bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary payer status and outcomes after autologous hematopoietic stem cell transplant: A national perspective.
Authors: Rahman Abu Ahmed Zahidur , Mujib Nusrat , Mujib Marjan , Nazir Tariq 
Published: March 2020

7042 Background: With healthcare cost in rise, it is of interest to explore variation in healthcare delivery outcome with different payment source. This study was aimed to analyze relationship between payment source and outcome following autologous hematopoietic stem cell transplant (AutoHSCT) in a national database. Methods: We identified all hospitalizations with AutoHSCT (n=1,673) from Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality 2010 database using the ICD 9 procedure codes 41.04 and 41.07. Based on sample weights an estimated 8,444 AutoHSCT procedures were performed nationwide in 2010. Patients were stratified on the basis of payer status: Medicare (27%), Medicaid (12%), private insurance (60%), and uninsured (0.8%). Multivariable logistic regression models were used to determine the association of primary payer status and outcomes. Results: Patients had a mean age of 54 (±13) years, 39% were women and 69% were whites. In-hospital mortality occurred in 1.1%, 2.9% and 3.3% of AutoHSCT patients with primary payer status of private insurance, Medicaid and Medicare respectively. AutoHSCT patients with primary payer status of Medicaid and Medicare had a statistically significant higher chance of in-hospital mortality compared to patients with private insurance (adjusted odds ratios and 95% confidence intervals, 2.68; 1.54-4.65; P <0.001 and 1.90; 1.21-2.99; P=0.005 respectively). Length of stay was longer for Medicare patients (20 ± 11 days) and Medicaid patients (20 ± 12 days) compared to private insurance (18 ± 8 days; P <0.001). Medicare and Medicaid patients also accrued higher hospital charges (USD 175,221 and USD 166,453), compared to private insurance patients (USD 157,120; P <0.001). Conclusions: In this national study Medicaid and Medicare patients had an independent risk for in-hospital mortality compared to private insurance patients. Medicaid and Medicare patients also had longer length of hospital stays and accrued higher hospital charges. This may mandate a closer look into the current resource utilization strategies to reduce such disparities among patients undergoing AutoHSCT.
Arsenic trioxide: Pharmacokinetics in acute promyelocytic leukemia (APL) patients.
Authors: Ghiuzeli Cristina Maria , Calabro Anthony , Saunders Randall Jesse , Budman Daniel R. , Styblo Miroslav , Devoe Craig E. , Allen Steven L. 
Published: March 2020

7055 Background: Arsenic (As) has significantly increased survival for APL patients. As and its metabolites’ effects on cell proliferation, apoptosis, and methylation, especially long term, remain largely unknown. It is imperative to study the pharmacokinetics of As at therapeutic doses in order to limit untoward effects resulting from treatment. Arsenic trioxide (ATO), available as arsenous acid (iAsIII), is readily metabolized through sequential methyl group additions and electron reduction steps: iAsIII →MAsV →MAsIII →DMAsV →DMAsIII →TMAsVO →TMAsIII. iAsIII, MAsIII and DMAsIII are more biologically active and more toxic than pentavalent forms. The key enzyme involved is arsenic methyltransferase, and polymorphisms contribute to metabolic differences between individuals. Methods: Cancer patients not treated with ATO (controls) had one collection of blood and urine samples, while APL patients receiving therapeutic doses of ATO had collections immediately prior to and at 1, 2, 4, 6, and 24 hours, days 4, 8, 15, and 4 weeks after ATO-free interval. Total iAs (iAsIII+iAsV), MAs (MAsIII+MAsV) and DMAs (DMAsIII+DMAsV) were measured in plasma using hydride generation cryotrapping atomic absorption spectrometry, a sensitive automated method of arsine detection. The same As species were measured in urine and in exfoliated bladder cells isolated from urine. Results: We report data on ten control patients and six treated patients (ATO 0.15 mg/kg/day). Initial average As concentrations in treated patients (0.051 ng/ml) were similar at baseline to the controls (0.046 ng/ml). We observed that iAs is quickly metabolized from a peak average plasma concentration of 32 ng As/ml to a trough of 10 ng As/ml within six hours from infusion, remaining unchanged for at least 24 hours. MAs and DMAs concentrations begin to increase at six hours, and continue to rise by day 4 to an average concentration of 8.5 and 10.4 ng As/ml respectively, followed by decline to baseline 4 weeks after final ATO infusion. Conclusions: Treatment with ATO leads to the formation of MAs and DMAs whose long term toxicity in APL patients is poorly understood. Studies involving analysis of As metabolites are needed to assess possible long term toxicities on non-targeted organs.
The role of salvage induction chemotherapy after azacitidine (AZA) treatment failure.
Authors: Yee Karen W. L. , Brandwein Joseph , Schimmer Aaron D. , Gupta Vikas , Minden Mark D. , Schuh Andre C. 
Published: March 2020

