bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arsenic trioxide, ascorbic acid, filgrastim and erythropoietin for the treatment of myelodysplastic syndromes
Authors: Khera N. , Miske H. , Shadduck R. K. , Rossetti J. M. , Lister J. 
Published: March 2020

17519 Background: Arsenic trioxide (ATO) has been reported to have activity when used as monotherapy for the myelodysplastic syndromes (MDS). Herein we report the results of MDS patients treated with ATO as a differentiating agent coupled with ascorbic acid and cytokine pharmacotherapy. Methods: Nine patients with MDS, regardless of IPSS category and prior treatment, were enrolled in this study. Patients with the proliferative variant of CMML and those with significant cardiac dysfunction or a prolonged QT interval were excluded. They received ATO and ascorbic acid combined with growth factors. All patients received induction therapy with ATO at 0.25 mg/kg IV infusion daily x 5 for one week, followed by twice weekly for seven weeks. Responders were eligible for one consolidation cycle of twice weekly ATO for eight weeks. Four patients received one cycle of consolidation. G-CSF 300 mcg was given thrice weekly and EPO 40,000 units twice weekly. Ascorbic acid 1 gm was given intravenously 30 minutes after each dose of ATO. Response to treatment was assessed using the International Working Group (IWG) criteria for MDS. Results: Median age of patients was 69.5 years (range = 56 to 83 years). IPSS scores were: Int-1 = 5, Int-2 = 2, High = 2. Patients had received prior therapy with azacitidine (n = 8), cytokines (n = 4), and transfusions alone (n = 1). The overall response rate was 56% (5/9): partial response (PR) = 2, hematologic improvement (HI) = 3. Platelet responses were seen in 44% of patients (4/9). Four patients had stable disease (44%). The average duration of response for PR and HI was 122 days and 70 days, respectively. The overall median duration of HI was 3.5 months (range = 0.6 to 4.1 months). There were no cytogenetic responses noted in four evaluable patients. Four patients died during the study. Two patients died due to disease related illness and two due to complications of their comorbid conditions. No treatment related mortality was seen. Conclusions: Arsenic trioxide in combination with ascorbic acid and cytokines has activity in patients with MDS. Larger studies are necessary to establish the efficacy of this regimen earlier in the treatment schema of MDS. No significant financial relationships to disclose.
The comparison of clinical features between JAK2V617F positive and negative subgroups of essential thrombocythemia
Authors: Zhang S. , Li J. , Lu M. 
Published: March 2020

17523 Background: JAK2V617F is a novel molecular mechanisms of BCR/ABL-negative MPD especially polycythemia vera. However, its role may not be clearly identified in essential thrombocythemia (ET). Methods: To investigate its prevalence and clinical significance in Chinese ET patients, Allele-Specific PCR (AS-PCR) in combination with sequence analysis were introduced to screen JAK2V617F mutation in our research. Genomic DNA of 40 ET patients was extracted from peripheral blood mononuclear cells, and AS-PCR was firstly adopted to amplify the exon 12 of JAK2 gene which harbored V617F mutation. The positive samples with JAK2V617F mutation were further confirmed by sequence analysis. In addition, the features of JAK2V617F positive and negative subgroup were compared according to laboratory examination. Results: The JAK2V617F mutation was identified in 18 ET patients (45%, 18/40) by AS-PCR and sequence analysis. Its presence is significantly associated with a higher hemoglobin, hematocrit and neutrophilic granulocyte percentage in ET patients. Conclusions: AS-PCR is a sensitive and accurate technique in identification of JAK2V617F mutation. JAK2V617F mutation is of important significance in Chinese ET patients. Moreover, this ET subgroup may be prone to transform to polycythemia vera. No significant financial relationships to disclose.
Grade 3/4 adverse events (AEs) of second generation tyrosine kinase inhibitors (TKIs) for imatinib resistant/intolerant patients in accelerated phase CML (AP-CML)
Authors: Snedecor S. J. , Stephens J. M. , Carpiuc K. T. , Liou S. Y. , Botteman M. F. 
Published: March 2020

