bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between ring sideroblasts and treatment with hypomethylating agents (HMA) in patients with refractory anemia with ring sideroblasts.
Authors: Nanah Rama , Zblewski Darci , He Rong , Nguyen Phuong L. , Gangat Naseema , Begna Kebede , Elliott Michelle A. , Hogan William J. , Patnaik Mrinal , Litzow Mark Robert , Al-Kali Aref 
Published: September 2018

e18559 Background: Myelodysplastic syndromes (MDS) are a group of myeloid neoplasms defined by ineffective hematopoiesis, dysplastic morphologic features, and variable risks of progression to acute myeloid leukemia (AML). Refractory anemia with ring sideroblasts (RARS) is a subtype of MDS defined by < 5% basts and > 15% ring sideroblasts (per 2008 WHO). Because RARS is a lower risk disease which does not frequently require HMA therapy, very little is known about the effects of HMA on RARS. Methods: A total of 1325 MDS patients’ data from 1993-2016 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our center. Patients were considered for our study if they received HMA for their RARS. Response was identified based on MDS IWG 2006 criteria. Prognostic factors were analyzed by univariate and multivariate analyses. Survival estimates were calculated using Kaplan-Meier curves. Results: 168 of the initial 1325 patient were RARS (14%); only 14 (8%) were treated with HMA. Median age was 72 years (range, 51-85); half were males, with median overall survival of 91.3 months. The median number of ring sideroblasts (RS) at diagnosis was 40% (range 10-85%). Of the 14 patients, 11 (79%) received azacitidine (AZA), 2 (14%) decitabine (DAC) and one received both (7%). The median number of cycles for AZA was 6.5 (range, 2-28) vs 6 cycles for DAC (range, 1-24). Of the 14 patients receiving HMA, only 3 responded (21%) achieving hematologic improvement. All 3 responders received AZA. 6 of the 14 RARS patients (43%) had their bone marrow biopsy repeated after HMA therapy, 3 of whom were among the responders to AZA therapy and 3 were non-responders. In 5 patients, ring sideroblasts decreased after HMA therapy by a median of 15% (range 0-80); they remained the same in 1 patient; one patient who had developed AML had a decrease in RS from 85% to 5%. Conclusions: RARS is a low-risk subtype of MDS that is infrequently treated with HMA (8% in our study). Response rate to HMA (21%) was inferior to known rates in MDS. HMA therapy seems to decrease the number of ring sideroblasts irrespective of response. RARS patients should be treated on clinical trials if available.
Response to induction or hypomethylating agent therapy among patients with myeloproliferative neoplasms progressing to accelerated or leukemic phase.
Authors: Hobbs Gabriela , Lombardi Story Jennifer , Blaney Maura A. , Amrein Philip C. , Fathi Amir Tahmasb , Brunner Andrew Mark 
Published: September 2018

e18561 Background: Post-myeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) and accelerated phase disease (AP) are associated with poor outcomes; the optimal management of these patients at transformation is uncertain in the era of widely available molecular testing. Methods: We performed a retrospective analysis of adult patients with MPN that had transformed into AML (greater than 20% blasts) or AP (10-19% blasts and dysplastic features) from 2006-2016. Patients were 18 or older at AML/AP diagnosis. Outcomes were described by Kaplan and Meier and the Log rank test. Results: We identified 30 patients, with transformed MPN into AML (n = 23) or AP (n = 7), including one patient in AP at presentation. Most were male (73%). Disease evolved from polycythemia vera (n = 6), essential thrombocythemia (n = 11), primary myelofibrosis (n = 9) and other MPN diagnoses (MPN/MDS overlap, n = 3; MPN NOS, n = 1). The median age at MPN diagnosis was 67.5 yrs, and at transformation 72 yrs. The median time from MPN diagnosis to transformation was 5.6 yrs (range 0.3-36.0). 12 patients had JAK2 V617F testing both at MPN diagnosis and AML diagnosis; 6 had JAK2 mutations at both time points and 2 lost JAK2 at transformation. At AML/AP transformation, 11 patients had NGS mutation testing; the most common somatic mutations were NRAS (5/11), RUNX1 (2/11), and SRSF2 (2/11). 20 patients received treatment outside of supportive care. Of these, 8 achieved a CR or CRi (40%; 7/10 with induction and 1/8 with HMA). The only HMA response was on a trial of HMA+SGN33a. The median survival from AML/AP transformation was 5.8 mo. Of treated patients, median survival was 7.4 mo; 37% of treated patients were alive at 1 yr. Nine patients (31%; 7 with AML and 2 with AP) underwent allogeneic transplantation; 2 relapsed during follow-up. 74% of patients treated with allo-HCT were alive at 1 yr after AML/AP transformation. Conclusions: AML or accelerated phase disease arising out of MPN carries a dismal prognosis. HMA monotherapy had little efficacy in this group (0/7 achieved remission). Allogeneic transplantation offered the best chance of survival at one year, but fewer than a third of patients were able to proceed to transplant.
The emotional journey among caregivers of patients with leukemia: The caregivers’ perspective using social media listening.
Authors: Gabriel Susan , Phillips Kerri , Slater Mary Ann , Zhou Jifang , Pathak Ashutosh K. , Lee Lulu K. 
Published: September 2018