7078 Background: Hypomethylating agents (HMA) such as AZA, are considered standard of care for patients (pts) with IPSS Int-2 or High-risk MDS. These agents are not curative. Many centers have used HMAs as a bridge to alloSCT in pts with MDS in an attempt to reduce tumor burden and prolong time to progression to AML. However, pts are at risk of AZA treatment failure, which may delay or prevent subsequent alloSCT. Recent data have demonstrated poor responses to intensive chemotherapy after AZA failure [ORR of 0% (0 of 4 pts) to 14% (3 of 22 pts) (J Clin Oncol 2011; Br J Haematol 2012)]. Methods: This retrospective analysis evaluates the outcomes of 18 pts with MDS, CMML and AML, who failed AZA therapy, and subsequently received induction chemotherapy at the Princess Margaret between July 2009 and December 2012. Results: Median age was 57.7 y (range, 19 - 75 y); only 1 pt was > 70 y. 56% were male. Of the 18 pts, 83% were treated for MDS, 6% CMML-2, and 11% AML. IPSS was Int-2/High-risk in 16 pts and Int-1 risk in 2 pts. 83% of pts had been treated with AZA as first-line therapy. Two pts had received growth factors & 1 pt hydroxyurea prior to AZA. Median number of AZA cycles administered was 5.5 (range, 1 - 18) with 72% of pts receiving < 6 cycles. Eleven (61%) pts had primary AZA failure, 5 (28%) secondary AZA failure, and 2 (11%) were taken off AZA to receive induction chemotherapy as an HLA-identical donor was found. At the time of induction chemotherapy, 15 pts had s/tAML, 2 RAEB-2 and 1 CMML-2. Cytogenetic risk was intermediate in 4 and poor in 11 pts, respectively. Karyotype analysis was not done or inconclusive in 3 pts. ORR was 44% and 37.5% in all pts and in AZA failures only, respectively. CR rate was 22% and 25%, CRi 27% and 12.5%, and MLFS 6% and 0% in all pts and in AZA failures only, respectively. Four pts died during induction. Four of 8 responders received an alloSCT, with the remaining 4 pts relapsing (3 while awaiting an alloSCT). Median F/U of all pts was 12.6 mos, with a median OS of 8.3 mos. Conclusions: Contrary to prior reports, salvage induction chemotherapy can yield responses in a significant number of pts who have failed AZA therapy. However, response duration and OS remain poor for AZA treatment failures. There is an unmet need for novel therapeutic agents in this group of patients.
Study of different mutations in chronic myeloid leukemia in India and their co-relation with drug resistance.
Authors: Mitra Priti , Dasgupta Swati , Basu Chinmay Kumar , Gharami Firoj Hossain , Mandal Subrata , Mukhopadhyay Ashis 
Published: March 2020