17525 Background: Toxicity profiles of targeted therapies for resistant CML may impact the resources required to manage patients (pts). The objective of this study was to systematically compare the rates of Grade 3/4 AEs reported for nilotinib and dasatinib in imatinib resistant/intolerant AP-CML in preparation for development of an economic analysis. Methods: A systematic literature review was conducted using online databases to identify published articles, registration studies, or abstracts of trials for nilotinib 400 mg bid or dasatinib 70 mg bid in AP-CML. The base case incidence rates were based on accelerated phase pt data from the dasatinib product label and the nilotinib phase II pivotal trial which had similar median durations of drug exposure of ∼5 months. Grade 3/4 AEs were selected because of likely economic impact for medical treatment/monitoring. The ranges (if available) for incidence of AEs were summarized from other papers/abstracts to provide ranges for sensitivity analyses. Results: The incidence of Grade 3/4 AEs having likely economic impact and occurring in >5% of pts are reported in the table . Rates of Grade 3/4 hematologic AEs for dasatinib were 1.8–2.6 times higher than those for nilotinib. Biochemistry abnormalities occurring in >5% of pts included lipase increase for nilotinib in 6.7%, and hypophosphatemia (13%) and hypocalcemia (9%) for dasatinib. Grade 3/4 non-hematologic AEs such as pleural/pericardial effusions were also higher for dasatinib than nilotinib, though they occurred in <5% of the population. Conclusions: The toxicity profiles of the second generation TKIs for imatinib resistant/intolerant AP-CML are different. Nilotinib’s lower rates of Grade 3/4 hematologic AEs and GI hemorrhage may result in reduced resource utilization. Further analysis is required to understand the economic impact of the differences in safety profiles. [Table: see text] No significant financial relationships to disclose.
Is autologous graft versus host disease (AutoGVHD) really reactivation of Epstein-Barr virus (EBV)?
Authors: Bitran J. D. , Ragam A. , Rowan J. , Klein L. , Majcher C. , Hurd M. 
Published: March 2020

17526 Background: AutoGVHD is a rare complication following autologous bone marrow transplantation(ABMT). It has been described as an autoimmune syndrome initiated by auto-effector T cells that recognize self-major histocompatibility complex class II antigens. AutoGVHD can be induced with immunosuppresives such as cyclosporine and alemtuzumab. Methods: We wish to report two patients among 17 patients who underwent ABMT this year of what was intially thought to be AutoGVHD but in both instances was really reactivation of EBV. Results: A 70 year old white man underwent ABMT for relapsed AML M2 in second CR. The conditioning regimen was cyclophosphamide and busulfan (BuCy). His hospital was uneventful and the prophylatic antibiotics used were ciprofloxacin, fluconazole, and valacyclovir. Neutropenic fever occured on day +11 and prophylatic antibiotics were discontinued and replaced with intravenous vancomycin, piperacillin&tazobactam, and caspofugin. Engraftment occured on day +15 and the patient was discharged on day + 20 on oral valacyclovir and fluconazole. An AutoGVHD rash occurred on day+29. The second patient was a 67 year old white with a stage IIIAE mantle cell lynphoma who underwent ABMT in first CR with the BEAM+rituximab regimen. His hospital course was uneventful; he received the identical prophylatic antibiotic regimen. Engraftment occured on day +12 and he was discharged on valacyclovir and fluconazole. On day +14 he developed an AutoGVHD rash. The first patient underwent a skin biopsy which showed a spongiotic dermatitis with intraepithelial vesicular formation and dermal perivascular lymphocytes. The immunostains of the lymphocytes showed a predominance of CD4 T cells. Immunostains for CMV, EBV, HSV1 and 2 were nonreactive. Serum antibodies to the Early EBV antigen and EBV capsid (IgG) and EBV nuclear (IgG) were elevated. Serologies for Human Herpes Virus 6, 7, and 8 were negative. The second patient had elevated antibodies to the Early EBV antigen, EBV capsid antigen, and the EBV nuclear antigen. He had elevated antibodies to Human Herpes Virus 6. Conclusions: These two patient suggests that what clinically is thought to be AutoGVHD may indeed be reactivation of EBV. The incidence of reactivation of EVB in ABMT needs to be studied prospectively. No significant financial relationships to disclose.
The cytogenetic features of Chinese patients with myeloproliferative diseases
Authors: Duan L. , Zhang S. , Li J. 
Published: March 2020

