Methods: In this single center, cross sectional study, all patients diagnosed with CML below 30 years of age were enrolled. After collection, data was analyzed using Spss version 23.Quantitative variable were presented as mean and percentages. Chi-square was used for correlation between variables with p<0.05 considered significant. Results: Total 101 patients, with age range 7-30 years (mean 21.99±6.3), including 18(17.8%) below 15 years, were enrolled. Fever was most common presenting symptoms seen in 61(60.4%) followed by fatigue, abdominal distension in 40(39.6%) and 33(32.7%).Mean presenting TLC was 158.9±136.95. Of these, 97(96.03%) patients were in chronic phase, 3(2.97%) had accelerated and 1(1%) in blast phase. As per SOKAL score, 27 (26.73%), 51(50.49%) and 23(22.77%) had low, intermediate and high risk disease respectively. Imatinib was started in 80.19% while Nilotinib in 19.80% as 1st line TKI. Among these, 88.1% achieved CHR by end of 3rd month. After 1st year, 60.8% achieved a molecular response (MR≥3). 1(1%) transformed from chronic to blast phase.2nd line TKI was started in 13.8% due to lack of response. Grade ¾ thrombocytopenia and grade ½ per-orbital edema were main toxicities seen in 10.7% and 9.6% respectively. Co-relation of increasing age with high TLC (p=0.039) and better response to TKI (p=0.014) was statistically significant. Conclusions: Distinct clinical behavior of CML in children and young adults necessitates further studies to ensure better disease management.[Table: see text]
Increased mortality among smokers with myelodysplastic syndrome (MDS).
Authors: Zavras Phaedon D. , Pophali Prateek , Shastri Aditi , Bachier-Rodriguez Lizamarie , Sica Alejandro R. , Goldfinger Mendel , Kornblum Noah , Braunschweig Ira , Verma Amit K. , Mantzaris Ioannis 
Published: June 2021

e19036 Background: Recent studies have shown smoking to be an independent risk factor for MDS. We aimed to assess whether smoking is associated with worse outcomes among patients (pts) with MDS at Montefiore Medical Center, Bronx, NY. Methods: Pts with MDS and chronic myelomonocytic leukemia (CMML) diagnosed between June 16, 2000 and November 13, 2020 were analyzed. Those without available tissue diagnosis or smoking history data were excluded. Descriptive statistics compared ever-smokers to non-smokers. Cox PH regression was used to analyze the risk of transformation to acute myeloid leukemia (AML) and mortality in the 2 groups and multivariable analysis (MVA) adjusted for age, sex, de novo disease and R-IPSS. Results: A total of 147 pts were identified, 109 (74.1%) had a diagnosis of de novo MDS, 89 (60.5%) had history of active or former smoking and 58 (39.5%) were non-smokers. Smokers were predominantly males (66.3%) in contrast to non-smokers (37.9%) (p=0.001). Smokers were diagnosed more frequently with high or very high risk MDS, although the difference was not statistically significant (38.1% vs 28.6%, respectively; p=0.28). TP53 mutations were numerically more frequent among smokers (24.4%), compared to non-smokers (12.8%) (p=0.16). Median follow-up time for smokers and non-smokers was 19.4 and 31.4 months, respectively. In MVA, there was a trend for increased risk of AML transformation in smokers vs non-smokers (HR 2.03, 95% CI 0.99 – 4.15; p=0.052). Smokers with MDS were found to have significantly greater mortality compared to non-smokers (HR 2.08, 95% CI, 1.22 – 3.54; p=0.007). Conclusions: Smoking was associated with worse survival among MDS pts in our cohort. Although not significantly different, the prevalence of TP53 mutations was higher among smokers. Larger studies are warranted to confirm our findings.
Acquired hypolipoproteinemia and hemophagocytic lymphohistiocytosis: A previously unexplored association?
Authors: Reap Leo Edward , Ma Vincent T , Takiar Radhika , Forman Adam Matthew 
Published: June 2021