7083 Background: Emergence of ABL point mutations is the most frequent cause for imatinib resistance in CML. Aim of our study is to investigate two potential resistance mechanisms i.e.,mutations of BCR-ABL tyrosine kinase domain (TKD) and Additional Chromosomal Abnormalities during TKI treatment in CML. Methods: Karyotyping and BCR-ABL TKD mutation screening are performed in 100 imatinib resistant CML patients who were on imatinib at the time of loss of hematologic response, cytogenetic or molecular response. Imatinib–Resistance Mutation Analysis (Qualitative) were detected by Nested RTPCR and Sanger’s Sequencing. In 100 cases, 34 received escalated imatinib, 34 nilotinib and another 32 dasatinib. Results: In 100 BCR-ABL positive imatinib, nilotinib and dasatinib resistant cases, 11 different BCR-ABL TKD mutations were detected. Analysis revealed no mutations-43 cases, M351T-12 cases, G250E-10 cases, F317L-8 cases, M244V-5 cases, E255K-4 cases, V379I-4 cases, F359V-3 cases, H396R-3 cases, Y253F-3 cases, E355G-3 cases, T315I-2 cases. 11 novel mutations (F317L, G250E, M244V, Y253F, E255K, M351T, F359V, H396R, V379I, E355G, T315I) conferring imatinib resistance, 10 nilotinib–resistant mutations (M244V, F359V, T315I, E355G, G250E) and 8 dasatinib-resistant mutations (H396R, F317L, H396R, T315I, M351T) were seen in our patient population. T315I was found more frequently in cases on dasatinib than on imatinib therapy. Conclusions: T315I which confers resistance to all TKIs was detected only in 2/100 patients who demonstrated loss of response in our population. As compared with other western studies, incidence of T315I mutation was very low in our study. In addition analysis of mutation patterns at baseline may help in stratifying patients for treatment. For cases with TKI resistance, mutation and ACA screening may play role in identifying patients with poorer prognosis. In our practice if nilotinib–resistant mutation was detected, dasatinib was preferred and for dasatinib-resistant mutation, nilotinib was preferred. We are planning for using bosutinib, panotinib and omacetaxine (SC route) in third line therapy in imatinib resistant different mutation positive chronic myeloid leukemia.
Predictive factors associated with achievement of major cytogenetic response (MCyR) to omacetaxine mepesuccinate among patients with chronic phase chronic myeloid leukemia (CML-CP).
Authors: Wetzler Meir , Kantarjian Hagop M. , Nicolini Franck E. , Lipton Jeffrey Howard , Akard Luke Paul , Baccarani Michele , Khoury Hanna Jean , Craig Adam , Cortes Jorge E. 
Published: March 2020

7088 Background: Omacetaxine mepesuccinate (OMA), a first-in-class cephalotaxine, is a protein synthesis inhibitor not dependent on Bcr-Abl signaling. OMA has shown clinical activity in CML patients resistant/intolerant to tyrosine kinase inhibitors (TKIs). This subanalysis of 2 phase 2 studies examines predictors of MCyR to OMA in patients failing ≥2 TKIs. Methods: OMA 1.25 mg/m2BID was given in 28-day cycles: ≤14 days for induction, ≤7 days for maintenance. MCyR was defined as ≤35% Ph+ metaphases in bone marrow. A full logistic regression model with 11 baseline parameters was examined by Hosmer and Lemeshow Goodness-of-Fit test. Results: Of 81 patients (median age 59 y; range 26-83), 16 (20%) achieved MCyR. Mean (SD) baseline body surface area (BSA) was 1.90 kg/m2(0.240). Median time since last TKI to start of study was 1.3 mo (range 0.2-28.0) and median time from diagnosis was 75.4 mo (range 7.9-234.3). The final model had 8 baseline predictors (goodness of fit of p=0.1473; Table). (Sex, 2 vs 3 TKIs, or status of any mutation were not in the final model.) Logistic regression analysis showed a significant association between MCyR and no hydroxyurea (HU) use at baseline (p=0.0118). Numerically higher MCyR rates occurred in patients with baseline CHR and BSA ≥1.94 kg/m2. Conclusions: This small sample suggests that omacetaxine may be an important option for a range of patients, regardless of Bcr-Abl T315I mutation status. Prior HU may indicate more proliferative disease. Support: Teva BPP R&D, Inc. Clinical trial information: NCT00375219, NCT00462943. [Table: see text]
Decreasing early mortality (30-day) in APL patients with use of streamlined treatment guidelines and support from core group of experts.
Authors: Jillella Anand P. , Awan Farrukh Tauseef , Pantin Jeremy Mark , Kolhe Ravindra B. , Kota Vamsi 
Published: March 2020