17533 Background: To investigate the cytogenetic features in Chinese patients with myeloproliferative diseases(MPD). Methods: The chromosomal abnormalities of 98 newly diagnosed essential thrombocytosis(ET) patients and 50 newly diagnosed polycythemia vera(PV) patients were studied by conventional cytogenetics (CC) and R-banding technique. Interphase fluorescence in situ hybridization (FISH) were used to detect trisomy 8 in 50 ET cases and detect trisomies 8 and 9 in 50 PV and 8 normal individuals. Results: CC showed 6.12% (6/98) of ET patients had chromosomal abnormalities including 1 case with 13q-, 2 with 5q-, 1 with 7q-, 1 with der(14)t(1;14) and 1 with Rob(13;14). FISH detected 1 case with trisomy 8 among 50 cases. CC showed 6% (3/50) of PV patients had chromosomal abnormalities including trisomy 8, deletion of chromosome Y and inversion of chromosome 11. FISH detected two cases of trisomy 8, including the confirmed one by CC technique, and one case of trisomy 9 neglected by CC technique. Conclusions: In our study, the incidence of chromosomal abnormalities in MPD by CC was rare. The frequency of trisomies 8 and 9was low in untreated MPD. No significant financial relationships to disclose.
EBV-positive lymphoproliferative disease with medullar, splenic and hepatic infiltration after imatinib mesylate therapy for chronic myeloid leukemia with two relapses and rituximab resistance
Authors: Leguay T. , Foucaud C. , Parrens M. , Fitoussi O. , Bouabdallah K. , Belaud-Rotureau M. , Tabrizi R. , Marit G. , Pigneux A. , Milpied N. 
Published: March 2020

17536 Background: Imatinib mesylate has transformed the management of the patients with chronic myeloid leukemia (CML). Initially, few undesirable effects was described. In 2003, Bekkenk presented the first EBV-positive cutaneous B-cell lymphoproliferative disease during imatinib mesylate therapy with disappearance of the cutaneous tumor after interruption of the specific inhibitor of BCR-ABL. Methods: Results: We reported a case of first EBV-positive lymphoproliferative disease with diffuse infiltration. Our patient 59 years old female was treated with imatinib mesylate for CML in chronic phase. CML was diagnosed on 2003 and imatinib mesylate therapy (400 mg/day) was initiated. A CCR was achieved after six months and a major molecular response after eighteen months. EBV-positive lymphoproliferative disease was diagnosed on 2005 and interruption of imatinib mesylate have not demonstrated efficiency. A response was initially obtained after treatment with rituximab alone, but our patient relapsed after reintroduction of imatinib at the same dose. A retreatment with rituximab have permitted a second biological complete remission and disappearance of clinical abnormalities but during only few months. At the second relapse, the disease transformed into a CD20-negative diffuse large B cell lymphoma and became resistant to rituximab therapy. Nevertheless, the lymphoproliferative disease remained responsive to conventional chemotherapy with CHOP and Interferon-alpha. Conclusions: Imatinib mesylate has modified the evolution of CML with an improvement of overall survival. In vitro studies have shown that imatinib mesylate is able to inhibit the proliferation and the activation of T-cells, and to reduce significantly the antigen-triggered expansion of CD8+ T cells in response to immunodominant EBV peptides. We speculate that such an effect might have occurred in our patient. Despite a growing number of patient receiving this tyrosine kinase inhibitor, case reports of EBV-positive lymphoproliferation disease remain rare. No significant financial relationships to disclose.
Non-myeloablative peripheral blood stem cell transplant in a patient with platelet (HPA) mismatch and pre-existing anti-donor platelet alloantibodies
Authors: Greene M. R. , Szczepiorkowski Z. , Meehan K. R. 
Published: March 2020

17541 Background: Platelets display a series of polymorphic epitopes which are known as the human platelet alloantigen (HPA) system. Alloantibodies directed against these HPA epitopes cause platelet destruction resulting in thrombocytopenia and refractoriness to platelet transfusions. We describe the rare and unique clinical course of a 61 year old patient with relapsed Non-Hodgkin’s lymphoma (NHL) who received an HLA matched, sibling, non-myeloablative, peripheral blood stem cell transplant (PBSCT) who had alloantibodies directed against a mismatched donor HPA antigen prior to transplant. Methods: The patient received a conditioning regimen of fludarabine (25 mg/m2 QD x4) and cyclophosphamide (1 g/m2 QD x2) followed by stem cell infusion. Graft versus host disease prophylaxis consisted of cyclosporine (1.5 mg/kg BID) and methotrexate (10 mg/m2 QD x 3) per routine protocol. Additionally, to protect donor platelets against the recipient’s alloantibody, the patient received 500 mg/kg gamma globulin (IVIG) on day -2 and +5. Results: The anticipated period of pancytopenia developed, with neutrophil and platelet engraftment occurring on day 19 and 29, respectively. The patient required only two platelet transfusions and did not experience bleeding. The patient remains in remission four years post transplant. Her platelet count is normal off immunosuppression. Conclusions: We have demonstrated that non-myeloablative transplant is possible in an HPA mismatched graft with detectable recipient anti-donor HPA alloantibodies using IVIG prophalaxis, in addition to routine immunosuppression. This has not been previously reported. We additionally provide a timeline showing time to platelet recovery and anti-platelet antibody kinetics that will be helpful in directing the care of future patients. No significant financial relationships to disclose.
The clinical implications of JAK2V617F mutation in idiopathic myelofibrosis
Authors: Li W. , Zhang S. , Li J. 
Published: March 2020