e19041 Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that is the result of macrophage hyperactivation, leading to disordered cellular phagocytosis that is highly fatal if left untreated. The precise precipitating factor that leads to HLH is presently unknown. Secondary HLH is more common in adults and has numerous causes, including several autoimmune diseases, rheumatological disorders, cancers, and infections. These predisposing conditions are similar in that they are characterized by increased rates of cellular replication and often accompanied by significant oxidative stress. Lipoprotein changes in HLH have not been previously described. Methods: Between August 2018 and June 2020, three cases of secondary HLH were discovered to have profound hypolipoproteinemia with severely reduced total cholesterol, undetectable LDL-C, and extremely depressed HDL-C levels. As a result, a retrospective review of the University of Michigan HLH registry was performed, identifying cases of HLH where full lipid panels were performed as part of their diagnosis and/or treatment between 2012 and 2020. 18 total patients were identified with a confirmed diagnosis of HLH and who had a full lipid panel performed as a part of their diagnostic evaluation. Results: 100% of patients were found to have HDL-C less than 30 mg/dL, consistent with severe HDL-C deficiency, and 84% had HDL-C less than 20 mg/dL. Similarly, 74% of patients were found to have LDL-C < 100 mg/dL, 47% with LDL-C < 50 mg/dL, and 33% had undetectable LDL-C levels. Median total cholesterol was 124 mg/dL, median LDL-C was 35 mg/dL, and median HDL-C was 7 mg/dL. Notably, these reductions were not explained by the observed variability in hypertriglyceridemia, and marked hypertriglyceridemia > 500 mg/dL was not seen in 88% of patients, with a median triglyceride value of 279. Interestingly, one patient displayed an opposite phenotype with extreme hyperlipidemia, with total cholesterol of 727 mg/dL and LDL-C of 658 md/dL. Conclusions: Severe derangements in circulating lipoproteins appear to be a common finding within sHLH.These findings have not been previously described within the context of the disease. Herein, we provide a framework for hypothesizing why HLH may potentially occur in the setting of hypolipidemia. Furthermore, we provide an additional hypothesis that serves to justify why these changes may occur in an evolutionary context.
A systematic review of post-transplant lymphoproliferative disorder after lung transplant.
Authors: Haider Mobeen Zaka , Zamani Zarlakhta , Kiran Fnu , Mirza Hasan Mehmood , Taqi Muhammad , Shahid Hafsa , Kumar Deepak , Neupane Karun , Khalid Yousra , Mughal Mohsin Sheraz , Faisal Muhammad Salman , Mushtaq Muhammad Umair , Anwer Faiz 
Published: June 2021

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (> 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (> 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]
Clinical and economic burden among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) receiving first-line (1L) chemoimmunotherapy (CIT) by risk status: A chart-linked claims analysis.
Authors: Leslie Lori A. , Gangan Nilesh , Tan Hiangkiat , Huang Qing 
Published: June 2021

e19505 Background: In patients with CLL/SLL, high risk genetic abnormalities are associated with inferior responses to CIT, and the economic burden of this remains uncertain. This study aimed to compare real world clinical and economic outcomes in high risk and perceived non-high risk patients initiating 1L CIT. Methods: This retrospective cohort study identified patients with CLL/SLL from the HealthCore Integrated Research Database representing a national managed care population with over 58 million members. Medical records were obtained for eligible patients who initiated 1L CIT between 1/1/2007 and 7/31/2019 and underwent prognostic testing to classify them as high risk (HR: del17p, TP53 mutation, del11q or unmutated IGHV) or as non-high risk by FISH only (NHR: non-del17p and non-del11q). The first CIT claim date was the index date. Patients were required to have ≥12 months of pre-index and ≥30 days of post-index eligibility. Study outcomes included testing rate, time to next treatment (NT) or death, time to treatment failure (TF; defined as time to change of therapy, non-chemotherapy intervention, hospice care or death), and total plan paid costs (medical + pharmacy) per patient per month (PPPM) in the 1L period. Cox proportional hazard models and generalized linear models were used to calculate adjusted hazard ratio or rate ratio. Results: Among the 1,808 patients with CLL/SLL, 612 were FISH or IGHV tested and the rate of testing increased from 2007 to 2019 (30% to 44%), especially after adding ibrutinib for 1L CLL with del17p in NCCN guidelines v4.2014. Risk status was available for 253 patients (HR: 119; NHR: 134), with 80% of patients initiating 1L BR/FCR-based therapy in both cohorts. Median follow up was 26.4 vs. 25.8 months (HR vs NHR). HR patients had 65% higher risk of NT/death (median time: 2.4 vs 3.7 years), and 65% higher risk of TF (median time: 3.0 vs 4.9 years) compared to NHR patients (Table). The total costs PPPM were also significantly higher for HR patients in the 1L period ($12,194 vs $9,055, p=0.027; Rate Ratio=1.33, p<0.001). Conclusions: Initiating 1L CIT among HR patients with CLL/SLL was associated with increased risks of NT/death, TF, and higher costs compared to NHR patients identified by FISH only. Assessment of cytogenetic/molecular risk status for appropriate treatment is vital to optimize clinical and economic outcomes, especially in the novel agent era. Recent testing practices to assess genetic risk in CLL remains suboptimal.[Table: see text]
Safety and efficacy of chidamide in combination with decitabine plus anti-PD-1 camrelizumab after relapse or progression on decitabine-plus-camrelizumab in classical Hodgkin lymphoma.
Authors: Wang Chunmeng , Nie Jing , Liu Yang , Yang Qingming , Han Weidong 
Published: June 2021