7091 Background: Recent evidence from population based studies in Brazil and US SEER data show that the early mortality (EM) in APL is around 30%. This is in contrast to observation in clinical trials where it is 5%. The common causes of death are hemorrhagic complications (HC), infection, differentiation syndrome (DS) and multi-organ failure. HC are unique to this condition due to DIC and HC are seen in upto 60% of patients. Hence, decreasing early deaths is a high priority at all leukemia treatment centers. We report our updated results showing that use of set of streamlined treatment guidelines along with support from experts decreases early deaths. Methods: At Georgia Regents University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. 7 patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high mortality rate of 37%. All patients who survived induction are still in remission at present. The high early death rate prompted us to develop a simple, 2 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. We also made our treatment protocol available to smaller treatment centers and helped the treating oncologists manage the patient during the first few days after diagnosis. Results: From 11/2010 to 12/2012, we treated 5 patients at GRU and helped manage 9 patients at 5 practices. Age range was 30-60 years. 4 patients were high-risk, 7 intermediate and three low-risk. There were no deaths during induction. Only 1 patient (8%) had HC and 4 had DS. Conclusions: While we recognize that this is a small cohort, our own experience and a similar approach pioneered by investigators in Brazil clearly shows this to be an effective model to decrease early deaths in APL. We believe our experience warrants large scale implementation of our protocol in an attempt to decrease early mortality in APL. We were awarded a 1.68 million grant by the Leukemia Lymphoma Society to implement this protocol in the states of Georgia and South Carolina with a catchment population of 15 million over a 3 year period.
Multivariate analysis of factors affecting overall survival, event free survival, and 60-day mortality among AML patients treated with CPX-351 or intensive chemotherapy.
Authors: Feldman Eric Jay , Lancet Jeffrey E. , Kolitz Jonathan E. , Hogge Donna , Tallman Martin S. , Goldberg Stuart L. , Kovacsovics Tibor , Louie Arthur Chin , Cortes Jorge E. 
Published: March 2020

7100 Background: CPX-351 encapsulates cytarabine (CYT) and daunorubicin (DNR) at a 5:1 molar ratio within liposomes, enabling preferential drug uptake within leukemic blasts and intracellular release, potentially enhancing efficacy in AML. A pair of randomized Phase IIb studies in newly diagnosed older patients (pts) and younger 1st relapse AML pts reported improved rates of morphologic leukemia-free state, CR + CRi, and significant improvements in survival among previously untreated high risk (secondary) pts and among poor-risk 1st relapse pts. This report presents the results of the multivariate analyses performed on all pts treated in both studies. Methods: Patients 60-75 yo with newly diagnosed AML and ≤ 65 yo with 1st relapse AML and ECOG PS= 0-2, SCR < 2.0 mg/dL, total bilirubin < 2.0 mg/dL, ALT/AST <3x ULN, and LVEF ≥ 50% were eligible. Pts with APL, DNR exposure >368 mg/m2, active CNS leukemia, and uncontrolled infections were excluded. Pts were randomized 2:1 to receive up to 2 inductions and 2 consolidations with CPX-351 (100 u/m2; D 1, 3, 5) or CYT + DNR (7+3) for newly diagnosed pts or investigator’s choice of salvage chemotherapy for relapsed pts. Allogeneic transplantation was permitted. Univariate and multivariate Cox and logistic regression were used to assess associations between baseline characteristics and overall (OS) and event-free survival (EFS) and 60-day mortality for all pts. The multivariate employed stepwise selection to identify statistically significant prognostic factors after accounting for potential treatment effects. Results: Patient characteristics including cytogenetics were well balanced. Significant negative prognostic factors affecting OS, EFS, and 60-day mortality included relapsed disease (Study 205 participation, HR=2.13, p<0.001), adverse cytogenetics (HR=1.52, p=0.024), and low (<3g/dL) serum albumin (HR=1.82, p=0.005). CPX-351 treatment was a significant positive factor in EFS (HR=0.62, p=0.006). Conclusions: This analysis identified and quantitated disease specific (adverse cytogenetics) and patient specific (albumin<3gm/dL) factors that can be used to better design future studies. Clinical trial information: NCT00788892 and NCT00822094.
Congestive heart failure (CHF) in acute myeloid leukemia patients during induction.
Authors: Raval Priyanka , Kota Vamsi , Zakharia Yousef , Carter Giovani , Christopherson Kala , Awan Farrukh Tauseef , Pantin Jeremy Mark , Jillella Anand P. 
Published: March 2020

