bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germinal Center Phenotype Determined by Immunohistochemistry on Tissue Microarray Does Not Correlate with Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with Immunochemotherapy in the Randomized Trial LNH98-5. A GELA Study.
Authors: Molina Thierry Jo , Gaulard Philippe , Jais Jean-Philippe , Salles Gilles Andre , Berger Françoise , Haioun Corinne , Tilly Herve , Emile Jean-François , Feugier Pierre , Leroy Karen , Briere Josette , Coiffier Bertrand 
Published: October 2019

Abstract
Germinal center (GC) subtype defined by immunohistochemistry in diffuse large B-cell lymphoma (DLBCL) treated by anthracycline-containing regimens has been found as a good prognostic parameter by some but not all authors. More recently, studies reporting series of patients treated with rituximab plus chemotherapy showed a loss of prognostic value of GC profile. However, these series did not include patients from randomized trials. We undertook an immunohistochemical study on tissue microarray (TMA) among patients included in the GELA LNH98-5 trial that compared CHOP and rituximab-CHOP (R-CHOP). Among the 399 patients (age 60 to 80 years) enrolled in this study with DLBCL, duplicate TMAs were available for 172 patients, consisting for each TMA of two cores of 0.6mm per case. We analyzed the expression of CD10, bcl-6 and mum-1 and classified patients as GC or non-GC (n-GC) according to the Hans’ algorithm. The samples were scored positive for bcl-6 and mum-1 if 30% or more of tumor cells were stained and for CD10 if there was a significant number of tumor cells positive. Internal controls for each spot were required for interpretation as well as concordance between the duplicate TMAs. T-cell-rich B-cell lymphomas (TCRBCL) were excluded because too few tumor cells could be evaluated. Overall 101 patients were evaluable (excluding 39 cases due to absence of internal controls or spots detachment, 25 discordant cases between the duplicates for bcl-6 and mum-1, and 7 TCRBCL). Patient characteristics were not statistically different from the whole series regarding sex, age, stage, LDH level, PS, number of extranodal sites, aa-IPI, IPI, median follow-up (85 months) as well as allocated regimens (CHOP, 49 patients; R-CHOP, 52 patients). 44 patients were classified as GC and 57 as n-GC. Patient characteristics were well balanced between GC and n-GC subtypes. EFS was not different among the 101 patients between GC and n-GC (p=0.28). Multivariate analyses confirmed that only aa-IPI (p=0.005), and treatment arm (p=0.005) influence EFS but not the GC/n-GC profile (p=0.17). Although the EFS among CHOP patients showed a borderline but not significant better prognosis among GC patients (p=0.11), this trend was completely abrogated among patients treated with R-CHOP (p =0.92). Overall survival was not different between the GC and n-GC profile among the whole population (p=0.41), the patients treated by CHOP (p=0.31) or by R-CHOP (p=0.74). Overall, our study demonstrates that in this randomized trial, GC profile defined by immunohistochemistry on TMA does not represent a significant prognostic parameter among DLBCL patients treated by CHOP with or without rituximab.
Age under 40 Does Not Confer Superior Prognosis in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transplant Despite High Response Rates.
Authors: Cheema Parneet K. , Zadeh Sahar , Reece Donna , Chen Christine I. , Trudel Suzanne , Kukreti Vishal , Mikhael Joseph R. 
Published: October 2019

Abstract
BACKGROUND: Multiple myeloma (MM) only occurs in 2% of patients under the age of 40. It has been reported that this young cohort of patients have a superior overall survival when compared to those over the age of 40.
OBJECTIVE: To evaluate the clinical and laboratory features of patients ≤40 years of age at diagnosis of MM and to compare survival outcomes to patients >40 years of age.
METHODS: Retrospective institutional review of all patients ≤40 years of age at time of diagnosis of MM that had underwent upfront ASCT at PMH from January 1, 1990 to July 31, 2007. Outcomes were compared to patients >40 years of age who had also undergone ASCT as upfront therapy.