17542 Background: JAK2V617F is a novel molecular mechanisms of BCR/ABL-negative MPD especially polycythemia vera. However, its role may not be well clarified in idiopathic myelofibrosis (IMF). Methods: To investigate its prevalence and clinical significance in Chinese IMF patients, Allele-Specific PCR (AS-PCR) in combination with sequence analysis were introduced to screen JAK2V617F mutation in our research. Genomic DNA of 12 IMF patients was extracted from peripheral blood mononuclear cells, and AS-PCR was firstly adopted to amplify the exon 12 of JAK2 gene which harbored V617F mutation. The positive samples with JAK2V617F mutation were further confirmed by sequence analysis. In addition, the clinical features of JAK2V617F positive and negative subgroup were compared. Results: The JAK2V617F mutation was identified in 6 IMF patients (50%, 6/12) by AS-PCR and sequence analysis. Its presence is significantly associated with a higher platelet counts, megakaryocyte counts of bone marrow and incidence rate of thrombosis in IMF patients. Conclusions: AS-PCR is a sensitive and accurate technique in identification of JAK2V617F mutation. JAK2V617F mutation of our research is similar to other reports. Moreover, the clinical process of JAK2V617F positive subgroup may be more invasive in comparison with JAK2V617F negative subgroup. No significant financial relationships to disclose.
Treatment patterns and clinical outcomes in lung cancer patients with brain metastasis
Authors: Gingerich J. R. , Lau E. , Xie L. , Navaratnam S. 
Published: March 2020

18010 Background: Controversies still exist in the optimal management of patients with meta- static brain cancer. Lung cancer is the most common cause of metastatic brain cancer and the present study examines the treatment pattern and clinical outcome of this group of patients. Methods: Using the provincial cancer registry, all patients in Manitoba, Canada, with a history of lung cancer diagnosed with brain metastases during 2003 and 2004 were identified and a detailed chart review was carried out. Univariate and multivariate logistic analysis were used to identify significant variables affecting 1-year survival. Results: A total of 229 patients were identified of which 112 were male. The median age was 65 (range = 39–90). Of these patients, 69% had non-small cell lung cancer, 17% had small cell cancer, and 14% did not have the histological diagnosis available. A single brain metastasis, 2–4 brain metastases, and >4 brain metastases was identified in 25%, 25%, and 44% of the patients, respectively. The treatments for brain metastases were surgery (8%), gamma-knife radiosurgery (GKS) (7%), whole brain radiotherapy (WBRT) (62%), and no treatment (22%). Median survival for all patients was 98 days. On univariate analysis, 1-year survival was significantly influenced by surgery/GKS, age < 65, and controlled systemic disease (Odds ratio = 7.90; 5.43; 3.72 respectively, P < 0.02 for all) but not by sex, number of brain metastases or time from initial diagnosis to brain metastasis. On multivariate analysis, surgery/GKS and age remained significant (Odds ratio = 5.56, and 4.80, P < 0.01). Median survival (days) by treatment type were: surgery/GKS = 297(178–461), WBRT = 105(82–119), none = 39(29–50); log rank <0.001. Conclusions: In our patient population, with metastatic brain cancer arising from the lung, aggressive focal therapy (surgery or GKS) in younger patients (< 65) was associated with significantly better overall survival. No significant financial relationships to disclose.
Phase I trial of Seneca Valley Virus (NTX-010), a newly discovered systemically deliverable oncolytic picornavirus, in patients with solid tumors with neuroendocrine features
Authors: Rudin C. M. , Lansey D. , Burroughs K. D. , Hales L. M. , Neefe J. R. , Reddy P. S. , Hallenbeck P. L. 
Published: March 2020