e18568 Background: The burden of cancer has largely focused on the patient. However, caregivers also experience considerable burden. The study's aim was to use social media posts to better understand the emotional journey of caregivers who provide care for patients with leukemia from their own perspective. Methods: Publicly available social media posts (in English) mentioning chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and acute promyelocytic leukemia (APL) from blogs, discussion boards, and Facebook were collected and linguistically analyzed. Results: A total of 145 social media posts by CML caregivers, 149 posts by CLL caregivers, and 65 posts by APL caregivers were analyzed. Common themes emerged among CML, CLL, and APL caregivers as they journeyed from pre-diagnosis, to diagnosis, and to survivorship alongside their loved ones. At the pre-diagnosis phase, caregivers expressed uneasiness or worry about the symptoms their loved ones were experiencing. Additionally, caregivers were often frustrated with doctors because they felt that their loved ones’ symptoms were ignored, which led to a delay in diagnosis. Once the diagnosis was confirmed, caregivers were shocked and scared. Further, caregivers were desperate for information on the disease and what the future would hold. During the survivorship phase of the journey, an amalgam of complex positive and negative emotions emerged among caregivers. Caregivers can become obsessed with finding ways to treat their loved ones, including use of alternative medicine. Caregivers experienced both positive (a more “enriched relationship”) and negative (felt alone or pushed away) relationship changes. Many caregivers were proud of their loved ones’ remission and felt triumphant. Caregivers felt a sense of gratitude toward doctors, friends, family, and social media sites for their support. Conclusions: Caregivers of CML, CLL, and APL patients experience a gamut of emotions at every stage of the disease. Additionally, the relationship between caregivers and loved ones can be negatively affected. Findings suggest that relationship counseling and social support groups could potentially relieve some caregiver burden.
Differences in outcomes between patients whose relapse was diagnosed radiologically versus clinically after autologous transplantation for relapsed/refractory diffuse large B-cell lymphoma.
Authors: Mohyuddin Ghulam Rehman , Clark Ashley Elizabeth , Shune Leyla Osman , Lin Tara L. , Abhyankar Sunil H. , Dias Ajoy , Dunavin Neil , McGuirk Joseph , Ganguly Siddhartha , Singh Anurag Kumar 
Published: September 2018

e19001 Background: Surveillance scans performed after autologous stem cell transplant (AutoSCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post AutoSCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. Methods: We retrospectively identified 139 patients from our institutional database with DLBCL who underwent AutoSCT from 2000 to 2014. All patients had surveillance scans performed at days 100, 180 and at 1-year post AutoSCT. Results: Among the 139 patients with RR DLBCL that underwent AutoSCT, 37 relapsed, of which 21 were clinical and 16 radiological. There were no statistically significant differences in patient characteristics, although more patients in the clinical cohort had extra-nodal and bulky disease (Table 1). The median time to progression was 167 days for the clinical cohort and 565 days for the radiological cohort (p= 0.03). Median follow-up was 587 days for the clinical cohort and 1503 days for the radiological cohort (p=0.002). Median overall survival (OS) was 587 days for the clinical cohort, and was not reached for the radiological cohort (p=0.006). Conclusions: In our review, most patients with relapsed DLBCL after AutoSCT were diagnosed clinically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Our data indicates that patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Given the known risks of excess radiation exposure, our data suggests that routine scanning may not be necessary in the majority of patients with DLBCL following AutoSCT. [Table: see text]
Dimethyl sulfoxide (DMSO) cryopreserved stem cell infusion-related seizures: A single institution experience.
Authors: Attarian Shirin , Janakiram Murali , Ezzati Ali , Gucalp Rasim A. 
Published: September 2018