e19515 Background: The anti-PD-1 combination therapy significantly improves clinical outcomes in patients with relapsed/refractory classical Hodgkin lymphoma (cHL), and up to 71% of patients who receive decitabine-plus-anti-PD-1 camrelizumab could achieve a complete response. However, a subset of patients is recalcitrant to decitabine-plus-camrelizumab and half of patients might experience disease progression within three years. Effective treatment regimens for those with relapsed or progressive cHL who failed decitabine-plus-camrelizumab are needed. This Phase II study was designed to assess the safety and efficacy of the combination of decitabine-plus-camrelizumab and chidamide, a histone deacetylase inhibitor, in decitabine-plus-camrelizumab resistant cHL patients. Methods: Patients with relapsed/refractory cHL who had primary resistance or progressed/relapsed on decitabine-plus-camrelizumab were enrolled and administrated with chidamide at 10 mg (days 1 to 4) and 20 mg (days 8, 11,15 and 18); plus decitabine at 10 mg (days 1 to 5); and camrelizumab at 200 mg (day 6), every 3 weeks. Safety was assessed by CTCAEv5.0, and antitumor response by PET-CT according to the revised Lugano classification. The primary endpoint was objective response rate. Recruitment is ongoing. This trial is registered with ClinicalTrial.gov number, NCT04233294. Results: Between January 19, 2020, and January 31, 2021, nineteen patients with relapsed/refractory cHL after relapse or progression on decitabine-plus-camrelizumab were enrolled. A median of 20 cycles of prior decitabine-plus-camrelizumab was given (range, 4-28). Fourteen patients completed response evaluation with a median follow-up of 5.7 months. All eligible patients received this triplet-agent regimen with a median of 8 cycles (range, 3 to 12). Thirteen of the fourteen evaluated patients (93%) had an objective response, including six acquiring a complete remission (43%) and seven reaching a partial response (50%). The most common adverse events were leukocytopenia (58%; grade 3: 16%), nausea (53%) and hypertriglyceridemia (26%). No immune-related adverse events were observed. Conclusions: The preliminary result shows a high objective response rate with the combination of chidamide, decitabine and camrelizumab in patients with resistance to decitabine-plus-camrelizumab therapy. The addition of chidamide to decitabine-plus-camrelizumab has an acceptable safety profile, and does not trigger immune-related adverse events. Clinical trial information: NCT04233294.
Polatuzumab vedotin-bendamustine-rituximab (PBR) versus tafasitamab-lenalidomide (TafaL) in ASCT-transplant ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): Economic evaluation including novel metrics.
Authors: Calamia Matthias , McBride Ali , Abraham Ivo 
Published: June 2021