RESULTS: 37 patients ≤40 years of age were identified. Twenty patients were male. Immunoglobulin subtype was as follows: 49% had IgG, 19% light chain,16% IgA, 8% IgD, and 5% IgG plasma cell leukemia. The main presenting clinical feature was bone pain (63%). 73% had radiological evidence of bony disease at diagnosis and 53% of these patients required radiation prior to ASCT. Clinical features included anemia in 81%, renal insufficiency in 39% and hypercalcemia in 28%. Conditioning regimens for ASCT were high dose melphalan (200mg/m2) alone in 25 pts, VP-16 & melphalan +/− TBI in 8 pts, bleomycin & cyclophosphamide in 3 pts, and in 1 pt it was unknown. Median time to engraftment of neutrophils (>0.5 x 109/L) and platelets (>20 x 109/L) was 11 days (range 8–18) and 12 days (range 0–54), respectively. Median duration of hospitalization was 17 days (range 10–54). No treatment related mortality was experienced. Response to ASCT was as follows in 29 evaluable pts: CR in 10 (34.5%), PR in 13 (44.8%), MR in 1 (3.4%), SD in 3 (10.3%), and PD in 2 (6.9%). Five patients underwent a tandem ASCT. Maintenance therapy was instituted in 11 pts. Median progression free survival (PFS) post ASCT was 23.0 months, which is similar to the PFS of 28.5 months in patients over 40 (p=0.559). There was also no difference in median overall survival (OS) from date of ASCT between the two groups (6.6 years in pts ≤40, 6.7 years in pts >40; p=0.797).
CONCLUSION: Young patients with MM present with advanced disease as evidenced by anemia, bone involvement and hypercalcemia. ASCT yields high response rates, but PFS post ASCT is less than 2 years. Although young age has been historically been considered to be a positive prognostic marker, OS post ASCT is only 6.6 years, which is equivalent to those >40 years of age. Strategies to better the outcomes of young patients with MM are required.
Clinical Characteristics of Patients with a RBC Fragment Flag on the Advia® 2120 Automated Hematology Analyzer.
Authors: Ben-Ezra Jonathan 
Published: October 2019

The clinical diagnosis of thrombotic thrombocytopenia purpura (TTP) is a difficult one to make. It is based on clinical criteria, one of which is a microangiopathic hemolytic anemia, characterized morphologically by the presence of schistocytes on the peripheral blood smear. The ADVIA 2120 automated hematology analyzer is able to quantify the presence of red blood cell (RBC) fragments. We studied the ability of the ADVIA 2120 to be able to detect RBC fragments in the blood of TTP patients, and the characteristics of all patients in whom RBC fragments were obtained. During the study period, 6 TTP patients were studied. The initial numbers of RBC fragments ranged from 0.02–0.05 × 106 cells/μl. During the course of plasmapheresis, these numbers decreased to 0.00–0.02 × 106 cells/μl, corresponding to a rise in the platelet count.
Figure Figure In the course of a month, 52 blood samples on 39 patients were flagged by the hematology analyzer to have RBC fragments (0.01–0.12 × 106 cells/μl).
52 Samples with RBC Fragment Flag Hemoglobin Platelets RDW Range 4– 14.3 g/dl 5–906 × 103/ul 13.9– 28.6% Number Abnormal 46 (<13.0 g/dl) 23 (<160 × 103/ul) 51 (>14.1%)
Within this population, there were two patients with TTP, and one with DIC. Four of the samples did not have detectable schistocytes upon visual inspection of the peripheral blood smear. There were 19 samples from 14 patients who had RBC fragment counts ≥ 0.04 × 106 cells/μl.
19 Specimens with RBC Fragments ≥ 0.04 × 106/ul Hemoglobin Platelets RDW Range 8– 14.1 g/dl 59– 906 × 103/ul 16.4– 25.3% Number Abnormal 15 (<13 g/dl) 4 (<160 × 103/ul) 19 (>14.1%)
The diagnoses in these 14 patients were iron deficiency anemia (4 patients), thalassemia trait (2), acute lymphoblastic leukemia (2), and one each with TTP, sickle cell anemia, heart failure, kidney stone, cerebrovascular accident (CVA), and end stage renal disease. We conclude that the RBC fragment flag on the ADVIA 2120 is nonspecific. Although it does detect schistocytes in TTP, these are often present in low numbers. Quantitatively, the most numerous RBC fragments are found in diseases with marked anisopoikilocytosis, such as iron deficiency anemia.