e19002 Background: An essential step in hematopoietic stem cell transplantation (HSCT) is the cryopreservation of stem cells in DMSO. Neurologic complications related to DMSO are well known and include strokes, seizures, encephalopathy and coma, but risk factors have not been identified. We focused on seizures as a DMSO-related neurologic adverse event. Methods: From 1/2006 to 4/2016, 982 cases of HSCT were reviewed. We identified neurologic adverse events within 24h of stem cell infusion (SCI). Results: 16 cases of neurologic adverse events occurred, including transient paresthesias (2), altered mental status (5), syncope (3), stroke (1), and 5 seizures. The mean age of the patients (pt) was 64.2 years (range 52-79), with 2 females and 3 males. All 5 pts developed seizures during SCI. 4 pts had conditioning: 2 Melphalan, 1 BEAM and 1 Bu/Cy. One pt received SCI without conditioning as a last resort to treat severe neutropenia and overwhelming sepsis. Of these 5 cases, one had a prior history of seizures in the setting of primary CNS lymphoma and 1 had a prior history of stroke, and 1 pt had an acute stroke during SCI. These 3 cases had abnormal EEG with a potential focus for seizure. Conclusions: Understanding the predisposing factors for developing seizures with SCI will improve patient safety and outcomes. History of structural brain lesions or seizure may be a risk factor for development of seizures. Applying prophylactic strategies, such as DMSO removal or prophylactic antiepileptic medications prior to SCI may decrease the risk of seizures. [Table: see text]
Additional value of quantitative expression of ZAP-70 and CD38 for prognostic factors in chronic lymphocytic leukemia.
Authors: Klabusay Martin , Hrabcakova Viera , Coupek Petr , Trbusek Martin , Pevna Michaela 
Published: September 2018

e19006 Background: Chronic lymphocytic leukemia (CLL) has heterogeneous clinical course. Identification of prognostic markers is important for proper management of disease. Cytogenetics, IgVH mutation status, TP53 functional status, CD38, ZAP-70 and CD49d expression are accepted prognostic factors in CLL. ζ-chain-associated protein kinase 70 (ZAP-70) is associated with disease progression. However, measurement of ZAP-70 and CD38 expression relies on qualitative flow cytometry. Authors tested hypothesis whether quantitative analysis of markers can improve information about prognosis of CLL. Methods: 217 CLL patients were included; diagnosis was made from peripheral blood by morphology and immunophenotyping by flow cytometry with common antibodies. Expressions of intracellular ZAP-70 and surface CD38 were measured using quantitative fluorescence cytometry. Standardized fluorescent microparticles were used to quantify molecules of equivalent soluble fluorochrome (MESF units). Analysis of rearrangement of the IgVH gene was performed according to the European recommendation. Deletions at 11q22-q23 ( ATM), 17p13 ( TP53), 13q34 ( RB1) loci and trisomy of chromosome 12 were detected by I-FISH. Results: Patients’ ages ranged from 33 to 86 years and included all Rai stages. Expression of ZAP-70 ranged from 546 to 5,955 MESF, CD38 from 1,886 to 31,619 MESF. 48% patients embodied mutated and 52% unmutated IgVH status. In cytogenetics, del(13q) was detected in 59%, trisomy 12 in 13%, del(11q) in 21%, and del(p53) in 8% of patients. IgVH (in %) was plotted against ZAP-70 (in MESF) and patients were divided into high (HR) and low risk (LR) groups by cluster analysis based on Kaplan-Meier overall survival curves. Patients in HR group had significantly poorer prognoses (p = 0.0001) than those in LR group. When patients from HR group were clustered according to CD38 expression, very high risk (VHR) group with high CD38 and significantly worse prognosis (p = 0.035) was identified. Conclusions: We have demonstrated that quantitative ZAP-70 and CD38 expressions cannot replace IgVH analysis, but, contrary to that, addition of quantitative data can further specify prognoses of patients with CLL.
Clinical and demographic characteristics of CLL patients receiving first-line bendamustine plus rituximab using the Flatiron Health database.
Authors: Tang Boxiong , Gabriel Susan , Pathak Ashutosh K. , Brander Danielle M. , Zhou Jifang 
Published: September 2018