e19535 Background: PBR and TafaL are two recently regulatory approved regimens that offer treatment options for R/R DLBCL patients who are ASCT ineligible or choose not to undergo ASCT. PBR is administered over 6 cycles, whereas TafaL is sustained until disease progression or death. We report here on an independent, naïve comparative, pharmacoeconomic evaluation of both regimens. Methods: Cost effectiveness and cost utility analyses were performed using a Markov model with 3 health states (progression free survival (PFS), post progression survival (PPS), death) parametrically extrapolated over a 5-year (y) time horizon (US payer perspective; 2020 USD). Cost inputs included main treatment, premedication, drug administration, adverse event management, and physician and laboratory fees. Incremental cost effectiveness ratios (ICER) and cost-utility ratios (ICUR) estimated the incremental costs to gain 1 unadjusted (LY) or quality adjusted life years (QALY), respectively. A novel metric of the incremental cost per 1% gain in probability of achieving objective response (OR), PFS and overall survival (OS) at trial follow up (̃2y) and PFS and OS at 5y with TafaL over PBR were estimated. Deterministic (DSA) and probabilistic (PSA) sensitivity analyses complemented base case analyses (BCA). Willingness to pay (WTP) thresholds were estimated. Results: At trial follow up (̃2y), PFS and OS rates were 38% and 63% for TafaL vs rates of 18% and 27.5% for PBR. The corresponding 5y PFS and OS rates were 13% and 32.7% for TafaL vs 5.2% and 11.3% for PBR. In BCAs, 5y TafaL costs ($470,949) exceeded PBR’s ($251,615) by $219,334 for incremental gains of 0.71 LY and 0.32 QALY. This yielded BCA ICER of $307,840/LYg and ICUR of $689,314/QALYg attenuated in PSA estimates of ICER of $280,042/LYg and ICUR of $589,215/QALYg. In DSAs, TafaL PFS utility value and PBR treatment costs were the most influential parameters. In PSAs, TafaL had a 50% probability of being cost effective at WTPs of $278,050/LYg and $560,360/QALYg. The incremental cost per 1% gain in probability to achieve OR, PFS and OS at follow up were $7,714, $5,785 and $3,259; and $28,120 and $10,249 for PFS and OS at 5 years. Conclusions: Considering that economic evaluations are intended to inform (but not set) policy, this independent analysis demonstrated that sustained TafaL treatment is associated with better survival outcomes than PBR though at greater cost. The incremental costs to gain a 1% improvement in 2y and 5y survival outcomes with TafaL over PBR were modest, underscoring the longer-term benefit of TafaL over PBR in pts ineligible for or opting out of ASCT.
T-cell clonality in peripheral blood as a predictor of progression to systemic treatment in patients with stage IB mycosis fungoides (MF).
Authors: Raychaudhuri Suravi , Yann Charli-Joseph , Mintz Michelle , Pincus Laura , Huang Chiung-Yu , Ai Weiyun Z. 
Published: June 2021

e19538 Background: A major unmet clinical need in the care of early-stage MF patients is the identification of those with a high risk of failing skin directed therapy or progressing to advanced disease. Herein, we inquired if the identification of a clonal T-cell receptor (TCR) gene rearrangement by PCR in peripheral blood could predict the clinical outcome, particularly the need for systemic treatment, in patients with stage IB MF. Methods: This is a retrospective cohort study of patients with stage IB MF who underwent peripheral blood TCR clonality analysis by PCR. The primary outcome of the study was time from diagnosis to initiation of systemic treatment. Secondary outcomes were: (1) time to progression to advanced-stage disease (stages IIB-IV) and (2) overall survival. Patients were censored at time of last clinical follow up. Log rank test was used to compare the survival distributions of the two groups; p value < 0.05 was considered significant. Results: From May 2014 to October 2019, 56 consecutive stage IB pts with > 6 months follow up were included in this analysis. Peripheral blood TCR clonality status was available in 42 patients: 18 pts had a positive TCR clone and 24 did not. Median follow up time was 36 months (range 8.5 – 198 months). At 3 years, 39% of patients with peripheral clone had progressed to systemic treatment versus 8% of those without a peripheral clone (log rank test, p-value = 0.003). For the secondary outcomes, at 3 years 17% of patients with peripheral clone had progressed to advanced stage versus 4% of those without (log rank test, p-value = 0.10); 5% of patients with peripheral clone had died versus 0% of those without (log rank test, p-value = 0.03). Conclusions: Detection of a predominant TCR clone by PCR in the peripheral blood is an important prognostic marker in the initial workup of MF, as its presence is highly correlated with subsequent progression to systemic treatment and death. If this finding is validated, it can be used to risk stratify and individualize therapy for MF patients.[Table: see text]