Osteonecrosis of the Jaw Related to Bisphosphonates Therapy in Multiple Myeloma and Metastatic Prostate Cancer Patients. A Latin American Report: An Adverse Event To Look For!!.
Authors: Beltran Brady , Riva Luis , del Carpio Daniel , Fernandez Ivan , Vera Luis , Reategui Rocio , de Mendoza Fernando Hurtado , Castillo Jorge , Carrasco-Yalan Antonio A. 
Published: October 2019

Abstract
Background: Association between osteonecrosis of the jaw (ONJ) and aminobisphosphonate treatment in patients (pts.) with multiple myeloma, breast cancer and prostate cancer has been increasingly reported in the literature. Risk factors for this complication include presence of infection, recent dental extraction and any oral surgical procedure with bone exposure.
Patients and Methods: All patients with myeloma multiple or prostate cancer diagnosis treated at two institutions from Lima with either IV zoledronic acid or pamidronate from 2005–2007 were evaluated using outpatient records. Patients with ONJ were identified and their characteristics were compared to all patients receiving bisphosphonate therapy.
Results: One hundred eighty three patients were evaluated. One hundred three had metastatic prostate cancer, and eighty myeloma multiple. All patients with myeloma multiple received pamidronate and all patients with prostate cancer received zoledronic acid. Six patients developed ONJ (3.2%). Five pts. were male and one female; a median age of 62 (range 50–74) and 5 had metastatic prostate cancer and 1 myeloma multiple. Zoledronic acid and pamidronate were involved in 5 and 1 cases respectively. The median number of bisphosphonate infusions prior to the development of ONJ was 16 (range 12–20). No patient had dental extraction or oral surgical procedure before ONJ. Bone exposition occurred in four cases. Treatment was antibiotics in all cases and surgery in two.
Conclusions: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our Latino american patients.
Imatinib Versus Interferon-alpha (IFN) for Patients with Newly Diagnosed Chronic-Phase (CP) Chronic Myeloid Leukemia (CML) from the Chinese Public Healthcare System Perspective: 12 Months Cost and Cost Per Responder Analyses.
Authors: Wang Chun , Chen Zi , Feng Weiwei 
Published: October 2019

Abstract
Background: Imatinib, a break-through oral molecular targeted therapy, has demonstrated impressive and durable responses as well as survival advantage over IFN based therapy in CML (1, 2). Reed et al. estimated the survival for a newly diagnosed CP CML patient treated with imatinib was 19.07 years vs. 9.09 years with IFN plus low dose cytarabine (LDAC) (3). However, imatinib has not been registered on the Chinese National Reimbursement Drug List (RDL) whereas IFN has. Although studies have shown IFN plus Ara-C is more effective than IFN alone, IFN is normally used alone in China in CP CML. Therefore, this study compared imatinib with IFN alone. Complete cytogenetic response (CCyR) at 12 months has been established as an effective measure for treatment efficacy in CML (4). The 12 months cost and cost per responder in CCyR analyses were conducted to compare imatinib with IFN alone from the Chinese public healthcare systems perspective.
Methods: The cost per responder at 12 months for a newly diagnosed CP CML patient was calculated as dividing the total 1-year cost of treatment by the CCyR rate at 12 months. The 1-year cost of treatment consists of the following occurred during one year: drug cost, office visits, and blood tests. The cost of managing adverse events was excluded as local China data were unavailable at the time of the analyses. The CCyR at 12 months for imatinib was obtained from the International Randomized Infereron vs. STI571 Study (IRIS) (1). The CCyR at 12 months for IFN was from the Baccarani et al. study (6). Price information on drugs was obtained from the listed retail price in China. The price for imported IFN was used as the cytogenetic response data were unavailable for domestic made IFN. Unit cost on office visit and blood test was estimated based on the average fees charged by tier 3 hospitals. Dosages for imatinib and IFN were based on the approved product labels in China.