e19010 Background: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world, with 20,110 new cases estimated for 2017 in the US alone. Combination therapy with bendamustine plus rituximab (BR) is among the approved first-line therapies for CLL patients without the 17p deletion. The purpose of this analysis was to characterize CLL patients receiving first-line BR therapy using real-world data. Methods: CLL patients (ICD-9: 204.1x or ICD-10: C91.1x, C83.0x) receiving first-line BR therapy between 11/01/2008 and 11/01/2016 were identified in the Flatiron Health electronic health records database. This database is a large, longitudinal, demographically and geographically diverse database consisting of 250 cancer clinics representing more than 1.5 million active US cancer patients. Results: Of the 2736 CLL patients in the database, 738 patients (male = 70%; mean age = 68.71 years, SD = 9.070) received first-line BR therapy. The majority of patients received treatment in a community setting (93%; 7% in academic hospitals). Prior to first-line BR therapy, immunoglobulin heavy chain variable region ( IGHV) mutation analysis was conducted in 21% of patients, of which 46% were IGHV mutated. Fluorescence in situhybridization (FISH) testing was conducted in 60% of patients: 17p deletion was detected in 8% and 11q deletion in 19%. Trisomy 12 and 13q deletion as a single abnormality was identified in 17% and 27% of tested patients, respectively. Conclusions: CLL patients from the Flatiron database initiating first-line BR therapy have an older median age, male predominance, and community-based treatment setting, which offers a more real-world patient population in comparison with patients reported from clinical trials. Less than a quarter of these CLL patients were tested for IGHV mutations, and only 60% were tested for FISH. The low frequency of testing prior to first-line therapy is similar to other published registry data. This representative patient population offers an insight into the real-world use of BR in CLL patients.
Frequency, cell lineage, and clinical correlates of lymphopenia in untreated T-cell lymphomas (TCL).
Authors: Denlinger Nathan , Hwang Sook (Susan) , Kline David , McLaughlin Eric , Fabbro Stephanie , Brammer Jonathan Edward , Mishra Anjali , William Basem M. , Porcu Pierluigi 
Published: September 2018

e19023 Background: Pre-treatment lymphopenia (Lp) independently predicts survival in TCL. However, lack of knowledge about the lineage of the decreased lymphocyte subset(s) prevents hypothesis formulation on pathophysiology of Lp and its effect on survival. Methods: We retrospectively identified 331 adult patients (pts) with biopsy-proven, newly diagnosed TCL between 2001-2016 at OSU. Pts had no prior chemotherapy or immunosuppressive treatment (tx). Clinical data including flow cytometry (FC) at diagnosis were abstracted from the EMR. Lp was defined as absolute lymphocyte count (ALC) <1,000/µL. Cutaneous TCL (CTCL) stage was defined according to modified EORTC/ISLC criteria. Lymphocyte subsets were defined by FC and reported as proportions of ALC. We examined group differences with Fisher’s Exact or the Wilcoxon Rank Sum tests. Survival was analyzed using Cox regression models. Results: Of 331 pts with TCL, 102 were excluded due to prior tx or incomplete data. Of the 229 pts included, 67 had peripheral TCL (PTCL) and 162 had CTCL; 112 mycosis fungoides/sezary syndrome; 99 (61%) early stage (Stage IA-B), 22 (13%) advanced stage (Stage IIB-IVB), and 41 (26%) cutaneous CD30+ lymphoproliferative disorder (CD30+ LPD). Lp was present in 10% of CTCL, 8% in early stage, 22% in late stage, 12% of CD30+LPD, and 34% of PTCL, with overall frequency of 17%. After median follow up of 1,105 days, Lp was associated with worse progression-free survival (PFS) in CTCL pts with an unadjusted hazard ratio of 3.19 (p=0.19). Adjusting for stage and albumin level on multivariate analysis, Lp retained statistical significance for PFS (HR 3.46, p=.04). For the entire cohort, lymphopenia was associated with inferior OS (p=.0027). Analysis of lymphocyte subsets in late stage CTCL compared to early stage showed a significant decrease in B (CD19+) p=.014, NK (CD56+) p=.012, and CD8+ (p=.0045) cell populations. Conclusions: Lp was prevalent (10-34%) in our cohort of newly diagnosed TCL pts and was associated with worse OS. Lp was more prevalent and lymphocyte subsets were significant altered in pts with advanced stage CTCL. These findings will inform further investigations into mechanisms of Lp in TCL, and its potential as predictive biomarker.
Autologous stem cell transplantation as a treatment modality for type 1 cryoglobulinemia in monoclonal gammopathy of renal significance.
Authors: Richter Joshua Ryan , Wang Zhen , Vesole David H. , Biran Noa , Donato Michele , Rowley Scott D. , Skarbnik Alan P. , Pecora Andrew , Siegel David Samuel DiCapua 
Published: September 2018