18014 Background: NTX-010 is a replication-competent cytolytic picornavirus with selective tropism for cancers with neuroendocrine features. NTX-010 mediates high selective cytotoxicity for tumor cells with neuroendocrine properties and has no cytotoxicity on any human adult cell type tested. Antitumor efficacy has been demonstrated in 11/11 xenograft models, including metastatic, orthotopic, and syngeneic models. Intravenous (IV) administration of doses as low as 107 vp/kg are effective in xenograft models of small cell lung cancer. No significant toxicity in animals is seen at doses up to 1013 vp/kg. Methods: We initiated a single dose administration phase I dose-escalation study in patients with advanced solid tumors with neuroendocrine markers (CD56+, synaptophysin+, or chromogranin A+), starting at 107 vp/kg IV over 1h. Planned dose escalation is in log increments. Results: The first dose cohort has been completed, with no dose-limiting toxicities observed. Low grade fever, chills, arthralgias and myalgias starting 3 - 4 days after virus administration and lasting less than a week have been noted. The first study subject, with a widely metastatic small cell cancer with bladder invasion, demonstrated viral replication in vivo peaking d4 with >10,000-fold amplification of the input dose. This subject had complete clearance of infectious virus by day 17, but persistence of viral RNA detectable by RT-PCR in blood and urine until the time of her death from metastatic cancer on day 28. Autopsy demonstrated extensive intratumoral necrosis, and immunohistochemistry confirmed the presence of NTX-010 capsid protein in liver metastases but not adjacent normal liver. Conclusions: NTX-010 is a novel first-in-class anticancer virus with selective tropism for tumors with neuroendocrine features. This is the first anticancer virus given intravenously with documented selective intratumoral infection and replication. Administration was well tolerated. Safety data and viral kinetics will be presented. No significant financial relationships to disclose.
A phase II study of oxaliplatin and pemetrexed plus bevacizumab in advanced non-squamous non-small cell lung cancer
Authors: Waples J. M. , Auerbach M. , Boccia R. , Wiggans R. G. , Steis R. 
Published: March 2020

18025 Background: As single agents, oxaliplatin and pemetrexed have shown activity in patients with non-small cell lung cancer (NSCLC) and pemetrexed has demonstrated synergistic effectiveness when combined with platinum-based drugs. Moreover, bevacizumab has an additive effect on many chemotherapy agents in several tumor types, including NSCLC. The purpose of this phase II, open-label, non- randomized study is to evaluate the efficacy and safety of the combination of bevacizumab, oxaliplatin, and pemetrexed as first-line treatment for NSCLC. This report presents preliminary safety information demonstrating the safety and tolerability of this combination. Methods: Patients = 18 years with histologically/pathologically confirmed Stage IIIB/IV non-squamous NSCLC received 6 cycles of oxaliplatin (120 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) on Day 1 of each 21-day cycle. Following 6 cycles, patients received bevacizumab alone every 21 days until disease progression or unacceptable toxicity. Results: At the time of analysis, 53 subjects received study medication and are evaluable for safety. Patient characteristics include: gender male/female/unknown, 16/34/3; median age 62.0 years (range 43–86); and ECOG performance status 0/1/unknown, 24/25/4. The median number of cycles administered is 4 (range 1–11). Fifty patients are still on study. The most common Grade 3 toxicities were neutropenia (10.4%), dyspnea (6.0%), fatigue (4.5%), thrombocytopenia (4.5%), hyperglycemia (4.5%), nausea (3.0%), and vomiting (3.0%). Grade 4 toxicities were dyspnea (1.5%), hyperglycemia (1.5%), asthenia (1.5%), thrombocytopenia (3.0%), neutropenia (3.0%), and pulmonary embolism (1.5%). Three patients died; 2 of progressive disease and 1 of hypoxia (not likely related to study drugs). Conclusions: These preliminary results suggest that the combination of oxaliplatin, pemetrexed, and bevacizumab demonstrates an acceptable safety profile for first-line treatment of stage IIIB/IV NSCLC. Conclusions concerning the efficacy of this combination await further treatment information. Supported by Genentech, Inc., Sanofi-Aventis, and Eli Lilly and Company. [Table: see text]