Results: The 12-month CCyR rate for imatinib was 69% vs. 3% for IFN. The 1-year cost of treatment associated with imatinib was RMB77,700, lower than that with IFN (RMB79,200). The cost to achieve 1 CCyR at 12 month was RMB112,609 with imatinib vs. RMB2,640,000 with IFN.
Conclusion: In newly diagnosed CP CML, patients treated with imatinib achieved a significantly higher CCyR at a lower cost than those treated with IFN at 12 months. Based on the 1 year analysis, imatinib is a dominant treatment option in comparison to IFN in newly diagnosed CP CML treatment from the Chinese public healthcare system’s perspective.
Acceptability and Validity of Use of a Patient-Reported Cost Diary To Capture Health Resource Utilization and Costs Associated with Deep Venous Thrombosis and Post-Thrombotic Syndrome.
Authors: El-Hadi Wissam , Ducruet Thierry , Johri Mira , Kahn Susan R. 
Published: October 2019

Abstract
OBJECTIVE: To assess the acceptability and validity of a patient-reported cost diary to estimate health resource utilization (HRU) and costs associated with deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS).
METHODS: We developed a cost diary for use in the Venous Thrombosis Outcomes (VETO) Study, a prospective multicenter cohort study of long-term outcomes after DVT. The VETO cost diary is a 28-item patient-reported questionnaire used to capture information pertaining to HRU and direct and indirect costs attributable to DVT and PTS. Data for HRU and direct costs included hospitalizations, physician visits, purchase of prescription and over-the-counter medications, use of transportation and other medical services and purchase or rental of equipment. Data pertaining to indirect costs included time lost from work by patients or their caregivers. Patients were asked to complete the cost diary monthly for 1 year, then for 3 randomly chosen months for the 2nd year. Acceptability of the cost diary was assessed by estimating the percent of time coverage per patient over the study follow-up period. Internal consistency was assessed by comparing data reported by patients in the cost diary to similar data collected in nurse-administered study questionnaires. External validity was assessed by comparing HRU data reported in the cost diaries to patient-specific data obtained from the administrative database of the Province of Quebec Health Insurance Board (RAMQ) for the same time period.
RESULTS: 387 patients with objectively diagnosed DVT participated in the VETO Study, of whom 359 from 7 hospitals in Quebec, Canada contributed to this analysis (∼ 40% developed PTS). Analyses showed that acceptability of the cost diary was high, with more than 82% of patients reporting data for > 90% of the study follow-up period. Internal consistency analyses revealed discrepancies in reporting of hospitalizations in cost diaries compared to nurse-administered questionnaires (144 vs. 97 hospitalizations, respectively, reported in the first year of the study). Analyses of external validity showed that for the first 4-month study period, the mean number of DVT-related prescriptions reported in the cost diary was comparable to that reported in the RAMQ database (2.48 vs. 3.84, respectively), as was the mean number of DVT-related medical visits (6.39 vs. 7.18, respectively).
CONCLUSION: Overall, the VETO cost diary appears to be an acceptable and valid patient-reported instrument that can be used to estimate HRU, direct and indirect costs attributable to DVT and PTS. Further analyses are needed to identify the factors affecting the internal consistency of the cost diary.
Cost of Myelosuppression with the Second Generation Tyrosine Kinase Inhibitors (TKIs) in Imatinib Resistant/Intolerant Chronic Myelogenous Leukemia (CML): An Economic Analysis Using Global Literature.
Authors: Stephens J. , Carpiuc K. , Botteman M. , Feng W. 
Published: October 2019

Abstract
Background: New targeted therapies such as nilotinib and dasatinib show promise as options for patients with imatinib-resistant or -intolerant CML; however, concerns exist for these agents related to myelosuppression. The objective of this study was to compare the short-term cost of myelosuppression, from a global perspective, for chronic and accelerated phase CML patients treated with nilotinib and dasatinib.