e19500 Background: Type I cryoglobulinemia (CRYO) can be driven by disorders such as plasma cell dyscrasias. Monoclonal gammopathy of renal significance (MGRS) represents a group of kidney disorders characterized by the presence of a paraprotein; though not fitting the criteria for a hematologic malignancy. There exists no standard approach to manage these patients. Our patient is a 56-year-old man who was initially evaluated for edema. Workup revealed worsening renal function and proteinuria (Figure 1). Renal biopsy revealed abundant cryofibrinogen deposits and cryoglobulinemic glomerulonephritis with membranoproliferative pattern. Bloodwork showed type I (IgG Kappa) CRYO. Bone marrow evaluation revealed 7% clonal plasma cells. Further evaluation did not confirm a diagnosis of myeloma. Methods: Treatment was initiated with bortezomib, cyclophosphamide and dexamethasone. After 3 cycles of therapy the patient had normalization of his creatinine and marked improvement in edema. Peripheral blood stem cells were mobilized following the administration of high-dose cyclophosphamide (2gm/m2) plus filgrastim. He was subsequently conditioned for transplantation with high-dose melphalan (200mg/m2; HDM) followed by autologous stem cell rescue. He tolerated the procedure well without any unexpected toxicities; achieving prompt hematologic recovery Results: Evaluations post transplant revealed resolution of any circulating cryoglobulins and reduction in proteinuria. At 1 year post transplant, the patient has returned to his premorbid condition. Conclusions: Type 1 CRYO associated MGRS represents a complicated disorder for which there is no consensus treatment approach. As this process may be driven by clonal plasma cells, classical anti-myeloma therapy may provide a strategy for management. Given the typical low plasma cell burden in these patients, HDM has the potential to offer deep and durable remissions. Prospective studies are needed to validate this approach. [Table: see text]
Unusual disease characteristics of multiple myeloma in eastern North Carolina.
Authors: Addepalli Srikala , Brigham Denise , Liles Darla K. 
Published: September 2018

e19512 Background:Multiple Myeloma (MM) is a relatively common malignancy in Eastern NC, especially in African American population. There have been several advances in treatment of MM but it is unclear how well current therapies are being utilized and what barriers prevent this. Our goal was to identify any unique clinical and epidemiological features of this disease in our patient population as this may help us to improve outcomes. Methods: Demographics, clinical features, FISH/ Cytogenetic features, clinical outcomes of the patients enrolled on MMRF CoMMpass study at our institution were reviewed and analyzed to identify any unusual features in our dataset. Results:The median age at diagnosis of MM is 69 years. There was a higher proportion of younger patients in our dataset, 40% of our patients were < 60 years and 11% of patients were < 40 years which may point to environmental and genetic factors in this population and needs to be studied further. About 20% of patients with MM are reported to have Light Chain Myeloma (LCM) while 30% patients had LCM in our dataset. More patients had a higher stage of disease, ISS stage III at diagnosis, 72%.The benefits of Autologous Stem Cell Transplant (ASCT) in management of Multiple Myeloma is well established but only 22% of the patients had ASCT as part of their management. This appears to be secondary to multiple factors including comorbidities, socioeconomic factors such as financial concerns, difficulty with access to treatment and availability of care givers Conclusions:There is a disproportionately high proportion of younger patients with Multiple Myeloma in Eastern NC, especially with LCM. The environmental and genetic factors responsible for this need to be studied further. Many patients have a high tumor burden at diagnosis. Improvement in access to care, enhancement of provider education, collaboration with regional oncologists and study of novel drug combinations to achieve deeper and more durable responses may help improve outcomes for this treatable malignancy. "These data were generated as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiatives (https://research.themmrf.org and www.themmrf.org)”.