7105 Background: Leukemia induction treatment is associated with significant morbidity and mortality. Myocardial stunning may be a result of chemotherapy as well as cytokines released from lysis of tumor cells leading to drop in ejection fraction (EF). When CHF is associated with sepsis, it may result in increased mortality. We report the incidence of CHF in leukemia patients undergoing induction. Methods: We performed a retrospective chart review on patients diagnosed with AML including acute promyelocytic leukemia (APL), who received chemotherapy between December 1, 2004 and December 31, 2012 at Georgia Regents University. Baseline and follow up EFs were recorded by echocardiogram or nuclear medicine scan. We evaluated patients who had a drop in EF after the first or subsequent inductions. We excluded patients who had a delayed drop in EF. Results: 217 consecutive patients with AML with normal ejection fraction at diagnosis were evaluated. 18 patients (8.2%) demonstrated a decrease in EF. This included 14 patients with AML and 4 with APL. 15 patients received one cycle of induction, 2 received re-induction and 1 was treated for relapsed disease. 2 patients did not receive anthracyclines(ACs). Median age of patients with CHF was 57 years (range 29-75). The median drop in EF was 23% (10-45%). Median days from the start of treatment to the observed drop were 25 (5-109). 6 patients are alive with median survival of 175 days. Overall, 5 out of 18 patients recovered their cardiac function with a median survival in these patients of 1,173 days. In 13 patients without recovery in EF survival was only 71 days. Conclusions: Chemotherapy by itself and cytokines released from treatment may result in reversible drop in EF in some patients and a persistent drop in the others. Re-induction is essential in a significant proportion of patients and ACs are commonly used that puts them at an increased risk for CHF. We propose that repeat cardiac evaluation, especially in patients getting re-induced, is necessary for identifying patients with cardiac abnormalities to prevent further cardiac injury and increased mortality.
Pregnancy outcome in chronic myeloid leukemia patients on imatinib therapy.
Authors: Dasgupta Swati , Mukhopadhyay Ashis , Ray Ujjal Kanti , Gharami Firoj Hossain , Basu Chinmay Kumar , Mukhopadhyay Soma 
Published: March 2020

7114 Background: Now that imatinib is being used to treat thousands of chronic myeloid leukemia (CML) patients for more than 10 year it is highly probable that many patients will get pregnant during its use. Company warns against any such use. But the fact remains that there is need for planned pregnancies in indicated cases. So we selected few cases both male and female for such pregnancies by interrupting treatment and following the pregnancy closely. Their outcome was studied so that we have an idea about what best could be suggested in such instance. Methods: From November 2002 to May 2010, 634 patients with CML in any stage of the disease were treated with imatinib at our tertiary cancer research institute. We selected 22 (12 females and 10 males) cases of pregnancies by interrupting treatment. We reported 9 accidental pregnancies and 13 planned pregnancies involving 22 patients who or their wives conceived while receiving imatinib for the treatment of CML. Results: Among 22 pregnancies there were 3 spontaneous abortions and 4 elective abortions. In case of 7 female patients, 3 and 4 were male and female babies respectably and in case of six male patients 4 and 4 were male and female babies. Two babies were with congenital anomaly such as one Hypospandium and one Mild-Hydrocephalus (in case of unplanned pregnancies and imatinib exposure during the first trimester of organogenesis). Conclusions: In conclusion, exposure to Imatinib during pregnancy might result in an increased risk of serious fetal abnormalities or spontaneous abortions. Women of childbearing potential should use adequate contraception while using Imatinib. We can suggest that planned pregnancy during therapy should be encouraged but imatinib therapy in unplanned pregnancy can cause spontaneous abortion or minor congenital anomaly.
Detection of the NRAS Q61R mutation in Erdheim-Chester disease.
Authors: Diamond Eli L. , Pentsova Elena , Borsu Laetitia , Chiu April E. , Hyman David Michael , Rosenblum Marc 
Published: March 2020

7120 Background: There is a high frequency of activating mutations in proteins of the Ras/Raf/MEK/ERK pathway in melanoma and other solid tumors. The BRAF V600E mutation has been found recently to be highly prevalent in ECD, a rare non-Langerhans cell histiocytosis with poor prognosis, as well as Langerhans cell histiocytosis (LCH). Treatment of patients with ECD and the BRAF V600E mutation with vemurafenib has been associated with unprecedented and dramatic response in a few cases. Methods: We present a 66 year-old man evaluated for several months of cognitive and motor decline. He was found to have multifocal enhancing lesions in the cerebral meninges, multiple masses in the abdomen and sacrum, and abnormal nuclear uptake in the long bones of the legs. Results: Biopsy of a renal mass demonstrated a foamy CD68+/CD1a- histiocytic infiltrate, consistent with ECD. Interrogation of tumor tissue with the Sequenom MassArray system demonstrated absence of the BRAF V600E mutation but presence of the NRAS Q61R mutation. Conclusions: This is, to our knowledge, the first report of an activating NRAS mutation in ECD. The finding of an oncogenic NRAS mutation in ECD further supports the hypothesis that this disease is driven by activation of the Ras/Raf/MEK/ERK pathway. Further investigation into the role of this pathway in ECD and LCH is warranted and may open new opportunities for targeted therapies for these disorders.