Methods: A global systematic literature review of the past 10 years was conducted using MEDLINE, Econlit and EMBASE to examine the potential costs of myelosuppression (specifically anemia, neutropenia and thrombocytopenia) in adult cancer patients, from the perspective of a health-care payer. An economic analysis was then developed using the ranges of cost data reported in literature, as well as the incidence rates of Grade 3/4 anemia, neutropenia and thrombocytopenia from nilotinib phase II clinical study reports and the dasatinib package insert for chronic and accelerated phase CML. All costs/currencies were converted to US dollars and inflated to 2006 using the country-specific medical inflation rates.
Results: The cost of managing myelosuppression varied widely among countries based on patterns of inpatient compared to outpatient treatment, as well as the use of transfusions compared to recombinant growth factors. The reported cost ranges per AE episode were $124–$12,646 for anemia, $300–$27,440 for neutropenia and $239–$12,223 for thrombocytopenia from the following countries: UK, France, Germany, Italy, Spain, Netherlands, Finland, Switzerland, Belgium, Canada and the US. Expected 6-month costs per patient for Grade 3/4 myelosuppression adverse events with nilotinib and dasatinib are shown as ranges below: Chronic Phase Accelerated Phase Nilotinib $238–$5,550 $394–$9,064 Dasatinib $415–$9,929 $1,155–$23,674
Conclusions: Reflecting a broad range of countries, the expected short-term costs of Grade 3/4 myelosuppression with dasatinib may be 1.7 to 2.9 times higher than that associated with nilotinib. When considering the economic implications of different treatment options for imatinib-resistant or -intolerant CML, both the cost of the drug and the cost of managing adverse events should be taken into account. Future observational studies should be conducted to prospectively assess real-world adverse event costs with the second generation TKIs.
Assessment of Epoetin Alfa in Patients with Myelodysplastic Syndrome Utilizing an Electronic Medical Record Database.
Authors: Feinberg Bruce , Gilmore James , Franco Carlos , Gondesen Tom 
Published: October 2019

Abstract
BACKGROUND: There are limited data from electronic medical record studies that provide a real-world view of practice patterns of epoetin alfa (EPO) as supportive therapy in patients with myelodysplastic syndrome (MDS). This retrospective, observational study was conducted to gain a better understanding of the demographics, real-world treatment patterns, and clinical outcomes for patients with MDS receiving EPO.
METHODS: Electronic medical record data from a large oncology/hematology practice in the southeastern United States were collected from January 1, 2005 to September 30, 2006. Inclusion criteria consisted of patients receiving ≥ 2 doses of EPO with a diagnosis of MDS within 30 days prior to or during EPO treatment episode. All other cancer diagnoses were excluded. Baseline characteristics, EPO dosing, change in Hb levels, and response to EPO (attainment of Hb ≥ 11.0 g/dL at any point during the treatment episode from a baseline Hb < 11g.dL) were measured. EPO treatment episode was defined as continuous treatment with EPO and without EPO administration 35 days prior to or after the last administration. Weekly (QW) dosing was defined as ≤ 9 days, every 2 week dosing (Q2W) was defined as 9.1–18.0 days, and every 3 weeks (Q3W) was defined as > 18.1 days.
RESULTS: A total of 166 patients were included in the analysis; 63.9% women, mean age was 76.2 ± 11.3 years. The mean starting dose was 44,518 ± 11,258 units (median = 40,000 units), and the mean administered dose (any dose of EPO) was 45,587 ± 10,351 units (median=40,000 units). The mean cumulative dose (sum of all EPO doses during the treatment episode) was 312,349 ± 453,551 units. Weekly dosing was administered in 38.0% of patients while 34.9% of patients received Q2W dosing and 27.1% received Q3W dosing. Mean Hb at baseline was 10.6 ± 1.1 mg/dL and increased to 11.3 ± 1.7 mg/dL after 12 weeks of EPO therapy. Fifty percent of the patients responded to treatment and the mean time to response was 33.2 days.
DISCUSSION: This study provides insight into real-world treatment patterns and clinical outcomes for patients with MDS treated with EPO. Additional real-world studies may be warranted to validate these findings.